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 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.
STUDY DESIGN: Systematic review.
SETTING & POPULATION: Adults requiring maintenance hemodialysis.
SELECTION CRITERIA: All randomized controlled trials and trial protocols reporting vascular access outcomes identified from ClinicalTrials.gov, Embase, MEDLINE, and the Cochrane Kidney and Transplant Specialized Register from January 2011 to June 2016.
INTERVENTIONS: Any hemodialysis-related intervention.
OUTCOMES: The frequency and characteristics of vascular access outcome measures were analyzed and classified.
RESULTS: From 168 relevant trials, 1,426 access-related outcome measures were extracted and classified into 23 different outcomes. The 3 most common outcomes were function (136 [81%] trials), infection (63 [38%]), and maturation (31 [18%]). Function was measured in 489 different ways, but most frequently reported as "mean access blood flow (mL/min)" (37 [27%] trials) and "number of thromboses" (30 [22%]). Infection was assessed in 136 different ways, with "number of access-related infections" being the most common measure. Maturation was assessed in 44 different ways at 15 different time points and most commonly characterized by vein diameter and blood flow. Patient-reported outcomes, including pain (19 [11%]) and quality of life (5 [3%]), were reported infrequently. Only a minority of trials used previously standardized outcome definitions.
LIMITATIONS: Restricted sampling frame for feasibility and focus on contemporary trials.
CONCLUSIONS: The reporting of access outcomes in hemodialysis trials is very heterogeneous, with limited patient-reported outcomes and infrequent use of standardized outcome measures. Efforts to standardize outcome reporting for vascular access are critical to optimizing the comparability, reliability, and value of trial evidence to improve outcomes for patients requiring hemodialysis.
METHODS: Data provided by the Fukuoka Prefecture Latter-stage Elderly Insurance Association was used. There were 11,821 patients aged ≥65 years with acute coronary syndromes who were identified from 2015 to 2017. Three-level multilevel logistic regression analyses were performed to quantify the small-area and hospital variations, as well as, to identify the determinants of PCI use.
RESULTS: The results showed significant variation (δ2 = 0.744) and increased PCI use (MOR = 2.425) at the hospital level. After controlling patient- and hospital-level characteristics, a large proportional change in cluster variance was found at the hospital level (PCV 14.7%). Fixed-effect estimation results showed that females, patients aged ≥80 years old, hypertension and dyslipidemia had significant association with the use of PCI. Hospitals with high physician density had a significantly positive relationship with PCI use.
CONCLUSIONS: Patients receiving care in hospitals located in small areas have equitable access to PCI. Hospital-level variation might be originated from the oversupply of physicians. A balanced number of physicians and beds should be taken into consideration during healthcare allocation. A treatment process guideline on PCI targeting older patients is also needed to ensure a more equitable access for healthcare resources.
OBJECTIVE: The aim of this study was to evaluate regular (4-hourly prior to each oral misoprostol dose with amniotomy when feasible) compared with restricted (only if indicated) vaginal assessments during labor induction with oral misoprostol in term nulliparous women MATERIALS AND METHODS: We performed a randomized trial between November 2016 and September 2017 in a university hospital in Malaysia. Our oral misoprostol labor induction regimen comprised 50 μg of misoprostol administered 4 hourly for up to 3 doses in the first 24 hours. Participants assigned to regular assessment had vaginal examinations before each 4-hourly misoprostol dose with a view to amniotomy as soon as it was feasible. Participants in the restricted arm had vaginal examinations only if indicated. Primary outcomes were patient satisfaction with the birth process (using an 11-point visual numerical rating scale), induction to vaginal delivery interval, and vaginal delivery rate at 24 hours.
RESULTS: Data from 204 participants (101 regular, 103 restricted) were analyzed. The patient satisfaction score with the birth process was as follows (median [interquartile range]): 7 [6-9] vs 8 [6-10], P = .15. The interval of induction to vaginal delivery (mean ± standard deviation) was 24.3 ± 12.8 vs 31.1 ± 15.0 hours (P = .013). The vaginal delivery rate at 24 hours was 27.7% vs 20.4%; (relative risk [RR], 1.4; 95% confidence interval [CI], 0.8-2.3; P = .14) for the regular vs restricted arms, respectively. The cesarean delivery rate was 50% vs 43% (RR, 1.1; 95% CI, 0.9-1.5; P = .36). When assessed after delivery, participants' fidelity to their assigned vaginal examination schedule in a future labor induction was 45% vs 88% (RR, 0.5; 95% CI, 0.4-0.7; P < .001), and they would recommend their assigned schedule to a friend (47% vs 87%; RR, 0.6; 95% CI, 0.5-0.7; P < .001) in the regular compared with the restricted arms, respectively.
CONCLUSION: Despite a shorter induction to vaginal delivery interval with regular vaginal examination and a similar vaginal delivery rate at 24 hours and birth process satisfaction score, women expressed a higher preference for the restricted examination schedule and were more likely to recommend such a schedule to a friend.
METHODS: Incident HD patients without permanent vascular access encountered from January to December 2014 were included in this study. Patients were divided into 2 groups: Group 1 were encountered within 6 months prior to introduction of in-patient IPD bridging therapy in substitution of noncuffed catheter (NCC) insertion while awaiting maturation of permanent vascular access. Group 2 were encountered within 6 months after the introduction of this policy. The number of NCC and peritoneal dialysiscatheter insertion, along with catheter-related infections were evaluated during this period.
RESULTS: Approximately 450 patients were distributed in each group. We achieved 45% reduction in internal jugular catheter insertion from 322 to 180 catheters after policy change. This led to a significant drop in catheter-related blood stream infection (53%, P <0.001). On the other hand, 30% more peritoneal dialysiscatheter were inserted to accommodate our IPD bridging therapy.
CONCLUSIONS: The introduction of IPD as bridging therapy while awaiting maturation of permanent vascular access significantly reduced the utilization of NCC in incident HD patients and catherter-related blodstream infection. With this, it is our hope that it will contribute to the preservation of central vein patency.
METHOD: A strain comprising 10% direct compression and 1% compressive shear was applied to bovine chondrocytes seeded in an agarose gel during two 12-hour conditioning periods separated by a 12-hour resting period.
RESULTS: The bi-axial-loaded chondrocytes demonstrated a significant increase in glycosaminoglycan synthesis compared with samples exposed to uni-axial or no loading over the same period (p<0.05). The use of a free-swelling recovery period prior to the loading regime resulted in additional glycosaminoglycan production and a significant increase in DNA content (p<0.05), indicating cell proliferation.
CONCLUSIONS: These results demonstrate that the use of a bi-axial loading regime results in increased matrix production compared with uni-axial loading.