Treatment of dental complications in sickle cell disease.

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. OBJECTIVES: To assess methods of treating dental complications in people 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.Date of last search: 11 April 2016.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: 03 March 2016. SELECTION CRITERIA: We searched for published or unpublished randomised controlled studies of treatments for dental complications in people with sickle cell disease.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.

Folate supplementation in people with sickle cell disease.

BACKGROUND: Sickle cell disease 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 sickle cell disease, it is hypothesized that they are at an increased risk for folate deficiency. For this reason, children and adults with sickle cell disease, 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 sickle cell disease. 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 sickle cell disease. 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 abstract books of conference proceedings. We also conducted additional searches in both electronic databases and clinical trial registries.Date of last search: 07 December 2015. SELECTION CRITERIA: Randomised, placebo-controlled trials of folate supplementation for sickle cell disease. DATA COLLECTION AND ANALYSIS: Four review authors assessed the eligibility and risk of bias of the included trials and extracted and analysed the data included in the review. We used the standard Cochrane-defined methodological procedures. 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 sickle cell disease. 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. 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. 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 0.99 (95% confidence interval 0.85 to 1.15); major infections, risk ratio 0.89 (95% confidence interval 0.47 to 1.66); dactylitis, risk ratio 0.67 (95% confidence interval 0.35 to 1.27); acute splenic sequestration, risk ratio 1.07 (95% confidence interval 0.44 to 2.57); or episodes of pain, risk ratio 1.16 (95% confidence interval 0.70 to 1.92). 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 sickle cell disease 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.Further trials 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 sickle cell disease-related morbidity. Trials should include people with sickle cell disease 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.

Maternal and foetal outcomes following natural vaginal versus caesarean section (c-section) delivery in women with bleeding disorders and carriers.

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. 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 abstract 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: 13 January 2015. 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 randomized 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.

Topical non-steroidal anti-inflammatory agents for diabetic cystoid macular oedema.

BACKGROUND: Diabetic cystoid macular oedema (CMO) is a condition which involves fluid accumulation in the inner portion of the retina. It often follows changes in retinal blood vessels which enhance the fluid to come out of vessels. Although it may be asymptomatic, symptoms are primarily painless loss of central vision, often with the complaint of seeing black spots in front of the eye.It is reported that CMO may resolve spontaneously, or fluctuate for months, before causing loss of vision. If left untreated or undiagnosed, progression of CMO may lead to permanent visual loss.It has been noted that patients with diabetic retinopathy have elevated inflammatory markers, and therefore it is likely that inflammation aids in the progression of vascular disease in these patients. Several topical non-steroidal anti-inflammatory drugs (NSAIDs) such as ketorolac 0.5%, bromfenac 0.09%, and nepafenac 0.1%, have therefore also been used topically to treat chronic diabetic CMO. Hence this review was conducted to find out the effects of topical NSAIDs in diabetic CMO. OBJECTIVES: To assess the effects of topical non-steroidal anti-inflammatory drugs (NSAIDs) for diabetic cystoid macular oedema (CMO). SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 12), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to January 2015), EMBASE (January 1980 to January 2015), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to January 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 12 January 2015. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs investigating the effects of topically applied NSAIDs in the treatment of people with diabetic CMO aged 18 years of age or over. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial eligibility and screened all available titles and abstracts for inclusion. There were no discrepancies and we did not have to contact trial investigators for missing data. MAIN RESULTS: We did not identify any RCTs matching the inclusion criteria for this review. AUTHORS' CONCLUSIONS: The review did not identify any RCTs investigating the effects of topical NSAIDs in the treatment of diabetic CMO. Most of the studies identified through the electronic searches had been conducted to analyse the effect of topical NSAIDs for pseudophakic CMO.In the absence of high quality evidence, clinicians need to use their clinical judgement and other low level evidence, such as observational non-randomised trials, to decide whether to use topical NSAIDs in cases of diabetic CMO.More research is needed to better understand the cause of this condition and its pathophysiology. This systematic review has identified the need for well designed, adequately powered RCTs to assess possible beneficial and adverse effects of topical NSAIDs in people with diabetic CMO. Future trials should aim to include a large sample size with an adequate follow-up period of up to one year.

Zinc supplements for treating thalassaemia and sickle cell disease.

BACKGROUND: Haemoglobinopathies, inherited disorders of haemoglobin synthesis (thalassaemia) or structure (sickle cell disease), are responsible for significant morbidity and mortality throughout the world. The WHO estimates that, globally, 5% of adults are carriers of a haemoglobin condition, 2.9% are carriers of thalassaemia and 2.3% are carriers of sickle cell disease. Carriers are found worldwide as a result of migration of various ethnic groups to different regions of the world. Zinc is an easily available supplement and intervention programs have been carried out to prevent deficiency in people with thalassaemia or sickle cell anaemia. It is important to evaluate the role of zinc supplementation in the treatment of thalassaemia and sickle cell anaemia to reduce deaths due to complications. OBJECTIVES: To assess the effect of zinc supplementation in the treatment of thalassaemia and sickle cell disease. 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 abstract books of conference proceedings.Date of most recent search: 01 February 2013. SELECTION CRITERIA: Randomised, placebo-controlled trials of zinc supplements for treating thalassaemia or sickle cell disease administered at least once a week for at least a month. DATA COLLECTION AND ANALYSIS: Two review authors assessed the eligibility and risk of bias of the included trials, extracted and analysed data and wrote the review. We summarised results using risk ratios or rate ratios for dichotomous data and mean differences for continuous data. We combined trial results where appropriate. MAIN RESULTS: We identified nine trials for inclusion with all nine contributing outcome data. Two trials reported on people with thalassaemia (n = 152) and seven on sickle cell anaemia (n = 307).In people with thalassaemia, in one trial, the serum zinc level value showed no difference between the zinc supplemented group and the control group, mean difference 47.40 (95% confidence interval -12.95 to 107.99). Regarding anthropometry, in one trial, height velocity was significantly increased in patients who received zinc supplementation for one to seven years duration, mean difference 3.37 (95% confidence interval 2.36 to 4.38) (total number of participants = 26). In one trial, however, there was no difference in body mass index between treatment groups.Zinc acetate supplementation for three months (in one trial) and one year (in two trials) (total number of participants = 71) was noted to increase the serum zinc level significantly in patients with sickle cell anaemia, mean difference 14.90 (95% confidence interval 6.94 to 22.86) and 20.25 (95% confidence interval 11.73 to 28.77) respectively. There was no significant difference in haemoglobin level between intervention and control groups, at either three months (one trial) or one year (one trial), mean difference 0.06 (95% confidence interval -0.84 to 0.96) and mean difference -0.07 (95% confidence interval -1.40 to 1.26) respectively. Regarding anthropometry, one trial showed no significant changes in body mass index or weight after one year of zinc acetate supplementation. In patients with sickle cell disease, the total number of sickle cell crises at one year were significantly decreased in the zinc sulphate supplemented group as compared to controls, mean difference -2.83 (95% confidence interval -3.51 to -2.15) (total participants 130), but not in zinc acetate group, mean difference 1.54 (95% confidence interval -2.01 to 5.09) (total participants 22). In one trial at three months and another at one year, the total number of clinical infections were significantly decreased in the zinc supplemented group as compared to controls, mean difference 0.05 (95% confidence interval 0.01 - 0.43) (total number of participants = 36), and mean difference -7.64 (95% confidence interval -10.89 to -4.39) (total number of participants = 21) respectively. AUTHORS' CONCLUSIONS: According to the results, there is no evidence from randomised controlled trials to indicate any benefit of zinc supplementation with regards to serum zinc level in patients with thalassaemia. However, height velocity was noted to increase among those who received this intervention.There is mixed evidence on the benefit of using zinc supplementation in people with sickle cell disease. For instance, there is evidence that zinc supplementation for one year increased the serum zinc levels in patients with sickle cell disease. However, though serum zinc level was raised in patients receiving zinc supplementation, haemoglobin level and anthropometry measurements were not significantly different between groups. Evidence of benefit is seen with the reduction in the number of sickle cell crises among sickle cell patients who received one year of zinc sulphate supplementation and with the reduction in the total number of clinical infections among sickle cell patients who received zinc supplementation for both three months and for one year.The conclusion is based on the data from a small group of trials,which were generally of good quality, with a low risk of bias. The authors recommend that more trials on zinc supplementation in thalassaemia and sickle cell disease be conducted given that the literature has shown the benefits of zinc in these types of diseases.