OBJECTIVES: To assess methods of treating dental complications in people with sickle cell disease.
SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Review Group's Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. Date of last search: 01 August 2019. Additionally, we searched nine online databases (PubMed, Google Scholar, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Literature in the Health Sciences in Latin America and the Caribbean database, African Index Medicus, Index Medicus for South East Asia Region, Index Medicus for the Eastern Mediterranean Region, Indexing of Indian Medical Journals). We also searched the reference lists of relevant articles and reviews and contacted haematologists, experts in fields of dentistry, organizations, pharmaceutical companies and researchers working in this field. Date of last search: 07 November 2019.
SELECTION CRITERIA: We searched for published or unpublished randomised controlled studies of treatments for dental complications in people with sickle cell disease.
DATA COLLECTION AND ANALYSIS: Two review authors intended to independently extract data and assess the risk of bias of the included studies using standard Cochrane methodologies; however, no studies were identified for inclusion in the review.
MAIN RESULTS: No randomised controlled studies were identified.
AUTHORS' CONCLUSIONS: This Cochrane Review did not identify any randomised controlled studies assessing interventions for the treatment of dental complications in people with sickle cell disease. There is an important need for randomised controlled studies in this area, so as to identify the most effective and safe method for treating dental complications in people with sickle cell disease.
OBJECTIVES: To investigate the hypothesis that vitamin D supplementation increases serum 25-hydroxyvitamin D level in children and adults with sickle cell disease.To determine the effects of vitamin D supplementation on general health such as growth status and health-related quality of life; on musculoskeletal health including bone mineral density, pain crises, bone fracture and muscle health; on respiratory health which includes lung function tests, acute chest syndrome, acute exacerbation of asthma and respiratory infections; and the safety of vitamin D supplementation in children and adults with sickle cell disease.
SEARCH METHODS: We searched the Cochrane Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched database such as PubMed, clinical trial registries and the reference lists of relevant articles and reviews.Date of last search: 15 December 2016.
SELECTION CRITERIA: Randomised controlled studies and quasi-randomised controlled studies (controlled clinical studies) comparing oral administration of any form of vitamin D supplementation to another type of vitamin D or placebo or no supplementation at any dose and for any duration, in people with sickle cell disease, of all ages, gender, and phenotypes including sickle cell anaemia, haemoglobin sickle cell disease and sickle beta-thalassaemia diseases.
DATA COLLECTION AND ANALYSIS: Two authors independently extracted the data and assessed the risk of bias of the included study. They used the GRADE guidelines to assess the quality of the evidence.
MAIN RESULTS: One double-blind randomised controlled study including 46 people with sickle cell disease (HbSS, HbSC, HbSβ+thal and HbSβ0thal) was eligible for inclusion in this review. Of the 46 enrolled participants, seven withdrew before randomisation leaving 39 participants who were randomised. Only 25 participants completed the full six months of follow up. Participants were randomised to receive oral vitamin D3 (cholecalciferol) (n = 20) or placebo (n = 19) for six weeks and were followed up to six months. Two participants from the treatment group have missing values of baseline serum 25-hydroxyvitamin D, therefore the number of samples analysed was 37 (vitamin D n = 18, placebo n = 19).The included study had a high risk of bias with regards to incomplete outcome data (high dropout rate in the placebo group), but a low risk of bias for other domains such as random sequence generation, allocation concealment, blinding of participants, personnel and outcome assessors, selective outcome reporting; and an unclear risk of other biases.Compared to the placebo group, the vitamin D group had significantly higher serum 25-hydroxyvitamin D (25(OH)D) levels at eight weeks, mean difference 29.79 (95% confidence interval 26.63 to 32.95); at 16 weeks, mean difference 12.67 (95% confidence interval 10.43 to 14.90); and at 24 weeks, mean difference 15.52 (95% confidence interval 13.50 to 17.54). We determined the quality of the evidence for this outcome to be moderate. There was no significant difference of adverse events (tingling of lips or hands) between the vitamin D and placebo groups, risk ratio 3.16 (95% confidence interval 0.14 to 72.84), but the quality of the evidence was low. Regarding the frequency of pain, the vitamin D group had significantly fewer pain days compared to the placebo group, mean difference -10.00 (95% confidence interval -16.47 to -3.53), but again the quality of the evidence was low. Furthermore, the review included physical functioning PedsQL scores which was reported as absolute change from baseline. The vitamin D group had a lower (worse) health-related quality of life score than the placebo group but this was not significant at eight weeks, mean difference -2.02 (95% confidence interval -6.34 to 2.30). However, the difference was significant at both 16 weeks, mean difference -12.56 (95% confidence interval -16.44 to -8.69) and 24 weeks, mean difference -12.59 (95% confidence interval -17.43 to -7.76). We determined the quality of evidence for this outcome to be low.
AUTHORS' CONCLUSIONS: We included only one low-quality clinical study which had a high risk of bias with regards to incomplete outcome data. Therefore, we consider that the evidence is not of sufficient quality to guide clinical practice. Until further evidence becomes available, clinicians should consider the relevant existing guidelines for vitamin D supplementation (e.g. the Endocrine Society Clinical Practice Guidelines) and dietary reference intakes for calcium and vitamin D (e.g. from the USA Institute of Medicine). Evidence of vitamin D supplementation in sickle cell disease from high quality studies is needed. Well-designed, randomised, placebo-controlled studies of parallel design, are required to determine the effects and the safety of vitamin D supplementation in children and adults with sickle cell disease.
OBJECTIVES: To determine the effectiveness of ACE inhibitor administration in people with sickle cell disease for decreasing intraglomerular pressure, microalbuminuria and proteinuria and to to assess the safety of ACE inhibitors as pertains to their adverse effects.
SEARCH METHODS: The authors searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Hameoglobinopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of the most recent search: 03 June 2015.
SELECTION CRITERIA: Randomized or quasi-randomized controlled trials of ACE inhibitors designed to reduce microalbuminuria and proteinuria in people with sickle cell disease compared to either placebo or standard treatment regimen.
DATA COLLECTION AND ANALYSIS: Three authors independently applied the inclusion criteria in order to select studies for inclusion in the review. Two authors assessed the risk of bias of studies and extracted data and the third author verified these assessments.
MAIN RESULTS: Five studies were identified through the searches, only one met our inclusion criteria. The included study randomized 22 participants (seven males and 15 females) having proteinuria or microalbuminuria with sickle cell disease and treated the participants for six months (median length of follow up of three months) with captopril or placebo. The overall quality of the outcomes reported was high, since most aspects that may contribute to bias were regarded to be of low risk, although allocation concealment was not reported. At six months, the study reported no significant difference in urinary albumin excretion between the captopril group and the placebo group, although the mean urinary albumin excretion in the captopril group was lower by a mean difference of -49.00 (95% confidence interval -124.10 to 26.10) compared to that of placebo. However, our analysis on the absolute change score showed significant changes between the two groups by a mean difference of -63.00 (95% confidence interval -93.78 to -32.22). At six months albumin excretion in the captopril group was noted to decrease from baseline by a mean of 45 ± 23 mg/day and the placebo group was noted to increase by 18 ± 45 mg/day. Serum creatinine and potassium levels were reported constant throughout the study. The potential for inducing hypotension should be highlighted; the study reported a decrease of 8 mmHg in systolic pressure and 5 mmHg in diastolic and mean blood pressure.
AUTHORS' CONCLUSIONS: There is not enough evidence to show that the administration of ACE inhibitors is associated with a reduction of microalbuminuria and proteinuria in people with sickle cell disease, although a potential for this was seen. More long-term studies involving multiple centers and larger cohorts using a randomized-controlled design are warranted, especially among the pediatric age group. Detailed reporting of each outcome measure is necessary to allow a clear cut interpretation in a systematic review. One of the difficulties encountered in this review was the lack of detailed data reported in the included study.
OBJECTIVES: To investigate the effects of vitamin D supplementation in children and adults with SCD and to compare different dose regimens. To determine the effects of vitamin D supplementation on general health (e.g. growth status and health-related quality of life), on musculoskeletal health (including bone mineral density, pain crises, bone fracture and muscle health), on respiratory health (including lung function, acute chest syndrome, acute exacerbation of asthma and respiratory infections) and the safety of vitamin D supplementation.
SEARCH METHODS: We searched the Cochrane Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. Date of last search: 19 March 2020. We also searched database such as PubMed, clinical trial registries and the reference lists of relevant articles and reviews. Date of last search: 14 January 2020.
SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs comparing oral administration of any form of vitamin D supplementation at any dose and for any duration to another type or dose of vitamin D or placebo or no supplementation in people with SCD, of all ages, gender, and phenotypes.
DATA COLLECTION AND ANALYSIS: Two authors independently extracted the data and assessed the risk of bias of the included studies. They used the GRADE guidelines to assess the quality of the evidence.
MAIN RESULTS: Vitamin D versus placebo One double-blind RCT (n = 39) compared oral vitamin D3 (cholecalciferol) supplementation (20 participants) to placebo (19 participants) for six weeks. Only 25 participants completed the full six months of follow-up. The study had a high risk of bias due to incomplete outcome data, but a low risk of bias for randomisation, allocation concealment, blinding (of participants, personnel and outcome assessors) and selective outcome reporting; and an unclear risk of other biases. Vitamin D supplementation probably led to higher serum 25(OH)D levels at eight weeks, mean difference (MD) 29.79 (95% confidence interval (CI) 26.63 to 32.95); at 16 weeks, MD 12.67 (95% CI 10.43 to 14.90); and at 24 weeks, MD 15.52 (95% CI 13.50 to 17.54) (moderate-quality evidence). There was little or no difference in adverse events (tingling of lips or hands) between the vitamin D and placebo groups, risk ratio 3.16 (95% CI 0.14 to 72.84) (low-quality evidence). Vitamin D supplementation probably caused fewer pain days compared to the placebo group at eight weeks, MD -10.00 (95% CI -16.47 to -3.53) (low-quality evidence), but probably led to a lower (worse) health-related quality of life score (change from baseline in physical functioning PedsQL scores); at both 16 weeks, MD -12.56 (95% CI -16.44 to -8.69) and 24 weeks, MD -12.59 (95% CI -17.43 to -7.76), although this may not be the case at eight weeks (low-quality evidence). Vitamin D supplementation regimens compared Two double-blind RCTs (83 participants) compared different regimens of vitamin D. One RCT (n = 62) compared oral vitamin D3 7000 IU/day to 4000 IU/day for 12 weeks, while the second RCT (n = 21) compared oral vitamin D3 100,000 IU/month to 12,000 IU/month for 24 months. Both RCTs had low risk of bias for blinding (of participants, personnel and outcome assessors) and incomplete outcome data, but the risk of selective outcome reporting bias was high. The bias from randomisation and allocation concealment was low in one study but not in the second. There was an unclear risk of other biases. When comparing oral vitamin D 100,000 IU/month to 12,000 IU/month, the higher dose may have resulted in higher serum 25(OH)D levels at one year, MD 16.40 (95% CI 12.59 to 20.21) and at two years, MD 18.96 (95% CI 15.20 to 22.72) (low-quality evidence). There was little or no difference in adverse events between doses (low-quality evidence). There were more episodes of acute chest syndrome in the high-dose group, at one year, MD 0.27 (95% CI 0.02 to 0.52) but there was little or no difference at two years, MD 0.09 (95% CI -0.04 to 0.22) (moderate-quality evidence). At one year and two years there was also little or no difference between the doses in the presence of pain (moderate-quality evidence) or forced expiratory volume in one second % predicted. However, the high-dose group had lower values for % predicted forced vital capacity at both one and two years, MD -7.20% predicted (95% CI -14.15 to -0.25) and MD -7.10% predicted (95% CI -14.03 to -0.17), respectively. There were little or no differences between dose regimens in the muscle health of either hand or the dominant hand. The study comparing oral vitamin D3 7000 IU/day to 4000 IU/day (21 participants) did not provide data for analysis, but median serum 25(OH)D levels were reported to be lower in the low-dose group at both six and 12 weeks. At 12 weeks the median serum parathyroid hormone level was lower in the high-dose group.
AUTHORS' CONCLUSIONS: We included three RCTs of varying quality. We consider that the current evidence presented in this review is not of sufficient quality to guide clinical practice. Until further evidence becomes available, clinicians should consider the relevant existing guidelines for vitamin D supplementation and dietary reference intakes for calcium and vitamin D. Well-designed RCTs of parallel design, are required to determine the effects and the safety of vitamin D supplementation as well as to assess the relative benefits of different doses in children and adults with SCD.
OBJECTIVES: To evaluate the effectiveness of various techniques of laser photocoagulation therapy in sickle cell disease-related retinopathy.
SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. Date of last search: 21 September 2015.We also searched the following resources (24 March 2015): Latin American and Carribean Health Science Literature Database (LILACS); WHO International Clinical Trials Registry Platforms (ICTRP); and ClinicalTrials.gov.
SELECTION CRITERIA: Randomised controlled trials comparing laser photocoagulation to no treatment in children and adults.
DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial eligibility, the risk of bias of the included trials and extracted and analysed data. We contacted the trial authors for additional information.
MAIN RESULTS: Two trials (341 eyes of 238 children and adults) were included comparing efficacy and safety of laser photocoagulation to no therapy in people with proliferative sickle retinopathy. There were 121 males and 117 females with an age range from 13 to 67 years. The laser photocoagulation technique used was different in the two trials; one single-centre trial employed sectoral scatter laser photocoagulation using an argon laser; and the second, two-centre trial, employed feeder vessel coagulation using argon laser in one centre and xenon arc in the second centre. The follow-up period ranged from a mean of 21 to 32 months in one trial and 42 to 47 months in the second. Both trials were at risk of selection bias (random sequence generation) because of the randomisation method employed for participants with bilateral disease. One study was considered to be at risk of reporting bias.Using sectoral scatter laser photocoagulation, one trial (174 eyes) reported that complete regression of proliferative sickle retinopathy was seen in 30.2% in the laser group and 22.4% in the control group (no difference between groups). The same trial reported the development of new proliferative sickle retinopathy in 34.3% of laser-treated eyes and in 41.3% of eyes given no treatment; again, there was no difference between treatment groups. The second trial, using feeder vessel coagulation, did not present full data for either treatment group for these outcomes.There was evidence from both trials (341 eyes) that laser photocoagulation using scatter laser or feeder vessel coagulation may prevent the loss of vision in eyes with proliferative sickle retinopathy (at median follow up of 21 to 47 months). Data from both trials indicated that laser treatment prevented the occurrence of vitreous haemorrhage with both argon and xenon laser; with the protective effect being greater with feeder vessel laser treatment compared to scatter photocoagulation.Regarding adverse effects, the incidence of retinal tear was minimal, with only one event reported. Combined data from both trials were available for 341 eyes; there was no difference between the laser and control arms for retinal detachment. In relation to choroidal neovascularization, treatment with xenon arc was found to be associated with a significantly higher risk, but visual loss related to this complication is uncommon with long-term follow up of three years or more.Data regarding quality of life and other adverse effects were not reported in the included trials.
AUTHORS' CONCLUSIONS: Our conclusions are based on the data from two trials conducted over 20 years ago. In the absence of further evidence, laser treatment for sickle cell disease-related retinopathy should be considered as a one of therapeutic options for preventing visual loss and vitreous haemorrhage. However, it does not appear to have a significant different effect on other clinical outcomes such as regression of proliferative sickle retinopathy and development of new ones. No evidence is available assessing efficacy in relation to patient-important outcomes (such as quality of life or the loss of a driving licence). There is limited evidence on safety, overall, scatter argon laser photocoagulation is superior in terms of adverse effects, although feeder vessel coagulation has a better effect in preventing vitreous haemorrhage. Further research is needed to examine the safety of laser treatment compared to other interventions such as intravitreal injection of anti-vascular endothelial growth factors. In addition, patient-important outcomes as well as cost-effectiveness should be addressed.