The effect of nicotine-containing products on peri-implant tissues: A systematic review and network meta-analysis.

INTRODUCTION: Smokers have a higher chance of developing peri-implant diseases and are therefore considered an at-risk population. Our aim was to compare peri-implant characteristics in users of electronic cigarettes (EC), waterpipes (WP), cigarettes (CS), smokeless tobacco (ST), and non-smokers (non-users of any nicotine and tobacco product; NS). METHODS: A systematic search of four electronic databases (PubMed, EMBASE, Web of Science, CENTRAL) was performed until April 2023, restricted to English language. Thirty-nine observational studies were included in the qualitative synthesis, of which 32 studies were included in a Bayesian network meta-analysis. Using a predesigned form, two researchers independently collected data about marginal bone loss (MBL), probing pocket depth (PPD), plaque index (PI), bleeding on probing (BOP), modified plaque index (mPI), probing pocket depth > 4mm (PPD>4), gingival index (GI), peri-implant sulcular fluid (PISF) volume, and TNF-α and IL-1ß levels. QUIPS and CINeMA were used to evaluate the risk of bias and certainty of evidence. RESULTS: NS had the smallest MBL. Most nicotine-containing product users had significantly higher MBL (CS, MD:1.34 CrI: 0.85, 1.79; WP, MD:1.58 CrI: 0.84, 2.35; ST, MD:2.53, CrI: 1.20, 3.87) than NS. EC did not show significant difference compared to NS (MD:0.52 CrI: -0.33, 1.36). In secondary outcomes NS were ranked in first place. Subset analysis based on smoking habit, implant duration, and maintenance control revealed no differences in ranking probability. CONCLUSION: Most nicotine-containing product users presented worse peri-implant parameters compared to non-smokers, while EC users did not show significant differences to NS in many outcomes. IMPLICATION: Alternative nicotine-containing products are gaining popularity and are often considered less harmful by the general public compared to traditional cigarettes. This is the first network meta-analysis comparing users of four nicotine-containing products and non-smokers. This study shows that CS, WP and ST have a detrimental effect on the overall health of peri-implant tissues. EC users also presented inferior parameters compared to NS, however, the difference was not significant in many outcomes. It is essential to educate patients who are using nicotine-containing products, and to provide proper maintenance and appropriate cessation support. Well-designed multi-armed studies are needed for direct comparison of different products, including heated tobacco products. Greater transparency of confounding factors is needed regarding smoking habit and oral hygiene.

Ranking the dietary interventions by their effectiveness in the management of polycystic ovary syndrome: a systematic review and network meta-analysis.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is a common condition in women, characterised by reproductive and metabolic dysfunction. While dietary approaches have been evaluated as a first-line treatment for patients with PCOS, there is limited evidence to support preference for a specific dietary composition. This systematic review and network meta-analysis was performed with the objective of comparing different dietary interventions in terms of positive impact. Metformin, the currently preferred treatment, was also compared. METHODS: The latest systematic search was performed on the 20th of March, 2023. Eligible randomised controlled trials (RCTs) included patients with PCOS and compared the dietary approach with another intervention or a standard diet. Outcomes were expressed via anthropometric measurements and hormonal, glycemic, and lipid levels. The Bayesian method was used to perform a network meta-analysis and to calculate the surface under the cumulative ranking curve (SUCRA) values in order to rank the dietary interventions. The overall quality of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation system. RESULTS: 19 RCTs were identified, comprising data from 727 patients who were variously treated with 10 types of dietary interventions and metformin. The Dietary Approaches to Stop Hypertension (DASH) diet was the most effective in reducing Homeostatic Model Assessment of Insulin Resistance (SUCRA 92.33%), fasting blood glucose (SUCRA 85.92%), fasting insulin level (SUCRA 79.73%) and triglyceride level (SUCRA 82.07%). For body mass index (BMI), the most effective intervention was the low-calorie diet (SUCRA 84.59%). For weight loss, the low-calorie diet with metformin (SUCRA 74.38%) was the most effective intervention. Metformin produced the greatest reductions in low-density lipoprotein cholesterol (SUCRA 78.08%) and total testosterone levels (SUCRA 71.28%). The low-carb diet was the most effective intervention for reducing cholesterol levels (SUCRA 69.68%), while the normal diet (SUCRA 65.69%) ranked first for increasing high-density lipoprotein cholesterol levels. CONCLUSION: Dietary interventions vary in their effects on metabolic parameters in women with PCOS. Based on our results, the DASH diet is the most effective dietary intervention for treating PCOS. Registration PROSPERO ID CRD42021282984.

Risk of chronic pancreatitis in carriers of the c.180C>T (p.Gly60=) CTRC variant: case-control studies and meta-analysis.

Chymotrypsin C (CTRC) is a digestive serine protease produced by the pancreas that regulates intrapancreatic trypsin activity and provides a defensive mechanism against chronic pancreatitis (CP). CTRC exerts its protective effect by promoting degradation of trypsinogen, the precursor to trypsin. Loss-of-function missense and microdeletion variants of CTRC are found in around 4% of CP cases and increase disease risk by approximately 3-7-fold. In addition, a commonly occurring synonymous CTRC variant c.180C>T (p.Gly60=) was reported to increase CP risk in various cohorts but a global analysis of its impact has been lacking. Here, we analyzed the frequency and effect size of variant c.180C>T in Hungarian and pan-European cohorts, and performed meta-analysis of the new and published genetic association data. When allele frequency was considered, meta-analysis revealed an overall frequency of 14.2% in patients and 8.7% in controls (allelic odds ratio (OR) 2.18, 95% confidence interval (CI) 1.72-2.75). When genotypes were examined, c.180TT homozygosity was observed in 3.9% of CP patients and in 1.2% of controls, and c.180CT heterozygosity was present in 22.9% of CP patients and in 15.5% of controls. Relative to the c.180CC genotype, the genotypic OR values were 5.29 (95% CI 2.63-10.64), and 1.94 (95% CI 1.57-2.38), respectively, indicating stronger CP risk in homozygous carriers. Finally, we obtained preliminary evidence that the variant is associated with reduced CTRC mRNA levels in the pancreas. Taken together, the results indicate that CTRC variant c.180C>T is a clinically relevant risk factor, and should be considered when genetic etiology of CP is investigated.

Galactomannans are the most effective soluble dietary fibers in type 2 diabetes: a systematic review and network meta-analysis.

BACKGROUND: Soluble dietary fibers are known to reduce the levels of blood glucose and lipids in patients with type 2 diabetes mellitus (type 2 diabetes). Although several different dietary fiber supplements are utilized, to our knowledge, no previous study has ranked their efficacy yet. OBJECTIVES: We performed this systematic review and network meta-analysis to rank the effects of different types of soluble dietary fibers. METHODS: We performed our last systematic search on November 20, 2022. Eligible randomized controlled trials (RCTs) included adult patients with type 2 diabetes and compared the intake of soluble dietary fibers with that of another type of dietary fiber or no fiber. The outcomes were related to glycemic and lipid levels. The Bayesian method was used to perform a network meta-analysis and calculate the surface under the cumulative ranking (SUCRA) curve values to rank the interventions. The Grading of Recommendations Assessment, Development, and Evaluation system was applied to evaluate the overall quality of the evidence. RESULTS: We identified 46 RCTs, including data from 2685 patients who received 16 types of dietary fibers as intervention. Galactomannans had the highest effect on reducing the levels of HbA1c (SUCRA: 92.33%) and fasting blood glucose (SUCRA: 85.92%). With regard to fasting insulin level, HOMA-IR, ß-glucans (SUCRA: 73.45%), and psyllium (SUCRA: 96.67%) were the most effective interventions. Galactomannans were ranked first in reducing the levels of triglycerides (SUCRA: 82.77%) and LDL cholesterol (SUCRA: 86.56%). With regard to cholesterol and HDL cholesterol levels, xylo-oligosaccharides (SUCRA: 84.59%) and gum arabic (SUCRA: 89.06%) were the most effective fibers. Most comparisons had a low or moderate certainty of evidence. CONCLUSIONS: Galactomannans were the most effective dietary fiber for reducing the levels of HbA1c, fasting blood glucose, triglycerides, and LDL cholesterol in patients with type 2 diabetes. This study was registered at PROSPERO as ID CRD42021282984.

Clinical bracket failure rates between different bonding techniques: a systematic review and meta-analysis.

BACKGROUND: Bracket failure increases the treatment time of orthodontic therapy and burdens patients with unnecessary costs, increased chair time, and possible new appointments. OBJECTIVE: To compare the bond failures of different orthodontic materials based on the results of available clinical studies. SEARCH METHODS: A systematic search of clinical trials was performed in the Cochrane, Embase, and Pubmed databases with no limitations. The list of investigated techniques contained conventional acid-etch primer (CM-AEP), self-etch primer (SEP), self-cure resin (SCR), and simple or resin-modified glass ionomer (RM-GIC) materials and procedures. SELECTION CRITERIA: Clinical studies reporting the failure rate of bonded brackets after using direct adhesive techniques on buccal sites of healthy teeth were included. DATA COLLECTION AND ANALYSIS: Bracket failure rates from eligible studies were extracted by two authors independently. Risk ratios (RRs) were pooled using the random-effects model with DerSimonian-Laird estimation. RESULTS: Thirty-four publications, involving 1221 patients, were included. Our meta-analysis revealed no significant difference in the risk of bracket failures between SEP and CM-AEP. After 6, 12, and 18 months of bonding, the values of RR were 1.04 [95% confidence interval (CI), 0.67-1.61], 1.37 (95% CI, 0.98-1.92), and 0.93 (95% CI, 0.72-1.20), respectively. At 18 months, bracket failure was 4.9 and 5.2% for SEP and CM-AEP, respectively. Heterogeneity was good or moderate (I2 < 42.2%). The results of RM-GIC at 12 months indicated a 57% lower risk of bracket failure using SCR as compared with RM-GIC (RR: 0.38; 95% CI, 0.24-0.61). At 18 months, bracket failures for SCR and RM-GIC were 15.8 and 36.6%, respectively (RR: 0.44; 95% CI, 0.37-0.52, I2 = 78.9%), demonstrating three to six times higher failure rate than in the case of etching primer applications. LIMITATIONS: A major limitation of the present work is that the included clinical trials, with no exceptions, showed variable levels of risk of bias. Another possible problem affecting the outcome is the difference between the clustering effects of the split mouth and the parallel group bracket allocation methods. CONCLUSIONS AND IMPLICATIONS: The results revealed no significant difference between SEP and CM-AEP up to 18 months after application. RM-GIC had much worse failure rates than acid-etching methods; additionally, the superiority of SCR over RM-GIC was evident, indicating strong clinical relevance. REGISTRATION: Prospero with CRD42020163362.

Bicarbonate defective CFTR variants increase risk for chronic pancreatitis: A meta-analysis.

INTRODUCTION: Cystic fibrosis transmembrane conductance regulator (CFTR) plays a central role in pancreatic ductal fluid secretion by mediating Cl- and HCO3- ion transport across the apical membrane. Severe CFTR mutations that diminish chloride conductance cause cystic fibrosis (CF) if both alleles are affected, whereas heterozygous carrier status increases risk for chronic pancreatitis (CP). It has been proposed that a subset of CFTR variants characterized by a selective bicarbonate conductance defect (CFTRBD) may be associated with CP but not CF. However, a rigorous genetic analysis of the presumed association has been lacking. AIMS: To investigate the role of heterozygous CFTRBD variants in CP by meta-analysis of published case-control studies. MATERIALS AND METHODS: A systematic search was conducted in the MEDLINE, Embase, Scopus, and CENTRAL databases for published studies that reported the CFTRBD variants p.R74Q, p.R75Q, p.R117H, p.R170H, p.L967S, p.L997F, p.D1152H, p.S1235R, and p.D1270N in CP patients and controls. RESULTS: Twenty-two studies were eligible for quantitative synthesis. Combined analysis of the 9 CFTRBD variants indicated enrichment in CP patients versus controls (OR = 2.31, 95% CI = 1.17-4.56). Individual analysis of CFTRBD variants revealed no association of p.R75Q with CP (OR = 1.12, 95% CI = 0.89-1.40), whereas variants p.R117H and p.L967S were significantly overrepresented in cases relative to controls (OR = 3.16, 95% CI = 1.94-5.14, and OR = 3.88, 95% CI = 1.32-11.47, respectively). The remaining 6 low-frequency variants gave inconclusive results when analyzed individually, however, their pooled analysis indicated association with CP (OR = 2.08, 95% CI = 1.38-3.13). CONCLUSION: Heterozygous CFTRBD variants, with the exception of p.R75Q, increase CP risk about 2-4-fold.

Examining the mental health adversity among healthcare providers during the two waves of the COVID-19 pandemic: results from a cross-sectional, survey-based study.

OBJECTIVES: The current global health crisis of the COVID-19 pandemic has drastically affected the whole population, but healthcare workers are particularly exposed to high levels of physical and mental stress. This enormous burden requires both the continuous monitoring of their health conditions and research into various protective factors. DESIGN: Cross-sectional surveys. SETTING AND PARTICIPANTS: Self-administered questionnaires were constructed assessing COVID-19-related worries of health workers in Hungary. The surveys were conducted during two consecutive waves of the COVID-19 pandemic (N-first wave=376, N-second wave=406), between 17 July 2020 and 31 December 2020. PRIMARY AND SECONDARY OUTCOME MEASURES: COVID-19-related worry, well-being and distress levels of healthcare workers. We also tested whether psychological resilience mediates the association of worry with well-being and distress. Multiple linear regression analyses were performed. RESULTS: The results indicated that healthcare workers had high levels of worry and distress in both pandemic waves. When comparing the two waves, enhanced levels of worry (Wald's χ2=4.36, p=0.04) and distress (Wald's χ2=25.18, p<0.001), as well as compromised well-being (Wald's χ2=58.64, p<0.001), were found in the second wave. However, not all types of worries worsened to the same extent across the waves drawing attention to some specific COVID-19-sensitive concerns. Finally, the protective role of psychological resilience was shown by a mediator analysis suggesting the importance of increasing resilience as a key factor in maintaining the mental health of healthcare workers in the burden of the COVID-19 pandemic. CONCLUSIONS: Our results render the need for regular psychological surveillance in healthcare workers. REGISTRATION: Hungarian Scientific and Research Ethics Committee of the Medical Research Council (IV/5079-2/2020/EKU).

EASY-APP: An artificial intelligence model and application for early and easy prediction of severity in acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is a potentially severe or even fatal inflammation of the pancreas. Early identification of patients at high risk for developing a severe course of the disease is crucial for preventing organ failure and death. Most of the former predictive scores require many parameters or at least 24 h to predict the severity; therefore, the early therapeutic window is often missed. METHODS: The early achievable severity index (EASY) is a multicentre, multinational, prospective and observational study (ISRCTN10525246). The predictions were made using machine learning models. We used the scikit-learn, xgboost and catboost Python packages for modelling. We evaluated our models using fourfold cross-validation, and the receiver operating characteristic (ROC) curve, the area under the ROC curve (AUC), and accuracy metrics were calculated on the union of the test sets of the cross-validation. The most critical factors and their contribution to the prediction were identified using a modern tool of explainable artificial intelligence called SHapley Additive exPlanations (SHAP). RESULTS: The prediction model was based on an international cohort of 1184 patients and a validation cohort of 3543 patients. The best performing model was an XGBoost classifier with an average AUC score of 0.81 ± 0.033 and an accuracy of 89.1%, and the model improved with experience. The six most influential features were the respiratory rate, body temperature, abdominal muscular reflex, gender, age and glucose level. Using the XGBoost machine learning algorithm for prediction, the SHAP values for the explanation and the bootstrapping method to estimate confidence, we developed a free and easy-to-use web application in the Streamlit Python-based framework (http://easy-app.org/). CONCLUSIONS: The EASY prediction score is a practical tool for identifying patients at high risk for severe AP within hours of hospital admission. The web application is available for clinicians and contributes to the improvement of the model.

Bearberry in the treatment of acute uncomplicated cystitis (BRUMI): protocol of a multicentre, randomised double-blind clinical trial.

BACKGROUND: Bearberry (Arctostaphylos uva-ursi) leaf is available as a treatment of uncomplicated cystitis in several European countries. The antimicrobial activity of its extracts and some of its individual constituents has been observed in vitro; however, the efficacy of bearberry compared with standard antimicrobial therapy has not been assessed yet. OBJECTIVE: The objective of the study is to assess the safety and non-inferiority of bearberry as an alternative therapy in the treatment of acute uncomplicated cystitis in comparison with standard antibiotic therapy (fosfomycin). METHODS AND ANALYSIS: This is a randomised controlled double-blinded multicentre trial. Eligible patients will be premenopausal women with a sum score of ≥6 for the typical acute uncomplicated cystitis symptoms (frequency, urgency, painful urination, incomplete emptying, suprapubic pain and visible haematuria) reported on the Acute Cystitis Symptom Score (ACSS) typical domain and pyuria. Patients will be randomly assigned to receive 3 g single dose of fosfomycin powder and two placebo tablets three times a day for 7 days or B a single dose of placebo powder and two tablets containing a dry extract of Uvae ursi folium. At least 504 patients (allocated as 1:1) will need to be enrolled to access non-inferiority with a non-inferiority limit of 14% for the primary endpoint.Improvement of symptoms of uncomplicated cystitis (based on the ACSS score) at day 7 is defined as the primary endpoint, whereas several secondary endpoints such as the number and ratio of patients with bacteriuria at day 7, frequency and severity of side effects; recurrence of urinary tract infection, concurrent use of other over the counter (OTC) medications and food supplements will be determined to elucidate more detailed differences between the groups. The number of recurrences and medications taken for treatment will be monitored for a follow-up period of 90 days (80-100 days). ETHICS AND DISSEMINATION: This study has been approved by the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (IV/4225-1/2021/EKU). The results will be disseminated by publication of peer-reviewed manuscripts. TRIAL REGISTRATION NUMBER: NCT05055544.

Goal-Directed Fluid Therapy Enhances Gastrointestinal Recovery after Laparoscopic Surgery: A Systematic Review and Meta-Analysis.

(1) Background: Whether goal-directed fluid therapy (GDFT) provides any outcome benefit as compared to non-goal-directed fluid therapy (N-GDFT) in elective abdominal laparoscopic surgery has not been determined yet. (2) Methods: A systematic literature search was conducted in MEDLINE, Embase, CENTRAL, Web of Science, and Scopus. The main outcomes were length of hospital stay (LOHS), time to first flatus and stool, intraoperative fluid and vasopressor requirements, serum lactate levels, and urinary output. Pooled risks ratios (RRs) with 95% confidence intervals (CI) were calculated for dichotomous outcomes and weighted mean difference (WMD) with 95% CI for continuous outcomes. (3) Results: Eleven studies were included in the quantitative, and fifteen in the qualitative synthesis. LOHS (WMD: -1.18 days, 95% CI: -1.84 to -0.53) and time to first stool (WMD: -9.8 h; CI -12.7 to -7.0) were significantly shorter in the GDFT group. GDFT resulted in significantly less intraoperative fluid administration (WMD: -441 mL, 95% CI: -790 to -92) and lower lactate levels at the end of the operation: WMD: -0.25 mmol L-1; 95% CI: -0.36 to -0.14. (4) Conclusions: GDFT resulted in enhanced recovery of the gastrointestinal function and shorter LOHS as compared to N-GDFT.

Risk of chronic pancreatitis in carriers of loss-of-function CTRC variants: A meta-analysis.

The digestive protease chymotrypsin C (CTRC) protects the pancreas against pancreatitis by degrading potentially harmful trypsinogen. Loss-of-function genetic variants in CTRC increase risk for chronic pancreatitis (CP) with variable effect size, as judged by the reported odds ratio (OR) values. Here, we performed a meta-analysis of published studies on four variants that alter the CTRC amino-acid sequence, are clinically relatively common (global carrier frequency in CP >1%), reproducibly showed association with CP and their loss of function phenotype was verified experimentally. We found strong enrichment of CTRC variants p.A73T, p.V235I, p.K247_R254del, and p.R245W in CP cases versus controls, yielding OR values of 6.5 (95% confidence interval (CI) 2.4-17.8), 4.5 (CI 2.2-9.1), 5.4 (CI 2.6-11.0), and 2.6 (CI 1.6-4.2), respectively. Subgroup analysis demonstrated disease association of variants p.K247_R254del and p.R245W in alcoholic CP with similar effect sizes as seen in the overall CP group. Homozygosity or compound heterozygosity were rare and seemed to be associated with higher risk. We also identified a so far unreported linkage disequilibrium between variant p.K247_R254del and the common c.180C>T (p.G60 =) haplotype. Taken together, the results indicate that heterozygous loss-of-function CTRC variants increase the risk for CP approximately 3-7-fold. This meta-analysis confirms the clinical significance of CTRC variants and provides further justification for the genetic screening of CP patients.

Association of Body Mass Index With Clinical Outcomes in Patients With Cystic Fibrosis: A Systematic Review and Meta-analysis.

IMPORTANCE: The prevalence of overweight (body mass index [BMI] = 25-29.9 [calculated as weight in kilograms divided by height in meters squared]) and obesity (BMI ≥30) is increasing among patients with cystic fibrosis (CF). However, it is unclear whether there is a benefit associated with increasing weight compared with the reference range (ie, normal) in CF. OBJECTIVE: To evaluate the association of altered BMI or body composition and clinical outcomes in patients with CF. DATA SOURCES: For this systematic review and meta-analysis, the literature search was conducted November 2, 2020, of 3 databases: MEDLINE (via PubMed), Embase, and Cochrane Central Register of Controlled Trials. STUDY SELECTION: Patients older than 2 years diagnosed with CF with altered body composition or BMI were compared with patients having the measured parameters within the reference ranges. Records were selected by title, abstract, and full text; disagreements were resolved by consensus. Cohort studies and conference abstracts were eligible; articles with no original data and case reports were excluded. DATA EXTRACTION AND SYNTHESIS: Two authors independently extracted data, which were validated by a third author. Studies containing insufficient poolable numerical data were included in the qualitative analysis. A random-effects model was applied in all analyses. MAIN OUTCOMES AND MEASURES: Pulmonary function, exocrine pancreatic insufficiency (PI), and CF-related diabetes (CFRD) were investigated as primary outcomes. Odds ratios (ORs) or weighted mean differences (WMDs) with 95% CIs were calculated. The hypothesis was formulated before data collection. RESULTS: Of 10 524 records identified, 61 met the selection criteria and were included in the qualitative analysis. Of these, 17 studies were included in the quantitative synthesis. Altogether, 9114 patients were included in the systematic review and meta-analysis. Overweight (WMD, -8.36%; 95% CI, -12.74% to -3.97%) and obesity (WMD, -12.06%; 95% CI, -23.91% to -0.22%) were associated with higher forced expiratory volume in the first second of expiration compared with normal weight. The odds for CFRD and PI were more likely in patients of normal weight (OR, 1.49; 95% CI, 1.10 to 2.00) than in those who were overweight (OR, 4.40; 95% CI, 3.00 to 6.45). High heterogeneity was shown in the analysis of pulmonary function (I2 = 46.7%-85.9%). CONCLUSIONS AND RELEVANCE: The findings of this systematic review and meta-analysis suggest that the currently recommended target BMI in patients with CF should be reconsidered. Studies with long-term follow-up are necessary to assess the possible adverse effects of higher BMI or higher fat mass in patients with CF.

Weight reduction added to CPAP decreases blood pressure and triglyceride level in OSA: Systematic review and meta-analysis.

Obstructive sleep apnea (OSA) is associated with treatment-resistant hypertension and high cardiovascular risk. Continuous positive airway pressure (CPAP) fails to reduce cardiovascular risks consistently. Obesity and OSA show reciprocal association and they synergistically increase hypertension via different pathways. Our meta-analysis aimed to assess the cardiovascular benefits of combining weight loss (WL) with CPAP (vs. WL or CPAP alone) in OSA. Outcomes included systolic and diastolic blood pressure (BP) and blood lipid parameters. We explored Medline, Embase, Cochrane, and Scopus. Eight randomized controlled studies (2627 patients) were included. The combined therapy decreased systolic BP more than CPAP alone. Weighted mean difference (WMD) for CPAP + WL versus CPAP was -8.89 mmHg, 95% confidence interval (95% CI; -13.67 to -4.10, p < 0.001) for systolic BP. For diastolic BP, this decrease was not significant. In case of blood lipids, the combined treatment decreased triglyceride levels more than CPAP alone (WMD = -0.31, 95% CI -0.58 to -0.04, p = 0.027). On the other hand, addition of CPAP to WL failed to suppress BP further. The certainty of evidence according to GRADE was very low to moderate. In conclusion, our results showed that the addition of WL to CPAP significantly improved BP and blood lipid values in OSA. On the other hand, the addition of CPAP to WL could not significantly improve BP or blood lipid values. Review protocol: PROSPERO CRD42019138998.

The Safety of Dronabinol and Nabilone: A Systematic Review and Meta-Analysis of Clinical Trials.

Dronabinol, a natural cannabinoid, and its semi-synthetic derivative, nabilone, are marketed as medicines in several countries. The aim of our work was to systematically evaluate the frequency of adverse events related to dronabinol or nabilone treatment compared to placebo. Scientific databases were searched for placebo-controlled clinical studies of patients receiving either dronabinol or nabilone therapy with placebo control groups. This meta-analysis was reported following the PRISMA guidelines using the PICO format, and it was registered with the PROSPERO register. There were 16 trials included in the meta-analysis. In the nabilone studies, drowsiness was more than 7 times as frequent in patients treated with nabilone than in the placebo group (OR: 7.25; 95% CI: 1.64-31.95), and the risk of dizziness (OR: 21.14; 95% CI: 2.92-152.75) and dry mouth was also higher (OR: 17.23; 95% CI: 4.33-68.55). The frequency of headache was not different in the two groups. In case of dronabinol, the frequency of dry mouth (OR: 5.58; 95% CI: 3.19-9.78), dizziness (OR: 4.60 95% CI: 2.39-8.83) and headache (OR: 2.90; 95% CI: 1.07-7.85) was significantly higher in the dronabinol groups, whereas in case of nausea, drowsiness and fatigue there was no difference. The severity of adverse events was typically mild-to-moderate and transient. In a risk-benefit assessment, these adverse effects are acceptable compared to the achievable benefit. However, considering the diversity of the adverse effects, more studies are needed to provide a more accurate assessment on the side effect profiles of these two compounds.

Exosomes as prognostic biomarkers in pancreatic ductal adenocarcinoma-a systematic review and meta-analysis.

Extensive research is focused on the role of liquid biopsy in pancreatic cancer since reliable diagnostic and follow-up biomarkers represent an unmet need for this highly lethal malignancy. We performed a systematic review and meta-analysis on the prognostic value of exosomal biomarkers in pancreatic ductal adenocarcinoma (PDAC). MEDLINE, Embase, Scopus, Web of Science, and CENTRAL were systematically searched on the 18th of January, 2021 for studies reporting on the differences in overall (OS) and progression-free survival (PFS) in PDAC patients with positive vs negative exosomal biomarkers isolated from blood. The random-effects model estimated pooled multivariate-adjusted (AHR) and univariate hazard ratios (UHRs) with 95% confidence intervals (CIs). Eleven studies comprising 634 patients were eligible for meta-analysis. Detection of positive exosomal biomarkers indicated increased risk of mortality (UHR = 2.81, CI:1.31-6,00, I2 = 88.7%, P < 0.001), and progression (UHR = 3.33, CI: 2.33-4.77, I2 = 0, P = 0.879) across various disease stages. Positive exosomal biomarkers identified preoperatively revealed a higher risk of mortality in resectable stages (UHR = 5.55, CI: 3.24-9.49, I2 = 0, P = 0.898). The risk of mortality in unresectable stages was not significantly increased with positive exosomal biomarkers (UHR = 2.51, CI: 0.55-11.43, I2 = 90.3%, P < 0.001). Detectable exosomal micro ribonucleic acids were associated with a decreased OS (UHR = 4.08, CI: 2.16-7.69, I2 = 46.9%, P = 0.152) across various stages. Our results reflect the potential of exosomal biomarkers for prognosis evaluation in PDAC. The associated heterogeneity reflects the variability of study methods and need for their uniformization before transition to clinical use.

The characteristics and prognostic role of acute abdominal on-admission pain in acute pancreatitis: A prospective cohort analysis of 1432 cases.

INTRODUCTION: Pain is the most common symptom in acute pancreatitis (AP) and is among the diagnostic criteria. Therefore, we aimed to characterize acute abdominal pain in AP. METHODS: The Hungarian Pancreatic Study Group prospectively collected multicentre clinical data on 1435 adult AP patients between 2012 and 2017. Pain was characterized by its intensity (mild or intense), duration prior to admission (hours), localization (nine regions of the abdomen) and type (sharp, dull or cramping). RESULTS: 97.3% of patients (n = 1394) had pain on admission. Of the initial population with acute abdominal pain, 727 patients answered questions about pain intensity, 1148 about pain type, 1134 about pain localization and 1202 about pain duration. Pain was mostly intense (70%, n = 511/727), characterized by cramping (61%, n = 705/1148), mostly starting less than 24 h prior to admission (56.7%, n = 682/1202). Interestingly, 50.9% of the patients (n = 577/1134) had atypical pain, which means pain other than epigastric or belt-like upper abdominal pain. We observed a higher proportion of peripancreatic fluid collection (19.5% vs. 11.0%; p = 0.009) and oedematous pancreas (8.4% vs. 3.1%; p = 0.016) with intense pain. Sharp pain was associated with AP severity (OR = 2.481 95% CI: 1.550-3.969) and increased mortality (OR = 2.263, 95% CI: 1.199-4.059) compared to other types. Longstanding pain (>72 h) on admission was not associated with outcomes. Pain characteristics showed little association with the patient's baseline characteristics. CONCLUSION: A comprehensive patient interview should include questions about pain characteristics, including pain type. Patients with sharp and intense pain might need special monitoring and tailored pain management. SIGNIFICANCE: Acute abdominal pain is the leading presenting symptom in acute pancreatitis; however, we currently lack specific guidelines for pain assessment and management. In our cohort analysis, intense and sharp pain on admission was associated with higher odds for severe AP and several systemic and local complications. Therefore, a comprehensive patient interview should include questions about pain characteristics and patients with intense and sharp pain might need closer monitoring.

Prognostic role of cell-free DNA biomarkers in pancreatic adenocarcinoma: A systematic review and meta-analysis.

This systematic review and meta-analysis evaluated the prognostic role of cell-free DNA (cfDNA) in pancreatic ductal adenocarcinoma (PDAC). Eligible studies reported differences in overall (OS) and progression-free survival (PFS) by cfDNA status. The random effect model yielded the pooled hazard ratios (HRs) and 95 % confidence intervals (CI). Detection of circulant-tumor DNA (ctDNA), KRAS mutations and other cfDNA alterations constitute detectable cfDNA biomarkers. Altogether, 38 studies (3,318 patients) were eligible. Progression-free and overall survival were decreased with detectable ctDNA (HR = 1.92, 95 %CI:(1.29,2.86); HR = 2.25, 95 %CI:(1.73,2.92)) and KRAS mutations (HR = 1.88, CI:1.22,2.92,); HR = 1.52, 95 %CI:(1.22,1.90)) respectively, across various stages. In unresectable cases, ctDNA (HR = 2.50, 95 %CI:(1.94,3.23)), but not KRAS mutations (HR = 1.16, 95 %CI:(0.46,2.94)) signaled risk for progression. Detectable cfDNA biomarkers correlated with worse prognosis in resectable cases and if detected during treatment. In conclusion, cfDNA biomarkers indicate accelerated progression and decreased survival in PDAC. Significance of KRAS mutations detection in unresectable cases is to be determined.

Addition of daratumumab to multiple myeloma backbone regimens significantly improves clinical outcomes: a systematic review and meta-analysis of randomised controlled trials.

Daratumumab has shown clinical benefit in multiple myeloma. We aimed to evaluate the safety and efficacy of adding daratumumab to backbone anti-myeloma treatments. Systematic search was performed up to August 2021 to identify randomised controlled trials comparing the outcomes of backbone therapy with and without daratumumab in relapsed/refractory and newly diagnosed myeloma (RRMM and NDMM, respectively). Odds ratios (ORs) and hazard ratios (HRs) were calculated with 95% confidence intervals (CIs). Primary outcomes were death or disease progression, minimal residual disease (MRD) negativity, and stringent complete response (sCR). Secondary outcomes were complete response or better and safety endpoints prespecified in the study protocol: PROSPERO (CRD42020222904). In NDMM, MRD negativity [OR = 3.61 (CI 2.33-5.61)] and sCR [OR = 2.29 (CI 1.49-3.51)] were more likely and death or disease progression [HR = 0.47 (CI 0.39-0.57)] was less likely to occur with daratumumab compared to control. Regarding RRMM, MRD negativity [OR = 5.43 (CI 2.76-10.66)] and sCR [OR = 3.08 (CI 2.00-4.76)] were more likely and death or disease progression was less likely [HR = 0.50 (CI 0.37-0.67)] with daratumumab compared to control. The addition of daratumumab has shown high clinical efficacy and acceptable toxicity profile for the treatment of NDMM and RRMM regarding the endpoints examined.

Efficacy of first-line treatment options in transplant-ineligible multiple myeloma: A network meta-analysis.

BACKGROUND: Despite major therapeutic advances, the rational choice of the most appropriate first-line regimen in newly diagnosed transplant-ineligible multiple myeloma (TIE-MM) is currently undefined. AIM: We aimed to identify the most effective first-line treatment for TIE-MM patients. METHODS: A total of 37 articles, including 34 treatments and 16,681 patients, were included in this Bayesian network meta-analysis. The outcomes of interest were risk ratios (RR) for progression-free survival (PFS) and overall survival (OS). RESULTS: Based on surface under cumulative ranking curve values, daratumumab-bortezomib-melphalan-prednisone (Dara-VMP) and daratumumab-lenalidomide-dexamethasone (Dara-Rd28) showed superiority compared to other combinations regarding 12-, 24-, 36-, and 48-month PFS. Dara-VMP also ranked first for 12-, 24-, 36-, and 48-month OS. CONCLUSION: Our finding supports the incorporation of daratumumab into first-line regimens. Additionally, these results highlight the relative benefit of incorporating novel agents like monoclonal antibodies, immunomodulatory derivatives, and proteasome inhibitors in combination with the currently existing treatment options.

Hyaluronic Acid Is an Effective Dermal Filler for Lip Augmentation: A Meta-Analysis.

Introduction: The lips and the mouth play an indispensable role in vocalization, mastication and face aesthetics. Various noxious factors may alter and destruct the original structure, and appearance of the lips and the anatomical area surrounding the mouth. The application of hyaluronic acid (HA) may serve as a safe method for lip regeneration. Although a number of studies exist for HA effectiveness and safety, its beneficial effect is not well-established. Aim: The present meta-analysis and systematic review was performed to investigate the effectiveness of HA on lip augmentation. We also investigated the types and nature of adverse effects (AEs) of HA application. Methods: We reported our meta-analysis in accordance with the PRISMA Statement. PROSPERO protocol registration: CRD42018102899. We performed the systematic literature search in CENTRAL, Embase, and MEDLINE. Randomized controlled trials, cohort studies, case series and case reports were included. The untransformed proportion (random-effects, DerSimonian-Laird method) of responder rate to HA injection was calculated. For treatment related AEs descriptive statistics were used. Results: The systematic literature search yielded 32 eligible records for descriptive statistics and 10 records for quantitative synthesis. The results indicated that the overall estimate of responders (percentage of subjects with increased lip fullness by one point or higher) was 91% (ES = 0.91, 95% CI:0.85-0.96) 2 months after injection. The rate of responders was 74% (ES = 0.74, 95% CI:0.66-0.82) and 46% (ES = 0.46, 95% CI:0.28-0.65) after 6 and 12 months, respectively. We included 1,496 participants for estimating the event rates of AEs. The most frequent treatment-related AEs were tenderness (88.8%), injection site swelling (74.3%) and bruising (39.5%). Rare AEs included foreign body granulomas (0.6%), herpes labialis (0.6%) and angioedema (0.3%). Conclusion: Our meta-analysis revealed that lip augmentation with injectable HA is an efficient method for increasing lip fullness for at least up to 6 months after augmentation. Moreover, we found that most AEs of HA treatment were mild or moderate, but a small number of serious adverse effects were also found. In conclusion, further well-designed RCTs are still needed to make the presently available evidence stronger.