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The Cochrane Database of Systematic... Apr 2023This is the second update of the original Cochrane review published in 2013 (issue 6), which was updated in 2016 (issue 11). Pruritus occurs in patients with disparate... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is the second update of the original Cochrane review published in 2013 (issue 6), which was updated in 2016 (issue 11). Pruritus occurs in patients with disparate underlying diseases and is caused by different pathologic mechanisms. In palliative care patients, pruritus is not the most prevalent but is a burdening symptom. It can cause considerable discomfort and negatively affect patients' quality of life.
OBJECTIVES
To assess the effects of different pharmacological treatments compared with active control or placebo for preventing or treating pruritus in adult palliative care patients.
SEARCH METHODS
For this update, we searched CENTRAL (the Cochrane Library), MEDLINE (OVID) and Embase (OVID) up to 6 July 2022. In addition, we searched trial registries and checked the reference lists of all relevant studies, key textbooks, reviews and websites, and we contacted investigators and specialists in pruritus and palliative care regarding unpublished data.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) assessing the effects of different pharmacological treatments, compared with a placebo, no treatment, or an alternative treatment, for preventing or treating pruritus in palliative care patients.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed the identified titles and abstracts, performed data extraction and assessed the risk of bias and methodological quality. We summarised the results descriptively and quantitatively (meta-analyses) according to the different pharmacological interventions and the diseases associated with pruritus. We assessed the evidence using GRADE and created 13 summary of findings tables.
MAIN RESULTS
In total, we included 91 studies and 4652 participants in the review. We added 42 studies with 2839 participants for this update. Altogether, we included 51 different treatments for pruritus in four different patient groups. The overall risk of bias profile was heterogeneous and ranged from high to low risk. The main reason for giving a high risk of bias rating was a small sample size (fewer than 50 participants per treatment arm). Seventy-nine of 91 studies (87%) had fewer than 50 participants per treatment arm. Eight (9%) studies had low risk of bias in the specified key domains; the remaining studies had an unclear risk of bias (70 studies, 77%) or a high risk of bias (13 studies, 14%). Using GRADE criteria, we judged that the certainty of evidence for the primary outcome (i.e. pruritus) was high for kappa-opioid agonists compared to placebo and moderate for GABA-analogues compared to placebo. Certainty of evidence was low for naltrexone, fish-oil/omega-3 fatty acids, topical capsaicin, ondansetron and zinc sulphate compared to placebo and gabapentin compared to pregabalin, and very low for cromolyn sodium, paroxetine, montelukast, flumecinol, and rifampicin compared to placebo. We downgraded the certainty of the evidence mainly due to serious study limitations regarding risk of bias, imprecision, and inconsistency. For participants suffering from uraemic pruritus (UP; also known as chronic kidney disease (CKD)-associated pruritus (CKD-aP)), treatment with GABA-analogues compared to placebo likely resulted in a large reduction of pruritus (visual analogue scale (VAS) 0 to 10 cm): mean difference (MD) -5.10, 95% confidence interval (CI) -5.56 to -4.55; five RCTs, N = 297, certainty of evidence: moderate. Treatment with kappa-opioid receptor agonists (difelikefalin, nalbuphine, nalfurafine) compared to placebo reduced pruritus slightly (VAS 0 to 10 cm, MD -0.96, 95% CI -1.22 to -0.71; six RCTs, N = 1292, certainty of evidence: high); thus, this treatment was less effective than GABA-analogues. Treatment with montelukast compared to placebo may result in a reduction of pruritus, but the evidence is very uncertain (two studies, 87 participants): SMD -1.40, 95% CI -1.87 to -0.92; certainty of evidence: very low. Treatment with fish-oil/omega-3 fatty acids compared to placebo may result in a large reduction of pruritus (four studies, 160 observations): SMD -1.60, 95% CI -1.97 to -1.22; certainty of evidence: low. Treatment with cromolyn sodium compared to placebo may result in a reduction of pruritus, but the evidence is very uncertain (VAS 0 to 10 cm, MD -3.27, 95% CI -5.91 to -0.63; two RCTs, N = 100, certainty of evidence: very low). Treatment with topical capsaicin compared with placebo may result in a large reduction of pruritus (two studies; 112 participants): SMD -1.06, 95% CI -1.55 to -0.57; certainty of evidence: low. Ondansetron, zinc sulphate and several other treatments may not reduce pruritus in participants suffering from UP. In participants with cholestatic pruritus (CP), treatment with rifampicin compared to placebo may reduce pruritus, but the evidence is very uncertain (VAS: 0 to 100, MD -42.00, 95% CI -87.31 to 3.31; two RCTs, N = 42, certainty of evidence: very low). Treatment with flumecinol compared to placebo may reduce pruritus, but the evidence is very uncertain (RR > 1 favours treatment group; RR 2.32, 95% CI 0.54 to 10.1; two RCTs, N = 69, certainty of evidence: very low). Treatment with the opioid antagonist naltrexone compared to placebo may reduce pruritus (VAS: 0 to 10 cm, MD -2.42, 95% CI -3.90 to -0.94; two RCTs, N = 52, certainty of evidence: low). However, effects in participants with UP were inconclusive (percentage of difference -12.30%, 95% CI -25.82% to 1.22%, one RCT, N = 32). In palliative care participants with pruritus of a different nature, the treatment with the drug paroxetine (one study), a selective serotonin reuptake inhibitor, compared to placebo may reduce pruritus slightly by 0.78 (numerical analogue scale from 0 to 10 points; 95% CI -1.19 to -0.37; one RCT, N = 48, certainty of evidence: low). Most adverse events were mild or moderate. Two interventions showed multiple major adverse events (naltrexone and nalfurafine).
AUTHORS CONCLUSIONS
Different interventions (GABA-analogues, kappa-opioid receptor agonists, cromolyn sodium, montelukast, fish-oil/omega-3 fatty acids and topical capsaicin compared to placebo) were effective for uraemic pruritus. GABA-analogues had the largest effect on pruritus. Rifampin, naltrexone and flumecinol tended to be effective for cholestatic pruritus. However, therapies for patients with malignancies are still lacking. Due to the small sample sizes in most meta-analyses and the heterogeneous methodological quality of the included trials, the results should be interpreted cautiously in terms of generalisability.
Topics: Animals; Humans; Capsaicin; Cromolyn Sodium; gamma-Aminobutyric Acid; Naltrexone; Ondansetron; Palliative Care; Paroxetine; Receptors, Opioid; Rifampin; Zinc Sulfate
PubMed: 37314034
DOI: 10.1002/14651858.CD008320.pub4 -
The Cochrane Database of Systematic... Jul 2020Foot ulcers in people with diabetes are non-healing, or poorly healing, partial, or full-thickness wounds below the ankle. These ulcers are common, expensive to manage... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Foot ulcers in people with diabetes are non-healing, or poorly healing, partial, or full-thickness wounds below the ankle. These ulcers are common, expensive to manage and cause significant morbidity and mortality. The presence of a wound has an impact on nutritional status because of the metabolic cost of repairing tissue damage, in addition to the nutrient losses via wound fluid. Nutritional interventions may improve wound healing of foot ulcers in people with diabetes.
OBJECTIVES
To evaluate the effects of nutritional interventions on the healing of foot ulcers in people with diabetes.
SEARCH METHODS
In March 2020 we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase and EBSCO CINAHL Plus. We also searched clinical trials registries for ongoing and unpublished studies, and scanned reference lists of relevant included studies as well as reviews, meta-analyses and health technology reports to identify additional studies. There were no restrictions with respect to language, date of publication or study setting.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that evaluated the effect of nutritional interventions on the healing of foot ulcers in people with diabetes.
DATA COLLECTION AND ANALYSIS
Two review authors, working independently, assessed included RCTs for their risk of bias and rated the certainty of evidence using GRADE methodology, using pre-determined inclusion and quality criteria.
MAIN RESULTS
We identified nine RCTs (629 participants). Studies explored oral nutritional interventions as follows: a protein (20 g protein per 200 mL bottle), 1 kcal/mL ready-to-drink, nutritional supplement with added vitamins, minerals and trace elements; arginine, glutamine and β-hydroxy-β-methylbutyrate supplement; 220 mg zinc sulphate supplements; 250 mg magnesium oxide supplements; 1000 mg/day omega-3 fatty acid from flaxseed oil; 150,000 IU of vitamin D, versus 300,000 IU of vitamin D; 250 mg magnesium oxide plus 400 IU vitamin E and 50,000 IU vitamin D supplements. The comparator in eight studies was placebo, and in one study a different dose of vitamin D. Eight studies reported the primary outcome measure of ulcer healing; only two studies reported a measure of complete healing. Six further studies reported measures of change in ulcer dimension, these studies reported only individual parameters of ulcer dimensions (i.e. length, width and depth) and not change in ulcer volume. All of the evidence identified was very low certainty. We downgraded it for risks of bias, indirectness and imprecision. It is uncertain whether oral nutritional supplement with 20 g protein per 200 mL bottle, 1 kcal/mL, nutritional supplement with added vitamins, minerals and trace elements, increases the proportion of ulcers healed at six months more than placebo (risk ratio (RR) 0.80, 95% confidence interval (CI) 0.42 to 1.53). It is also uncertain whether arginine, glutamine and β-hydroxy-β-methylbutyrate supplement increases the proportion of ulcers healed at 16 weeks compared with placebo (RR 1.09, 95% CI 0.85 to 1.40). It is uncertain whether the following interventions change parameters of ulcer dimensions over time when compared with placebo; 220 mg zinc sulphate supplement containing 50 mg elemental zinc, 250 mg magnesium oxide supplement, 1000 mg/day omega-3 fatty acid from flaxseed oil supplement, magnesium and vitamin E co-supplementation and vitamin D supplementation. It is also uncertain whether 150,000 IU of vitamin D, impacts ulcer dimensions when compared with 300,000 IU of vitamin D. Two studies explored some of the secondary outcomes of interest for this review. It is uncertain whether oral nutritional supplement with 20 g protein per 200 mL bottle, 1 kcal/mL, nutritional supplement with added vitamins, minerals and trace elements, reduces the number of deaths (RR 0.96, 95% CI 0.06 to 14.60) or amputations (RR 4.82, 95% CI 0.24 to 95.88) more than placebo. It is uncertain whether arginine, glutamine and β-hydroxy-β-methylbutyrate supplement increases health-related quality of life at 16 weeks more than placebo (MD -0.03, 95% CI -0.09 to 0.03). It is also uncertain whether arginine, glutamine and β-hydroxy-β-methylbutyrate supplement reduces the numbers of new ulcers (RR 1.04, 95% CI 0.71 to 1.51), or amputations (RR 0.66, 95% CI 0.16 to 2.69) more than placebo. None of the included studies reported the secondary outcomes cost of intervention, acceptability of the intervention (or satisfaction) with respect to patient comfort, length of patient hospital stay, surgical interventions, or osteomyelitis incidence. One study exploring the impact of arginine, glutamine and β-hydroxy-β-methylbutyrate supplement versus placebo did not report on any relevant outcomes.
AUTHORS' CONCLUSIONS
Evidence for the impact of nutritional interventions on the healing of foot ulcers in people with diabetes compared with no nutritional supplementation, or compared with a different dose of nutritional supplementation, remains uncertain, with eight studies showing no clear benefit or harm. It is also uncertain whether there is a difference in rates of adverse events, amputation rate, development of new foot ulcers, or quality of life, between nutritional interventions and placebo. More research is needed to clarify the impact of nutritional interventions on the healing of foot ulcers in people with diabetes.
Topics: Arginine; Diabetic Foot; Dietary Proteins; Dietary Supplements; Fatty Acids, Omega-3; Female; Glutamine; Humans; Magnesium; Magnesium Oxide; Male; Middle Aged; Minerals; Randomized Controlled Trials as Topic; Trace Elements; Valerates; Vitamins; Wound Healing; Zinc Sulfate
PubMed: 32677037
DOI: 10.1002/14651858.CD011378.pub2 -
Journal of International Society of... 2023The use of medicinal herbs to prevent gingival and periodontal diseases has become increasingly popular due to their anti-inflammatory and antioxidant properties. This... (Review)
Review
AIMS AND OBJECTIVES
The use of medicinal herbs to prevent gingival and periodontal diseases has become increasingly popular due to their anti-inflammatory and antioxidant properties. This systematic review aims to provide the current literature to validate the traditional use of medicinal herbs in the management of gingival and periodontal diseases.
MATERIALS AND METHODS
An online literature search was conducted to identify research papers published from 2010 to 2022 in three major scientific databases, PubMed, Scopus, and Web of Science, in June 2022. Original research studies, case reports, and systematic reviews on medicinal plants' application in oral health care were selected to be included in this systematic review. Only high-quality articles identified in the quality assessment were included for evidence synthesis.
RESULTS
Initial keyword research yielded 726 free-text articles published between 2010 and 2022. Of these, 14 articles (8 research papers and 6 reviews) were included for evidence synthesis. The review's findings indicate that the antibacterial property of medicinal plants is due to their alkaline nature and prevents plaque and calculus formation by maintaining acid-alkali balance in saliva. Various parts of medicinal plants help maintain periodontal health. , , and effectively inhibit primary plaque colonizers and periodontal pathogens. , Miller, and have excellent applications in treating periodontal diseases. , , the husk of , the root of and , leaves of and , fruits of and , Ocimum extract, and pomegranate peel extract can serve as a promising alternative in managing chronic gingivitis.
CONCLUSION
The anti-inflammatory, antioxidant, antibacterial, and astringent action of extracts obtained from various parts of medicinal plants make them effective in reducing gingival and periodontal diseases. Herbal medicine may be a viable alternative to contemporary pharmaceuticals as an adjuvant to scaling and root planning procedures.
PubMed: 37153928
DOI: 10.4103/jispcd.JISPCD_210_22 -
Clinical Otolaryngology : Official... Nov 2023Otitis externa is a condition causing inflammation of the outer ear canal, which presents with itching, discharge and pain. Most cases of acute otitis externa are caused... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Otitis externa is a condition causing inflammation of the outer ear canal, which presents with itching, discharge and pain. Most cases of acute otitis externa are caused by bacterial infection and are thus treated with antibiotics. This systematic review and meta-analysis of randomised controlled trials aims to assess the effectiveness of topical non-antibiotic treatments compared to topical antibiotic treatment for the treatment of acute otitis externa.
METHODS
Systematic review and meta-analysis databases searched: Cochrane Library including ClinicalTrials.gov; MEDLINE; World Health Organisation International Clinical Trials Registry Platform and Web of Science to identify randomised clinical trials evaluating topical antibiotics and topical non-antibiotic agents in adults and children with acute otitis externa. Non-antibiotic therapeutics for comparison with topical antibiotics included antiseptics, steroids, non-pharmaceuticals and astringents.
RESULTS
Seventeen trials were eligible for inclusion, with 10 combined in meta-analysis. Data could be pooled comparing antiseptic and steroid monotherapies with topical antibiotic agents. There were no significant differences in cure rates in any pairwise comparisons. Individually, the majority of studies favoured topical antiseptics or steroids over antibiotics, however these differences were not significant when pooled in meta-analysis.
CONCLUSION
Antiseptic, steroid and antibiotic monotherapies are all effective for the management of acute otitis externa. There is insufficient evidence to suggest that topical antiseptic or steroid agents are superior or inferior to topical antibiotics.
Topics: Adult; Child; Humans; Anti-Bacterial Agents; Otitis Externa; Anti-Infective Agents, Local; Inflammation; Acute Disease; Steroids
PubMed: 37550850
DOI: 10.1111/coa.14084 -
The Cochrane Database of Systematic... Apr 2015This Cochrane Review was withdrawn in April 2015, and this withdrawal notice was updated in September 2016. The review was withdrawn as result of comments submitted... (Meta-Analysis)
Meta-Analysis Review
This Cochrane Review was withdrawn in April 2015, and this withdrawal notice was updated in September 2016. The review was withdrawn as result of comments submitted via the Cochrane Library by Harri Hemilä in February 2015. Hemilä identified multiple errors in this Cochrane Review and made allegations of plagiarism of text and data from a previously published systematic review (Hemilä H. Zinc Lozenges may shorten the duration of colds: a systematic review. 2011;5:51‐58. dx.doi.org/10.2174/1874306401105010051). The comments referred to the version of this review first published in June 2013 (Singh M, Das RR. Zinc for the common cold. 2013;(6):CD001364. http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD001364.pub4/full). The Cochrane Acute Respiratory Infections Group, which maintains the review, withdrew the review in April 2015, pending an assessment of the errors reported, and the group referred the allegations of plagiarism to the Editor in Chief. The Editor in Chief notified the authors of the concerns, and followed the Committee for Publication Ethics (COPE) guidelines. Replication of text was identified in the Cochrane Review. This was limited to copying of short phrases and was acknowledged by the authors. The level of text plagiarism was minor and at a level that would be addressed by a correction. The Editor in Chief carried out further investigation into the alleged plagiarism of data, with the co‐operation of the review authors, who provided supplementary information in support of their work. The allegations related to the derivation of means and standard deviations of data from some of the included studies. Although the authors acknowledge and cite the Hemilä 2011 review, the Editor in Chief considered that the authors’ explanation regarding some similarities in presented data between the two reviews was not conclusive. This version of the review will therefore remain withdrawn. This review was withdrawn due to concerns raised via the feedback mechanism regarding the calculation and analysis of data in the review in April 2015. Whilst it is not unusual for reviews to be withdrawn, the editorial group took the view that it would be better to take a cautious approach and explore the source and calculation of data used in the analysis in more detail, rather than keep the review on the Cochrane Database of Systematic Reviews for the time being. The editorial group responsible for this previously published document have withdrawn it from publication.
Topics: Common Cold; Dosage Forms; Gluconates; Humans; Randomized Controlled Trials as Topic; Severity of Illness Index; Zinc; Zinc Acetate; Zinc Compounds; Zinc Sulfate
PubMed: 25924708
DOI: 10.1002/14651858.CD001364.pub5 -
Food & Function Apr 2021Food industries are challenged to reformulate foods and beverages with higher protein contents to lower fat and sugar content. However, increasing protein concentration...
Food industries are challenged to reformulate foods and beverages with higher protein contents to lower fat and sugar content. However, increasing protein concentration can reduce sensory acceptability due to astringency perception. Since the properties of food-saliva mixtures govern mouthfeel perception, understanding how saliva and protein interact is key to guide development of future protein-rich reformulations with optimal sensory attributes. Hence, this systematic review investigated protein-saliva interaction using both model and real human saliva, including a quality assessment. A literature search of five databases (Medline, Pubmed, Embase, Scopus and Web of Science) was undertaken covering the last 20 years, yielding 36 604 articles. Using pre-defined criteria, this was reduced to a set of 33 articles with bulk protein solutions (n = 17), protein-stabilized emulsions (n = 13) and protein-rich food systems (n = 4). Interaction of dairy proteins, lysozyme and gelatine with model or human saliva dominated the literature. The pH was shown to have a strong effect on electrostatic interaction of proteins with negatively-charged salivary mucins, with greater interactions occurring below the isoelectric point of proteins. The effect of protein concentration was unclear due to the limited range of concentrations being studied. Most studies employed a 1 : 1 w/w protein : saliva ratio, which is not representative of true oral conditions. The interaction between protein and saliva appears to affect mouthfeel through aggregation and increased friction. The searches identified a gap in research on plant proteins. Accurate simulation of in vivo oral conditions should clarify understanding of protein-saliva interaction and its influence on sensory perception.
Topics: Dietary Proteins; Humans; Saliva
PubMed: 33900320
DOI: 10.1039/d0fo03180a -
Journal of Cosmetic Dermatology Apr 2023Various topical agents have been used to treat melasma; however, a large-scale evaluation among the currently available treatment is lacking. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Various topical agents have been used to treat melasma; however, a large-scale evaluation among the currently available treatment is lacking.
OBJECTIVES
The aim of this study was to evaluate the efficacy and safety of topical agents for melasma.
METHODS
The MEDLINE, Embase, Web of Science, Cochrane, and Alt-Healthwatch databases were searched in November 2021. Original studies that reported pre- and post-treatment Melasma Area Severity Index (MASI)/modified Melasma Area Severity Index (mMASI) scores and/or adverse effects (AEs) were eligible for inclusion. The main outcome was the efficacy analyzed by the changes in the pre- and post-treatment with standardized mean difference (SMD) of MASI/mMASI scores; the AEs were calculated with incidence proportion by the reported percentage of skin irritations.
RESULTS
A total of 45 studies (2359 patients) and 55 studies (4539 patients) met the inclusion criteria for efficacy and AEs, respectively. Hydroquinone (HQ) monotherapy (SMD -1.3, 95% CI [-1.6 to -1.0]), HQ-containing combination therapy (-1.4, [-1.7 to -1.1]), cysteamine (-1.6, [-2.0 to -1.2]), tranexamic acid (-1.5, [-2.0 to -1.1]), azelaic acid (-1.3, [-1.7 to -1.0]), and kojic acid (-0.9, [-1.3 to -0.5]) demonstrated comparable efficacy, while zinc sulfate did not exhibit statistically significant improvement (-1.2, [-2.7 to 0.4]). HQ-containing combination therapy (50.9%) and cysteamine (42.2%) demonstrated the highest incidence of irritation, while azelaic acid (18.7%), kojic acid (5.3%), and tranexamic acid (0.8%) revealed a lower risk.
CONCLUSIONS
In this meta-analysis, non-HQ agents except zinc sulfate may be considered as an alternative to HQ-containing agents. However, treatment should be guided by patient's tolerance, availability, and physicians' experience.
Topics: Humans; Treatment Outcome; Tranexamic Acid; Cysteamine; Zinc Sulfate; Melanosis
PubMed: 36566490
DOI: 10.1111/jocd.15566 -
Phytotherapy Research : PTR Dec 2015As a natural traditional Chinese medicine, Galla chinensis has been widely used since ancient times for its astringency, stypticity, detoxification, and antibacterial... (Review)
Review
As a natural traditional Chinese medicine, Galla chinensis has been widely used since ancient times for its astringency, stypticity, detoxification, and antibacterial activity. Our group has concentrated on the research about its potential of being an applicable anti-caries agent. The crude extract and some other components purified from it show remarkable efficacy on anticaries, and the most likely mechanism is proposed through specific research. For the fact that crude drugs consist of numerous compounds, and their bioactivity is a result of synergistic effects and/or antagonistic effects of several compounds, it is difficult to clarify the exact mechanism and evaluate the safety and effectiveness of G. chinensis. This review article systematically summarizes previous findings from the following aspects: (1) inhibitory effect on oral bacteria; (2) the demineralization inhibition property; (3) the remineralization-enhancing property; and (4) stability and toxicity evaluation, and thus indicates the further research direction.
Topics: Animals; Anti-Bacterial Agents; Bacteria; Calcification, Physiologic; Dental Caries; Drugs, Chinese Herbal; Humans; Medicine, Chinese Traditional; Mouth; Plant Extracts
PubMed: 26331796
DOI: 10.1002/ptr.5444 -
The Cochrane Database of Systematic... Sep 2014Leg ulcers affect up to one percent of people at some time in their life. Leg ulceration is chronic in nature and ulcers may be present for months or even years without... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Leg ulcers affect up to one percent of people at some time in their life. Leg ulceration is chronic in nature and ulcers may be present for months or even years without healing. After healing there is a high risk of recurrence. Treatments include wound dressings alongside the treatment of underlying medical problems such as poor blood supply, infection and poor nutrition.
OBJECTIVES
To assess the effectiveness of oral zinc in healing arterial or venous leg ulcers.
SEARCH METHODS
For this seventh update we searched The Cochrane Wounds Group Specialised Register (searched 02 September 2014) and The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 8). In the original version of the review a company manufacturing zinc sulphate tablets was asked for references to relevant trials.
SELECTION CRITERIA
Randomised controlled trials comparing oral zinc sulphate with placebo or no treatment in people with arterial or venous leg ulcers were eligible for inclusion. There were no restrictions on date or language of publication. The main outcome measure used was complete healing of the ulcers. Trials were eligible for inclusion if they measured ulcer healing objectively by documenting time to complete healing, proportion of ulcers healed during the study, or healing rates of ulcers.
DATA COLLECTION AND ANALYSIS
All data extraction and assessment of trial quality was done by both authors independently.
MAIN RESULTS
Six small trials (183 participants) were eligible for inclusion. Four trials considered people with venous ulcers, one trial involved people with arterial ulcers and one people with mixed aetiology ulcers. Serum zinc was measured in four trials and four trials compared oral zinc sulphate with placebo in people with venous ulcers; pooling these trials indicated no statistically significant difference between the two groups for healing (RR 1.22, 95%CI 0.88 to 1.68). Overall, there is no evidence that oral zinc increases the healing of arterial or venous leg ulcers.
AUTHORS' CONCLUSIONS
Oral zinc sulphate does not appear to aid the healing of arterial and venous leg ulcers, however all included studies were small and at unclear risk of bias (due to poor reporting).
Topics: Administration, Oral; Astringents; Humans; Leg Ulcer; Randomized Controlled Trials as Topic; Wound Healing; Zinc; Zinc Sulfate
PubMed: 25202988
DOI: 10.1002/14651858.CD001273.pub3 -
The Cochrane Database of Systematic... Mar 2016Osteoporosis is a systemic skeletal disease characterized by low bone mass and micro-architectural deterioration of bone tissue with a consequent increase in bone... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Osteoporosis is a systemic skeletal disease characterized by low bone mass and micro-architectural deterioration of bone tissue with a consequent increase in bone fragility and susceptibility to fracture. Osteoporosis represents an important cause of morbidity in people with beta-thalassaemia and its pathogenesis is multifactorial. Factors include bone marrow expansion due to ineffective erythropoiesis, resulting in reduced trabecular bone tissue with cortical thinning; endocrine dysfunction secondary to excessive iron loading, leading to increased bone turnover; and lastly, a predisposition to physical inactivity due to disease complications with a subsequent reduction in optimal bone mineralization.A number of therapeutic strategies have been applied to treat osteoporosis in people with beta-thalassaemia, which include bisphosphonates, with or without, hormone replacement therapy. There are various forms of bisphosphonates, such as clodronate, pamidronate, alendronate and zoledronic acid. Other treatments include calcitonin, calcium, zinc supplementation, hydroxyurea and hormone replacement therapy for preventing hypogonadism.
OBJECTIVES
To review the evidence on the efficacy and safety of treatment for osteoporosis in people with beta-thalassaemia.
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: 04 February 2016.
SELECTION CRITERIA
Randomised, placebo-controlled trials in people with thalassaemia with a bone mineral density z score of less than -2 standard deviations for: children less than 15 years old; adult males (15 to 50 years old); and all pre-menopausal females above 15 years and a bone mineral density t score of less than -2.5 standard deviations for post-menopausal females and males above 50 years old.
DATA COLLECTION AND ANALYSIS
Two review authors assessed the eligibility and risk of bias of the included trials, extracted and analysed data and completed 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
Four trials (with 211 participants) were included; three trials investigated the effect of bisphosphonate therapies and one trial investigated the effect of zinc supplementation. Only one trial was judged to be of good quality (low risk of bias); the remaining trials had a high or unclear risk of bias in at least one key domain.One trial (data not available for analysis) assessing the effect of neridronate (118 participants) reported significant increases in favour of the bisphosphonate group for bone mineral density at the lumbar spine and hip at both six and 12 months. For the femoral neck, a significant difference was noted at 12 months only. A further trial (25 participants) assessed the effect of alendronate and clodronate and found that after two years, bone mineral density increased significantly in the alendronate and clodronate groups as compared to placebo at the lumbar spine, mean difference 0.14 g/cm(2) (95% confidence interval 0.05 to 0.22) and at the femoral neck, mean difference 0.40 g/cm(2) (95% confidence interval 0.22 to 0.57). One 12-month trial (26 participants) assessed the effects of different doses of pamidronate (30 mg versus 60 mg) and found a significant difference in bone mineral density in favour of the 60 mg dose at the lumbar spine and forearm, mean difference 0.43 g/cm(2) (95% CI 0.10 to 0.76), mean difference 0.87 g/cm(2) (95% CI 0.23 to 1.51), respectively, but not at the femoral neck.In a zinc sulphate supplementation trial (42 participants), bone mineral density increased significantly compared to placebo at the lumbar spine after 12 months (37 participants), mean difference 0.15 g/cm(2) (95% confidence interval 0.10 to 0.20) and after 18 months (32 participants), mean difference 0.34 g/cm(2) (95% confidence interval 0.28 to 0.40). The same was true for bone mineral density at the hip after 12 months, mean difference 0.15 g/cm(2) (95% confidence interval 0.11 to 0.19) and after 18 months, mean difference 0.26 g/cm(2) (95% confidence interval 0.21 to 0.31).Fractures were not observed in one trial and not reported in three trials. There were no major adverse effects reported in two of the bisphosphonate trials; in the neridronate trial there was a reduction noted in the use of analgesic drugs and in the reported back pain score in favour of bisphosphonate treatment. Adverse effects were not reported in the trial of different doses of pamidronate or the zinc supplementation trial.
AUTHORS' CONCLUSIONS
There is evidence to indicate an increase in bone mineral density at the femoral neck, lumbar spine and forearm after administration of bisphosphonates and at the lumbar spine and hip after zinc sulphate supplementation. The authors recommend that further long-term randomised control trials on different bisphosphonates and zinc supplementation therapies in people with beta-thalassaemia and osteoporosis are undertaken.
Topics: Adolescent; Adult; Alendronate; Bone Density; Bone Density Conservation Agents; Child; Clodronic Acid; Diphosphonates; Female; Femur Neck; Humans; Male; Middle Aged; Osteoporosis; Randomized Controlled Trials as Topic; Zinc Sulfate; beta-Thalassemia
PubMed: 26964506
DOI: 10.1002/14651858.CD010429.pub2