Non-randomized Clinical Trials Research Articles

(107) Uncovering the Role of Mast Cell Dysfunction in the Pathophysiology of Vulvodynia, Post-orgasmic Illness Syndrome, and Interstitial Cystitis

Abstract Introduction Certain sexual disorders are under-reported, under-researched, and rarely discussed. Many patients have suffered from ailments such as vulvodynia, a subset of vulvodynia called vestibulodynia, post-orgasmic illness syndrome (POIS), and interstitial cystitis (IC) without clear and optimal treatment strategies. To bring more awareness to these conditions, researchers and other medical professionals are working to elucidate their pathophysiologies in order to provide patients with therapeutic solutions. Mast cell dysfunction is one proposed mechanism of disease for these conditions. Mast cells are CD34+/CD117+/CD13 pluripotent progenitors of hematopoietic stem cells. They serve as innate immune cells that play a significant role in allergic responses, inflammation, and tissue homeostasis. They undergo maturation via growth factors and interleukins in the periphery and are heavily implicated in processes such as anaphylaxis, arthritis, coronary artery disease, autoimmune disorders, and cancer. As the body of research grows surrounding the function of mast cells and mast cell activation, researchers are finding that they may be implicated in multiple disease processes, even in genitourinary disorders. We know little about the etiology of disorders that affect sexual function like vulvodynia, POIS, and IC, but when considering their inflammatory and/or allergic-type symptoms, such as itching, burning, and congestion, we hypothesize that their pathophysiology may be correlated to mast cell function impairment. Objective The purpose of this study is to determine if mast cell dysfunction correlates with the pathophysiology of vulvodynia, POIS, and IC based on a literature review. Methods The authors reviewed existing literature published from January 2010 - June 2022 that explored the histopathological, pathophysiological, and etiological nature of vulvodynia, POIS, and IC. The selection criteria for this narrative review included: original articles (randomized and non-randomized clinical trials, including prospective observational studies, retrospective cohort studies, and case-control studies), review articles, and Cochrane analyses concerning the relationship between sexual disorders and allergens and/or immunology. Eighteen articles met the inclusion criteria. Results From the studies evaluated, it is reasonable to infer that vulvodynia, POIS, and IC have an immunological component to their pathophysiology. The inflammatory nature of all the diseases above indicates a definite immunological involvement, but as more research emerges, several medical providers and authors alike are noting that immunology and, certainly, mast cells may play a more significant role than initially hypothesized. While mast cells are likely not the sole cause of disease, it would be in the patient’s and provider’s best interest to consider their involvement in multifactorial pathophysiology for sexual disorders. Conclusions The pathophysiology of sexual disorders like vulvodynia, POIS, and IC is not currently well understood. However, review of existing literature supports that mast cell activation and, to a lesser extent, Toll-like receptors (TLRs) and lymphocytes may play a cardinal role in the pathophysiology of the sexual disorders described. Further research needs to be conducted on the possible pathophysiology of sexual disorders broadly so healthcare practitioners can provide effective, evidence-based treatment that will provide patients optimal relief. Disclosure No

Tonsillectomy in adults—to do or not to do

Recurrent acute tonsillitis describes the repeated occurrence of acute bacterial infections of palatine tonsils with symptom-free intervals. Acute tonsillitis accounts for around a third of respiratory tract infections in primary care among people of all ages, 1 Petersen I Johnson AM Islam A Duckworth G Livermore DM Hayward AC Protective effect of antibiotics against serious complications of common respiratory tract infections: retrospective cohort study with the UK General Practice Research Database. BMJ. 2007; 335: 982 Crossref PubMed Scopus (210) Google Scholar with an estimated 600 million symptomatic cases of group A streptococcus tonsillitis worldwide annually. 2 Carapetis JR Steer AC Mulholland EK Weber M The global burden of group A streptococcal diseases. Lancet Infect Dis. 2005; 5: 685-694 Summary Full Text Full Text PDF PubMed Scopus (1995) Google Scholar Recurrent episodes occur in 12% of patients with tonsillitis—ie, around 12 000 per 100 000 people. 3 Kvestad E Kværner KJ Røysamb E Tambs K Harris JR Magnus P Heritability of recurrent tonsillitis. Arch Otolaryngol Head Neck Surg. 2005; 131: 383-387 Crossref PubMed Scopus (26) Google Scholar Beyond the relation to group A streptococcus infections, little is known about risk factors for the development of recurrent acute tonsillitis. 4 Roberts AL Connolly KL Kirse DJ et al. Detection of group A Streptococcus in tonsils from pediatric patients reveals high rate of asymptomatic streptococcal carriage. BMC Pediatr. 2012; 12: 3 Crossref PubMed Scopus (97) Google Scholar Recurrent acute tonsillitis could be a genetic immunosusceptibility disease because patients younger than 12 years show some subclinical antibody deficiency and aberrant T-cell function 5 Dan JM Havenar-Daughton C Kendric K et al. Recurrent group A Streptococcus tonsillitis is an immunosusceptibility disease involving antibody deficiency and aberrant TFH cells. Sci Transl Med. 2019; 11eaau3776 Crossref PubMed Scopus (1) Google Scholar and many undergo tonsillectomy. More than 30 000 tonsillectomies are performed annually in the UK. 6 Keltie K Donne A Daniel M et al. Paediatric tonsillectomy in England: a cohort study of clinical practice and outcomes using Hospital Episode Statistics data (2008–2019). Clin Otolaryngol. 2021; 46: 552-561 Crossref PubMed Scopus (16) Google Scholar Tonsillectomy can produce severe postoperative pain, complicated by postoperative bleeding which can result in death in rare cases. Clearly, we need evidence-based policies to guide health-care professionals for the indication of tonsillectomy. 7 Mandavia R Schilder AGM Dimitriadis PA Mossialos E Addressing the challenges in tonsillectomy research to inform health care policy: a review. JAMA Otolaryngol Head Neck Surg. 2017; 143: 943-947 Crossref PubMed Scopus (10) Google Scholar Unfortunately, not much has changed in the past 40 years. National guidelines are still based on the Paradise criteria from 1984, 8 Paradise JL Bluestone CD Bachman RZ et al. Efficacy of tonsillectomy for recurrent throat infection in severely affected children—results of parallel randomized and nonrandomized clinical trials. N Engl J Med. 1984; 310: 674-683 Crossref PubMed Google Scholar stating that a tonsillectomy is indicated when around seven or more treated tonsillitis episodes occur in 1 year. The Paradise criteria were based on paediatrics clinical trials and later extrapolated for adult guidelines without any justifying research in the adult population. Thus, the 2014 Cochrane Review concluded that the effectiveness of tonsillectomy is low. 9 Burton MJ Glasziou PP Chong LY Venekamp RP Tonsillectomy or adenotonsillectomy versus non-surgical treatment for chronic/recurrent acute tonsillitis. Cochrane Database Syst Rev. 2014; 2014CD001802 PubMed Google Scholar Until now, there was no basis to make confident decisions using national guidelines. 7 Mandavia R Schilder AGM Dimitriadis PA Mossialos E Addressing the challenges in tonsillectomy research to inform health care policy: a review. JAMA Otolaryngol Head Neck Surg. 2017; 143: 943-947 Crossref PubMed Scopus (10) Google Scholar Conservative management versus tonsillectomy in adults with recurrent acute tonsillitis in the UK (NATTINA): a multicentre, open-label, randomised controlled trialCompared with conservative management, immediate tonsillectomy is clinically effective and cost-effective in adults with recurrent acute tonsillitis. Full-Text PDF Open Access

Clinical and Radiological Benefits of Hyaluronic Acid in Periodontal Infrabony Defects: A Systematic Review and Meta-analysis

Purpose: There is no consensus on the clinical and radiological benefits of hyaluronic acid (HA) in patients with periodontitis having infrabony defects. Hence, this study examined the effects of HA in periodontitis patients with infrabony defects through a comprehensive systematic review process. Methodology: A systematic literature search was performed using PubMed/Medline, Scopus, Embase and Cochrane Library from inception to March 2022. Randomized or non-randomized clinical trials and single-arm clinical trials that assessed the clinical and radiological benefits of HA in periodontitis patients with infrabony defects with a minimum of 6 months follow-up were included in this study. Surgical regenerative therapy was considered as the comparator. The Cochrane risk of bias assessment tool and Downs and Black checklist was used for the quality assessment of randomized and non-randomized interventional studies, respectively. A subgroup and sensitivity analyses were performed to explore the heterogeneity and robustness of the findings, respectively. Results: A total of 13 out of 725 studies were included in this systematic review, of which 9 were considered for meta-analysis. The meta-analysis indicated significant benefits of HA in terms of reduction in probing pocket depth (SMD: 1.12mm; 95%CI: 0.60-1.65; 9 studies), bone defect depth (SMD: 1.04mm; 95%CI: 0.62-1.47; 3 studies) and gain in clinical attachment level (SMD: 1.40 mm; 95%CI: 0.33-2.47; 8 studies). Overall, the quality of included studies was good. Conclusion: The current evidence indicates that the administration of HA in the periodontal regenerative treatment of infrabony defects was significantly effective in increasing clinical attachment levels and reducing probing pocket and bone defect depth.

Airway dimensional changes following bone anchored maxillary protraction: a systematic review

BackgroundThe introduction of skeletal anchorage utilized for maxillary protraction with a face mask or class III elastics has been developed for the management of class III malocclusions with minimal dental effect. The objective of the present review was to evaluate the current evidence regarding airway dimensional changes following bone-anchored maxillary protraction. A search was conducted by two authors (S.A & B.A) in the following databases: MEDLINE via PubMed, Cochrane Library, Web of Science, Scopus, Google Scholar and Open Grey; besides a hand search in references of selected articles and developing a search alert in electronic databases. Selection criteria comprised randomized as well as prospective clinical trials evaluating airway dimensional changes following bone-anchored maxillary protraction. Relevant data were extracted after studies retrieval and selection. The risk of bias was thereafter evaluated using the revised RoB 2 tool for randomized clinical trials and the ROBINS-I tool was used for non-randomized clinical trials. The quality of studies was assessed using the modified Jadad score. After examining (eligibility) full-text articles, four clinical trials were ultimately included. These studies evaluated the airway dimensional changes, following bone-anchored maxillary protraction in comparison to different control study groups. Based on the available evidence, all the bone-anchored maxillary protraction devices used in the eligible studies in the present systematic review resulted in an improvement in the airway dimensions. However, due to the few numbers of studies available and the guarded evidence due to the low quality of evidence of three out of four included articles, there is no strong evidence to support a significant increase in the airway dimensions following bone-anchored maxillary protraction. Therefore, there is a need for more randomized controlled clinical trials with similar bone-anchored protraction devices and similar assessment methods for more valid comparisons, excluding any confounding factors, on airway dimensional changes.

Treatment Effectiveness of Clear Aligners in Correcting Complicated and Severe Malocclusion Cases Compared to Fixed Orthodontic Appliances: A Systematic Review.

This systematic review aimed to critically assess the available evidence regarding the effectiveness and efficiency of clear aligners in the comprehensive treatment of complex cases accompanied by premolars extraction. An electronic literature search by two reviewers was independently done on 27 February 2023 in the following databases without time and language limitations: Pubmed®, Scoups®, Google Scholar, Cochrane Library database, Web of Science™, and Proquest Database Open. Randomized controlled trials (RCTs) of any type, non-randomized clinical trials (CCT), cohort studies, and prospective, retrospective, and cross-sectional studies were reviewed. The risk of bias in included studies was assessed using the Risk of Bias (RoB 2.0) tool for randomized trials and the Risk of Bias in Non-randomized Studies (ROBINS-I) tool for non-randomized studies. After carefully searching the literature, six trials were included in this systematic review, three RCTs, two retrospective cohort studies, and one CCT. Two hundred eighty-three patients were included (186 females, 97 males). Three studies found that there were no differences between the clear aligners and fixed appliances when evaluations were done using the American Board of Orthodontists Objective Grading System (ABO-OGS) or the Peer Assessment Rating (PAR) index. Two studies found that there were some differences between predicted and achieved tooth movements when clear aligners were used in premolars extraction cases. Based on the included studies, the duration of treatment was shorter with fixed appliances than the clear aligners when applied to orthodontic extraction cases. Both clear aligners and fixed appliances were found effective in the orthodontic treatment of premolar extraction-based cases. Fixed appliances have the advantage of achieving better buccolingual inclination and occlusal contacts in a shorter treatment duration. Treatment with clear aligners might be associated with differences between predicted and achieved tooth movements. Therefore, the characteristics of these techniques should be considered when making a treatment decision.

Meta-analysis of couple therapy in non-randomized clinical trial studies: Individual and couple level outcomes.

Couple therapy has outperformed control conditions in randomized clinical trials (RCTs). However, there have been some questions whether couple treatment in naturalistic settings is as effective as those with more rigorous controls. The current meta-analysis examined 48 studies of couple therapy in non-randomized clinical trials. The pre-post effect size was Hedge's g = 0.522 for relational outcomes and Hedge's g = 0.587 for individual outcomes. However, there was significant heterogeneity in the results. Several moderators explained some of the variance in these estimates. For relationship outcomes, studies who had older couples and longer length of relationship had better outcomes. Studies with a higher percentage of racial/ethnic minority (REM) couples and studies in Veteran Affairs Medical Centers (VAMC) had lower relational outcomes. For individual outcomes, studies that had more sessions, older couples, and VAMC had better outcomes. Studies with a higher percentage of REM couples also had worse individual outcomes. Trainee status was not consistently related to relational or individual outcomes. Implications for research and practice are provided.

Effectiveness of physical rehabilitation interventions in critically ill patients-A protocol for an overview of systematic reviews.

Adult and pediatric patients admitted to intensive care units (ICUs) requiring invasive ventilatory support, sedation, and muscle blockade may present neuromusculoskeletal deterioration. Different physical rehabilitation interventions have been studied to evaluate their effectiveness in improving critically ill patients' outcomes. Given that many published systematic reviews (SRs) aims to determine the effectiveness of different types of physical rehabilitation interventions, it is necessary to group them systematically and assess the methodological quality of SRs to help clinicians make better evidence-based decisions. This overview of SRs (OoSRs) aims to map the existing evidence and to determine the effectiveness of physical rehabilitation interventions to improve neuromusculoskeletal function and other clinical outcomes in adult and pediatric critically ill patients. An OoSRs of randomized and non-randomized clinical trials involving critically ill adult and pediatric patients receiving physical rehabilitation intervention will be conducted. A sensitive search of MEDLINE (Ovid), Embase (Ovid), CINAHL (EBSCOhost), Cochrane Library, Epistemonikos, and other search resources will be conducted. Two independent reviewers will conduct study selection, data extraction, and methodological quality assessment. Discrepancies will be resolved by consensus or a third reviewer. The degree of overlap of studies will be calculated using the corrected covered area. The methodological quality of the SRs will be measured using the AMSTAR-2 tool. The GRADE framework will report the certainty of evidence by selecting the "best" SR for each physical rehabilitation intervention and outcome. The findings of this overview are expected to determine the effectiveness and safety of physical rehabilitation interventions to improve neuromusculoskeletal function in adult and pediatric critically ill patients based on a wide selection of the best available evidence and to determine the knowledge gaps in this topic by mapping and assessing the methodological quality of published SRs. CRD42023389672.

Is Ozone a Valid Adjuvant Therapy for Periodontitis and Peri-Implantitis? A Systematic Review.

Ozone is a naturally occurring unstable compound with three oxygen atoms that generally transforms into an oxygen molecule, releasing one oxygen atom. This feature has been exploited in dentistry for numerous applications, including for periodontal diseases and peri-implantitis. This review was performed in relation to the PRISMA flow chart and was annotated in the PROSPERO register. PICO questions were used as research questions. The risk of bias in the non-randomized clinical trials was appraised using the ROBINS-I tool. An electronic search found a total of 1073 records, in particular, 842 from MEDLINE/PubMed, 13 from Bio Med Central, 160 from Scopus, 1 from the Cochrane library databases, and 57 from the PROSPERO register. A total of 17 studies were included in the present systematic review. Information regarding the characteristics of the periodontal clinical and radiographic parameters for gaseous ozone, ozonate water, ozonate oil, and ozone gel, including clinical attachment loss (CAL) probing depth (PPD), bleeding on probing (BoP), plaque index (PI), gingival index (GI), and marginal bone levels (MBL), were obtained. The studies included in this systematic review show different results regarding the ozone in periodontal treatment in association with or without SRP.

Effect of Montelukast on Treatment of Coronavirus Pneumonia (COVID-19): A Systematic Review

Background: The coronavirus disease 2019 (COVID‐19) exhibits the most important global public health emergency. Montelukast (MTL), a prototype cysteinyl leukotriene receptor antagonist, is commonly considered in the therapy of exercise- and aspirin-induced asthma. The purpose of this study was to present a systematic review of the literature on the effectiveness of MTL against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and exuberant immune activation in COVID‐19 disease. Methods: PubMed, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials were searched from the database on August 15, 2021and updated on November 19, 2022. Two reviewers independently screened articles, appraised methodological quality, and extracted the data. Results: A total of 118 related reports were recognized after eliminating duplicates. Of these, 30 references were screened based on titles and abstracts. After removing unrelated studies, 20 studies were included in the full-text review and evaluated for appropriateness. Finally, eight studies fitting the inclusion criteria for data extraction were selected. One of them was a prospective, randomized, controlled, and single-blinded study, three were open-label randomized or non-randomized controlled clinical trials, two were retrospective studies, and two were case series or comparative studies. A total of 1083 patients infected with COVID-19 infection (999 adults and 84 children) were examined on the effectiveness of MTL on symptom severity as well as hospitalization length. The results of the mentioned studies showed a low risk of clinical deterioration in the MTL group. In addition, the length of hospital stay was low in the treatment group compared to the standard management. Conclusion: MTL as a potential adjuvant therapy in COVID-19 may improve lung injury, inflammation, and symptoms. Moreover, the use of MTL could decrease the severity and mortality of COVID-19. Additional well-designed randomized controlled trials are necessary to approve the role of MTL in SARS-CoV-2 prevention or COVID-19 symptoms improvement.

Pathologic Complete Response and Clinical Outcomes in Patients With Localized Soft Tissue Sarcoma Treated With Neoadjuvant Chemoradiotherapy or Radiotherapy

Pathologic complete response (pCR) may be associated with prognosis in patients with soft tissue sarcoma (STS). We sought to determine the prognostic significance of pCR on survival outcomes in STS for patients receiving neoadjuvant chemoradiotherapy (CT-RT) (Radiation Therapy Oncology Group [RTOG] 9514) or preoperative image-guided radiotherapy alone (RT, RTOG 0630) and provide a long-term update of RTOG 0630. RTOG has completed 2 multi-institutional, nonrandomized phase 2 clinical trials for patients with localized STS. One hundred forty-three eligible patients from RTOG 0630 (n = 79) and RTOG 9514 (n = 64) were included in this ancillary analysis of pCR and 79 patients from RTOG 0630 were evaluated for long-term outcomes. Patients in trial 9514 received CT interdigitated with RT, whereas those in trial 0630 received preoperative RT alone. Overall and disease-free survival (OS and DFS) rates were estimated by the Kaplan-Meier method. Hazard ratios (HRs) and P values were estimated by multivariable Cox model stratified by study, where possible; otherwise, P values were calculated by stratified log-rank test. Analysis took place between December 14, 2016, to April 13, 2017. Overall there were 42 (53.2%) men; 68 (86.1%) were white; with a mean (SD) age of 59.6 (14.5) years. For RTOG 0630, at median follow-up of 6.0 years, there was 1 new in-field recurrence and 1 new distant failure since the initial report. From both studies, 123 patients were evaluable for pCR: 14 of 51 (27.5%) in trial 9514 and 14 of 72 (19.4%) in trial 0630 had pCR. Five-year OS was 100% for patients with pCR vs 76.5% (95% CI, 62.3%-90.8%) and 56.4% (95% CI, 43.3%-69.5%) for patients with less than pCR in trials 9514 and 0630, respectively. Overall, pCR was associated with improved OS (P = .01) and DFS (HR, 4.91; 95% CI, 1.51-15.93; P = .008) relative to less than pCR. Five-year local failure rate was 0% in patients with pCR vs 11.7% (95% CI, 3.6%-25.1%) and 9.1% (95% CI, 3.3%-18.5%) for patients with less than pCR in 9514 and 0630, respectively. Histologic types other than leiomyosarcoma, liposarcoma, and myxofibrosarcoma were associated with worse OS (HR, 2.24; 95% CI, 1.12-4.45). This ancillary analysis of 2 nonrandomized clinical trials found that pCR was associated with improved survival in patients with STS and should be considered as a prognostic factor of clinical outcomes for future studies. ClinicalTrials.gov Identifiers: RTOG 0630 (NCT00589121); RTOG 9514 (NCT00002791).

A multicenter randomized-controlled trial of nucleos(t)ide analogue cessation in HBeAg-negative chronic hepatitis B

Nucleos(t)ide analogues (NUCs) are the standard and mostly lifelong treatment for chronic HBeAg-negative hepatitis B, as functional cure (loss of HBsAg) is rarely achieved. Discontinuation of NUC treatment may lead to functional cure; however, to date, the evidence for this has been based on small or non-randomized clinical trials. The STOP-NUC trial was designed with the aim of increasing the HBsAg loss rate using a NUC treatment interruption approach. In this multicenter, randomized-controlled trial, 166 HBeAg-negative patients with chronic hepatitis B on continuous long-term NUC treatment, with HBV DNA <172 IU/ml (1,000 copies/ml) for ≥4 years, were randomized to either stop (Arm A) or continue NUC treatment (Arm B) for a 96-week observation period. In total, 158 patients were available for final analysis, 79 per arm. The primary endpoint was sustained HBsAg loss up to week96. Our study met its primary objective by demonstrating HBsAg loss in eight patients (10.1%, 95% CI 4.8%-19.5%) in Arm A and in no patient in Arm B (p=0.006). Among patients with baseline HBsAg levels <1,000 IU/ml, seven (28%) achieved HBsAg loss. In Arm A, re-therapy was initiated in 11 (13.9%) patients, whereas 32 (40.5%) patients achieved sustained remission. A decrease of HBsAg >1 log IU/ml was observed in 16 patients (20.3%) in Arm A and in one patient (1.3%) in Arm B. No serious adverse events related to treatment cessation occurred. Cessation of NUC treatment was associated with a significantly higher rate of HBsAg loss than continued NUC treatment, which was largely restricted to patients with end of treatment HBsAg levels <1,000 IU/ml. As HBeAg-negative patients with chronic hepatitis B on nucleos(t)ide analogues (NUCs) rarely achieve functional cure, treatment is almost always lifelong. The STOP-NUC trial was conducted to investigate whether discontinuing long-term NUC treatment can increase the cure rate. We found that some patients achieved functional cure after stopping NUCs, which was especially pronounced in patients with HBsAg levels <1,000at the end of NUC treatment, and that many did not need to resume therapy. The results of the Stop-NUC trial provide evidence for the concept of stopping NUC treatment as a therapeutic option that can induce functional cure.

Orthodontic Approaches in the Management of Mandibular Fractures: A Scoping Review.

Non-surgical approaches have been proposed in the management of mandibular fractures, especially in children, but there is a lack of clear guidelines on the clinical indications of conservative approaches. The aim of this scoping review is to provide the available evidence of the role of the orthodontist in the management of mandibular fractures. The PRISMA-ScR guidelines were followed to select eligible articles from the PubMed, Scopus, and Web of Science databases according to precise inclusion criteria. The research questions were formulated as follows: "what is the scientific evidence concerning the rule of orthodontists in the management of mandibular fractures" and "the preferential use of the direct bonding technique with orthodontic brackets rather than rigid arch bars"? Seventeen articles were included. Five articles presented the use of removable acrylic splints or functional appliances, six articles concerned the employment of cemented acrylic or rigid splints, and six articles described the management of mandibular fractures in adults and children using orthodontic brackets or mini-screws. Most of these techniques have been employed in children and growing subjects, while fewer data were available regarding conservative treatments in adults. Preliminary evidence suggests that condylar and some minor parasymphyseal fractures in children may be managed with conservative approaches. In adults, minor condylar and stable body mandibular fractures with minimal displacement have been reduced similarly. However, there are no sufficient elements that could suggest the preferential use of orthodontic brackets over rigid arch bars in adults. Further randomized and non-randomized clinical trials with long follow-ups will be needed to better define the clinical indications of the orthodontic approaches in the management of mandibular fractures based on severity, location, and age.

Digital Interventions for Social Participation in Adults with Long-term Physical Conditions: A Systematic Review.

This review aims to identify and evaluate digital interventions for social participation in the growing population of adults with long-term physical conditions. Articles were sourced from MEDLINE, EMBASE, CINAHL and PsycINFO databases using subject headings and keywords related to "social participation" and "digital technology". Studies that adopted digital technology interventions to improve social participation in adults with long-term physical conditions were included. Data on study methodology, participant and digital intervention characteristics, and findings related to social participation were extracted. The search yielded a total of 4646 articles and 14 articles met criteria for final review with five randomized controlled trials, two non-randomized clinical trials and seven one-group pretest-posttest clinical trials. Studies were organized based on the digital intervention strategy implemented to improve social participation: group support (n = 4), individual skill training or counseling (n = 6), education and support (n = 3), and mixed intervention (n = 1). The group support interventions developed a social network among participants through videoconference, app, or virtual reality platform. Three studies reported positive improvements in different aspects of social participation. Individual skill training or counseling mainly utilized phone calls to help participants cope with activity participation and interpersonal relationship issues. Only two studies demonstrated benefits for social participation. The education and support intervention, which used messages and website information to increase participants' knowledge and provide support, showed positive findings in three studies. This review suggests digital interventions for improving social participation in adults with long-term physical conditions are feasible and the effectiveness of different strategies may vary.Registration: This review was prospectively registered on the International Prospective Register of Systematic Reviews (PROSPERO) (registry number: CRD42021254105).

Medication-Related Osteonecrosis of the Jaws (MRONJ) in Children and Young Patients—A Systematic Review

Medication-related osteonecrosis of the jaw (MRONJ) is defined by the American Association of Oral and Maxillofacial Surgeons (AAOMS) as the presence of an exposed bone area in the maxillofacial region, present for more than eight weeks in patients treated with the use of antiresorptive or antiangiogenic agents, with no history of radiation or metastatic disease. Bisphosphonates (BF) and denosumab (DS) are widely used in adults for the management of patients with cancer and osteoporosis, and recently there has been an increase in their use in child and young patients for the management of disorders such as osteogenesis imperfecta (OI), glucocorticoid-induced osteoporosis, McCune-Albright syndrome (MAS), malignant hypercalcemia, and others. There are differences between case reports in adults compared to child and young patients related to the use of antiresorptive/antiangiogenic drugs and the development of MRONJ. The aim was to analyze the presence of MRONJ in children and young patients, and the relation with oral surgery. A systematic review, following the PRISMA search matrix based on the PICO question, was conducted in PubMed, Embase, ScienceDirect, Cochrane, Google Scholar, and manual search in high-impact journals between 1960 and 2022, publications in English or Spanish, including randomized and non-randomized clinical trials, prospective and retrospective cohort studies, cases and controls studies, and series and case reports. A total of 2792 articles were identified and 29 were included; all of them published between 2007 and 2022, identifying 1192 patients, 39.68% male and 36.24% female, aged 11.56 years old on average, using these drugs mainly for OI (60.15%); 4.21 years on average was the therapy time and 10.18 drug doses administered on average; oral surgery was observed in 216 subjects, reporting 14 cases of MRONJ. We concluded that there is a low presence of MRONJ in the child and youth population treated with antiresorptive drugs. Data collection is weak, and details of therapy are not clear in some cases. Deficiencies in protocols and pharmacological characterization were observed in most of the included articles.

Rapid Maxillary Expansion and Upper Airway Volume: Systematic Review and Meta-analysis on the Role of Rapid Maxillary Expansion in Mouth Breathing.

Rapid maxillary expansion (RME) has been extensively used in orthodontic practice for over a century, and it is claimed to benefit upper airway morphology. However, its effect in actually alleviating mouth breathing has remained unexplored. This systematic review was planned with an objective to provide a comprehensive synthesis of the effects of RME on upper airway volume and most importantly, its role in alleviating mouth breathing. A literature search of electronic databases were done for the time period of 2000-2018. Randomized controlled trials (RCTs) and non-RCTs conducted on 8-15-year-old children who received bonded or banded RME and upper airway measured using three-dimensional (3D) imaging were included. Twelve studies (two RCTs, nine nonrandomized clinical trials, and one non-RCT) were included in this systematic review, and nine studies were included for meta-analysis. Among the evaluated parameters, nasal cavity volume showed a significant increase which was maintained even after the retention phase, whereas nasopharyngeal and oropharyngeal volume did not report a significant change. Based on this systematic review, it can be concluded that RME causes a significant increase in nasal cavity volume, but its effect on nasopharyngeal and oropharyngeal volume is not statistically significant in majority of studies. This increase in volume may not be considered as an equivalent for enhancement of airway and function unless proven so. In order to establish its significance in the improvement of breathing, it is necessary to conduct more well-designed RCTs with samples actually comprising mouth breathers. Balasubramanian S, Kalaskar R, Kalaskar A. Rapid Maxillary Expansion and Upper Airway Volume: Systematic Review and Meta-analysis on the Role of Rapid Maxillary Expansion in Mouth Breathing. Int J Clin Pediatr Dent 2022;15(5):617-630.

The Evolving Landscape of Leptomeningeal Cancer from Solid Tumors: A Systematic Review of Clinical Trials.

Leptomeningeal carcinomatosis (LMC) is a fatal but uncommon complication occurring in 5-15% of patients with stage IV cancer. Current treatment options are ineffective at managing leptomeningeal spread, with a median overall survival (mOS) of 2-6 months. We aimed to conduct a systematic review of the literature to identify past and future therapies for LMC from solid tumors. Forty-three clinical trials (CTs) published between 1982-2022 were identified. Of these, 35 (81.4%) were non-randomized CTs and 8 (18.6%) were randomized CTs. The majority consisted of phase I (16.3%) and phase II CTs (65.1%). Trials enrolled patients with LMC from various primary histology (n = 23, 57.5%), with one CT evaluating LCM from melanoma (2.4%). A total of 21 trials evaluated a single modality treatment. Among CTs, 23.7% closed due to low accrual. Intraventricular (ITV)/intrathecal (IT) drug delivery was the most common route of administration (n = 22, 51.2%) vs. systemic drug delivery (n = 13, 30.3%). Two clinical trials evaluated the use of craniospinal irradiation for LMC with favorable results. LMC continues to carry a dismal prognosis, and over the years, increments in survival have remained stagnant. A paradigm shift towards targeted systemic therapy with continued standardization of efficacy endpoints will help to shed light on promising treatments.

PS-C25-11: PILATES AS AN ALTERNATIVE METHOD OF EXERCISE TO LOWER BLOOD PRESSURE IN WOMEN WITH SYSTEMIC HYPERTENSION: A SCIENTIFIC LITERATURE REVIEW

Objective: This review aimed at studying the effects of Pilates as an alternative method of exercise on blood pressure in women with hypertension. Design and Methods: A systematic literature search was performed as per the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines 2020. Databases searched were PubMed (MEDLINE), Scopus, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Trial Registry and Database, Physical Therapy Evidence Database (PEDro) applying keywords as pilates, mat pilates, blood pressure, hypertension, elevated blood pressure, systemic hypertension, women. Filters applied were studies published between (01/01/2002 up to 25/06/2022), randomized, non-randomized clinical trials and English language. The Boolean operators used were AND, OR, NOT. Eligibility criteria: The articles selected for data synthesis required the following criteria for inclusion: Population: women with systemic hypertension, Intervention: Pilates in any mode of administration (Mat, Reformer, Cadillac, Barrel) Comparison group: Control group that has not undergone Pilates training, Outcomes: Arterial blood pressure parameters measured using both mercurial, oscillometric sphygmomanometers, Study Design: Randomized or non-randomized clinical trials. Results: A total of 137 records were retrieved from the databases (Cochrane Reviews and Trials Registry (n = 6), PubMed (MEDLINE) (n = 23), CINAHL (n = 13), Scopus (n = 90) and PEDro (n = 5). Deduplication was implemented using the Mendeley® software version yielding a total of 126 records. Records were further excluded based on eligibility (differences in target population: pregnancy, normotensive women, diabetes mellitus, cardiac disease, obesity, pulmonary disease, cancer, mental health, reviews, registered trial protocols and others). The included records (n = 7) were screened (title, abstract and full text) for eligibility by two independent reviewers. Data extraction and synthesis was done using Rayyan® software for systematic reviews by two independent reviewers regulated by a third senior reviewer. Quality assessment of each article was done using the Jadad® Scale for quality of evidence provided in each article. Out of the 7 studies selected, 3 studies were randomized controlled clinical trials. Significant reduction in systolic, mean arterial blood pressures was reported (n = 5). Diastolic blood pressure did not significantly change with Pilates training (n = 3). Reduction in ambulatory blood pressures, diurnal blood pressures were reported (n = 3). Pilates training was either administered using mats (n = 5) or equipments (n = 2) in combination with aerobic exercise or alone (n = 1). Conclusion: Systolic and mean arterial blood pressure have been found to be significantly lowered with Mat Pilates or equipment based Pilates in combination or alone in pre and postmenopausal women with hypertension.

Critical appraisal of systematic reviews of intervention studies in periodontology using AMSTAR 2 and ROBIS tools.

Systematic reviews of intervention studies are used to support treatment recommendations. The aim of this study was to assess the methodological quality and risk of bias of systematic reviews of intervention studies in in the field of periodontology using AMSTAR 2 and ROBIS. Systematic reviews of randomized and non-randomized clinical trials, published between 2019 and 2020, were searched at MedLine, Embase, Web of Science, Scopus, Cochrane Library, LILACS with no language restrictions between October 2019 to October 2020. Additionally, grey literature and hand search was performed. Paired independent reviewers screened studies, extracted data and assessed the methodological quality and risk of bias through the AMSTAR 2 and ROBIS tools. One hundred twenty-seven reviews were included. According to AMSTAR 2, the methodological quality was mainly critically low (64.6%) and low (24.4%), followed by moderate (0.8%) and high (10.2%). According to ROBIS, 90.6% were at high risk of bias, followed by 7.1% low, and 2.4% unclear risk of bias. The risk of bias decreased with the increased in the impact factor of the journal. Current systematic reviews of intervention studies in periodontics were classified as low or critically low methodological quality and high risk of bias. Both tools led to similar conclusions. Better adherence to established reporting guidelines and stricter research practices when conducting systematic reviews are needed. Key words:Bias, evidence-based dentistry, methods, periodontics, systematic review.

Can lingual spurs alter the oral health-related quality of life during anterior open bite interceptive treatment? A systematic review

The use of lingual spurs has been described as one efficient option, with great stability of results, but with scarce information of toleration for use in the mixed and permanent dentition phases. The purpose of this study was to assess the impact of lingual spurs on the oral health-related quality of life of children and/or adolescents during anterior open bite treatment. The review was recorded in the PROSPERO database. Eight electronic databases and partial gray literature were searched, without restrictions until march 2022. A manual search was also performed in the references of the included articles. Studies assessing the impact of lingual spurs on the oral health-related quality of life were included. Risk of bias was assessed using JBI or ROBINS-I tool, according to the study design. The level of evidence was assessed through GRADE. Five studies met the eligibility criteria. Two non-randomized clinical trials had a serious risk of bias. Of the case-series studies, two had a low risk of bias and the other, a moderate risk of bias. The certainty of the evidence was classified as very low for all the evaluated results. In general, the studies reported an initial negative impact with the use of lingual spurs, however this was transitory in nature. A quantitative analysis was not performed due to the great heterogeneity between the studies. Current evidence, although limited, suggests that lingual spurs have an initial transient negative impact during interceptive treatment. Additional well-conducted randomized clinical trials are needed.

Assessing the Effectiveness of Chin-Cup Therapy in the Treatment of Developing Class 3 Malocclusions

Background: Mandibular prognathism in Class 3 malocclusion (CLIII) is one of the most severe maxillofacial deformities. Fortunately, most of this malocclusion cases can be treated by facial growth modification, using extra and/or intra-oral appliances in growing individuals. Occipital-pull chin cup is the extra-oral orthopaedic appliance, which was mostly used for the treatment of mandibular prognathism in growing Class 3 1(Ngan, Sung, 2015). Unjustifiably, most orthodontists I know do not use chin cup therapy in the treatment of CLIII. Therefore, being new to the field of orthodontics, I needed to build a highly evidenced based knowledge on chin cup therapy’s effectiveness in the treatment of developing CLIII with prognathic mandible. Objective: Through a narrative literature review, the aim of the study was assessed following scientific methodology. Articles published from January 2010- November 2020 (commencement of the current review) were collected using keywords derived from PICO. Only highly evidence based studies (randomised and non-randomised clinical trials) with the least risk of bias scores were selected, and critically appraised using the Critical Appraisal Skill Programme (CASP). Results were used to draw the conclusion. Material and Method: The study title was broken down into its PICO (population, intervention, comparative, outcome) components and search keywords were derived. These were used to carry out a literature search through electronic search engines (Medline-PUBMED, Science Direct, ISI Web of Knowledge, Research gate, Google Scholar, Cochrane library and hand searching of references list. Collected articles were assessed for risk of bias using Downs and Black (D&amp;B) scale. Papers with score ‘good’ and above’ on the D&amp;B assessment were critically appraised. PRISMA statement reporting format and Harvard referencing system were adopted in the study. Result: Following the Downs and Black assessment only 4 studies were found at a level worthy to be critically appraised. Results of all the four articles revealed that chin cup therapy produced significant growth modification in the mandible, when applied at an early age. Moreover, chin cup was also found to increase the lower anterior facial height significantly. All the papers considered only the short-term effect of chin cup, but not the long-term effect. Treatment results stability was also not reported. Conclusion: The significant improvement in CLIII manifestation in the selected articles, make it possible to conclude that chin cup is viable for the treatment of CLIII malocclusion with mandibular prognatism. However, treatment results stability needs to be researched.