Background
Dentistry is a profession with a high prevalence of work‐related musculoskeletal disorders (WMSD) among practitioners, with symptoms often starting as early in the career as the student ...phase. Ergonomic interventions in physical, cognitive, and organisational domains have been suggested to prevent their occurrence, but evidence of their effects remains unclear.
Objectives
To assess the effect of ergonomic interventions for the prevention of work‐related musculoskeletal disorders among dental care practitioners.
Search methods
We searched CENTRAL, MEDLINE PubMed, Embase, PsycINFO ProQuest, NIOSHTIC, NIOSHTIC‐2, HSELINE, CISDOC (OSH‐UPDATE), ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform (ICTRP) Search Portal to August 2018, without language or date restrictions.
Selection criteria
We included randomised controlled trials (RCTs), quasi‐RCTs, and cluster RCTs, in which participants were adults, aged 18 and older, who were engaged in the practice of dentistry. At least 75% of them had to be free from musculoskeletal pain at baseline. We only included studies that measured at least one of our primary outcomes; i.e. physician diagnosed WMSD, self‐reported pain, or work functioning.
Data collection and analysis
Three authors independently screened and selected 20 potentially eligible references from 946 relevant references identified from the search results. Based on the full‐text screening, we included two studies, excluded 16 studies, and two are awaiting classification. Four review authors independently extracted data, and two authors assessed the risk of bias. We calculated the mean difference (MD) with 95% confidence intervals (CI) for continuous outcomes and risk ratios (RR) with 95% confidence intervals for dichotomous outcomes. We assessed the quality of the evidence for each outcome using the GRADE approach.
Main results
We included two RCTs (212 participants), one of which was a cluster‐randomised trial. Adjusting for the design effect from clustering, reduced the total sample size to 210. Both studies were carried out in dental clinics and assessed ergonomic interventions in the physical domain, one by evaluating a multi‐faceted ergonomic intervention, which consisted of imparting knowledge and training about ergonomics, work station modification, training and surveying ergonomics at the work station, and a regular exercise program; the other by studying the effectiveness of two different types of instrument used for scaling in preventing WMSDs. We were unable to combine the results from the two studies because of the diversity of interventions and outcomes.
Physical ergonomic interventions. Based on one study, there is very low‐quality evidence that a multi‐faceted intervention has no clear effect on dentists' risk of WMSD in the thighs (RR 0.57, 95% CI 0.23 to 1.42; 102 participants), or feet (RR 0.64, 95% CI 0.29 to 1.41; 102 participants) when compared to no intervention over a six‐month period. Based on one study, there is low‐quality evidence of no clear difference in elbow pain (MD −0.14, 95% CI −0.39 to 0.11; 110 participants), or shoulder pain (MD −0.32, 95% CI −0.75 to 0.11; 110 participants) in participants who used light weight curettes with wider handles or heavier curettes with narrow handles for scaling over a 16‐week period.
Cognitive ergonomic interventions. We found no studies evaluating the effectiveness of cognitive ergonomic interventions.
Organisational ergonomic interventions. We found no studies evaluating the effectiveness of organisational ergonomic interventions.
Authors' conclusions
There is very low‐quality evidence from one study showing that a multi‐faceted intervention has no clear effect on dentists' risk of WMSD in the thighs or feet when compared to no intervention over a six‐month period. This was a poorly conducted study with several shortcomings and errors in statistical analysis of data. There is low‐quality evidence from one study showing no clear difference in elbow pain or shoulder pain in participants using light weight, wider handled curettes or heavier and narrow handled curettes for scaling over a 16‐week period.
We did not find any studies evaluating the effectiveness of cognitive ergonomic interventions or organisational ergonomic interventions.
Our ability to draw definitive conclusions is restricted by the paucity of suitable studies available to us, and the high risk of bias of the studies that are available. This review highlights the need for well‐designed, conducted, and reported RCTs, with long‐term follow‐up that assess prevention strategies for WMSDs among dental care practitioners.
Background
Thalassaemia is a quantitative abnormality of haemoglobin caused by mutations in genes controlling production of alpha or beta globins. Abnormally unpaired globin chains cause membrane ...damage and cell death within organ systems and destruction of erythroid precursors in the bone marrow, leading to haemolytic anaemia. The life‐long management of the general health effects of thalassaemia is highly challenging, and failure to deal with dental and orthodontic complications exacerbates the public health, financial and personal burden of the condition. There is a lack of evidence‐based guidelines to help care seekers and providers manage such dental and orthodontic complications. This review aimed to evaluate the available evidence on methods for treating dental and orthodontic complications in people with thalassaemia to inform future recommendations. This is an update of a Cochrane Review first published in 2019.
Objectives
To assess different methods for treating dental and orthodontic complications in people with thalassaemia.
Search methods
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register in September 2022, and we searched nine online databases and trials registries in January 2022. We searched the reference lists of relevant articles and reviews and contacted haematologists, experts in fields of dentistry, organisations, pharmaceutical companies and researchers working in this field.
Selection criteria
We searched for published or unpublished randomised controlled trials (RCTs) that evaluated treatment of dental and orthodontic complications in individuals diagnosed with thalassaemia, irrespective of phenotype, severity, age, sex and ethnic origin.
Data collection and analysis
Two review authors independently screened the 37,242 titles retrieved by the search. After deduplication, we identified two potentially relevant RCTs. On assessing their eligibility against our inclusion and exclusion criteria, we excluded one and included the other.
Main results
We included one parallel‐design RCT conducted in Saudi Arabia and involving 29 participants (19 males, 10 females) with thalassaemia. It aimed to assess the effectiveness of photodynamic therapy as an adjuvant to conventional full‐mouth ultrasonic scaling for the treatment of gingivitis. The average age of participants was around 23 years.
There is very low‐certainty evidence from this trial that full‐mouth ultrasonic scaling plus photodynamic therapy compared to full‐mouth ultrasonic scaling alone may improve gingival index score and bleeding on probing after 12 weeks in people with thalassaemia.
We found no studies that assessed other interventions for the various dental or orthodontic complications of thalassaemia.
Authors' conclusions
Although the included study showed greater reduction in gingivitis in the group treated with full‐mouth ultrasonic scaling plus photodynamic therapy, the evidence is of very low certainty. The study had unclear risk of bias, a short follow‐up period and no data on safety or adverse effects. We cannot make definitive recommendations for clinical practice based on the limited evidence of a single trial. Future studies will very likely affect the conclusions of this review.
This review highlights the need for high‐quality RCTs that investigate the effectiveness of various treatment modalities for dental and orthodontic complications in people with thalassaemia. It is crucial that future trials assess adverse effects of interventions.
Background
Bleeding disorders are uncommon but may pose significant bleeding complications during pregnancy, labour and following delivery for both the woman and the foetus. While many bleeding ...disorders in women tend to improve in pregnancy, thus decreasing the haemorrhagic risk to the mother at the time of delivery, some do not correct or return quite quickly to their pre‐pregnancy levels in the postpartum period. Therefore, specific measures to prevent maternal bleeding and foetal complications during childbirth, are required. The safest method of delivery to reduce morbidity and mortality in these women is controversial. This is an update of a previously published review.
Objectives
To assess the optimal mode of delivery in women with, or carriers of, bleeding disorders.
Search methods
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Coagulopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference books. We also searched the Cochrane Pregnancy and Childbirth Group's Trials Register as well as trials registries and the reference lists of relevant articles and reviews.
Date of last search of the Group's Trials Registers: 21 June 2021.
Selection criteria
Randomised controlled trials and quasi‐randomised controlled clinical trials investigating the optimal mode of delivery in women with, or carriers of, any type of bleeding disorder during pregnancy were eligible for the review.
Data collection and analysis
No trials matching the selection criteria were eligible for inclusion.
Main results
No trials matching the selection criteria were eligible for inclusion.
Authors' conclusions
The review did not identify any randomised controlled trials investigating the safest mode of delivery and associated maternal and foetal complications during delivery in women with, or carriers of, a bleeding disorder. In the absence of high quality evidence, clinicians need to use their clinical judgement and lower level evidence (e.g. from observational trials, case studies) to decide upon the optimal mode of delivery to ensure the safety of both mother and foetus.
Given the ethical considerations, the rarity of the disorders and the low incidence of both maternal and foetal complications, future randomised controlled trials to find the optimal mode of delivery in this population are unlikely to be carried out. Other high quality controlled studies (such as risk allocation designs, sequential design, and parallel cohort design) are needed to investigate the risks and benefits of natural vaginal and caesarean section in this population or extrapolation from other clinical conditions that incur a haemorrhagic risk to the baby, such as platelet alloimmunisation.
Background
Thalassaemia is a quantitative abnormality of haemoglobin caused by mutations in genes controlling production of alpha or beta globins. Abnormally unpaired globin chains cause haemolytic ...anaemia by causing membrane damage and cell death within organ systems and destruction of erythroid precursors in the bone marrow. The life‐long management of the general health effects of thalassaemia in affected individuals is a highly challenging issue in and of itself; and failure to deal with dental and orthodontic complications in people with thalassaemia exacerbates the public health, financial and personal burden posed by the condition. There exists a lack of evidence‐based guidelines for care‐seekers and providers to best deal with such dental and orthodontic complications in thalassaemia, which this review seeks to address.
Objectives
The main objective of this review was to assess different methods to treat dental and orthodontic complications in people with thalassaemia.
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 books. We searched the reference lists of relevant articles and reviews.
Date of last search: 01 August 2019.
We also 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 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: 22 July 2019.
Selection criteria
We searched for published or unpublished randomised controlled trials for treatment of dental and orthodontic complications in individuals diagnosed with thalassaemia, irrespective of phenotype, severity, age, gender and ethnic origin.
Data collection and analysis
Two review authors independently screened 35,202 titles from search results. We identified four unique randomised controlled trials, of which one seemed potentially relevant. Based on closer inspection, the trial was found not to be eligible for inclusion.
Main results
We did not find any relevant trials for inclusion in the review.
Authors' conclusions
We were unable to draw any conclusions due to the lack of available data and trials. This review highlights the need for conducting and appropriate reporting, of high‐quality randomised controlled trials investigating the effectiveness of various treatment modalities for dental and orthodontic complications in people with thalassaemia.
Background
Bleeding disorders are uncommon but may pose significant bleeding complications during pregnancy, labour and following delivery for both the woman and the foetus. While many bleeding ...disorders in women tend to improve in pregnancy, thus decreasing the haemorrhagic risk to the mother at the time of delivery, some do not correct or return quite quickly to their pre‐pregnancy levels in the postpartum period. Therefore, specific measures to prevent maternal bleeding and foetal complications during childbirth, are required. The safest method of delivery to reduce morbidity and mortality in these women is controversial. This is an update of a previously published review.
Objectives
To assess the optimal mode of delivery in women with, or carriers of, bleeding disorders.
Search methods
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Coagulopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference books. We also searched the Cochrane Pregnancy and Childbirth Group's Trials Register as well as trials registries and the reference lists of relevant articles and reviews.
Date of last search of the Group's Trials Registers: 16 February 2017.
Selection criteria
Randomised controlled trials and all types of controlled clinical trials investigating the optimal mode of delivery in women with, or carriers of, any type of bleeding disorder during pregnancy were eligible for the review.
Data collection and analysis
No trials matching the selection criteria were eligible for inclusion
Main results
No results from randomised controlled trials were found.
Authors' conclusions
The review did not identify any randomised controlled trials investigating the safest mode of delivery and associated maternal and foetal complications during delivery in women with, or carriers of, a bleeding disorder. In the absence of high quality evidence, clinicians need to use their clinical judgement and lower level evidence (e.g. from observational trials, case studies) to decide upon the optimal mode of delivery to ensure the safety of both mother and foetus.
Given the ethical considerations, the rarity of the disorders and the low incidence of both maternal and foetal complications, future randomised controlled trials to find the optimal mode of delivery in this population are unlikely to be carried out. Other high quality controlled studies (such as risk allocation designs, sequential design, and parallel cohort design) are needed to investigate the risks and benefits of natural vaginal and caesarean section in this population or extrapolation from other clinical conditions that incur a haemorrhagic risk to the baby, such as platelet alloimmunisation.
Background
Sickle cell disease is the most common single gene disorder and the commonest haemoglobinopathy found with high prevalence in many populations across the world. Management of dental ...complications in people with sickle cell disease requires special consideration for three main reasons. Firstly, dental and oral tissues are affected by the blood disorder resulting in several oro‐facial abnormalities. Secondly, living with a haemoglobinopathy and coping with its associated serious consequences may result in individuals neglecting their oral health care. Finally, the treatment of these oral complications must be adapted to the systemic condition and special needs of these individuals, in order not to exacerbate or deteriorate their general health.
Guidelines for the treatment of dental complications in this population who require special care are unclear and even unavailable in many aspects. Hence this review was undertaken to provide a basis for clinical care by investigating and analysing the existing evidence in the literature for the treatment of dental complications in people with sickle cell disease. This is an update of a previously published review.
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 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.
Background
Sickle cell disease (SCD) is a genetic chronic haemolytic and pro‐inflammatory disorder. With increased catabolism and deficits in energy and nutrient intake, individuals with SCD suffer ...multiple macro‐ and micro‐nutritional deficiencies, including vitamin D deficiency. This is an update of a previous review.
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 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.
Background
Sickle cell disease (SCD), one of the most common inherited disorders, is associated with vaso‐occlusive pain episodes and haemolysis leading to recurrent morbidity, hospital admissions ...and work or school absenteeism. The crises are conventionally treated with opioids, non‐opioids and other adjuvants with the risk of developing complications, addictions and drug‐seeking behaviour. Different non‐pharmacological treatments, such as transcutaneous electrical nerve stimulation (TENS) have been used for managing pain in other painful conditions. Hence, the efficacy of TENS for managing pain in SCD needs to be reviewed.
Objectives
To assess the benefits and harms of TENS for managing pain in people with SCD who experience pain crises or chronic pain (or both).
Search methods
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Register, comprising of references identified from comprehensive electronic database searches and handsearches of relevant journals and books of conference proceedings. We also searched online trial registries and the reference lists of relevant articles and reviews.
Date of the last search: 26 Febraury 2020.
Selection criteria
We included randomised controlled trials (RCTs) and quasi‐RCTs, where TENS was evaluated for managing pain in people with SCD.
Data collection and analysis
Two review authors independently assessed the eligibility of the trials identified by the literature searches according to the inclusion criteria. Two review authors then independently extracted data, assessed for risk of bias using the Cochrane standard tool and rated the quality of evidence using the GRADE guidelines.
Main results
One double‐blind cross‐over RCT with 22 participants with SCD (aged 12 to 27 years) was eligible for inclusion. Following stratification into four pain crises severity grades, participants were then randomised to receive TENS or placebo (sham TENS). The trial was concluded after 60 treatment episodes (30 treatment episodes of each treatment group).
There is a lack of clarity regarding the trial design and the analysis of the cross‐over data. If a participant was allocated to TENS treatment for an episode of pain and subsequently returned with a further episode of a similar degree of pain, they would then receive the sham TENS treatment (cross‐over design). For those experiencing a pain episode of a different severity, it is not clear whether they were re‐randomised or given the alternate treatment. Reporting and analysis was based on the total number pain events and not on the number of participants. It is unclear how many participants were crossed over from the TENS group to the sham TENS group and vice versa. The trial had a high risk of bias regarding random sequence generation and allocation concealment; an unclear risk regarding the blinding of participants and personnel; and a low risk regarding the blinding of the outcome assessors and selective outcome reporting.
The trial was small and of very low quality; furthermore, given the issue with trial design we were unable to quantitatively analyse the data. Therefore, we present only a narrative summary and caution is advised in interpreting the results. In relation to our pre‐defined primary outcomes, the included trial did not report pain relief at two to four weeks post intervention. The trial authors reported that no difference was found in the changes in pain ratings (recorded at one hour and four hours post intervention) between the TENS and the placebo groups. In relation to our secondary outcomes, the analgesic usage during the trial also did not show any difference between groups. Given the quality of the evidence, we are uncertain whether TENS improves overall satisfaction as compared to sham TENS. The ability to cope with activities of daily living was not evaluated. Regarding adverse events, although one case of itching was reported in the TENS group, the site and nature of itching was not clearly stated; hence it cannot be clearly attributed to TENS. Also, two participants receiving 'sham' TENS reported a worsening of pain with the intervention.
Authors' conclusions
Since we have only included one small and very low‐quality trial, with a high risk of bias across several domains, we are unable to conclude whether TENS is harmful or beneficial for managing pain in people with SCD. There is a need for a well‐designed, adequately‐powered, RCT to evaluate the role of TENS in managing pain in people with SCD.
Background
Sickle cell disease (SCD) is a group of disorders that affects haemoglobin, which causes distorted sickle‐ or crescent‐shaped red blood cells. It is characterized by anaemia, increased ...susceptibility to infections and episodes of pain. The disease is acquired by inheriting abnormal genes from both parents, the combination giving rise to different forms of the disease. Due to increased erythropoiesis in people with SCD, it is hypothesized that they are at an increased risk for folate deficiency. For this reason, children and adults with SCD, particularly those with sickle cell anaemia, commonly take 1 mg of folic acid orally every day on the premise that this will replace depleted folate stores and reduce the symptoms of anaemia. It is thus important to evaluate the role of folate supplementation in treating SCD.
Objectives
To analyse the efficacy and possible adverse effects of folate supplementation (folate occurring naturally in foods, provided as fortified foods or additional supplements such as tablets) in people with SCD.
Search methods
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group’s Haemoglobinopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and books of conference proceedings. We also conducted additional searches in both electronic databases and clinical trial registries.
Date of last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group’s Haemoglobinopathies Trials Register: 17 November 2017.
Selection criteria
Randomised, placebo‐controlled trials of folate supplementation for SCD.
Data collection and analysis
Four review authors assessed We used the standard Cochrane‐defined methodological procedures.
Four review authors independently assessed the eligibility and risk of bias of the included trials and extracted and analysed the data included in the review. The quality of the evidence was assessed using GRADE.
Main results
One trial, undertaken in 1983, was eligible for inclusion in the review. This was a double‐blind placebo‐controlled quasi‐randomised triaI of supplementation of folic acid in people with SCD. A total of 117 children with homozygous sickle cell (SS) disease aged six months to four years of age participated over a one‐year period (analysis was restricted to 115 children).
Serum folate measures, obtained after trial entry at six and 12 months, were available in 80 of 115 (70%) participants. There were significant differences between the folic acid and placebo groups with regards to serum folate values above 18 µg/L and values below 5 µg/L (low‐quality evidence). In the folic acid group, values above 18 µg/L were observed in 33 of 41 (81%) compared to six of 39 (15%) participants in the placebo (calcium lactate) group. Additionally, there were no participants in the folic acid group with serum folate levels below 5 µg/L, whereas in the placebo group, 15 of 39 (39%) participants had levels below this threshold. Haematological indices were measured in 100 of 115 (87%) participants at baseline and at one year. After adjusting for sex and age group, the investigators reported no significant differences between the trial groups with regards to total haemoglobin concentrations, either at baseline or at one year (low‐quality evidence). It is important to note that none of the raw data for the outcomes listed above were available for analysis.
The proportions of participants who experienced certain clinical events were analysed in all 115 participants, for which raw data were available. There were no statistically significant differences noted; however, the trial was not powered to investigate differences between the folic acid and placebo groups with regards to: minor infections, risk ratio (RR) 0.99 (95% confidence interval (CI) 0.85 to 1.15) (low‐quality evidence); major infections, RR 0.89 (95% CI 0.47 to 1.66) (low‐quality evidence); dactylitis, RR 0.67 (95% CI 0.35 to 1.27) (low‐quality evidence); acute splenic sequestration, RR 1.07 (95% CI 0.44 to 2.57) (low‐quality evidence); or episodes of pain, RR 1.16 (95% CI 0.70 to 1.92) (low‐quality evidence). However, the investigators reported a higher proportion of repeat dactylitis episodes in the placebo group, with two or more attacks occurring in 10 of 56 participants compared to two of 59 in the folic acid group (P < 0.05).
Growth, determined by height‐for‐age and weight‐for‐age, as well as height and growth velocity, was measured in 103 of the 115 participants (90%), for which raw data were not available. The investigators reported no significant differences in growth between the two groups.
The trial had a high risk of bias with regards to random sequence generation and incomplete outcome data. There was an unclear risk of bias in relation to allocation concealment, outcome assessment, and selective reporting. Finally, There was a low risk of bias with regards to blinding of participants and personnel. Overall the quality of the evidence in the review was low.
There were no trials identified for other eligible comparisons, namely: folate supplementation (fortified foods and physical supplementation with tablets) versus placebo; folate supplementation (naturally occurring in diet) versus placebo; folate supplementation (fortified foods and physical supplementation with tablets) versus folate supplementation (naturally occurring in diet).
Authors' conclusions
One doubIe‐blind, placebo‐controlled triaI on folic acid supplementation in children with SCD was included in the review. Overall, the trial presented mixed evidence on the review's outcomes. No trials in adults were identified. With the limited evidence provided, we conclude that, while it is possible that folic acid supplementation may increase serum folate levels, the effect of supplementation on anaemia and any symptoms of anaemia remains unclear.
If further trials were conducted, these may add evidence regarding the efficacy of folate supplementation. Future trials should assess clinical outcomes such as folate concentration, haemoglobin concentration, adverse effects and benefits of the intervention, especially with regards to SCD‐related morbidity. Such trials should include people with SCD of all ages and both sexes, in any setting. To investigate the effects of folate supplementation, trials should recruit more participants and be of longer duration, with long‐term follow‐up, than the trial currently included in this review. However, we do not envisage further trials of this intervention will be conducted, and hence the review will no longer be regularly updated.
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
The main objective of this review is to assess different methods to treat dental and orthodontic complications ...in people with thalassaemia.
The term 'dental complications' is used to represent all oral infections, diseases and conditions affecting the teeth, jaws, orofacial region and associated structures, such as dental caries, periodontal disease, odontogenic infections, osteomyelitis, cellulitis etc. Under 'orthodontic complications' we will include craniofacial deformities, jaw abnormalities, malocclusion or any other condition necessitating orthodontic and its adjunctive treatment procedures including orthognathic surgery.
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