Transcutaneous bilirubinometry versus total serum bilirubin measurement for newborns.

BACKGROUND: Jaundice is a very common condition in newborns, affecting up to 60% of term newborns and 80% of preterm newborns in the first week of life. Jaundice is caused by increased bilirubin in the blood from the breakdown of red blood cells. The gold standard for measuring bilirubin levels is obtaining a blood sample and processing it in a laboratory. However, noninvasive transcutaneous bilirubin (TcB) measurement devices are widely available and used in many settings to estimate total serum bilirubin (TSB) levels. OBJECTIVES: To determine the diagnostic accuracy of transcutaneous bilirubin measurement for detecting hyperbilirubinaemia in newborns. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL and trial registries up to 18 August 2022. We also checked the reference lists of all included studies and relevant systematic reviews for other potentially eligible studies. SELECTION CRITERIA: We included cross-sectional and prospective cohort studies that evaluated the accuracy of any TcB device compared to TSB measurement in term or preterm newborn infants (0 to 28 days postnatal age). All included studies provided sufficient data and information to create a 2 × 2 table for the calculation of measures of diagnostic accuracy, including sensitivities and specificities. We excluded studies that only reported correlation coefficients. DATA COLLECTION AND ANALYSIS: Two review authors independently applied the eligibility criteria to all citations from the search and extracted data from the included studies using a standard data extraction form. We summarised the available results narratively and, where possible, we combined study data in a meta-analysis. MAIN RESULTS: We included 23 studies, involving 5058 participants. All studies had low risk of bias as measured by the QUADAS 2 tool. The studies were conducted in different countries and settings, included newborns of different gestational and postnatal ages, compared various TcB devices (including the JM 101, JM 102, JM 103, BiliChek, Bilitest and JH20-1C) and used different cutoff values for a positive result. In most studies, the TcB measurement was taken from the forehead, sternum, or both. The sensitivity of various TcB cutoff values to detect significant hyperbilirubinaemia ranged from 74% to 100%, and specificity ranged from 18% to 89%. AUTHORS' CONCLUSIONS: The high sensitivity of TcB to detect hyperbilirubinaemia suggests that TcB devices are reliable screening tests for ruling out hyperbilirubinaemia in newborn infants. Positive test results would require confirmation through serum bilirubin measurement.

A Network Meta-Analysis of Intravenous Versus Oral Acetaminophen for Patent Ductus Arteriosus.

The use of acetaminophen to close a PDA in preterm infants is increasing; however, the most effective route of administration is not yet known. This network meta-analysis compares the efficacy of IV versus PO routes of acetaminophen administration on clinical outcomes related to the presence of a PDA in preterm neonates. Medline, Embase, Cochrane Central Register of Controlled Trials, Embase, Web of Science, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform were searched from inception to October 2020. A total 21 randomized controlled trials in neonates less than 37 weeks at birth, comparing oral or intravenously administered acetaminophen to close a PDA based on study criteria were included. Two authors extracted data independently and in duplicate. All outcomes were binary, and a frequentist network meta-analysis was performed. After one or two courses, both PO and IV acetaminophen were efficacious in closing a PDA with oral ranking higher than IV (low confidence). Neither medication was better than no treatment for secondary outcomes of NEC or BPD (moderate and low confidence respectively). We did not test the rectal route of acetaminophen administration and cannot make generalized statements. This study suggests oral acetaminophen increases the odds of being able to close a PDA in preterm neonates when compared to IV acetaminophen.

A Quality Improvement Project to Reduce Time to Full Enteral Feeds for Very Low Birth Weight Neonates.

BACKGROUND: Adherence to standardized feeding guidelines has been proposed as a strategy to limit morbidity in very low birth weight neonates. Fostering adherence limits the variability in medicine that affects the quality of patient care. The aim of this study was to reduce by 20% the time to full enteral feeds in very low birth weight neonates in the NICU within a 12-month period. METHODS: In a level IV regional perinatal center with low utilization of its feeding protocol, a 12-month quality improvement project was conducted with a key intervention of a feeding schedule calculator based on the unit standardized feeding protocol. Through studied education and implementation cycles, these feeding schedules were used to reduce time to full enteral feeds while monitoring adverse events related to their use. RESULTS: During the course of this quality improvement project, our time to full enteral feeds of 160 ml/kg/day of feeds reduced from 24.7 days to 17.7 days after process changes with special-cause variation noted on control charts. We also showed a significant reduction in mean central line duration over the course of the project from a baseline of 19 days to 14.5 days. CONCLUSION: Through a key intervention of a feeding volume calculator, we were able to reduce the time to full enteral feeds in neonates without any increase in adverse events of necrotizing enterocolitis or poor weight gain.

Factors related to passing the safety fast test among neonates with hypoglycaemia in the neonatal intensive care unit.

AIM: To investigate the success rates and predictors of safety fast test among neonates admitted to the neonatal intensive care unit for hypoglycaemia. METHODS: A retrospective review of neonates transferred from the newborn nursery unit to the neonatal intensive care unit for intravenous dextrose therapy for hypoglycaemia from January 2016 to June 2019. Neonatal clinical and demographic variables were abstracted from the medical records. A successful safety fast test was defined by blood glucose >60 mg/dL (3.3 mmol/L) at 3, 4, 5 and 6 h after a feed. RESULTS: Of the 76 neonates who had a safety fast test, 80% passed on their first attempt. Neonates who passed the safety fast test were less likely to be premature/small for gestational age (54.1% vs. 92.9%, P = 0.03), required less maximum glucose infusion rate (median 6 vs. 7 mg/kg/min; P = 0.04), and were younger at fasting challenge (median 5 vs. 9 days; P = 0.02), required lower overall intravenous glucose load (median 12 vs. 24 g/kg; P = 0.006). CONCLUSION: Safety fast test may be a useful tool evaluating discharge readiness of neonates with persistent hypoglycaemia.

Gene therapy for sickle cell disease.

BACKGROUND: Sickle cell disease encompasses a group of genetic disorders characterized by the presence of at least one hemoglobin S (Hb S) allele, and a second abnormal allele that could allow abnormal haemoglobin polymerisation leading to a symptomatic disorder. Autosomal recessive disorders (such as sickle cell disease) are good candidates for gene therapy because a normal phenotype can be restored in diseased cells with only a single normal copy of the mutant gene. This is an update of a previously published Cochrane Review. OBJECTIVES: The objectives of this review are: - to determine whether gene therapy can improve survival and prevent symptoms and complications associated with sickle cell disease; - to examine the risks of gene therapy against the potential long-term gain for people with sickle cell disease. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which comprises of references identified from comprehensive electronic database searches and searching relevant journals and abstract books of conference proceedings. We also searched online trial registries, Date of the most recent search of the Group's Haemoglobinopathies Trials Register: 21 September 2020. SELECTION CRITERIA: All randomised or quasi-randomised clinical trials (including any relevant phase 1, 2 or 3 trials) of gene therapy for all individuals with sickle cell disease, regardless of age or setting. DATA COLLECTION AND ANALYSIS: No trials of gene therapy for sickle cell disease were found. MAIN RESULTS: No trials of gene therapy for sickle cell disease were reported. AUTHORS' CONCLUSIONS: No randomised or quasi-randomised clinical trials of gene therapy for sickle cell disease were reported. Thus, no objective conclusions or recommendations in practice can be made on gene therapy for sickle cell disease. This systematic review has identified the need for well-designed, randomised controlled trials to assess the benefits and risks of gene therapy for sickle cell disease.

Ultrasound imaging versus palpation method for diagnostic lumbar puncture in neonates and infants: a systematic review and meta-analysis.

IMPORTANCE: Lumbar puncture (LP) failure rates vary and can be as high as 65%. Ultrasound guidance could increase the success of performing LP. OBJECTIVE: To summarise the evidence on the use of ultrasound guidance versus palpation method for LP. DATA SOURCES: We searched computerised databases and published indexes, registries and references identified from bibliographies of pertinent articles without any language restrictions to find studies that compared ultrasound guidance to palpation method for performing an LP. STUDY SELECTION: Studies were included if they were randomised or quasirandomised trials in neonates and infants that compared ultrasound guidance with palpation method for performing an LP. DATA EXTRACTION AND SYNTHESIS: Standardised data collection tool was used for data extraction, and two reviewers independently assessed the quality of the studies. MAIN OUTCOMES AND MEASURES: The primary outcome was the risk of LP failure, while the risk of traumatic tap, needle redirections/reinsertions and procedure durations were secondary outcomes. RESULTS: Data from four studies and 308 participants is included in the analysis. Ultrasound imaging reduced the risk of LP failure, risk ratio of 0.58 (95% CI 0.15 to 2.28), but it was not statistically significant (p=0.44). Ultrasound imaging significantly reduced the risk of a traumatic tap risk ratio of 0.33 (95% CI 0.13 to 0.82) and p=0.02. The included studies had low to moderate quality; the studies differed based on mean age and with variability on outcome definition. CONCLUSIONS AND RELEVANCE: This meta-analysis suggests that ultrasound imaging has no effect in increasing lumbar success but is beneficial in reducing the risk of traumatic taps in neonates and infants. TRIAL REGISTRATION NUMBER: CRD42017055800.

Gene therapy for sickle cell disease.

BACKGROUND: Sickle cell disease encompasses a group of genetic disorders characterized by the presence of at least one hemoglobin S (Hb S) allele, and a second abnormal allele that could allow abnormal hemoglobin polymerisation leading to a symptomatic disorder.Autosomal recessive disorders (such as sickle cell disease) are good candidates for gene therapy because a normal phenotype can be restored in diseased cells with only a single normal copy of the mutant gene. This is an update of a previously published Cochrane Review. OBJECTIVES: The objectives of this review are:- to determine whether gene therapy can improve survival and prevent symptoms and complications associated with sickle cell disease;- to examine the risks of gene therapy against the potential long-term gain for people with sickle cell disease. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which comprises of references identified from comprehensive electronic database searches and searching relevant journals and abstract books of conference proceedings. We also searched online trial registries,Date of the most recent search of the Group's Haemoglobinopathies Trials Register: 19 July 2018. SELECTION CRITERIA: All randomised or quasi-randomised clinical trials (including any relevant phase 1, 2 or 3 trials) of gene therapy for all individuals with sickle cell disease, regardless of age or setting. DATA COLLECTION AND ANALYSIS: No trials of gene therapy for sickle cell disease were found. MAIN RESULTS: No trials of gene therapy for sickle cell disease were reported. AUTHORS' CONCLUSIONS: No randomised or quasi-randomised clinical trials of gene therapy for sickle cell disease were reported. Thus, no objective conclusions or recommendations in practice can be made on gene therapy for sickle cell disease. This systematic review has identified the need for well-designed, randomised controlled trials to assess the benefits and risks of gene therapy for sickle cell disease.

Newborn follow-up after discharge from a tertiary care hospital in the Western Cape region of South Africa: a prospective observational cohort study.

BACKGROUND: Current practice in the Western Cape region of South Africa is to discharge newborns born in-hospital within 24 h following uncomplicated vaginal delivery and two days after caesarean section. Mothers are instructed to bring their newborn to a clinic after discharge for a health assessment. We sought to determine the rate of newborn follow-up visits and the potential barriers to timely follow-up. METHODS: Mother-newborn dyads at Tygerberg Hospital in Cape Town, South Africa were enrolled from November 2014 to April 2015. Demographic data were obtained via questionnaire and medical records. Mothers were contacted one week after discharge to determine if they had brought their newborns for a follow-up visit, and if not, the barriers to follow-up. Factors associated with follow-up were analyzed using logistic regression. RESULTS: Of 972 newborns, 794 (82%) were seen at a clinic for a follow-up visit within one week of discharge. Mothers with a higher education level or whose newborns were less than 37 weeks were more likely to follow up. The follow-up rate did not differ based on hospital length of stay. Main reported barriers to follow-up included maternal illness, lack of money for transportation, and mother felt follow-up was unnecessary because newborn was healthy. CONCLUSIONS: Nearly 4 in 5 newborns were seen at a clinic within one week after hospital discharge, in keeping with local practice guidelines. Further research on the outcomes of this population and those who fail to follow up is needed to determine the impact of postnatal healthcare policy.

Incidence, Predictors, and Outcomes of Permanent Pacemaker Implantation Following Transcatheter Aortic Valve Replacement: Analysis From the U.S. Society of Thoracic Surgeons/American College of Cardiology TVT Registry.

OBJECTIVES: The purpose of this study was to evaluate the incidence, predictors, and clinical outcomes of permanent pacemaker (PPM) implantation following transcatheter aortic valve replacement (TAVR). BACKGROUND: Conduction abnormalities leading to PPM implantation are common complications following TAVR. Whether PPM placement can be predicted or is associated with adverse outcomes is unclear. METHODS: A retrospective cohort study of patients undergoing TAVR in the United States at 229 sites between November 2011 and September 2014 was performed using the Society of Thoracic Surgeons/American College of Cardiology TVT Registry and the Centers for Medicare and Medicaid Services database. RESULTS: PPM placement was required within 30 days of TAVR in 651 of 9,785 patients (6.7%) and varied among those receiving self-expanding valves (25.1%) versus balloon-expanding valves (4.3%). Positive predictors of PPM implantation were age (per 5-year increment, odds ratio: 1.07; 95% confidence interval [CI]: 1.01 to 1.15), prior conduction defect (odds ratio: 1.93; 95% CI: 1.63 to 2.29), and use of self-expanding valve (odds ratio: 7.56; 95% CI: 5.98 to 9.56). PPM implantation was associated with longer median hospital stay (7 days vs. 6 days; p < 0.001) and intensive care unit stay (56.7 h vs. 45.0 h; p < 0.001). PPM implantation was also associated with increased mortality (24.1% vs. 19.6%; hazard ratio [HR]: 1.31; 95% CI: 1.09 to 1.58) and a composite of mortality or heart failure admission (37.3% vs. 28.5%; hazard ratio HR: 1.33; 95% CI: 1.13 to 1.56) at 1 year but not with heart failure admission alone (16.5% vs. 12.9%; HR: 1.23; 95% CI: 0.92 to 1.63). CONCLUSIONS: Early PPM implantation is a common complication following TAVR, and it is associated with higher mortality and a composite of mortality or heart failure admission at 1 year.

Gene therapy for sickle cell disease.

BACKGROUND: Sickle cell disease encompasses a group of genetic disorders characterized by the presence of at least one hemoglobin S (Hb S) allele, and a second abnormal allele that could allow abnormal hemoglobin polymerisation leading to a symptomatic disorder.Autosomal recessive disorders (such as sickle cell disease) are good candidates for gene therapy because a normal phenotype can be restored in diseased cells with only a single normal copy of the mutant gene. This is an update of a previously published Cochrane Review. OBJECTIVES: The objectives of this review are:to determine whether gene therapy can improve survival and prevent symptoms and complications associated with sickle cell disease;to examine the risks of gene therapy against the potential long-term gain for people with sickle cell disease. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which comprises of references identified from comprehensive electronic database searches and searching relevant journals and abstract books of conference proceedings.Date of the most recent search of the Group's Haemoglobinopathies Trials Register: 15 August 2016. SELECTION CRITERIA: All randomised or quasi-randomised clinical trials (including any relevant phase 1, 2 or 3 trials) of gene therapy for all individuals with sickle cell disease, regardless of age or setting. DATA COLLECTION AND ANALYSIS: No trials of gene therapy for sickle cell disease were found. MAIN RESULTS: No trials of gene therapy for sickle cell disease were reported. AUTHORS' CONCLUSIONS: No randomised or quasi-randomised clinical trials of gene therapy for sickle cell disease were reported. Thus, no objective conclusions or recommendations in practice can be made on gene therapy for sickle cell disease. This systematic review has identified the need for well-designed, randomised controlled trials to assess the benefits and risks of gene therapy for sickle cell disease.

Ablation of Complex Fractionated Atrial Electrograms for Atrial Fibrillation Rhythm Control: A Systematic Review and Meta-analysis.

BACKGROUND: Pulmonary vein isolation (PVI) has become an increasingly important therapy in the management of atrial fibrillation (AF), however, the best procedural techniques to ensure success have not been determined. We assessed the incremental benefit of complex fractionated atrial electrograms (CFAEs) ablation for AF rhythm control. METHODS: PubMed, Embase, CENTRAL, and Clinicaltrials.gov databases were searched up until May 7, 2015. Included were randomized controlled trials that compared PVI with PVI and CFAEs ablation (PVI+) with a minimum of 3 months' follow-up. Statistical analysis was performed with Review Manager version 5.3 (Cochrane Collaboration, Oxford, United Kingdom). Categorical and continuous outcomes were reported as summary risk differences and mean differences (MDs), respectively. P < 0.05 was considered statistically significant for all analyses. RESULTS: Ten randomized controlled trials randomized patients to PVI+ (n = 635) and PVI (n = 427) with follow-up ranging from 3 to 23 months. There was no significant difference in freedom from atrial tachyarrhythmias without antiarrhythmic agents after a single ablation between PVI+ and PVI (313 of 635 vs 230 of 427; risk difference, 0.01 [95% confidence interval (CI)-0.08 to 0.10]; P = 0.78; I(2) = 52%). Findings were not different for any prespecified subgroup analyses, including paroxysmal vs nonparoxysmal AF, automated vs manual detection of CFAEs, and left atrial vs biatrial ablation. PVI+ led to significantly increased procedure time (MD, 49.81 minutes [95% CI 42.86-56.76]; P < 0.001), fluoroscopy time (MD, 11.55 minutes [95% CI 8.02-15.07]; P < 0.001), and radiofrequency energy application time (MD, 19.16 minutes [95% CI 6.61-31.70]; P = 0.003) compared with PVI. CONCLUSIONS: Ablation of CFAEs in addition to PVI did not increase freedom from atrial tachyarrhythmias but procedural times were increased.

Association Between Implementation of a Cardiovascular Step-Down Unit and Process-of-Care Outcomes in Patients With Congenital Heart Disease.

BACKGROUND: The Joint Commission's 2009 National Patient Safety Goals aimed to improve identification of and response to clinical deterioration in hospital-ward patients. Some hospitals implemented intermediate-care units for patients without intensive care-level support needs. No studies have evaluated what effect changes associated with a move to a pediatric cardiovascular step-down unit (CVSDU) has on process-of-care outcomes. METHODS: A retrospective cohort study comparing process-of-care outcomes in units caring for children with congenital heart disease (n=1415) 1 year before (July 1, 2010-June 30, 2011) and 1 year after (August 1, 2011-July 30, 2012) implementation of a CVSDU following the move to a new hospital building. Units caring for noncardiac tracheostomy and/or ventilator-dependent patients were used as controls (n=606). Primary outcomes included length of stay (LOS) and transfers to higher levels of care. Secondary outcomes included rapid response team, cardiopulmonary arrest, and code blue rates. Mann-Whitney U and z tests were used for all analyses. RESULTS: When compared with a medical-surgical unit, cardiac patients admitted to a CVSDU had a significantly decreased total LOS (median 7.0 vs 5.4 days, P=.03), non-ICU LOS (median 3.5 vs 3.0 days, P=.006), and rapid response team/code blue rate per 1000 non-ICU patient days (11.2 vs 7.0, P=.04). No significant differences in primary or secondary outcomes were seen within the control group. CONCLUSIONS: Changes associated with a new CVSDU were associated with decreased LOS and lower rates of rapid response and code blue events for patients with congenital heart disease.

Gene therapy for sickle cell disease.

BACKGROUND: Sickle cell disease encompasses a group of genetic disorders characterized by the presence of at least one hemoglobin S (Hb S) allele, and a second abnormal allele that could allow abnormal hemoglobin polymerisation leading to a symptomatic disorder.Autosomal recessive disorders (such as sickle cell disease) are good candidates for gene therapy because a normal phenotype can be restored in diseased cells with only a single normal copy of the mutant gene. OBJECTIVES: The objectives of this review are:- to determine whether gene therapy can improve survival and prevent symptoms and complications associated with sickle cell disease;- to examine the risks of gene therapy against the potential long-term gain for people with sickle cell disease. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which comprises of references identified from comprehensive electronic database searches and searching relevant journals and abstract books of conference proceedings.Date of the most recent search of the Group's Haemoglobinopathies Trials Register: 21 July 2014. SELECTION CRITERIA: All randomised or quasi-randomised clinical trials (including any relevant phase 1, 2 or 3 trials) of gene therapy for all individuals with sickle cell disease, regardless of age or setting. DATA COLLECTION AND ANALYSIS: No trials of gene therapy for sickle cell disease were found. MAIN RESULTS: No trials of gene therapy for sickle cell disease were reported. AUTHORS' CONCLUSIONS: No randomised or quasi-randomised clinical trials of gene therapy for sickle cell disease were reported. Thus, no objective conclusions or recommendations in practice can be made on gene therapy for sickle cell disease. This systematic review has identified the need for well-designed, randomised controlled trials to assess the benefits and risks of gene therapy for sickle cell disease.

Hypertensive disorders of pregnancy and risk of screening positive for Posttraumatic Stress Disorder: A cross-sectional study.

OBJECTIVES: Hypertensive Disorders of Pregnancy (HDP) encompass a spectrum of disorders that affect 6-8% of US pregnancies. We aim to determine the impact of self-reported history of HDP as a risk factor for screening positive for Posttraumatic Stress Disorder (PTSD), which results from exposure to a traumatic event, and to evaluate whether the risk of PTSD differed by severity of HDP. STUDY DESIGN: We conducted an online survey on the Preeclampsia Foundation website that is accessed worldwide by women who have experienced HDP, as well as their friends and family. 1448 women in total responded to the survey, including 1076 women who reported a history of HDP in at least one prior pregnancy and 372 women who reported no history of HDP during any prior pregnancy. MAIN OUTCOME MEASURES: We measured PTSD outcome with the Breslau Short Screening Scale for DSM-IV PTSD. We used logistic regression to model the relationship between PTSD and HDP. RESULTS: Women who reported a history of HDP were more than four times as likely to screen positive for PTSD than women who reported having a normotensive pregnancy history (ORadj=4.46, 95% CI: 3.20-6.20). In addition, there was a marked trend toward increasing risk of screening positive for PTSD as the severity of HDP increased from gestational hypertension to eclampsia (p<0.001). CONCLUSIONS: Women with a history of HDP may be at increased risk of PTSD, with severe cases most likely to suffer from symptoms. Clinicians should consider implementing routine screenings during post-partum visits in this vulnerable population.

Gene therapy for sickle cell disease.

BACKGROUND: Sickle cell disease encompasses a group of genetic disorders characterized by the presence of at least one hemoglobin S (Hb S) allele, and a second abnormal allele that could allow abnormal hemoglobin polymerisation leading to a symptomatic disorder.Autosomal recessive disorders (such as sickle cell disease) are good candidates for gene therapy because a normal phenotype can be restored in diseased cells with only a single normal copy of the mutant gene. OBJECTIVES: The objectives of this review are:- to determine whether gene therapy can improve survival and prevent symptoms and complications associated with sickle cell disease;- to examine the risks of gene therapy against the potential long-term gain for people with sickle cell disease. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which comprises of references identified from comprehensive electronic database searches and searching relevant journals and abstract books of conference proceedings.Date of the most recent search of the Group's Haemoglobinopathies Trials Register: 21 June 2012. SELECTION CRITERIA: All randomised or quasi-randomised clinical trials (including any relevant phase 1, 2 or 3 trials) of gene therapy for all individuals with sickle cell disease, regardless of age or setting. DATA COLLECTION AND ANALYSIS: No trials of gene therapy for sickle cell disease were found. MAIN RESULTS: No trials of gene therapy for sickle cell disease were reported. AUTHORS' CONCLUSIONS: No randomised or quasi-randomised clinical trials of gene therapy for sickle cell disease were reported. Thus, no objective conclusions or recommendations in practice can be made on gene therapy for sickle cell disease. This systematic review has identified the need for well-designed, randomised controlled trials to assess the benefits and risks of gene therapy for sickle cell disease.

Gene therapy for sickle cell disease.

BACKGROUND: Sickle cell disease encompasses a group of genetic disorders characterized by the presence of at least one hemoglobin S (Hb S) allele, and a second abnormal allele that could allow abnormal hemoglobin polymerisation leading to a symptomatic disorder.Autosomal recessive disorders (such as sickle cell disease) are good candidates for gene therapy because a normal phenotype can be restored in diseased cells with only a single normal copy of the mutant gene. OBJECTIVES: The objectives of this review are:- to determine whether gene therapy can improve survival and prevent symptoms and complications associated with sickle cell disease;- to examine the risks of gene therapy against the potential long-term gain for people with sickle cell disease. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which comprises of references identified from comprehensive electronic database searches and searching relevant journals and abstract books of conference proceedings.Date of the most recent search of the Group's Haemoglobinopathies Trials Register: 05 March 2010. SELECTION CRITERIA: All randomised or quasi-randomised clinical trials (including any relevant phase 1, 2 or 3 trials) of gene therapy for all individuals with sickle cell disease, regardless of age or setting. DATA COLLECTION AND ANALYSIS: No trials of gene therapy for sickle cell disease were found. MAIN RESULTS: No trials of gene therapy for sickle cell disease were reported. AUTHORS' CONCLUSIONS: No randomised or quasi-randomised clinical trials of gene therapy for sickle cell disease were reported. Thus, no objective conclusions or recommendations in practice can be made on gene therapy for sickle cell disease. This systematic review has identified the need for well-designed, randomised controlled trials to assess the benefits and risks of gene therapy for sickle cell disease.