Search Results (76)

Orofacial pain (OFP) includes a broad spectrum of odontogenic and non-odontogenic conditions with overlapping clinical features that often limit diagnostic accuracy, driving increasing interest in artificial intelligence (AI) as a tool to enhance diagnostic precision and support clinical decision-making. A narrative review was conducted using PubMed/MEDLINE, Scopus, and Web of Science to identify studies (2016–2026) applying AI to the diagnosis, classification, or prediction of OFP in adults. Eligible studies reported at least two diagnostic performance metrics and were thematically grouped into odontogenic and non-odontogenic categories, the latter including musculoskeletal, neurovascular, and neuropathic pain. Twenty studies were included. Neurovascular pain, particularly migraine, showed the most consistent and highest diagnostic performance, likely due to the greater availability of structured clinical data and standardized diagnostic criteria. Musculoskeletal pain, especially temporomandibular disorders, also demonstrated high and reproducible performance. In contrast, odontogenic pain showed lower and more heterogeneous performance, with better results mainly in imaging-based models, while signal- and behavior-based approaches were less robust. Neuropathic pain exhibited moderate to high performance in selected radiomics studies, but overall results remained inconsistent due to phenotypic variability and limited objective biomarkers. Currently, AI shows promising potential in OFP diagnosis, especially for neurovascular and musculoskeletal pain, but clinical translation is limited by data heterogeneity and lack of validation. Progress in clinical practice depends on multimodal datasets and multicenter studies to ensure robust, generalizable tools. Full article

Background and Objectives: The insertion of a throat pack is a routine practice during anesthesia in maxillofacial and upper airway surgeries to prevent the aspiration of blood and secretions. However, this technique is associated with postoperative adverse effects such as pharyngitis and nausea. The objective of this systematic review and meta-analysis was to analyze the clinical evidence regarding the effect of throat packs on the incidence of Postoperative Nausea and Vomiting (PONV), throat pain, and gastric volume. Materials and Methods: Conducted according to PRISMA 2020 and registered in PROSPERO (CRD420251027016), an exhaustive search was performed in PubMed, Scopus, WOS, and Cochrane Library. Randomized Controlled Trials (RCTs) comparing throat pack use versus non-use under general anesthesia were included. Quality was assessed using Cochrane RoB 2. Meta-analyses utilized Standardized Mean Difference (SMD) and Mean Difference (MD) through a random-effects model. Results: Fourteen articles (2002–2024) involving 1147 patients were included. Methodological quality predominantly raised “some concerns”, with only 7.1% of studies assessed at low risk of bias. Statistical analysis of pain intensity (k = 6) revealed a significant increase in the intervention group (SMD = 0.35; 95% CI: 0.09 to 0.62; p = 0.01). Regarding PONV (k = 3), no statistically significant differences were observed between groups (SMD = −0.47; 95% CI: −1.51 to 0.58; p = 0.38). Ultrasound measurements showed significant increases in gastric parameters in the throat pack group, including anteroposterior diameter (MD = −3.67 mm; p = 0.002) and antral cross-sectional area (MD = −223.10 mm²; p = 0.005). Conclusions: Current evidence does not demonstrate a clear benefit for the routine use of oropharyngeal packing in maxillofacial and upper airway surgeries, and suggests a possible increase in postoperative throat discomfort. While acknowledging the limited number of studies, clinical heterogeneity, and the influence of perioperative co-interventions, these results should be interpreted with caution. Full article

Background: Temporomandibular disorders (TMDs) are frequently underdiagnosed in patients with psoriatic arthritis (PsA), and the mechanisms underlying their development remain poorly understood. While inflammatory processes may contribute, central pain sensitization and psychological factors could play a significant role in TMD pathogenesis. Objective: The objectives of this study were to evaluate clinical characteristics, disease activity, psychiatric comorbidities, and pain processing mechanisms in PsA patients with and without TMD and to identify factors independently associated with temporomandibular involvement. Methods: This cross-sectional observational study included 190 consecutive PsA patients (CASPAR criteria) from a single tertiary center. Patients with fibromyalgia were excluded. TMD was assessed by maxillofacial specialists. Disease activity (cDAPSA), functional status (HAQ-DI), disease impact (PsAID-12), central sensitization (Central Sensitization Inventory, CSI), kinesiophobia (Tampa Scale for Kinesiophobia, TSK-11), pressure pain threshold (algometry), and emotional comorbidities (Hospital Anxiety and Depression Scale, HADS) were evaluated. An exploratory binary logistic regression identified a factor independently associated with TMD. Results: Twenty-five patients (13.1%) had confirmed TMD, with a significant female predominance (76% vs. 39%; p = 0.001). Only 24% of patients exhibited structural damage on orthopantomography. TMD patients showed higher CSI scores (52 vs. 32; p < 0.001), greater kinesiophobia (TSK-11: 30 vs. 23; p = 0.002), lower pressure pain thresholds (2.1 vs 2.7 kg/cm²; p = 0.03), and higher anxiety (HADS-A: 9 vs. 5; p = 0.001) and depression scores (HADS-D: 6.5 vs. 3; p = 0.001). TMD patients also exhibited worse functional status (HAQ-DI: 0.7 vs. 0.3; p = 0.001) and greater disease impact (PsAID-12: 4.8 vs. 2.9; p = 0.001). In multivariate analysis, central sensitization (OR: 1.1; 95%CI: 1.04–1.18; p = 0.001) and anxiety (OR: 1.2; 95%CI: 1.02–1.61; p = 0.02) were independently associated with TMD (Nagelkerke R² = 0.48). Conclusion: TMD in PsA is associated with central sensitization and anxiety rather than mechanisms secondary to bone damage. These findings support a multidimensional approach incorporating screening for central sensitization and psychiatric comorbidities in PsA patients with temporomandibular symptoms. Full article

Medication-related osteonecrosis of the jaw (MRONJ) represents a major clinical challenge for oral and maxillofacial surgery departments as well as dental practices. With increasing life expectancy and the more frequent use of medications associated with osteonecrosis, the incidence of MRONJ continues to rise. To date, there are no uniform treatment standards with scientifically proven effectiveness for this condition. To evaluate the impact of platelet-rich fibrin (PRF) on the outcomes of MRONJ treatment and to identify factors that may influence the effectiveness of PRF therapy, we conducted a comparative prospective study including 22 patients divided into two groups: patients treated with PRF and patients treated without PRF. PRF was prepared according to the PRF Duo Quattro Process protocol for PRF (Nice, France). The study was registered at ClinicalTrials.gov (NCT07464678). The following parameters were assessed: age, smoking status, gender, lesion location, body mass index (BMI), C-reactive protein (CRP) concentration, pain intensity, presence or absence of fistulas, soft tissue healing and radiological findings. Patients were evaluated preoperatively and postoperatively at 14 days, 6 weeks, and 6 months. The study demonstrated a reduction in pain after surgery among patients treated with PRF. In addition, the use of PRF resulted in improved healing outcomes in patients with elevated CRP. Higher BMI was associated with poorer therapeutic response to PRF. Improvements in soft tissue healing and disease stage were observed in the PRF group; however, these differences did not reach statistical significance. All findings should be interpreted with caution due to the limited sample size. There is still no standardized treatment for MRONJ. The use of platelet-rich fibrin as an inexpensive and safe adjunctive therapy may provide clinical benefits for patients, particularly through a significant reduction in pain. Further large-scale, multicenter studies are required to confirm these findings. Full article

Background and Objectives: Osteonecrosis of the jaw (ONJ) occurring after infection with SARS-CoV-2 has emerged as an increasingly reported complication in the post-COVID-19 era. Post-COVID-19 osteonecrosis of the jaw (PC-ONJ) has been described in association with both COVID-19-associated mucormycosis (CAM) and non-fungal phenotypes. This narrative review aims to synthesize and critically analyze the available evidence regarding terminology and classification, epidemiology and risk factors, pathophysiological mechanisms, clinical and imaging characteristics, diagnostic challenges, and management strategies relevant to oral and maxillofacial surgery practice. Materials and Methods: An extensive literature search was conducted in the PubMed/MEDLINE, Scopus, Web of Science, ScienceDirect, and Google Scholar databases. The search targeted peer-reviewed publications published between 2020 and 2025, reflecting the post-pandemic emergence of this clinical spectrum. Original studies, systematic and narrative reviews, multicenter case series, consensus guidelines, and well-documented case reports were considered. Results: Available data, largely derived from case reports and small series, demonstrate a predominance of maxillary involvement and frequent association with diabetes mellitus and systemic corticosteroid therapy. Proposed mechanisms include COVID-19-associated endothelial dysfunction, microvascular thrombosis, immune dysregulation, metabolic imbalance, and treatment-related effects. Clinically, patients may present with persistent orofacial pain, tooth mobility, exposed or probeable bone, and frequent sinonasal extension, with symptoms sometimes preceding bone exposure. Diagnostic challenges arise from the overlap with medication-related osteonecrosis of the jaw (MRONJ), osteoradionecrosis (ORN), and chronic osteomyelitis. Imaging is essential for assessing disease extent but remains insufficient for etiologic differentiation, making histopathological examination and targeted microbiological investigations necessary, particularly to exclude invasive fungal infection. Conclusions: Management must be etiology-driven. CAM requires urgent antifungal therapy combined with surgical debridement, whereas non-fungal forms are generally managed with conservative surgery and appropriate antimicrobial stewardship. Standardized diagnostic criteria and prospective multicenter studies are needed to reduce nosological ambiguity and optimize clinical decision-making in this emerging post-viral condition. Full article

Surgical wound complications, particularly surgical site infection (SSI), remain common despite advances in perioperative care, and modern dressings—including emerging smart systems—are intended to optimize moisture balance, reduce bioburden, and support monitoring of healing. This narrative review, informed by PRISMA 2020, synthesized comparative clinical evidence on postoperative dressings across surgical specialties. PubMed and Embase were searched for peer-reviewed comparative human studies published in 2015–2025 involving adults undergoing surgery with primary closure or secondary intention healing. Outcomes included SSI, time to epithelialization/closure, scar outcomes, pain, peri-wound skin integrity, and dressing change frequency. Nine studies met the inclusion criteria across orthopedics, general and endocrine surgery, otolaryngology, maxillofacial surgery, and surgical oncology. In hip/knee arthroplasty, hydrofiber dressings were associated with lower SSI rates versus standard/absorbent dressings. A meta-analysis suggested that moist and silver-based dressings generally outperformed gauze, with ionic silver ranking highest for healing and metallic silver for SSI prevention, and hydrocolloids reduced dressing change frequency. Oxygen diffusion therapy improved scar outcomes after cervicotomy, and chitosan gel reduced synechiae after endoscopic sinus surgery. Evidence in oncologic surgery was inconclusive, and heterogeneity in interventions, endpoints, and follow-up limited pooling. Overall, advanced postoperative dressings may improve selected outcomes compared with traditional gauze, but effects appear procedure- and context-dependent; future studies should standardize outcomes, extend follow-up, and incorporate cost-effectiveness and patient-reported measures, alongside evaluation of sensor-enabled smart dressings. Full article

Experimental animal models of orofacial pain have been instrumental in elucidating biological pathways underlying the antinociceptive effect of botulinum neurotoxin type A (BoNT/A). Although several mechanisms have been proposed to explain how BoNT/A relieves pain, the precise modes of action, particularly in the oral and maxillofacial areas, remain elusive. The purpose of this review was to synthesize and assess the latest proposed mechanisms of action through which BoNT/A attenuates orofacial pain in established animal models. A comprehensive search was conducted using the terms “botulinum neurotoxin,” “mechanism,” and “orofacial pain” or “trigeminal neuralgia.” Only animal studies involving the establishment of an orofacial pain model were selected. Additional relevant studies were identified through manual screening of cited references. Over the past five years, several animal pain models have been established to decipher the mechanisms underlying the BoNT/A-mediated antinociception in orofacial pain. The proposed mechanisms include retrograde transport, neuronal excitability regulation, neuropeptide inhibition, inflammatory modulation, and opioid system stimulation in both the peripheral and central nervous systems. Despite the insubstantial number of investigations and findings, BoNT/A exhibits multidimensional modulation of nociceptive responses and, therefore, remains a promising therapeutic agent for managing orofacial pain conditions, with animal studies consistently providing insights into the mechanism of its antinociceptive action. Full article

Background: Odontogenic sinusitis (ODS) is a frequent but under-recognized cause of chronic maxillary sinusitis, often requiring multidisciplinary management. Understanding clinical and microbiological predictors for oral and maxillofacial surgery (OMS) treatment may aid in early risk stratification. Methods: We retrospectively reviewed 47 patients diagnosed with ODS at a tertiary referral center between January 2023 and April 2025. Clinical characteristics, dental pathologies, and microbiological findings were analyzed. Univariate and multivariate logistic regression analyses were performed to identify independent predictors of OMS intervention. Results: The cohort included 20 males and 27 females, with a mean age of 59.5 years. OMS intervention was performed for 21 patients (44.7%). These patients were younger, and more frequently presented with gingival pain or swelling, oroantral fistula, antibiotic-resistant organisms, and polymicrobial infections compared with the non-OMS group. Staphylococcus epidermidis was the most common isolate, followed by Streptococcus constellatus, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Antibiotic resistance was observed in 29.8% of patients and was significantly more prevalent in the OMS group (52.4% vs. 7.7%, p < 0.001). Multivariate analysis identified dental diagnosis and antibiotic resistance as independent predictors for OMS intervention. All patients achieved full recovery following surgery, with no treatment failures. Conclusions: ODS demonstrates distinct clinical and microbiological characteristics, with antibiotic resistance and specific dental pathologies serving as independent risk factors for OMS intervention. Recognition of these features may guide early multidisciplinary planning and improve clinical outcomes. Full article

Objective: Lower third impacted molar extraction, despite being a routinary procedure for oral and maxillo-facial surgeons, may often result in a significantly negative impact in patient’s post-operatory quality of life. Among others, treatments based on oxygen-enriched oils have been shown to provide valuable therapeutic benefits in promoting wound healing, and therefore improving the immediate post-operatory symptomatology. The aim of this triple-blinded randomized controlled study is to supplement the existing evidence in the scientific literature by assessing the effectiveness of NovoX^®-Drop (Moss S.p.A., Lesa, Novara), a specific type of oxygen enriched oil-based device in reducing pain and inflammatory stimulus of post-surgical wounds following the extraction of lower third impacted molars. Materials and methods: Seventy-one patients undergoing surgical extraction of a single lower third impacted molar were randomly assigned to receive either NovoX^®-Drop (Group A) or a glycerin-based gel (Group B). Additionally, both patient groups followed the same standard therapy with amoxicillin-clavulanic acid and ibuprofen. Data were collected preoperative (T0) and after three (T3) and seven (T7) days postoperative in order to assess the following outcomes: mean visual analogue scale (VAS) score during the seven days protocol treatment, total duration of nonsteroidal anti-inflammatory drug (NSAID) usage, trismus (maximum mouth opening) and facial oedema. Results: Group A (treatment group) reported significatively lower pain levels at T7 compared to group B (average VAS value during the week: Group A: 3.57 ± 0.39 cm; Group B: 4.47 ± 0.40 cm; p-value = 0.0014) despite a significatively shorter period of NSAID usage (average NSAID usage duration: Group A: 2.43 ± 0.38 days; Group B: 3.38 ± 0.44 days; p-value = 0.00001). Therefore, trismus seems to be better controlled in group A, although the difference between the groups did not reach the threshold for statistical significance. Conclusions: The results of this study suggest that application of NovoX^®-Drop is capable of significantly reducing the post-operatory pain as well as NSAID usage, representing a promising and effective option for third impacted molar extraction surgery management. Full article

Background and Objectives: Diabetes mellitus (DM) and hypertension (HTN) continue to increase and pose a significant burden on the health system worldwide. These patients comprise a significant portion of the hospitalized Oral and Maxillofacial Surgery (OMFS) department. Addressing and controlling DM and HTN during hospitalization should thus be one of the treatment goals. This study aims to investigate the management and outcomes of DM and HTN during the hospitalization period in the OMFS department. Materials and Methods: A retrospective analysis of patients with community-diagnosed DM and/or HTN admitted to the OMFS department between 2017 and 2019 was conducted at Rambam Healthcare Campus, Haifa, Israel. Linear regression analysis was used to determine trends in changes in blood pressure and blood glucose levels during hospitalization. The impact of consults from internal medicine experts and endocrinologists was tested using a paired-samples t-test. Results: A statistically significant reduction was observed in all systolic HTN patients categorized as stages 1 and 2, p = 0.012 and p = 0.001, respectively. A statistically significant (p = 0.012) reduction in blood glucose levels in all DM patients with initial values higher than 250 mg/dL was observed. A statistically significant reduction in blood glucose levels was observed in the DM group of patients who received endocrinologist consultations (p = 0.012). Conclusions: Addressing patients with systemic conditions during hospitalization in the OMFS department is mandatory. External medical consulting can be of great value for short-term treatment during hospitalization and may also have long-term benefits after discharge to the community. The main limitations of this study include retrospective data acquisition, a small sample size, and a lack of data regarding the impact of pain management on blood pressure and glucose levels. Full article

Background and Clinical Significance: Renal cell carcinoma (RCC) is the third most common cancer that metastasizes to the oral and maxillofacial region following breast and lung cancers. Metastatic involvement in the oral cavity is rare and can present as a diagnostic challenge due to non-specific clinical features that mimic other benign or malignant conditions. The limited information available regarding oral metastasis of RCC highlights the importance of recognizing this uncommon presentation. Case Presentation: A 50-year-old female presented with a painful swelling in the buccal and palatal mucosa of the right maxilla that progressively enlarged over several months. Initially, this lesion was diagnosed clinically as a pyogenic granuloma. However, given the lesion’s continued growth and unusual presentation, a biopsy was performed. Histopathological examination confirmed the lesion as metastatic renal clear-cell carcinoma (ccRCC), with immunohistochemical analysis verifying the renal origin. Further diagnostic tests, including a computed tomography (CT) urogram, chest CT, and bone scintigraphy, revealed additional metastases in the left adrenal gland, lungs, and bone. Conclusions: This case is notable because the oral lesion was the first visible sign of RCC, making it a rare presentation of metastatic RCC. This underscores the importance of thorough history taking, detailed clinical evaluations, and considering rare metastatic conditions in the differential diagnosis of oral swellings. Additionally, this case reinforces the significance of routine cancer screenings for early detection of undiagnosed cancer. We also updated a previous literature review of metastatic RCC to the head and neck region, covering cases until 2023. Full article

Background/Objectives: Oroantral fistulas (OF) are a challenging complication in oral and maxillofacial surgery, often requiring surgical intervention to restore sinus integrity. The Bichat’s buccal fat pad (BFP) has gained attention as a viable option for OF closure. This study aimed to evaluate the efficacy, safety, and clinical outcomes of BFP advancement for OF treatment. Methods: This prospective study included 20 patients diagnosed with OF. The surgical procedure involved isolation and advancement of the BFP to close the defect. Patients were followed up at 7 days, 45 days, and 6 months postoperatively, with clinical and radiographic assessments. The primary outcome was successful fistula closure at 6 months, while secondary outcomes included complication rates, sinus opacification on CT scans, pain levels, and quality of life improvements. Results: The overall success rate was 85.7%, with complete fistula closure achieved in 18 out of 21 cases (including one bilateral case). Minor complications occurred in 14.3% of cases. CT scans at 6 months showed complete resolution of sinus opacification in 81% of cases. Patients reported significant improvements in pain scores and quality of life. Conclusions: BFP advancement is an effective, safe, and minimally invasive technique for OF closure, offering high success rates and favorable clinical and radiographic outcomes. These findings support the use of BFP as a reliable option for managing OF in oral and maxillofacial surgery. Full article

Background/Objectives: Autogenous palatal free gingival graft (FGG) harvesting presents challenges for patients due to the increased risk of postoperative morbidity related to a second intraoral surgical wound that heals with secondary intention. This parallel-group, randomized, controlled, open-label trial aimed to evaluate the efficacy of the application of leukocyte- and platelet-rich fibrin (L-PRF) membrane to the palatal donor site on wound healing, hemostasis, and pain control after FGG harvesting. Methods: Twenty-eight adult patients with insufficient attached gingiva underwent soft tissue augmentation using FGG harvested from the palate at the Department of Oral and Maxillofacial Surgery, Baskent University, Turkey. Patients were randomized to either an L-PRF group or a control group. In the L-PRF group, the L-PRF membrane was sutured to the donor sites, whereas in the control group, donor sites healed by secondary intention. Postoperative evaluations were conducted on days 1, 3, 5, and 7 and at weeks 2, 3, 4, 5, and 6. Donor sites were evaluated clinically for pain, burning sensation, bleeding, wound healing, and color match to adjacent tissues. Donor site wound areas were analyzed using digital images. Results: Two patients were excluded from the analysis due to loss of contact, leaving 26 (n = 13, n = 13) patients for analysis. Donor site pain and burning sensation were significantly lower in the L-PRF group compared to the control group during the first two postoperative weeks (p < 0.001). Bleeding was significantly lower in the L-PRF group on postoperative days 1 and 3 (p < 0.001). Clinical healing index scores were significantly higher in the L-PRF group at weeks 3 and 4 (p < 0.001). Additionally, palatal wound area reductions from baseline were significantly greater in the L-PRF group at all follow-up intervals (p < 0.001). Conclusions: The application of an L-PRF membrane to palatal donor wounds after FGG harvesting significantly reduces postoperative pain, decreases bleeding, and accelerates healing, providing a valuable autologous biomaterial for enhanced wound healing and improved patient comfort. Full article

Background: Advanced platelet-rich fibrin (A-PRF) is produced by centrifuging the patient’s blood in vacuum tubes for 14 min at 1500 rpm. The most important component of A-PRF is the platelets, which release growth factors from their ⍺-granules during the clotting process. This process is believed to be the main source of growth factors. The aim of this paper was to systematically review the literature and to summarize the role of A-PRF in oral and maxillo-facial surgery. Materials and Methods: A systematic review was carried out, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (PROSPERO: CRD42024584161). Results: Thirty-eight articles published before 11 November 2024 were included in the systematic review. The largest study group consisted of 102 patients, and the smallest study group consisted of 10 patients. A-PRF was most often analyzed compared to leukocyte-PRF (L-PRF) or blood cloth. A-PRF was correlated with lower postoperative pain. Also, A-PRF was highlighted to have a positive effect on grafting material integration. A-PRF protected areas after free gingival graft very well, promoted more efficient epithelialization of donor sites and enhanced wound healing. Conclusions: Due to its biological properties, A-PRF could be considered a reliable addition to the surgical protocols, both alone and as an additive to bio-materials, with the advantages of healing improvement, pain relief, soft tissue management and bone preservation, as well as graft integration. However, to determine the long-term clinical implications and recommendations for clinical practice, more well-designed randomized clinical trials are needed in each application, especially those with larger patient cohorts, as well as additional blinding of personnel and long follow-up periods. Full article

Background and Objectives: Third molar (wisdom tooth) extraction is one of the most common surgical procedures in oral and maxillofacial surgery. Traditional rotary instruments and burs have long been the standard tools for this procedure. However, recent advancements in surgical techniques, such as piezoelectric surgery, have gained popularity due to their purported advantages in terms of precision, safety, and postoperative outcomes. This systematic review aims to evaluate the efficacy, safety, and clinical outcomes of third molar surgery performed using burs versus piezoelectric surgery. Materials and Methods: This systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive literature search was performed using the PubMed, Scopus, Web of Science, and Cochrane databases to identify relevant studies published up until October 2024. Randomized controlled trials (RCTs), clinical trials, and comparative studies assessing third molar surgery using either burs or piezoelectric instruments were included. The primary outcomes evaluated were surgical time, postoperative pain, swelling, nerve damage, and healing time. The data extraction and quality assessment were performed independently by two reviewers using standardized tools, and any discrepancies were resolved by a third reviewer. Results: A total of five studies met the inclusion criteria, and the meta-analysis revealed that piezoelectric surgery resulted in significantly lower postoperative pain and swelling compared to traditional bur techniques (p < 0.05). Additionally, the incidence of nerve injury was lower in the piezoelectric group, though the difference was not statistically significant. Surgical time was found to be longer with piezoelectric devices, but this was offset by improved healing outcomes and patient comfort. Conclusions: Piezoelectric surgery offers a less traumatic alternative to traditional burs for third molar extraction, with reduced postoperative morbidity and enhanced patient outcomes. Although the longer surgical duration may be a drawback, the overall benefits, particularly in terms of pain management and tissue preservation, support the adoption of piezoelectric techniques in clinical practice. Further high-quality randomized trials are recommended to strengthen the evidence base for these findings. Full article