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PloS One 2022While peptides can be excellent therapeutics for several conditions, their limited in vivo half-lives have been a major bottleneck in the development of therapeutic... (Meta-Analysis)
Meta-Analysis
While peptides can be excellent therapeutics for several conditions, their limited in vivo half-lives have been a major bottleneck in the development of therapeutic peptides. Conjugating the peptide to an inert chemical moiety is a strategy that has repeatedly proven to be successful in extending the half-life of some therapeutics. This systematic review and meta-analysis was conducted to examine the available literature and assess it in an unbiased manner to determine which conjugates, both biological and synthetic, provide the greatest increase in therapeutic peptide half-life. Systematic searches run on PubMed, Scopus and SciFinder databases resulted in 845 studies pertaining to the topic, 16 of these were included in this review after assessment against pre-specified inclusion criteria registered on PROSPERO (#CRD42020222579). The most common reasons for exclusion were non-IV administration and large peptide size. Of the 16 studies that were included, a diverse suite of conjugates that increased half-life from 0.1 h to 33.57 h was identified. Amongst these peptides, the largest increase in half-life was seen when conjugated with glycosaminoglycans. A meta-analysis of studies that contained fatty acid conjugates indicated that acylation contributed to a statistically significant extension of half-life. Additionally, another meta-analysis followed by a sensitivity analysis suggested that conjugation with specifically engineered recombinant peptides might contribute to a more efficient extension of peptide half-life as compared to PEGylation. Moreover, we confirmed that while polyethylene glycol is a good synthetic conjugate, its chain length likely has an impact on its effectiveness in extending half-life. Furthermore, we found that most animal studies do not include as much detail when reporting findings as compared to human studies. Inclusion of additional experimental detail on aspects such as independent assessment and randomization may be an easily accomplished strategy to drive more conjugated peptides towards clinical studies.
Topics: Animals; Peptides
PubMed: 35259149
DOI: 10.1371/journal.pone.0255753 -
Knee Surgery, Sports Traumatology,... Sep 2022Total knee arthroplasty (TKA) has experienced exponential growth over the last decade, including increasingly younger patients with high functional demands. Highly... (Meta-Analysis)
Meta-Analysis Review
Comparable results between crosslinked polyethylene and conventional ultra-high molecular weight polyethylene implanted in total knee arthroplasty: systematic review and meta-analysis of randomised clinical trials.
PURPOSE
Total knee arthroplasty (TKA) has experienced exponential growth over the last decade, including increasingly younger patients with high functional demands. Highly crosslinked polyethylene (HXLPE) has been proven effective in reducing osteolysis and loosening revisions while improving long-term survival and performance in total hip arthroplasty; nevertheless, this superiority is not demonstrated in TKA. The aim of this systematic review and meta-analysis was to examine whether HXLPE improved overall survival and postoperative functional and radiological outcomes compared to conventional polyethylene (CPE) in TKA.
METHODS
According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline, a literature search of five databases (PubMed, Medline, Scopus, Science Direct and Embase) was made. A PICOS model was performed. The initial screening identified 2541 studies. Each eligible clinical article was analysed according to the Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence (LoE). Only randomised clinical trials (RCTs) of LoE 1 and 2 were included. The methodological quality of the articles was assessed using the Risk of Bias 2 (RoB 2) tool.
RESULTS
Six clinical studies were included in the final study. This systematic review and meta-analysis were registered on the International Prospective Register of Systematic Reviews (PROSPERO). A total of 2285 knees were included. Eight outcomes (total reoperations, reoperations for prosthesis loosening and infections, radiolucent lines, osteolysis, mechanical failure, postoperative KSS knee score and function score) were analysed. For none of them, a statistically significant difference was found about the superiority of HXLPE over CPE (p > 0.05).
CONCLUSIONS
There were no statistically significant differences between HXLPE and CPE for TKA concerning clinical, radiological, and functional outcomes; nevertheless, HXLPE did not show higher failure rates or complications and can be safely used for TKA.
LEVEL OF EVIDENCE
II.
Topics: Arthroplasty, Replacement, Knee; Humans; Knee Prosthesis; Osteolysis; Polyethylene; Polyethylenes; Prosthesis Design; Prosthesis Failure; Randomized Controlled Trials as Topic
PubMed: 35182171
DOI: 10.1007/s00167-022-06879-7 -
F1000Research 2021Patients with severe hemophilia often present with painful joint and soft tissue bleeding which may restrict them from their daily activities. The current standard of... (Meta-Analysis)
Meta-Analysis
Efficacy, safety, and immunogenicity of rurioctocog alfa pegol for prophylactic treatment in previously treated patients with severe hemophilia A: a systematic review and meta-analysis of clinical trials.
Patients with severe hemophilia often present with painful joint and soft tissue bleeding which may restrict them from their daily activities. The current standard of care still relies on a regular prophylactic factor VIII (FVIII), which has a high daily treatment burden. Recently, rurioctocog alfa pegol, a third-generation recombinant FVIII with a modification in its polyethylene glycol (PEG) component, has been developed. Several trials have studied this synthetic drug as bleeding prophylaxis in severe hemophilia A. This study aims to evaluate the efficacy, safety, and immunogenicity of rurioctocog alfa pegol for previously treated patients with severe hemophilia A. : This study was conducted in conformity with the PRISMA guidelines. Data were retrieved from PubMed, Scopus, Cochrane Library, Wiley Online Library, and CINAHL (via EBSCOhost). Study qualities were assessed using the Methodological Index for Non-Randomized Studies (MINORS) and Modified Jadad scales. Four studies involving 517 previously treated severe hemophilia A patients were included in this study. The pooled mean of total annualized bleeding rate (ABR) and hemostatic efficacy was 2.59 (95% CI = 2.04-3.14) and 92% (95% CI = 85%-97%), respectively. Only 30 (2.3%) non-serious and one (1.4%) serious adverse events were considered related to rurioctocog alfa pegol treatment. At the end of the studies, no development of FVIII inhibitory antibodies was observed. None of the developed binding antibodies to FVIII, PEG-FVIII, or PEG was correlated to the treatment efficacy and safety. Despite the limited availability of direct comparison studies, our analyses indicate that rurioctocog alfa pegol could serve as a safe and effective alternative for bleeding prophylaxis in previously treated hemophilia A patients. Moreover, it appears to have low immunogenicity, which further increases the safety profile of the drug in such clinical conditions.
Topics: Factor VIII; Hemophilia A; Hemorrhage; Humans; Polyethylene Glycols; Treatment Outcome
PubMed: 35136579
DOI: 10.12688/f1000research.73884.3 -
Digestive Endoscopy : Official Journal... Jul 2022We conducted a systematic review and meta-analysis of population-based studies to explore pooled prevalence and magnitude of electrolyte changes after bowel preparation... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND STUDY AIMS
We conducted a systematic review and meta-analysis of population-based studies to explore pooled prevalence and magnitude of electrolyte changes after bowel preparation for colonoscopy based on the most recent guidelines.
PATIENTS AND METHODS
PubMed and Cochrane were queried for population-based studies examining changes in electrolyte values after bowel preparation, published by July 1, 2021. We report prevalences of serum hypokalemia, hyponatremia, hyperphosphatemia, and hypocalcemia after bowel preparation and changes in mean electrolyte values after vs. before bowel preparation using sodium phosphate (NaP) and polyethylene glycol (PEG).
RESULTS
Thirteen studies met the inclusion criteria; 2386 unique patients were included. Overall, hypokalemia was found in 17.2% (95% CI 6.7, 30.9) in the NaP group vs. 4.8% (95% CI 0.27, 13.02) in the PEG group. The magnitude of potassium decrease after NaP bowel preparation was significantly increased compared to PEG (mean difference -0.38; 95% CI -0.49 to -0.27, P < 0.001). No study reported on major complications.
CONCLUSIONS
Hypokalemia was found in 17.2% of patients after bowel preparation with NaP and in 4.8% of patients with PEG, a finding that is clinically relevant with respect to choosing the type of bowel preparation. The magnitude of the potassium decrease after NaP was significantly higher compared to PEG. These data provide the evidence that supports the recommendation of the European Society of Gastrointestinal Endoscopy against routine use of NaP for bowel preparation.
Topics: Cathartics; Colonoscopy; Electrolytes; Humans; Hypokalemia; Polyethylene Glycols; Potassium
PubMed: 35037327
DOI: 10.1111/den.14237 -
Frontiers in Surgery 2021This meta-analysis aimed to compare ceramic-on-ceramic (COC) components and ceramic-on-polyethylene (COP) components during total hip arthroplasty (THA). A...
This meta-analysis aimed to compare ceramic-on-ceramic (COC) components and ceramic-on-polyethylene (COP) components during total hip arthroplasty (THA). A meta-analysis of randomized controlled trials (RCTs) comparing COC and COP during primary THA was conducted. Electronic searches were current to March 2021. Trials were included for meta-analysis if they compared at least the bearing surfaces of COC and COP for patients undergoing primary THA and if they reported the outcomes of THA after a certain period of follow-up and only RCTs in English were included. The primary endpoints consist of audible noise, prosthesis fracture, and revision. Secondary endpoints include dislocation, deep infection, osteolysis, and prosthesis loosening. Extracted data were statistically analyzed with the Stata11.0. A total of 15 RCTs containing 2,702 patients (2,813 hips) were included in this study. The audible noise [odds ratio (OR) = 5.919; 95% CI: 2.043, 17.146; ≤ 0.001] and prosthesis fracture (OR = 35.768; 95% CI: 8.957, 142.836; = 0.001) were significantly higher in the COC group. Hip function, revision rate, dislocation rate, deep infection rate, osteolysis rate, and prosthesis loosening rate were comparable between these two groups, while the wear rate was higher in the COP group. This study indicated comparable outcomes of COC and COP bearing surfaces in primary THA; high-quality RCTs with a long-term follow-up are still urgently needed to provide more evidence on the optimal bearing surfaces in primary THA.
PubMed: 34977138
DOI: 10.3389/fsurg.2021.751121 -
BioMed Research International 2021Adding vitamin E to highly cross-linked polyethylene liners is frequently performed in clinical practice, aiming at reducing liner wear, increasing liner survival, and... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Adding vitamin E to highly cross-linked polyethylene liners is frequently performed in clinical practice, aiming at reducing liner wear, increasing liner survival, and delaying revision surgery. This study is aimed at evaluating the revision rate, total femoral head penetration, and postoperative clinical function of highly cross-linked polyethylene liners with and without vitamin E in total hip arthroplasty.
METHODS
We conducted a systematic literature search to identify the use of highly cross-linked vitamin E liners compared to other liners in patients who received total hip arthroplasty (THA) before April 2021. The study quality assessment and data collection were conducted by two independent reviewers. Studies were artificially grouped, and vitamin E-enhanced liners (VE-PE) were compared with vitamin E-free liners (non-VE-PE). Analyses were executed using Review Manager version 5.4.1.
RESULTS
From the preliminary screening of 568 studies, fourteen studies met the research criteria. Compared to non-VE-PE, using VE-PE reduced the all-cause revision rate (odds ratio = 0.54; 95% confidence interval (CI) 0.40, 0.73; < 0.0001). The total femoral head penetration of the VE-PE was lower than that of the non-VE-PE (mean difference = -0.10; 95% CI -0.17, -0.03; = 0.007). However, there was no difference in clinical function, including the Harris Hip Score and EuroQol Five-Dimension Questionnaire scores.
CONCLUSION
Compared to the liners without vitamin E, the addition of vitamin E to liners could reduce the all-cause revision rate by approximately 46% in the short-term follow-up. In addition, even though addition of vitamin E could also slow down femoral head penetration, there is no contribution to clinical function.
Topics: Arthroplasty, Replacement, Hip; Femur Head; Humans; Polyethylene; Postoperative Period; Plastic Surgery Procedures; Vitamin E
PubMed: 34912888
DOI: 10.1155/2021/3236679 -
Clinical Orthopaedics and Related... Mar 2022Approximately one-fourth of TKAs will be performed in patients 55 years or younger within the next decade. Postoperative outcomes for younger patients who had a knee...
BACKGROUND
Approximately one-fourth of TKAs will be performed in patients 55 years or younger within the next decade. Postoperative outcomes for younger patients who had a knee arthroplasty were systematically reviewed in 2011; however, numerous studies evaluating young patients who had both a TKA and unicompartmental knee arthroplasty (UKA) have been reported in the past decade. Therefore, to better counsel this growing population of young patients undergoing knee arthroplasty, an updated understanding of their expected postoperative outcomes is warranted.
QUESTIONS/PURPOSES
In this systematic review, we evaluated (1) all-cause survivorship, (2) reasons for revision, (3) patient-reported outcomes, and (4) return to physical activity and sport in patients 55 years or younger undergoing primary TKA or UKA.
METHODS
A comprehensive search of PubMed, Medline, SportDiscus, and CINAHL was performed to identify all original studies evaluating outcomes after primary knee arthroplasty for young patients (55 years of age or younger) from inception until March 2021. The following keywords were used: knee, arthroplasty, replacement, pain, function, revision, survivorship, sport, physical activity, and return to play. Only original research studies that were related to knee arthroplasty and reported postoperative outcomes with a minimum 1-year follow-up for patients 55 years or younger were included. Unpublished materials, publications not available in English, and studies with a primary diagnosis of rheumatoid arthritis were excluded. The Methodological Index for Non-Randomized Studies (MINORS) score was used to evaluate the study quality of case series and comparative studies, while the Cochrane Risk of Bias tool and the Jadad scale were used for randomized studies. The primary outcomes of interest for this study were all-cause survivorship rate, reasons for all-cause revision, Knee Society and Knee Society Function scores (minimum clinically important difference [MCID] 7.2 and 9.7, respectively), WOMAC scores (MCID 10), Tegner scores (no reported MCID for knee arthroplasty), and return to physical activity or sport. Knee Society and Knee Society Function scores range from 0 to 100, with scores from 85 to 100 considered excellent and below 60 representing poor outcomes. All-cause survivorship rate and reasons for revision were both reported in 17 total studies. Knee Society scores were presented in 19 and Knee Society Function scores were reported in 18 included studies. WOMAC scores and Tegner scores were each found in four included studies, and return to physical activity and return to sport analyses were performed in seven studies. Overall, 21 TKA studies and five UKA studies were included in this analysis, featuring 3095 TKA knees and 482 UKA knees.
RESULTS
Kaplan-Meier estimates of all-cause survivorship ranged from 90% to 98% at 5 to 10 years of follow-up after TKA and from 84% to 99% (95% CI 93% to 98%) at 10 years to 20 years post-TKA. All-cause UKA survivorship was 90% at 10 years and 75% at 19 years in the largest Kaplan-Meier estimate of survivorship for patients younger than 55 who underwent UKA. Common reasons for revision in TKA patients were polyethylene wear/loosening, aseptic tibial loosening, and infection, and in UKA patients the common reasons for revision were knee pain, aseptic loosening, progression of knee osteoarthritis, and polyethylene wear/loosening. Knee Society scores ranged from 85 to 98 for 5-year to 10-year follow-up and ranged from 86 to 97 at 10-year to 20-year follow-up in TKA patients. Knee Society Function scores ranged from 70 to 95 for 5-year to 10-year follow-up and ranged from 79 to 86 at 10-year to 20-year follow-up. Return to physical activity and sport was reported variably; however, most patients younger than 55 have improved physical activity levels after knee arthroplasty relative to preoperative levels.
CONCLUSION
Although all-cause survivorship rates were frequently above 90% and patient-reported outcome scores were generally in the good to excellent range, several studies reported long-term survivorship rates from 70% to 85% and fair patient-reported outcome scores, which must be factored into any preoperative counseling with patients. We could not control for surgeon volume in this report, and prior research suggests that increasing volume is associated with less frequent complications; in addition, the studies we included were variably affected by selection bias, transfer bias, and assessment bias, which makes it likely that the findings of our review represent best-case estimates. To limit the frequency of revision in patients younger than 55 years undergoing TKA, clinicians should be cautious of polyethylene wear/loosening, aseptic tibial loosening, and infection, while knee pain and progression of knee osteoarthritis are also common reasons for revision in patients younger than 55 undergoing UKA. Further research should isolate younger knee arthroplasty patients and evaluate postoperative activity levels while accounting for preoperative physical activity and sport participation.
LEVEL OF EVIDENCE
Level IV, therapeutic study.
Topics: Age Factors; Arthroplasty, Replacement, Knee; Patient Reported Outcome Measures; Prosthesis Failure; Recovery of Function; Reoperation; Return to Sport
PubMed: 34846307
DOI: 10.1097/CORR.0000000000002023 -
Bioengineering (Basel, Switzerland) Oct 2021The inherent resistance of synthetic plastics to degradation has led to an increasing challenge of waste accumulation problem and created a pollution issue that can only... (Review)
Review
The inherent resistance of synthetic plastics to degradation has led to an increasing challenge of waste accumulation problem and created a pollution issue that can only be addressed with novel complementary methods such as biodegradation. Since biocontrol is a promising eco-friendly option to address this challenge, the identification of suitable biological agents is a crucial requirement. Among the existing options, organisms of the genus have been reported to biodegrade several complex polymeric macromolecules such as chitin, lignin, and cellulose. Therefore, this systematic review aimed to evaluate the potential of strains for the biodegradation of synthetic plastics. The results showed that although strains are widely distributed in different ecosystems in nature, few studies have explored their capacity as degraders of synthetic polymers. Moreover, most of the research in this field has focused on strains with promising biotransforming potential against polyethylene-like polymers. Our findings suggest that this field of study is still in the early stages of development. Moreover, considering the diverse ecological niches associated with , these actinobacteria could serve as complementary agents for plastic waste management and thereby enhance carbon cycle dynamics.
PubMed: 34821720
DOI: 10.3390/bioengineering8110154 -
Shoulder & Elbow Oct 2021Several articles have been published reporting on the clinical performance of a novel pegged, all-polyethylene glenoid component design which features a central peg,...
BACKGROUND
Several articles have been published reporting on the clinical performance of a novel pegged, all-polyethylene glenoid component design which features a central peg, circumferentially fluted, interference-fit peg for tissue integration and three small peripheral pegs for cementing. However, no systematic review exists to this date.
METHODS
The US National Library of Medicine (PubMed/MEDLINE), EMBASE, and the Cochrane Database of Systematic Reviews were queried for publications up to May 2020.
RESULTS
Overall, 13 articles were included for analysis (560 operated shoulders, range of mean follow-up: 2-6 years). The survival rate was 98.2% (550 out of 560 cases), while the rate of aseptic loosening was 0.2% (1 out of 560 cases). There were 139 cases (out of 399 reported; 34.1%) with peri-glenoid radiolucency, and 35 cases (out of 223 reported; 15.7%) of asymptomatic central peg osteolysis, with 1 of them undergoing revision.
CONCLUSIONS
There was fair quality of evidence to show that partially cemented all-polyethylene pegged bone-ingrowth glenoid components produce promising results, with a low revision rate in the short- to medium-term follow-up. Nevertheless, this analysis showed high rates of both radiolucency of the glenoid component and osteolysis around the central peg which raise concern for potential failure of this glenoid component in the long-term follow-up.
LEVEL OF EVIDENCE
Systematic review, IV.
PubMed: 34804212
DOI: 10.1177/1758573220944168 -
Frontiers in Immunology 2021Expanding antiviral therapy to benefit more populations and optimizing treatment to improve prognoses are two main objectives in current guidelines on antiviral therapy.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Expanding antiviral therapy to benefit more populations and optimizing treatment to improve prognoses are two main objectives in current guidelines on antiviral therapy. However, the guidelines do not recommend antiviral therapy for inactive hepatitis B surface antigen (HBsAg) carriers (IHCs). Recent studies have shown that antiviral therapy is effective with good treatment outcomes in IHC populations. We conducted a systematic review and meta-analysis of HBsAg clearance and conversion in IHCs.
METHODS
We searched PubMed, Embase, Medline, and Web of Science to retrieve articles on HBsAg clearance in IHCs published between January 2000 and August 2021. Data were collected and analysed using the random-effects model for meta-analysis.
RESULTS
A total of 1029 IHCs from 11 studies were included in this analysis. The overall HBsAg clearance rate was 47% (95% confidence interval (CI): 31% - 64%), with a conversion rate of 26% (95% CI: 15% - 38%) after 48 weeks of Pegylated interferon (Peg-IFN) treatment. In the control group (including nucleos(t)ide analogue (NA) treatment or no treatment), the overall HBsAg clearance rate was only 1.54% (95% CI: 0.56% - 3.00%), which was markedly lower than that in the Peg-IFN group. Further analysis showed that a low baseline HBsAg level and long treatment duration contributed to a higher HBsAg clearance rate.
CONCLUSION
This study showed that treatment of IHCs can be considered to achieve a clinical cure for chronic hepatitis B virus (HBV) infection. After Peg-IFN treatment, the HBsAg clearance rate was 47%, and the conversion rate was 26%, which are markedly higher than those reported by previous studies on Peg-IFN treatment in patients with chronic hepatitis B (CHB). A low baseline HBsAg level and long treatment duration were associated with HBsAg clearance in IHCs. Therefore, antiviral therapy is applicable for IHCs, a population who may be clinically cured.
SYSTEMATIC REVIEW REGISTRATION
http://www.crd.york.ac.uk/PROSPERO, CRD): CRD42021259889.
Topics: Adult; Antiviral Agents; Biomarkers; Female; Hepatitis B; Hepatitis B Surface Antigens; Hepatitis B virus; Humans; Interferons; Male; Middle Aged; Polyethylene Glycols; Recombinant Proteins; Time Factors; Treatment Outcome; Viral Load; Young Adult
PubMed: 34804072
DOI: 10.3389/fimmu.2021.779347