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AAPS PharmSciTech Jun 2024Inclusion complexes require higher concentration of Beta cyclodextrins (βCD) resulting in increased formulation bulk, toxicity, and production costs. This systematic...
Inclusion complexes require higher concentration of Beta cyclodextrins (βCD) resulting in increased formulation bulk, toxicity, and production costs. This systematic review offers a comprehensive analysis using Quality by design (QbD) as a tool to predict potential applications of Polyvinylpyrrolidone (PVP) as a ternary substance to address issues of inclusion complexes. We reviewed 623 documents from 2013 to 2023 and Eighteen (18) research papers were selected for statistical and meta-analysis using the QbD concept to identify the most critical factors for selecting drugs and effect of PVP on inclusion complexes. The QbD analysis revealed that Molecular weight (MW), Partition coefficient (Log P), and the auxiliary substance ratio directly affected complexation efficiency (CE), thermodynamic stability in terms of Gibbs free energy (ΔG), and percent drug release. However, Stability constant (K) remained unaffected by any of these parameters. The results showed that low MW (250), median Log P (6), and a βCD: PVP ratio of 2:3 would result in higher CE, lower G, and improved drug release. PVP improves drug solubility, enhances delivery and therapeutic outcomes, and counteracts increased drug ionization due to decreased pH. In certain cases, its bulky nature and hydrogen bonding with CD molecules can form non-inclusion complexes. The findings of the study shows that there is potential molecular interaction between PVP and β-cyclodextrins, which possibly enhances the stability of inclusion complexes for drug with low MW and log P values less than 9. The systematic review shows a comprehensive methodology based on QbD offers a replicable template for future investigations into drug formulation research.
Topics: beta-Cyclodextrins; Chemistry, Pharmaceutical; Cyclodextrins; Drug Liberation; Excipients; Molecular Weight; Pilot Projects; Povidone; Solubility; Thermodynamics
PubMed: 38862663
DOI: 10.1208/s12249-024-02845-3 -
Exploration (Beijing, China) Feb 2024Colorectal cancer (CRC) is generally characterized by a high prevalence of (), a spindle-shaped, Gram-negative anaerobe pathogen derived from the oral cavity. This... (Review)
Review
Colorectal cancer (CRC) is generally characterized by a high prevalence of (), a spindle-shaped, Gram-negative anaerobe pathogen derived from the oral cavity. This tumor-resident microorganism has been closely correlated with the occurrence, progression, chemoresistance and immunosuppressive microenvironment of CRC. Furthermore, can specifically colonize CRC tissues through adhesion on its surface, forming biofilms that are highly resistant to commonly used antibiotics. Accordingly, it is crucial to develop efficacious non-antibiotic approaches to eradicate and its biofilms for CRC treatment. In recent years, various antimicrobial strategies, such as natural extracts, inorganic chemicals, organic chemicals, polymers, inorganic-organic hybrid materials, bacteriophages, probiotics, and vaccines, have been proposed to combat and biofilms. This review summarizes the latest advancements in anti- research, elucidates the antimicrobial mechanisms employed by these systems, and discusses the benefits and drawbacks of each antimicrobial technology. Additionally, this review also provides an outlook on the antimicrobial specificity, potential clinical implications, challenges, and future improvements of these antimicrobial strategies in the treatment of CRC.
PubMed: 38854496
DOI: 10.1002/EXP.20230092 -
Modulation of the skin and gut microbiome by psoriasis treatment: a comprehensive systematic review.Archives of Dermatological Research Jun 2024The microbiome is intricately linked to the development of psoriasis, serving as both a potential cause and consequence of the psoriatic process. In recent years, there... (Review)
Review
The microbiome is intricately linked to the development of psoriasis, serving as both a potential cause and consequence of the psoriatic process. In recent years, there has been growing interest among psoriasis researchers in exploring how psoriasis treatments affect the skin and gut microbiome. However, a comprehensive evaluation of the impact of modern treatment approaches on the microbiome has yet to be conducted. In this systematic review, we analyze studies investigating alterations in the skin and gut microbiome resulting from psoriasis treatment, aiming to understand how current therapies influence the role of the microbiome in psoriasis development. The systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. PubMed and Scopus databases were searched for eligible studies from the inception dates until July 5, 2023. Study selection, data extraction, and risk of bias assessment were carried out by three overlapping pairs of reviewers, resolving any disagreements through consensus. Our analysis of various treatments, including biologics, conventional medications, phototherapy, and probiotics, reveals significant shifts in microbial diversity and abundance. Importantly, favorable treatment outcomes are associated with microbiota alterations that approach those observed in healthy individuals. While the studies reviewed exhibit varying degrees of bias, underscoring the need for further research, this review supports the potential of microbiome modulation as both a preventive and therapeutic strategy for psoriasis patients. The findings underscore the importance of personalized therapeutic approaches, recognizing the profound impact of treatment on the microbiome. They also highlight the promise of probiotics, prebiotics, and dietary interventions in psoriasis management.
Topics: Psoriasis; Humans; Gastrointestinal Microbiome; Skin; Probiotics; Phototherapy; Biological Products; Treatment Outcome; Dermatologic Agents
PubMed: 38850443
DOI: 10.1007/s00403-024-03024-x -
Archives of Dermatological Research Jun 2024Fast gut cutaneous sutures have become more prominent due to their low tissue reactivity, rapid absorption, and elimination of suture removal visits. It is not known how... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Fast gut cutaneous sutures have become more prominent due to their low tissue reactivity, rapid absorption, and elimination of suture removal visits. It is not known how fast gut sutures compare to other closure modalities.
METHODS
A comprehensive literature review was conducted to identify randomized controlled trials comparing fast gut sutures to alternative closure methods during dermatologic surgery. Data collected included patient and physician assessed cosmetic outcome as well as standardized complication rates.
RESULTS
Six studies were included in final analysis and reported on 208 patients. Fast gut sutures were associated with lower physician opinions of final scar when compared to polypropylene sutures (SMD 0.438; 95% CI 0.082 to 0.794). No differences existed between physician opinion of fast gut sutures and cyanoacrylate tissue adhesive (SMD - 0.024; 95% CI - 0.605 to 0.556). Complications with fast gut suture placement were rare, and included infection, dehiscence, and hematomas. Fast gut sutures were less likely to experience wound dehiscence than tissue adhesive (p = 0.01).
CONCLUSION
If no contraindications to polypropylene sutures exist, they may provide superior cosmetic outcomes compared to fast gut sutures. Further research is required to better quantify cosmetic outcomes and optimal use of fast gut sutures.
Topics: Humans; Sutures; Dermatologic Surgical Procedures; Suture Techniques; Tissue Adhesives; Polypropylenes; Cicatrix; Randomized Controlled Trials as Topic; Cyanoacrylates; Wound Healing
PubMed: 38850366
DOI: 10.1007/s00403-024-02973-7 -
BMC Oral Health Jun 2024To provide an overview of the available scientific evidence from in vitro studies regarding the effect induced by the flavonoids contained in grape seed extracts (GSE)... (Review)
Review
OBJECTIVE
To provide an overview of the available scientific evidence from in vitro studies regarding the effect induced by the flavonoids contained in grape seed extracts (GSE) and cranberry on the microbiological activity of Streptococcus mutans (S. mutans).
METHODS
This systematic review was performed following the parameters of the PRISMA statement (Preferred Reporting Items for Systematic Reviews and Meta-Analysis). Electronic and manual searches were conducted using PubMed, ScienceDirect, Web of Science, EBSCO, and Cochrane databases. Reference lists of selected articles were reviewed to identify relevant studies. The search was not limited by year and was conducted solely in English. Eligible studies comprised publications describing in vitro studies that evaluated the effect of flavonoids derived from GSE and cranberry extracts on the microbiological activity of S. mutans. Common variables were identified to consolidate the data. Authors of this review independently screened search results, extracted data, and assessed the risk of bias.
RESULTS
Of the 420 studies identified from the different databases, 22 publications were finally selected for review. The risk of bias was low in 13 articles and moderate in 9. The studies analyzed in this review revealed that cranberry extract has an inhibitory effect on the bacterial growth of S. mutans in ranges from 0.5 mg/mL to 25 mg/mL, and GSE exerts a similar effect from 0.5 mg/mL to 250 mg/mL. Additionally, the extracts or their fractions showed reduced biofilm formation capacity, decreased polymicrobial biofilm biomass, deregulation of glycosyltransferases (Gtf) B and C expression, and buffering of pH drop. In addition to adequate antioxidant activity related to polyphenol content.
CONCLUSIONS
The overall results showed that the extracts of cranberry and grape seed were effective in reducing the virulence factors of the oral pathogen. According to the data, proanthocyanidins are the active components in cranberry and grape seed that effectively resist S. mutans. They can inhibit the formation of insoluble polysaccharides in the extracellular matrix and prevent glycan-mediated adhesion, cohesion, and aggregation of the proteins in S. mutans. This suggests that these natural extracts could play an important role in the prevention of cariogenic bacterial colonization, as well as induce a decrease in their microbiological activity.
Topics: Streptococcus mutans; Vaccinium macrocarpon; Plant Extracts; Flavonoids; Grape Seed Extract; Biofilms; Humans; Vitis; Proanthocyanidins
PubMed: 38840232
DOI: 10.1186/s12903-024-04263-0 -
Evidence-based Dentistry Jun 2024Three electronic databases (Pubmed, Embase and the Cochrane Library) were searched in December 2022, and again for additional literature on 3-5th January 2023. Reference... (Review)
Review
DATA SOURCES
Three electronic databases (Pubmed, Embase and the Cochrane Library) were searched in December 2022, and again for additional literature on 3-5th January 2023. Reference lists of relevant systematic reviews were hand searched for other eligible studies for inclusion.
STUDY SELECTION
Randomised controlled clinical trials and controlled clinical trials conducted on children (aged ≤ 18 years), conducted between 1974-2022 and available in English, were eligible for inclusion. Studies were excluded if caries was not an outcome, the control group was not sufficient, they were lab-based studies or studies where xylitol delivery was not a sweet or chewing gum and where the xylitol product contained a component such as fluoride which may influence the outcomes.
DATA EXTRACTION AND SYNTHESIS
Four calibrated reviewers independently screened titles and abstracts, and disagreements were resolved via group discussion. Preventative effect was determined by comparing the mean caries increment in the control and intervention groups, producing a preventative fraction. A total of 617 titles were initially screened for relevance. After duplicate removal, 268 abstracts were screened and 16 full text articles reviewed, with one more study then excluded. 10 studies investigated xylitol-containing chewing gum, and six looked at xylitol candy (one did both). Eight included studies were randomised controlled trials. Data extraction was undertaken by two reviewers.
RESULTS
3466 participants were included in the 10 studies that investigated xylitol chewing gum, and all 10 studies reported a statistically significant preventive effect compared to a no chewing gum or placebo control. In 9 studies, the preventive fraction was clinically significant. The six studies investigating xylitol candies contained a total of 1023 participants, and only one study demonstrated a significant preventative effect.
CONCLUSIONS
There is some evidence that incorporating xylitol chewing gum daily has a caries-reducing effect in those with a moderate-to-high baseline caries level. This effect was not present for xylitol sweets.
Topics: Xylitol; Chewing Gum; Dental Caries; Humans; Child; Sweetening Agents; Adolescent; Randomized Controlled Trials as Topic; Cariostatic Agents; Child, Preschool
PubMed: 38796554
DOI: 10.1038/s41432-024-01018-2 -
Evidence-based Dentistry Jun 2024A systematic review and meta-analysis of the literature was carried out assessing the success rate of root canal retreatment using gutta percha. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
A systematic review and meta-analysis of the literature was carried out assessing the success rate of root canal retreatment using gutta percha.
DATA SOURCES
Four of the largest databases were used to identify existing literature with no date or language restrictions. PubMed, Cochrane, ScienceDirect, Scopus and other additional sources were searched. Grey literature was also reviewed.
STUDY SELECTION
Two authors, with Master's degrees in endodontics and with extensive university teaching experience, were selected to screen the databases to identify suitable studies. In case the authors were not able to agree during the study selection process, a third investigator was consulted. Specific inclusion and exclusion criteria were outlined and adhered to in the study selection. Two randomised controlled trials, seven single arm prospective studies and one single arm ambispective study published before the 10th of December 2022 were included. These studies evaluated the success of root canal re-treatment, obturated with gutta percha with at least a 1-year follow-up. Nine of the studies were published between 1998 and 2022. Seven studies were conducted in Europe, one in North America and one in Asia.
DATA EXTRACTION AND SYNTHESIS
Standard Cochrane methods to assess interval validity were used. Risk of bias in individual studies was assessed using The Newcastle-Ottawa quality assessment scale (NOS) for single-arm studies, and the Cochrane risk of bias tool (RoB2) was used for randomised controlled trials. Outcome measures were standardised as either success or failure of root canal retreatment. Success was classified into 2 different criteria: Strict criteria = absence of clinical signs and symptoms and radiographically normal periodontal ligament space; and Loose criteria = absence of clinical signs and symptoms and absence or reduction of apical radiolucency in the control radiograph. Statistical analysis was undertaken using R software and the Freeman-Turkey transformation was performed. Results were visualised using forest plots. Heterogeneity between studies was measured using the Cochrane Q test and I values.
RESULTS
Whilst following strict criteria, the success rate of non-surgical root canal retreatment obturated with gutta percha was 71% for 1-3 years follow-up (95% CI, 0.66-0.77) and 77% for 4-5 years follow-up (95% CI, 0.67-0.86). Heterogeneity was moderate (I = 61.4) and low (I = 0.0), respectively. Factors reducing the success rate of root canal re-retreatment under the strict criteria were older patients, mandibular teeth, molar teeth, the presence of a peri-apical radiolucency, teeth with a previous radiolucency, large peri-apical radiolucency's, higher initial periapical index scores and multiple visit-retreatments. Following the loose criteria, the success rate of non-surgical root canal re-treatment obturated with gutta percha was 87% for 1-3 years follow-up (95% CI, 0.79-0.93) with significant heterogeneity across the studies (I = 88.5%). Factors influencing the success rate under the loose criteria were large periapical lesions >5 mm and higher initial periapical index (PAI) scores.
CONCLUSIONS
Non-surgical root canal retreatment results in favourable outcomes. However, there are several factors which can result in a lower success rate: the presence and size of a periapical radiolucency, a higher initial PAI score, multiple-visit retreatments, and the size and position of the tooth.
Topics: Gutta-Percha; Humans; Retreatment; Root Canal Therapy; Root Canal Filling Materials; Root Canal Obturation; Treatment Outcome
PubMed: 38796553
DOI: 10.1038/s41432-024-01019-1 -
Pharmaceutics May 2024Andrographolide (ADG) has poor aqueous solubility and low bioavailability. This study systematically reviews the use of solid dispersion (SD) techniques to enhance the... (Review)
Review
Andrographolide (ADG) has poor aqueous solubility and low bioavailability. This study systematically reviews the use of solid dispersion (SD) techniques to enhance the solubility and absorption of ADG, with a focus on the methods and polymers utilized. We searched electronic databases including PubMed, Web of Science, Scopus, Embase and ScienceDirect Elsevier up to November 2023 for studies on the solubility or absorption of ADG in SD formulations. Two reviewers independently reviewed the retrieved articles and extracted data using a standardized form and synthesized the data qualitatively. SD significantly improved ADG solubility with up to a 4.7-fold increase and resulted in a decrease in 50% release time (T) to less than 5 min. SD could also improve ADG absorption, as evidenced by higher C and AUC and reduced T. Notably, Soluplus-based SDs showed marked solubility and absorption enhancements. Among the five SD techniques (rotary evaporation, spray drying, hot-melt extrusion, freeze drying and vacuum drying) examined, spray drying emerged as the most effective, enabling a one-step process without the need for post-milling. SD techniques, particularly using Soluplus and spray drying, effectively enhance the solubility and absorption of ADG. This insight is vital for the future development of ADG-SD matrices.
PubMed: 38794350
DOI: 10.3390/pharmaceutics16050688 -
The Cochrane Database of Systematic... May 2024Peripheral arterial catheters (ACs) are used in anaesthesia and intensive care settings for blood sampling and monitoring. Despite their importance, ACs often fail,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Peripheral arterial catheters (ACs) are used in anaesthesia and intensive care settings for blood sampling and monitoring. Despite their importance, ACs often fail, requiring reinsertion. Dressings and securement devices maintain AC function and prevent complications such as infection.
OBJECTIVES
To evaluate the effectiveness of peripheral AC dressing and securement devices to prevent failure and complications in hospitalised people.
SEARCH METHODS
We searched the Cochrane Wounds Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL Plus up to 16 May 2023. We also searched ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform up to 16 May 2023.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) comparing different dressing and securement devices for the stabilisation of ACs in hospitalised people.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials for inclusion, extracted data, and assessed risk of bias using Cochrane's RoB 1 tool. We resolved disagreements by discussion, or by consulting a third review author when necessary. We assessed the certainty of evidence using GRADE.
MAIN RESULTS
We included five RCTs with 1228 participants and 1228 ACs. All included studies had high risk of bias in one or more domains. We present the following four comparisons, with the remaining comparisons reported in the main review. Standard polyurethane (SPU) plus tissue adhesive (TA) compared with SPU: we are very uncertain whether use of SPU plus TA impacts rates of AC failure (risk ratio (RR) 0.44, 95% confidence interval (CI) 0.20 to 0.98; I² = 0%; 2 studies, 165 participants; very low-certainty evidence). Neither study (165 participants) reported catheter-related bloodstream infections (CRBSI), thus we are very uncertain whether SPU plus TA impacts on the incidence of CRBSI (very low-certainty evidence). It is very uncertain whether use of SPU plus TA impacts AC dislodgement risk (RR 0.54, 95% CI 0.03 to 9.62; I² = 44%; 2 studies, 165 participants; very low-certainty evidence). We are very uncertain whether use of SPU plus TA impacts AC occlusion rates (RR 1.20, 95% CI 0.37 to 3.91; I² = 3%; 2 studies, 165 participants; very low-certainty evidence). We are very uncertain whether use of SPU plus TA impacts rates of adverse events with few reported events across groups (RR 0.89, 95% CI 0.09 to 8.33; I² = 0%; 2 studies, 165 participants; very low-certainty evidence). Bordered polyurethane (BPU) compared to SPU: we are very uncertain whether use of BPU impacts rates of AC failure (RR 0.67, 95% CI 0.21 to 2.13; 1 study, 60 participants; very low-certainty evidence). BPU may make little or no difference to CRBSI compared to SPU (RR 3.05, 95% CI 0.12 to 74.45; I² = not applicable as 1 study (60 participants) reported 0 events; 2 studies, 572 participants; low-certainty evidence). BPU may make little or no difference to the risk of AC dislodgement compared with SPU (RR 0.75, 95% CI 0.17 to 3.22; I² = 0%; 2 studies, 572 participants; low-certainty evidence). BPU may make little or no difference to occlusion risk compared with SPU (RR 0.80, 95% CI 0.60 to 1.07; I² = 0%; 2 studies, 572 participants; low-certainty evidence). It is very uncertain whether BPU impacts on the risk of adverse events compared with SPU (RR 0.33, 95% CI 0.01 to 7.87; 1 study, 60 participants; very low-certainty evidence). SPU plus sutureless securement devices (SSD) compared to SPU: we are very uncertain whether SPU plus SSD impacts risk of AC failure compared with SPU (RR 0.78, 95% CI 0.40 to 1.52; I² = 0%; 2 studies, 157 participants; very low-certainty evidence). We are very uncertain if SPU plus SSD impacts CRBSI incidence rate with no events in both groups (2 studies, 157 participants; very low-certainty evidence). It is very uncertain whether SPU plus SSD impacts risk of dislodgement (RR 0.14, 95% CI 0.01 to 2.57; I² = not applicable as 1 study (96 participants) reported 0 events; 2 studies, 157 participants; very low-certainty evidence). It is very uncertain whether SPU plus SSD impacts risk of AC occlusion (RR 1.94, 95% CI 0.50 to 7.48; I² = 38%; 2 studies, 157 participants; very low-certainty evidence). We are very uncertain whether SPU plus SSD impacts on the risk of adverse events (RR 1.94, 95% CI 0.19 to 20.24; I² = not applicable as 1 study (96 participants) reported 0 events; 2 studies, 157 participants; very low-certainty evidence). Integrated securement dressings compared to SPU: integrated securement dressings may result in little or no difference in risk of AC failure compared with SPU (RR 1.96, 95% CI 0.80 to 4.84; 1 study, 105 participants; low-certainty evidence); may result in little or no difference in CRBSI incidence with no events reported (1 study, 105 participants; low-certainty evidence); may result in little or no difference in the risk of dislodgement (RR 0.33, 95% CI 0.04 to 3.04; 1 study, 105 participants; low-certainty evidence), may result in little or no difference in occlusion rates with no events reported (1 study, 105 participants; low-certainty evidence), and may result in little or no difference in the risk of adverse events (RR 0.35, 95% CI 0.01 to 8.45; 1 study, 105 participants; low-certainty evidence).
AUTHORS' CONCLUSIONS
There is currently limited rigorous RCT evidence available about the relative clinical effectiveness of AC dressing and securement products. Limitations of current evidence include small sample size, infrequent events, and heterogeneous outcome measurements. We found no clear difference in the incidence of AC failure, CRBSI, or adverse events across AC dressing or securement products including SPU, BPU, SSD, TA, and integrated securement products. The limitations of current evidence means further rigorous RCTs are needed to reduce uncertainty around the use of dressing and securement devices for ACs.
Topics: Humans; Randomized Controlled Trials as Topic; Catheterization, Peripheral; Bandages; Catheter-Related Infections; Polyurethanes; Bias; Equipment Failure
PubMed: 38780138
DOI: 10.1002/14651858.CD013023.pub2 -
The Cochrane Database of Systematic... May 2024Sickle cell disease (SCD) refers to a group of genetic disorders characterized by the presence of an abnormal haemoglobin molecule called haemoglobin S (HbS). When... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Sickle cell disease (SCD) refers to a group of genetic disorders characterized by the presence of an abnormal haemoglobin molecule called haemoglobin S (HbS). When subjected to oxidative stress from low oxygen concentrations, HbS molecules form rigid polymers, giving the red cell the typical sickle shape. Antioxidants have been shown to reduce oxidative stress and improve outcomes in other diseases associated with oxidative stress. Therefore, it is important to review and synthesize the available evidence on the effect of antioxidants on the clinical outcomes of people with SCD.
OBJECTIVES
To assess the effectiveness and safety of antioxidant supplementation for improving health outcomes in people with SCD.
SEARCH METHODS
We used standard, extensive Cochrane search methods. The latest search date was 15 August 2023.
SELECTION CRITERIA
We included randomized and quasi-randomized controlled trials comparing antioxidant supplementation to placebo, other antioxidants, or different doses of antioxidants, in people with SCD.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data, assessed the risk of bias and certainty of the evidence, and reported according to Cochrane methodological procedures.
MAIN RESULTS
The review included 1609 participants in 26 studies, with 17 comparisons. We rated 13 studies as having a high risk of bias overall, and 13 studies as having an unclear risk of bias overall due to study limitations. We used GRADE to rate the certainty of evidence. Only eight studies reported on our important outcomes at six months. Vitamin C (1400 mg) plus vitamin E (800 mg) versus placebo Based on evidence from one study in 83 participants, vitamin C (1400 mg) plus vitamin E (800 mg) may not be better than placebo at reducing the frequency of crisis (risk ratio (RR) 1.18, 95% confidence interval (CI) 0.64 to 2.18), the severity of pain (RR 1.33, 95% CI 0.40 to 4.37), or adverse effects (AE), of which the most common were headache, nausea, fatigue, diarrhoea, and epigastric pain (RR 0.56, 95% CI 0.31 to 1.00). Vitamin C plus vitamin E may increase the risk of SCD-related complications (acute chest syndrome: RR 2.66, 95% CI 0.77 to 9.13; 1 study, 83 participants), and increase haemoglobin level (median (interquartile range) 90 (81 to 96) g/L versus 93.5 (84 to 105) g/L) (1 study, 83 participants) compared to placebo. However, the evidence for all the above effects is very uncertain. The study did not report on quality of life (QoL) of participants and their caregivers, nor on frequency of hospitalization. Zinc versus placebo Zinc may not be better than placebo at reducing the frequency of crisis at six months (rate ratio 0.62, 95% CI 0.17 to 2.29; 1 study, 36 participants; low-certainty evidence). We are uncertain whether zinc is better than placebo at improving sickle cell-related complications (complete healing of leg ulcers at six months: RR 2.00, 95% CI 0.60 to 6.72; 1 study, 34 participants; very low-certainty evidence). Zinc may be better than placebo at increasing haemoglobin level (g/dL) (MD 1.26, 95% CI 0.44 to 1.26; 1 study, 36 participants; low-certainty evidence). The study did not report on severity of pain, QoL, AE, and frequency of hospitalization. N-acetylcysteine versus placebo N-acetylcysteine (NAC) 1200 mg may not be better than placebo at reducing the frequency of crisis in SCD, reported as pain days (rate ratio 0.99 days, 95% CI 0.53 to 1.84; 1 study, 96 participants; low-certainty evidence). Low-certainty evidence from one study (96 participants) suggests NAC (1200 mg) may not be better than placebo at reducing the severity of pain (MD 0.17, 95% CI -0.53 to 0.87). Compared to placebo, NAC (1200 mg) may not be better at improving physical QoL (MD -1.80, 95% CI -5.01 to 1.41) and mental QoL (MD 2.00, 95% CI -1.45 to 5.45; very low-certainty evidence), reducing the risk of adverse effects (gastrointestinal complaints, pruritus, or rash) (RR 0.92, 95% CI 0.75 to 1.14; low-certainty evidence), reducing the frequency of hospitalizations (rate ratio 0.98, 95% CI 0.41 to 2.38; low-certainty evidence), and sickle cell-related complications (RR 5.00, 95% CI 0.25 to 101.48; very low-certainty evidence), or increasing haemoglobin level (MD -0.18 g/dL, 95% CI -0.40 to 0.04; low-certainty evidence). L-arginine versus placebo L-arginine may not be better than placebo at reducing the frequency of crisis (monthly pain) (RR 0.71, 95% CI 0.26 to 1.95; 1 study, 50 participants; low-certainty evidence). However, L-arginine may be better than placebo at reducing the severity of pain (MD -1.41, 95% CI -1.65 to -1.18; 2 studies, 125 participants; low-certainty evidence). One participant allocated to L-arginine developed hives during infusion of L-arginine, another experienced acute clinical deterioration, and a participant in the placebo group had clinically relevant increases in liver function enzymes. The evidence is very uncertain whether L-arginine is better at reducing the mean number of days in hospital compared to placebo (MD -0.85 days, 95% CI -1.87 to 0.17; 2 studies, 125 participants; very low-certainty evidence). Also, L-arginine may not be better than placebo at increasing haemoglobin level (MD 0.4 g/dL, 95% CI -0.50 to 1.3; 2 studies, 106 participants; low-certainty evidence). No study in this comparison reported on QoL and sickle cell-related complications. Omega-3 versus placebo Very low-certainty evidence shows no evidence of a difference in the risk of adverse effects of omega-3 compared to placebo (RR 1.05, 95% CI 0.74 to 1.48; 1 study, 67 participants). Very low-certainty evidence suggests that omega-3 may not be better than placebo at increasing haemoglobin level (MD 0.36 g/L, 95% CI -0.21 to 0.93; 1 study, 67 participants). The study did not report on frequency of crisis, severity of pain, QoL, frequency of hospitalization, and sickle cell-related complications.
AUTHORS' CONCLUSIONS
There was inconsistent evidence on all outcomes to draw conclusions on the beneficial and harmful effects of antioxidants. However, L-arginine may be better than placebo at reducing the severity of pain at six months, and zinc may be better than placebo at increasing haemoglobin level. We are uncertain whether other antioxidants are beneficial for SCD. Larger studies conducted on each comparison would reduce the current uncertainties.
Topics: Humans; Anemia, Sickle Cell; Antioxidants; Ascorbic Acid; Bias; Dietary Supplements; Oxidative Stress; Placebos; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 38775255
DOI: 10.1002/14651858.CD013590.pub2