Systematic Review Of Clinical Trials Research Articles

Examining nutrition strategies to influence DNA methylation and epigenetic clocks: a systematic review of clinical trials

Nutrition has powerful impacts on our health and longevity. One of the mechanisms by which nutrition might influence our health is by inducing epigenetic modifications, modulating the molecular mechanisms that regulate aging. Observational studies have provided evidence of a relationship between nutrition and differences in DNA methylation. However, these studies are limited in that they might not provide an accurate control of the interactions between different nutrients, or between nutrition and other lifestyle behaviors. Here we systematically reviewed clinical studies examining the impact of nutrition strategies on DNA methylation. We examined clinical studies in community-dwelling adults testing the effects of nutrition interventions on i) global DNA methylation and its proxies, and ii) epigenetic clocks. We included 21 intervention studies that focused on the effects of healthy nutrition patterns, specific foods or nutrients, as well as the effect of multivitamin or multimineral supplements. In four studies on the methylation effects of healthy dietary patterns, as defined by being rich in vegetables, fruits, whole-grains, and nuts and reduced in the intake of added sugars, saturated fat, and alcohol, two of them suggested that a healthy diet, is associated with lower epigenetic age acceleration, one of them reported increases in global DNA methylation, while another one found no diet effects. Studies examining epigenetic effects of specific foods, nutrients, or mixtures of nutrients were scarce. For both folic acid and polyunsaturated fatty acids, the available independent studies produced conflicting findings. Although more evidence is still needed to draw firm conclusions, results begin to suggest that healthy dietary patterns have positive effects on DNA methylation. Additional evidence from large randomized-controlled clinical trials is needed to support the effects of healthy nutrition on the DNA methylome.

Nutrition in Gilbert’s Syndrome—A Systematic Review of Clinical Trials According to the PRISMA Statement

Nutrition in Gilbert’s Syndrome—A Systematic Review of Clinical Trials According to the PRISMA Statement

Examining the Impact of Ertugliflozin on Cardiovascular Outcomes in Patients with Diabetes and Metabolic Syndrome: A Systematic Review of Clinical Trials

Examining the Impact of Ertugliflozin on Cardiovascular Outcomes in Patients with Diabetes and Metabolic Syndrome: A Systematic Review of Clinical Trials

Women are Underrepresented in Non-small Cell Lung Cancer Clinical Trials: A Systematic Review.

To perform a systematic review of clinical trials examining non-small cell lung cancer (NSCLC) to better understand the equity afforded to women in the study of lung cancer. An electronic search was conducted for all NSCLC clinical trials published between 2010 and 2020 with included words "carcinoma, non-small cell, lung" and "non-small cell lung cancer." Studies from PubMed, Cochrane, and SCOPUS were included and were uploaded into Covidence to assist with systematic review. All articles were screened by two separate individuals and reviewed for location, study type, cancer stage, field of study of the research team, and percentage of females included. Student's t-test was used to compare the means of males and females. Across the 269 studies that met inclusion criteria, fewer females than males were enrolled (38.7% vs. 61.1%; p < 0.0001). Compared with studies from 2010 to 2015, those from 2016 to 2020 had greater representation of females (36.7% vs. 41.4%, p = 0.0091, respectively). Both nonsurgical and surgical studies enrolled fewer female than male patients (38.1% vs. 61.7%, p < 0.0001; 43.1% vs. 57.2%, p = 0.0002, respectively). Clinical trials from the USA had the least difference between sexes with an average of 46.7% females enrolled. Less females compared with males were enrolled in early-stage NSCLC (37.6% female vs. 62.6% male, p < 0.0001) and late-stage NSCLC trials (37.6% female vs. 62.0% male, p < 0.0001). Despite recent improvement, there continues to be significant underrepresentation of females compared with males in NSCLC clinical trials.

Women are Underrepresented in Non-small Cell Lung Cancer Clinical Trials: A Systematic Review.

To perform a systematic review of clinical trials examining non-small cell lung cancer (NSCLC) to better understand the equity afforded to women in the study of lung cancer. An electronic search was conducted for all NSCLC clinical trials published between 2010 and 2020 with included words "carcinoma, non-small cell, lung" and "non-small cell lung cancer." Studies from PubMed, Cochrane, and SCOPUS were included and were uploaded into Covidence to assist with systematic review. All articles were screened by two separate individuals and reviewed for location, study type, cancer stage, field of study of the research team, and percentage of females included. Student's t-test was used to compare the means of males and females. Across the 269 studies that met inclusion criteria, fewer females than males were enrolled (38.7% vs. 61.1%; p < 0.0001). Compared with studies from 2010 to 2015, those from 2016 to 2020 had greater representation of females (36.7% vs. 41.4%, p = 0.0091, respectively). Both nonsurgical and surgical studies enrolled fewer female than male patients (38.1% vs. 61.7%, p < 0.0001; 43.1% vs. 57.2%, p = 0.0002, respectively). Clinical trials from the USA had the least difference between sexes with an average of 46.7% females enrolled. Less females compared with males were enrolled in early-stage NSCLC (37.6% female vs. 62.6% male, p < 0.0001) and late-stage NSCLC trials (37.6% female vs. 62.0% male, p < 0.0001). Despite recent improvement, there continues to be significant underrepresentation of females compared with males in NSCLC clinical trials.

Assessment of the Efficacy in Athletes and Non-Athletes of the Use of Creatine Monohydrate in Physical Exercise: A Systematic Review

Background: Considering the growing awareness of the population regarding the importance of engaging in physical activity, the utilization of supplements, such as creatine monohydrate, is also expanding in search of the attributed benefits of these substances. This study describes and analyzes the relationship between supplementation with creatine monohydrate and the improvement in the athletic performance of athletes from various disciplines and training levels, as well as non-athletes. Material and methods: A systematic review of clinical trials that address the use of creatine monohydrate in various sports contexts was conducted, followed by an analysis of the results based on body composition, jump capacity, and strength performance to determine points of correlation between the data presented in each publication. Results: A significant improvement in body composition, jump capacity, and strength performance was observed among participants who used supplementation, although in many cases, the results were heterogeneous. Conclusion: Creatine monohydrate supplementation positively influences body composition and physical performance, but further research is needed to understand its effects in specific populations.

Radiofrequency of suprascapular nerve as an analgesic strategy for chronic pain management. Systematic review and meta-analysis

IntroductionChronic shoulder pain is highly prevalent in the general population. Many different analgesic strategies have been described, including radiofrequency treatment to the suprascapular nerve (RFS); however, the effectiveness this approach remains unclear, and no strong recommendation can be made. The aim of this systematic review is to analyse the latest clinical trials evaluating the effectiveness of RFS techniques applied to the suprascapular nerve in terms of management of chronic shoulder pain, post-procedural functionality, and adverse effects. MethodsWe performed a systematic review of clinical trials retrieved from Medline, Embase and the CENTRAL databases. We included trials comparing RFS with other strategies, including placebo, that had as their primary outcome measures pain rated on a visual analogue scale, functionality rated on a shoulder pain and disability index (SPADI), and the incidence of adverse events. Risk of bias was analysed using the Cochrane RoB2 tool. Evidence was analysed using a random effects model and heterogeneity was quantified using the I2 test. ResultsWe identified 3030 trials, of which 8 met the inclusion criteria (n = 408). Seven had a high risk of bias. Pain intensity at 1 and 3 months was lower in patients receiving RFS, with a standardised mean difference (SMD) of −0.9 (95% CI [−1.1, 0.33], p = 0.29; I2 88%, p < 0.001) and −1.17 (95% CI [−2.49, 0.14], p = 0.08; I2 97%, p < 0.001), respectively. Functional compromise at 1 and 3 months decreased in patients receiving RFS, with an SMD of −0.31 (95% CI [−0.91, 0.29], p = 0.31; I2 80%, p < 0.001) and −1.54 (95% CI [−3.26, 0.19], p = 0.08; I2 98%, p < 0.001), respectively. No RFS-related adverse events were described. ConclusionThe evidence suggests that RFS reduces pain and improves functionality. However, the certainty of the evidence is low.

Radiofrequency of suprascapular nerve as an analgesic strategy for chronic pain management. systematic review and meta-analysis

IntroductionChronic shoulder pain is highly prevalent in the general population. Many different analgesic strategies have been described, including radiofrequency treatment to the suprascapular nerve (RFS); however, the effectiveness this approach remains unclear, and no strong recommendation can be made. The aim of this systematic review is to analyse the latest clinical trials evaluating the effectiveness of RFS techniques applied to the suprascapular nerve in terms of management of chronic shoulder pain, post-procedural functionality, and adverse effects. MethodsWe performed a systematic review of clinical trials retrieved from Medline, Embase and the CENTRAL databases. We included trials comparing RFS with other strategies, including placebo, that had as their primary outcome measures pain rated on a visual analogue scale, functionality rated on a shoulder pain and disability index (SPADI), and the incidence of adverse events. Risk of bias was analysed using the Cochrane RoB2 tool. Evidence was analysed using a random effects model and heterogeneity was quantified using the I2 test. ResultsWe identified 3030 trials, of which 8 met the inclusion criteria (n = 408). Seven had a high risk of bias. Pain intensity at 1 and 3 months was lower in patients receiving RFS, with a standardised mean difference (SMD) of -0.9 (95% CI [-1.1, 0.33], p = 0.29; I2 88%, p < 0.001) and -1.17 (95% CI [-2.49, 0.14], p = 0.08; I2 97%, p < 0.001), respectively. Functional compromise at 1 and 3 months decreased in patients receiving RFS, with an SMD of -0.31 (95% CI [-0.91, 0.29], p = 0.31; I2 80%, p < 0.001) and -1.54 (95% CI [-3.26, 0.19], p = 0.08; I2 98%, p < 0.001), respectively. No RFS-related adverse events were described. ConclusionThe evidence suggests that RFS reduces pain and improves functionality. However, the certainty of the evidence is low.

Physical exercise intervention for gaming disorder: a systematic review of clinical trials

Gaming disorder (GD) is continuously rising in prevalence with no specific treatment modalities proven most effective yet. Physical exercise (PE) has been used as an additional modality in treating addiction. Our study explores the outcome of PE intervention in treating GD. A structured search of the literature was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement guideline, with a pre-determined search strategy starting from study identification, title and abstract screening, eligibility assessment, and inclusion of relevant study. PubMed, ProQuest, and EBSCO databases were searched in February 2024 with additional manual exploration, using “exercise” and “gaming disorder” as keywords. Three studies were included in the final systematic review, all of which are randomized controlled trials (RCTs). PE interventions were found to be effective in diminishing the score of gaming addiction scale. Improvement of gaming duration and mood were also reported. This study supports PE intervention as a favorable method of adjunctive treatment in GD, especially in reducing GD severity in adolescent and young adult.

Intradialytic parenteral nutrition in malnourished patients with chronic kidney disease: a systematic review

Introduction: Malnutrition is a prevalent condition among patients with chronic kidney disease (CKD). Objective: To answer the question of the effect of intradialytic parenteral nutrition (IPN) on malnourished CKD patients undergoing dialysis, a systematic review of clinical trials was performed. Methods: The systematic review was performed according with PRISMA. The review was carried out between September and October 2022. The search strategy included PubMed, Web of Science and LILACS databases. The selection of articles was carried out using the Rayyan platform and to assess the chance of bias, the Rob2 instrument recommended by Cochrane was employed. Results and Conclusions: From 762 article retrieved in the initial strategy only 4 articles were included in the review. In a general view, the use of IPN increased the levels of prealbumin and albumin in the participants. Studies evaluating this topic are sparse. More studies are needed to recommend the use of IPN universally in the context of malnourished patients with CKD.

A Mediterranean diet improves glycation markers in healthy people and in those with chronic diseases: a systematic review of clinical trials.

Consumption of the Mediterranean diet (MedDiet) has beneficial effects on cardiometabolic health and aging. This systematic review aimed to critically investigate the effect of the MedDiet on glycation markers in healthy or overweight individuals with type 2 diabetes or cardiovascular disease. MEDLINE, EMBASE, Web of Science, and the Cochrane Library were searched, using the terms "Mediterranean diet" AND "glycation end products, advanced". Three randomized and 3 nonrandomized clinical trials, containing data on 2935 adult and elderly individuals with normal weight or overweight, were included. All extracted data were compiled, compared, and critically analyzed. The authors of most of the studies demonstrated a reduction in serum concentrations of advanced glycation end products (AGEs), such as εN-carboxymethyllysine and methylglyoxal, and in skin autofluorescence levels after at least 4 weeks of adherence to the MedDiet. The MedDiet also led to positive effects on gene expression of receptors for AGEs, as RAGE and AGER1, and an enzyme involved in detoxification (glyoxalase I). There is no evidence that short-term adherence affects glycation markers. Glycation markers improved in response to the MedDiet. The possible mechanisms involved may be related to the low AGE and refined sugars content of the diet, as well as its high monounsaturated fatty acid, phenolic compound, and dietary fiber contents. PROSPERO registration no. CRD42021284006.

Anticonvulsants in the Treatment of Behavioral and Psychological Symptoms in Dementia: A Systematic Review

ObjectivesBehavioral and psychological symptoms of dementia (BPSD) are common and impart a significant burden to patients, caregivers, and the health system. However, there are few pharmacological options for treating BPSD. We conducted a systematic review of clinical trials examining the efficacy of anticonvulsants in BPSD. MethodsWe searched five electronic databases through January 2023, for randomized controlled trials and systematic reviews evaluating the efficacy of non-benzodiazepine anticonvulsants for the treatment of BPSD. We used the Cochrane risk of bias tool to ascertain the risk of bias in included trials. Because statistical pooling of results using meta-analysis was not feasible, we synthesized findings using the Cochrane Synthesis Without Meta-analysis reporting guidelines. ResultsWe identified 12 studies, including randomized controlled trials (RCTs) and 1 systematic review. Five RCTs evaluating valproic acid were synthesized by a recent Cochrane review which concluded that this drug is likely ineffective for BPSD. We extracted data from 6 trials involving 248 individuals comparing non-benzodiazepine anticonvulsants to either placebo or risperidone. Four trials (n = 97 participants) evaluated carbamazepine, only one of which demonstrated an improvement in the Brief Psychiatric Rating Scale measuring agitation, hostility, psychosis, and withdrawal/depression (effect size: 1.13; 95% confidence interval [CI]: 0.54–1.73) relative to placebo. Adverse effects were more common in patients receiving carbamazepine (20/27; 74%) relative to placebo (5/24; 21%). There is low quality evidence that oxcarbazepine is likely ineffective and that topiramate may be comparable to risperidone. ConclusionAnticonvulsants are unlikely to be effective in BPSD, although the quality of existing evidence is low.

Tooth movement with dental anchorage vs. skeletal anchorage: A systematic review of clinical trials.

The aim of this study is to compare the time and movement of orthodontic treatment using dental anchorage and skeletal anchorage in adolescent and adult patients with dental malocclusions. A systematic search was conducted in the Embase, PubMed, Lilacs, Cochrane, Trip, and Scopus databases up to October 2022. All the articles were selected using title and abstract, applying the inclusion and exclusion criteria. Disagreements were resolved with a third author. Finally, a full-text selection took place. The data extraction was conducted by two authors who independently evaluated the risk of bias. The methodological quality of the randomized clinical trials was evaluated using the Cochrane tool for the evaluation of the randomized clinical trials. Six articles were included in the data analysis. There were four clinical trials and two randomized clinical trials. A total of 176 patients was obtained with an age range between 14 and 46 years. Four studies showed significant differences when comparing the two anchorages in retraction or distalization of tooth groups, and two showed no differences when using dental and skeletal anchorage for vertical movements; only the articles with vertical movements showed relapse. We can conclude that skeletal anchorage generates precise and stable horizontal movements without overloading or changing the position of the molar. Future studies must incorporate three-dimensional technology for greater clinical accuracy.

Clinical Effectiveness of High-viscosity Glass Ionomer Cement and Composite Resin as a Restorative Material in Primary Teeth: A Systematic Review of Clinical Trials

Clinical Effectiveness of High-viscosity Glass Ionomer Cement and Composite Resin as a Restorative Material in Primary Teeth: A Systematic Review of Clinical Trials

Comparison of revision rates and epidemiological data of a single total knee arthroplasty system of different designs (cruciate retaining, posterior stabilized, mobile bearing, and fixed bearing): a meta-analysis and systematic review of clinical trials and national arthroplasty registries

BackgroundThis study aimed to meta-analyze epidemiological data, revision rates, and incidences of different designs of a single Total Knee Arthroplasty System and compare these factors across different countries.MethodsA systematic review was conducted on clinical studies and arthroplasty registries of ATTUNE TKA from 1999 to 2020. The main endpoints analyzed were revision rates and epidemiological data.ResultsThe average age of patients was 67.8 years, with a gender distribution of 60% female and 40% male. The pooled average BMI was 29.4 kg/m2. Eight clinical studies showed a pooled revision rate per 100 observed CY of 0.5 (n = 1343 cases). Cumulative revision rates after 1, 3, and 5 years varied among registries, with the Swiss registry having the highest revision data (after 5 years: 6.3%) and the American registry having the lowest revision data (after 5 years: 1.7%). A comparison of the revision rates of mobile bearing and fixed bearing (41,200 cases) as well as cruciate retaining and posterior stabilized (n = 123,361 cases) showed no significant advantage in the first 5 years after implantation.ConclusionIn conclusion, pooled data from 41,200 cases of TKA with a single Total Knee Arthroplasty System in two arthroplasty registries revealed that there was no significant difference in revision rates between the mobile bearing and fixed bearing design within the first 5 years after implantation. In addition, a comparison of the revision rates in n = 123,361 cases showed no significant advantage for cruciate retaining or posterior stabilized in the first 5 years after implantation.

Effect of level of sedation on outcomes in critically ill adult patients: a systematic review of clinical trials with meta-analysis and trial sequential analysis

Sedation is routinely administered to critically ill patients to alleviate anxiety, discomfort, and patient-ventilator asynchrony. However, it must be balanced against risks such as delirium and prolonged intensive care stays. This study aimed to investigate the effects of different levels of sedation in critically ill adults. Systematic review with meta-analysis and trial sequential analysis (TSA) of randomised clinical trials including critically ill adults admitted to the intensive care unit. CENTRAL, MEDLINE, Embase, LILACS, and Web of Science were searched from their inception to 13 June 2023. Risks of bias were assessed using the Cochrane risk of bias tool. Primary outcome was all-cause mortality. Aggregate data were synthesised with meta-analyses and TSA, and the certainty of the evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. This study is registered with PROSPERO: CRD42023386960. Fifteen trials randomising 4352 patients were included, of which 13 were assessed high risk of bias. Meta-analyses comparing lighter to deeper sedation showed no evidence of a difference in all-cause mortality (risk ratio (RR) 0.94, 95% confidence interval (CI) 0.83-1.06; p=0.28; 15 trials; moderate certainty evidence), serious adverse events (RR 0.99, CI 0.92-1.06; p=0.80; 15 trials; moderate certainty evidence), or delirium (RR 1.01, 95% CI 0.94-1.09; p=0.78; 11 trials; moderate certainty evidence). TSA showed that when assessing mortality, a relative risk reduction of 16% or more between the compared interventions could be rejected. The level of sedation has not been shown to affect the risks of death, delirium, and other serious adverse events in critically ill adult patients. While TSA suggests that additional trials are unlikely to significantly change the conclusion of the meta-analyses, the certainty of evidence was moderate. This suggests a need for future high-quality studies with higher methodological rigor. None.

Evaluating Glass Ionomer Cement Longevity in the Primary and Permanent Teeth-An Umbrella Review.

The aim of this umbrella review was to evaluate the longevity of glass ionomer cement (GIC) as a restorative material for primary and permanent teeth. Research in the literature was conducted in three databases (MedLine/PubMed, Web of Science, and Scopus). The inclusion criteria were: (1) to be a systematic review of clinical trials that (2) evaluated the clinical longevity of GICs as a restorative material in primary and/or permanent teeth; the exclusion criteria were: (1) not being a systematic review of clinical trials; (2) not evaluating longevity/clinical performance of GICs as a restorative material; and (3) studies of dental restorative materials in teeth with enamel alterations, root caries, and non-carious cervical lesions. Twenty-four eligible articles were identified, and 13 were included. The follow-up periods ranged from 6 months to 6 years. Different types of GICs were evaluated in the included studies: resin-modified glass ionomer cement (RMGIC), compomers, and low- and high-viscosity glass ionomer cement. Some studies compared amalgam and composite resins to GICs regarding longevity/clinical performance. Analyzing the AMSTAR-2 results, none of the articles had positive criteria in all the evaluated requisites, and none of the articles had an a priori design. The criteria considered for the analysis of the risk of bias of the included studies were evaluated through the ROBIS tool, and the results of this analysis showed that seven studies had a low risk of bias; three studies had positive results in all criteria except for one criterion of unclear risk; and two studies showed a high risk of bias. GRADE tool was used to determine the quality of evidence; for the degree of recommendations, all studies were classified as Class II, meaning there was still conflicting evidence on the clinical performance/longevity of GICs and their recommendations compared to other materials. The level of evidence was classified as Level B, meaning that the data were obtained from less robust meta-analyses and single randomized clinical trials. To the best of our knowledge, this is the first umbrella review approaching GIC in permanent teeth. GICs are a good choice in both dentitions, but primary dentition presents more evidence, especially regarding the atraumatic restorative treatment (ART) technique. Within the limitation of this study, it is still questionable if GIC is a good restorative material in the medium/long term for permanent and primary dentition. Many of the included studies presented a high risk of bias and low quality. The techniques, type of GIC, type of cavity, and operator experience highly influence clinical performance. Thus, clinical decision-making should be based on the dental practitioner's ability, each case analysis, and the patient's wishes. More evidence is needed to determine which is the best material for definitive restorations in permanent and primary dentition.

The effect of Oenothera biennis (Evening primrose) oil on inflammatory diseases: a systematic review of clinical trials

BackgroundEvening primrose oil (EPO), extracted from the seeds of Oenothera biennis, has gained attention for its therapeutic effects in various inflammatory conditions.MethodWe performed a systematic search in multiple databases and defined the inclusion criteria based on the following PICOs: P: Patients with a form of inflammatory condition, I: EPO, C: Placebo or other therapeutic interventions, O: changes in inflammatory markers or patients’ symptoms; S: randomized controlled trials. The quality of the RCTs was evaluated using Cochrane’s RoB tool.ResultsSeveral conditions were investigated in the literature. In rheumatoid arthritis, mixed results were observed, with some studies reporting significant improvements in symptoms while others found no significant impact. EPO showed some results in diabetes mellitus, atopic eczema, menopausal hot flashes, and mastalgia. However, it did not demonstrate effectiveness in chronic hand dermatitis, tardive dyskinesia, psoriatic arthritis, cystic fibrosis, hepatitis B, premenstrual syndrome, contact lens-associated dry eyes, acne vulgaris, breast cyst, pre-eclampsia, psoriasis, or primary Sjogren's syndrome. Some results were reported from multiple sclerosis after EPO consumption. Studies in healthy volunteers indicated no significant effect of EPO on epidermal atrophy, nevertheless, positive effects on the skin regarding hydration and barrier function were achieved.ConclusionSome evidence regarding the potential benefits of EPO in inflammatory disorders were reported however caution is due to the limitations of the current survey. Overall, contemporary literature is highly heterogeneous and fails to provide strong recommendations regarding the efficacy of EPO on inflammatory disorders. Further high-quality studies are necessitated to draw more definite conclusions and establish O. biennis oil effectiveness as an assuring treatment option in alleviating inflammatory conditions.

Safety, Efficacy, and Immunogenicity of Therapeutic Vaccines for Patients with High-Grade Cervical Intraepithelial Neoplasia (CIN 2/3) Associated with Human Papillomavirus: A Systematic Review

Despite the knowledge that HPV is responsible for high-grade CIN and cervical cancer, little is known about the use of therapeutic vaccines as a treatment. We aimed to synthesize and critically evaluate the evidence from clinical trials on the safety, efficacy, and immunogenicity of therapeutic vaccines in the treatment of patients with high-grade CIN associated with HPV. A systematic review of clinical trials adhering to the PRISMA 2020 statement in MEDLINE/PubMed, Embase, CENTRAL Cochrane, Web of Science, Scopus, and LILACS was undertaken, with no data or language restrictions. Primary endpoints related to the safety, efficacy, and immunogenicity of these vaccines were assessed by reviewing the adverse/toxic effects associated with the therapeutic vaccine administration via histopathological regression of the lesion and/or regression of the lesion size and via viral clearance and through the immunological response of individuals who received treatment compared to those who did not or before and after receiving the vaccine, respectively. A total of 1184 studies were identified, and 16 met all the criteria. Overall, the therapeutic vaccines were heterogeneous regarding their formulation, dose, intervention protocol, and routes of administration, making a meta-analysis unfeasible. In most studies (n = 15), the vaccines were safe and well tolerated, with clinical efficacy regarding the lesions and histopathological regression or viral clearance. In addition, eleven studies showed favorable immunological responses against HPV, and seven studies showed a positive correlation between immunogenicity and the clinical response, indicating promising results that should be further investigated. In summary, therapeutic vaccines, although urgently needed to avoid progression of CIN 2/3 patients, still present sparse data, requiring greater investments in a well-designed phase III RCT.

Compositional music therapy: A systematic review of clinical trials

Purpose: Compositional music therapy involves the creation of original music by the therapist, the patient/client, or both together. The purpose of this systematic review is to examine techniques of compositional music therapy and the evidence for its therapeutic uses. Methods: PRISMA guidelines were followed in performing this systematic review. Studies published in the last 25 years from January 1998 to December 2023 were identified through the use of the PubMed, PsycInfo, and Google Scholar databases, using the following keywords: Musi*, AND Therap*, AND Compos*. Two authors independently conducted a focused analysis and reached a final consensus on nine studies that met the specific selection criteria and passed the study quality checks. Results: Review yielded four key compositional music therapy techniques: songwriting, lyric analysis, instrumental composition, and therapeutic rap and singing. Eight out of the nine studies showed positive results for compositional music therapy. These techniques were associated with reduction in anxiety levels and an enhancement of positive affective states, the development of coping strategies, and improvement of emotional regulation. Conclusion: This review shows a body of positive evidence for compositional music therapy, highlighting its potential to foster psychological and physiological well-being across various demographics, especially in terms of coping strategies and emotion regulation. Future directions include the use of digital music technology for composition in music therapy.