Trends and regional differences in antidiabetic medication use: a nationwide retrospective observational study.

BACKGROUND: The prevalence of diabetes is increasing, and several new drug groups have been authorized and used successfully in the treatment of diabetes, while older drug groups are still in use. Our aim was to assess the utilization tendencies and regional differences in antidiabetic medication consumption in Hungary between 2015 and 2021 and to identify the possible determinants of regional differences in antidiabetic medication use. METHODS: For this retrospective drug utilization study, yearly wholesale database was used, which provides total coverage for ambulatory antidiabetic drug sales in Hungary, including both reimbursed and non-reimbursed medications. Data were expressed as Defined Daily Dose per 1000 inhabitants per day (DDD/TID), percentage of total use and the ratio of the highest and lowest utilization values among the counties (max/min ratio). To assess the potential reasons for regional differences in antidiabetic drug use, we analyzed the associations between regional drug utilization data and possible determinants. RESULTS: The total national antidiabetic medication use has increased by 7.6% and reached 94.8 DDD/TID in 2021. Regarding antidiabetic subgroups, the use of metformin and novel antidiabetics (DPP4Is, GLP1As and SGLT2Is) and their combinations increased in all counties, while sulfonylurea consumption decreased, and insulin use was stable. In 2021, 19.2-24.1% of the total antidiabetic medication consumption was novel antidiabetics, 39.1-47.2% metformin, 14.8-25.8% sulfonylureas and 23.6-30.5% were insulins. Regional differences in antidiabetic medication consumption were considerable mainly in the case of GLP1As (max/min ratio:3.00), sulfonylureas (2.03) and SGLT2Is (1.92) in 2021. The association between antidiabetic medication use and possible determinants was confirmed in the case of unemployment rate and sulfonylurea use, the number of public medical card holders per ten thousand inhabitants and human insulin and sulfonylurea use. GLP1As were the only antidiabetic drug group that did not correlate with any of the investigated factors. CONCLUSIONS: Although novel antidiabetic drug use was growing dynamically in Hungary, sulfonylurea use is still considerable. Differences in antidiabetic drug consumption were substantial between the regions.

Assessment of the practical impact of adjusting beta-lactam dosages based on therapeutic drug monitoring in critically ill adult patients: a systematic review and meta-analysis of randomized clinical trials and observational studies.

An estimated 70% of critically ill patients receive antibiotics, most frequently beta-lactams. The pharmacokinetic properties of these substances in this patient population are poorly predictable. Therapeutic drug monitoring (TDM) is helpful in making personalized decisions in this field, but its overall impact as a clinical decision-supporting tool is debated. We aimed to evaluate the clinical implications of adjusting beta-lactam dosages based on TDM in the critically ill population by performing a systematic review and meta-analysis of available investigations. Randomized controlled trials and observational studies were retrieved by searching three major databases. The intervention group received TDM-guided beta-lactam treatment, that is, at least one dose reconsideration based on the result of the measurement of drug concentrations, while TDM-unadjusted dosing was employed in the comparison group. The outcomes were evaluated using forest plots with random-effects modeling and subgroup analysis. Eight eligible studies were identified, including 1044 patients in total. TDM-guided beta-lactam treatment was associated with improved clinical cure from infection [odds ratio (OR): 2.22 (95% confidence interval (CI): 1.78-2.76)] and microbiological eradication [OR: 1.72 (CI: 1.05-2.80)], as well as a lower probability of treatment failure [OR: 0.47 (CI: 0.36-0.62)], but the heterogeneity of studies was remarkably high, especially in terms of mortality (70%). The risk of bias was moderate. While the TDM-guided administration of beta-lactams to critically ill patients has a favorable impact, standardized study designs and larger sample sizes are required for developing evidence-based protocols in this field.

Aromatase Inhibitors and Plasma Lipid Changes in Postmenopausal Women with Breast Cancer: A Systematic Review and Meta-Analysis.

Background: Women are typically diagnosed with estrogen receptor-positive breast cancer around the postmenopausal period when declining estrogen levels initiate changes in lipid profiles. Aromatase inhibitors (AI) are used to prevent the progression of cancer; however, a further reduction in estrogen levels may have detrimental effects on lipid levels, which was our working hypothesis. Methods: Our meta-analysis was conducted on the lipid profiles of postmenopausal breast cancer patients at baseline and at different treatment time points. Results: We identified 15 studies, including 1708 patients. Studies using anastrozole (ANA), exemestane (EXE), letrozole (LET), and tamoxifen (TMX) were involved. Subgroup analyses revealed that 3- and 12-month administrations of LET and EXE lead to negative changes in lipid profiles that tend to alter the lipid profile undesirably, unlike ANA and TMX. Conclusions: Our results suggest that, despite statistically significant results, EXE and LET may not be sufficient to cause severe dyslipidemia in patients without cardiovascular comorbidities according to the AHA/ACC Guideline on the Management of Blood Cholesterol. However, the results may raise the question of monitoring the effects of AIs in patients, especially those with pre-existing cardiovascular risk factors such as dyslipidemia.

Storage Conditions Influence the Quality of Ginger - A Stability Study Inspired by Clinical Trials.

Ginger has traditionally been used to treat and prevent nausea and vomiting; however, the results of clinical trials are ambiguous. The efficacy of ginger is attributed to gingerols and their metabolites, shogaols. Since these compounds have different pharmacological profiles, the clinical efficacy of ginger products is largely dependent on their chemical composition. The goal of our study was to examine the stability of ginger, determining the 6-gingerol contents in order to assess the effects of different storage conditions. We have performed a 6-month stability test with dry ginger rhizome samples stored in a constant climate chamber in three different storage containers (uncovered glass container, glass container sealed with rubber stopper, and plastic container). The 6-gingerol contents were measured by HPLC method. The concentration of 6-gingerol decreased in all samples. In the sealed glass container, the decrease in 6-gingerol content was significantly lower than in the unsealed glass container and in the plastic container. These results demonstrate that storage conditions have a significant impact on the quality of ginger, which may also affect efficacy.

Exploring the Clinical Applications of Lemongrass Essential Oil: A Scoping Review.

Lemongrass is a medicinal plant that produces essential oil with a variety of therapeutic properties. Although lemongrass essential oil (LGEO) is promising in clinical applications, the existing knowledge on the efficacy and safety of LGEO remains limited. This scoping review aimed to identify, summarize, and synthesize existing literature related to the clinical applications of LGEO to provide an overview of its potential therapeutic benefits for patients. Three databases (PubMed, Web of Science, Scopus) were used following the PRISMA-ScR guidelines to find articles published between 1 January 2013, and 1 November 2022. A total of 671 records were identified and 8 articles were included in this scoping review. The majority of patients received oromucosal and topical treatment. The results of the studies suggest that LGEO might be a useful tool in the treatment of periodontitis, gingivitis and oral malodour, with similar efficacy to chlorhexidine (anti-gingivitis effect) and doxycycline (periodontitis). Additionally, LGEO has the potential for treating pityriasis versicolor and preventing skin aging and may have anti-dandruff effects. These findings not only underscore the diverse clinical potential of LGEO but also emphasize its comparable efficacy to established treatments. Further research is imperative to comprehensively evaluate LGEO's effectiveness, safety, mechanisms of action, potential interactions with other medications, and its long-term tolerability across diverse populations.

Hospital Antibiotic Consumption before and during the COVID-19 Pandemic in Hungary.

The aim of this study was to assess antibiotic use in the Hungarian hospital care sector during and before the pandemic. Aggregated systemic antibiotic (ATC: J01) utilisation data were obtained for the 2010-2021 period. Classifications and calculations were performed according to the WHO ATC/DDD index and expressed as DDD per 1000 inhabitants and per day (DID), DDD per 100 patient-days (DHPD) and DDD/discharge. A linear regression (trend analysis) was performed for the pre-COVID years (2010-2019) and a prediction interval was set up to assess whether the pandemic years' observed utilisation fit in. Antibiotic utilisation was constant in DID before and during the pandemic (2019: 1.16; 2020: 1.21), while we observed a substantial increase in antibiotic use when expressed in DDD per 100 patient-days (2019: 23.3, 2020: 32.2) or DDD/discharge (2019: 1.83, 2020: 2.45). The observed utilisation level of penicillin combinations; first-, third- and fourth-generation cephalosporins; carbapenems; glycopeptides; nitroimidazoles and macrolides exceeded the predicted utilisation values in both pandemic years. Before the pandemic, co-amoxiclav headed the top list of antibiotic use, while during the pandemic, ceftriaxone became the most widely used antibiotic. Azithromycin moved up substantially on the top list of antibiotic use, with a 397% increase (2019: 0.45; 2020: 2.24 DHPD) in use. In summary, the pandemic had a major impact on the scale and pattern of hospital antibiotic use in Hungary.

Nafamostat Reduces the Incidence of post-ERCP Pancreatitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). As the management of pancreatitis is limited, clinical approaches focus on the prevention of post-ERCP pancreatitis (PEP). In theory, the serine protease inhibitor nafamostat can reduce circulating inflammatory mediators in pancreatitis. We aimed to investigate the effect of nafamostat in the prevention of PEP in this systematic review and meta-analysis. The protocol for this review was registered in PROSPERO (CRD42022367988). We systematically searched 5 databases without any filters on September 26, 2022. The eligible population was adult patients undergoing ERCP. We compared the PEP preventive effect of nafamostat to placebo. The main outcome was the occurrence of PEP. We calculated the pooled odds ratios (ORs), mean differences, and corresponding 95% confidence intervals (95% CIs) and multilevel model. The risk of bias was assessed using the Rob2 tool. Seven randomized controlled trials involving 2,962 patients were eligible for inclusion. Nafamostat reduced the overall incidence rate of PEP (20 mg, OR: 0.50, 95% CI: 0.30-0.82 and 50 mg, OR: 0.48, 95% CI: 0.24-0.96). However, the occurrence of mild PEP was significantly reduced only in the subgroup receiving 20 mg nafamostat (OR, 0.49, 95% CI: 0.31-0.77). Overall, nafamostat therapy reduced moderate PEP in high-risk patients (OR: 0.18, 95% CI: 0.0.4-0.84) and mild PEP in low-risk patients (OR: 0.32, 95% CI: 0.17-0.61). Nafamostat is an effective therapy in the prevention of mild post-ERCP pancreatitis. Further research is required to determine the cost-effectiveness of this therapy.

Allelopathic studies with furanocoumarins isolated from Ducrosia anethifolia. In vitro and in silico investigations to protect legumes, rice and grain crops.

Six different furanocoumarins were isolated from the aerial parts of Ducrosia anethifolia and tested in vitro for plant cell elongation in etiolated wheat coleoptile. They were also tested for their ability to control three different weeds: ribwort plantain, annual ryegrass, and common purslane. These compounds exhibited strong inhibition of plant cell elongation. In the case of (+)-heraclenin, the IC50 was lower than 20 µM, indicating a better inhibition than the positive control Logran®. Computational experiments for docking and molecular dynamics revealed for the investigated furanocoumarins bearing an epoxide moiety an improved fitting and stronger interaction with the auxin-like TIR1 ubiquitin ligase. Furthermore, the formed inhibition complex remained also stable during dynamic evaluation. Bidental interaction at the active site, along with an extended hydrogen-bond lifetime, explained the enhanced activity of the epoxides. The in vitro weed bioassay results showed that Plantago lanceolata was the most affected weed for germination, root, and shoot development. In addition, (+)-heraclenin displayed better inhibition values than positive control even at 300 µM concentration.

Nabiximols is Efficient as Add-On Treatment for Patients with Multiple Sclerosis Spasticity Refractory to Standard Treatment: A Systematic Review and Meta-Analysis of Randomised Clinical Trials.

BACKGROUND: Spasticity affects 54% of multiple sclerosis (MS) patients at disease onset, but this rate gradually increases with disease progression. Spasticity does not fully respond to standard treatment in one-third of the patients. OBJECTIVE: Our systematic review and meta-analysis assessed whether add-on nabiximols, can improve MS-associated refractory spasticity. METHODS: The systematic literature search was performed in Web of Science, MEDLINE, Scopus, CENTRAL, and Embase, on 15/10/2021, without restrictions. We included in the review blinded, randomized, placebo-controlled trials evaluating the efficacy of nabiximols in adult MS patients with refractory spasticity, by comparison with placebo. The primary outcome was responder rate by spasticity numerical rating scale (NRS). Secondary outcomes were spasticity-related parameters. We used random effect models to calculate odds ratios (OR) or mean differences and the corresponding 95% CI. Bias-factors were assessed with Cochrane risk of bias tool (RoB2). (PROSPERO ID: CRD42021282177). RESULTS: We identified 9 eligible articles, of which 7 (1128 patients) were included in the meta-analysis. The spasticity numerical rating scale (NRS) was significantly higher in the nabiximols group than in the placebo group (OR 2.41 (95% CI 1.39; 4.18)). Secondary outcomes were in accordance with our primary results. At least some concerns were detected in the risk of bias analysis. CONCLUSION: Our results indicate that nabiximols is efficient in MS associated spasticity, refractory to standard treatment and it may be considered as add-on symptomatic therapy. Nevertheless, further studies are needed to establish the optimal treatment protocol - dose, duration, moment of initiation, disease type.

[Deprescribing: an essential part of rational pharmacotherapy]. / Gyógyszerrosta: a racionális gyógyszeres terápia meghatározó eleme.

Deprescribing is a planned, systematic process supervised by a healthcare professional. It is considered to be a fundamental part of good prescribing. Deprescribing can be defined as the complete withdrawal of medications as well as dose reduction. The patient's health status, life expectancy, values, preferences and the therapeutic goals should be given serious consideration while planning the deprescribing process. The main objective of deprescribing may vary but reaching the patients' goals and improving their quality of life remain constant priorities. In our article, based on the international literature, we review potential deprescribing targets such as the characteristics of high-risk patients, medications that should prompt a therapy review and the ideal settings for deprescribing. We also cover the steps, risks and benefits of the process, and discuss the existing specific guidelines and algorithms. We provide information on the enablers and barriers of deprescribing among both patients and healthcare professionals, and discuss international initiatives as well as the future of deprescribing. Orv Hetil. 2023; 164(24): 931-941.

Efficacy of Topical Essential Oils in Musculoskeletal Disorders: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Essential oils (EOs) are widely used topically in musculoskeletal disorders (MSDs); however, their clinical efficacy is controversial. Our aim was to find evidence that topical EOs are beneficial as an add-on treatment in MSDs. We performed a systematic review and meta-analysis to summarize the evidence on the available data of randomized controlled trials (RCTs). The protocol of this work was registered on PROSPERO. We used Web of Science, EMBASE, PubMed, Central Cochrane Library and Scopus electronic databases for systematic search. Eight RCTs were included in the quantitative analysis. In conclusion, EO therapy had a favorable effect on pain intensity (primary outcome) compared to placebo. The greatest pain-relieving effect of EO therapy was calculated immediately after the intervention (MD of pain intensity = -0.87; p = 0.014). EO therapy had a slightly better analgesic effect than placebo one week after the intervention (MD of pain intensity = -0.58; p = 0.077) and at the four-week follow-up as well (MD of pain intensity = -0.52; p = 0.049). EO therapy had a beneficial effect on stiffness (a secondary outcome) compared to the no intervention group (MD = -0.77; p = 0.061). This systematic review and meta-analysis showed that topical EOs are beneficial as an add-on treatment in reducing pain and stiffness in the investigated MSDs.

Impact of the COVID-19 Pandemic on Ambulatory Care Antibiotic Use in Hungary: A Population-Based Observational Study.

The COVID-19 pandemic and related restrictions have potentially impacted the use of antibiotics. We aimed to analyze the use of systemic antibiotics (J01) in ambulatory care in Hungary during two pandemic years, to compare it with pre-COVID levels (January 2015-December 2019), and to describe trends based on monthly utilization. Our main findings were that during the studied COVID-19 pandemic period, compared to the pre-COVID level, an impressive 23.22% decrease in the use of systemic antibiotics was detected in ambulatory care. A significant reduction was shown in the use of several antibacterial subgroups, such as beta-lactam antibacterials, penicillins (J01C, -26.3%), and quinolones (J01M, -36.5%). The trends of antibiotic use moved in parallel with the introduction or revoking of restriction measures with a nadir in May 2020, which corresponded to a 55.46% decrease in use compared to the previous (pre-COVID) year's monthly means. In general, the systemic antibiotic use (J01) was lower compared to the pre-COVID periods' monthly means in almost every studied pandemic month, except for three months from September to November in 2021. The seasonal variation of antibiotic use also diminished. Active agent level analysis revealed an excessive use of azithromycin, even after evidence of ineffectiveness for COVID-19 emerged.

Neuropharmacological Potential of Diterpenoid Alkaloids.

This study provides a narrative review of diterpenoid alkaloids (DAs), a family of extremely important natural products found predominantly in some species of Aconitum and Delphinium (Ranunculaceae). DAs have long been a focus of research attention due to their numerous intricate structures and diverse biological activities, especially in the central nervous system (CNS). These alkaloids originate through the amination reaction of tetra or pentacyclic diterpenoids, which are classified into three categories and 46 types based on the number of carbon atoms in the backbone structure and structural differences. The main chemical characteristics of DAs are their heterocyclic systems containing ß-aminoethanol, methylamine, or ethylamine functionality. Although the role of tertiary nitrogen in ring A and the polycyclic complex structure are of great importance in drug-receptor affinity, in silico studies have emphasized the role of certain sidechains in C13, C14, and C8. DAs showed antiepileptic effects in preclinical studies mostly through Na+ channels. Aconitine (1) and 3-acetyl aconitine (2) can desensitize Na+ channels after persistent activation. Lappaconitine (3), N-deacetyllapaconitine (4), 6-benzoylheteratisine (5), and 1-benzoylnapelline (6) deactivate these channels. Methyllycaconitine (16), mainly found in Delphinium species, possesses an extreme affinity for the binding sites of α7 nicotinic acetylcholine receptors (nAChR) and contributes to a wide range of neurologic functions and the release of neurotransmitters. Several DAs such as bulleyaconitine A (17), (3), and mesaconitine (8) from Aconitum species have a drastic analgesic effect. Among them, compound 17 has been used in China for decades. Their effect is explained by increasing the release of dynorphin A, activating the inhibitory noradrenergic neurons in the ß-adrenergic system, and preventing the transmission of pain messages by inactivating the Na+ channels that have been stressed. Acetylcholinesterase inhibitory, neuroprotective, antidepressant, and anxiolytic activities are other CNS effects that have been investigated for certain DAs. However, despite various CNS effects, recent advances in developing new drugs from DAs were insignificant due to their neurotoxicity.

Isolation of compounds from the roots of Ambrosia artemisiifolia and their effects on human cancer cell lines.

Common ragweed (Ambrosia artemisiifolia L.) is an invasive plant in Europe with spreading use in the contemporary folk medicine. The chemical composition of the above-ground parts is extensively studied, however, the metabolites of the roots are less discovered. By multiple chromatographic purification of the root extracts, we isolated thiophene A (1), n-dodecene (2), taraxerol-3-O-acetate (3), α-linoleic acid (4), (+)-pinoresinol (5), and thiophene E (7,10-epithio-7,9-tridecadiene-3,5,11-triyne-1,2-diol) (6). The 1H NMR data published earlier for 1 were supplemented together with the assignment of 13C NMR data. Thiophene E (6), which is reported for the first time from this species, exerted cytotoxic and antiproliferative effects on A-431 epidermoid skin cancer cells, whereas taraxerol-3-O-acetate (3) and α-linoleic acid (4) had slight antiproliferative effect on gynecological cancer cell lines. Thiophene E (6) and taraxerol-3-O-acetate (3) displayed antiproliferative and cytotoxic effects on MRC-5 fibroblast cells. Thiophene E (6) exerted weak antibacterial activity (MIC 25 µg/mL) on MRSA ATCC 43300, on Staphylococcus aureus ATCC 25923, Escherichia coli AG100 and E. coli ATCC 25922 both thiophenes were inactive. Although the isolated compounds exerted no remarkable cytotoxic or antiproliferative activities, the effects on MRC-5 fibroblast cells highlight the necessity of further studies to support the safety of ragweed root.

Results of a systematic review and meta-analysis of early studies on ivermectin in SARS-CoV-2 infection.

Ivermectin, an antiparasitic drug, has been repurposed for COVID-19 treatment during the SARS-CoV-2 pandemic. Although its antiviral efficacy was confirmed early in vitro and in preclinical studies, its clinical efficacy remained ambiguous. Our purpose was to assess the efficacy of ivermectin in terms of time to viral clearance based on the meta-analysis of available clinical trials at the closing date of the data search period, one year after the start of the pandemic. This meta-analysis was reported by following the PRISMA guidelines and by using the PICO format for formulating the question. The study protocol was registered on PROSPERO. Embase, MEDLINE (via PubMed), Cochrane Central Register of Controlled Trials (CENTRAL), bioRvix, and medRvix were searched for human studies of patients receiving ivermectin therapy with control groups. No language or publication status restrictions were applied. The search ended on 1/31/2021 exactly one year after WHO declared the public health emergency on novel coronavirus. The meta-analysis of three trials involving 382 patients revealed that the mean time to viral clearance was 5.74 days shorter in case of ivermectin treatment compared to the control groups [WMD = -5.74, 95% CI (-11.1, -0.39), p = 0.036]. Ivermectin has significantly reduced the time to viral clearance in mild to moderate COVID-19 diseases compared to control groups. However, more eligible studies are needed for analysis to increase the quality of evidence of ivermectin use in COVID-19.

No evidence for the benefit of PPIs in the treatment of acute pancreatitis: a systematic review and meta-analysis.

Although current guidelines do not recommend the use of proton pump inhibitors (PPIs) in the standard of care of acute pancreatitis (AP), they are often prescribed in clinical practice, mainly for ulcer stress prophylaxis. In this systematic review and meta-analysis we evaluated the association between the use of PPIs in the management of AP and various clinical outcomes. We conducted the systematic research in six databases without restrictions on January 24th, 2022. We investigated adult patient with AP, who were treated with PPI compared to conventional therapy. The pooled odds ratios, mean differences, and corresponding 95% confidence intervals were calculated with random effect model. We included six RCTs and three cohort studies, consisting of 28,834 patients. We found a significant decrease in the rate of pancreatic pseudocyst formation in patients who received PPI treatment. PPI use was associated with a higher risk of GI bleeding, however this finding could be due to the patients' comorbid conditions. We found no significant difference in the rates of 7-day mortality, length of hospital stay, and acute respiratory distress syndrome between the groups. The available data on this topic are limited; therefore, further well designed RCTs are needed to evaluate the potential benefits and adverse effects of PPIs in AP.

Factors influencing successful reconstruction of tympanic membrane perforations: a systematic review and meta-analysis.

PURPOSE: Based on a systematic review and meta-analysis, our study aimed to provide information about the factors that influence the success of tympanic membrane reconstruction. METHODS: Our systematic search was conducted on November 24, 2021, using the CENTRAL, Embase, and MEDLINE databases. Observational studies with a minimum of 12 months of follow-up on type I tympanoplasty or myringoplasty were included, while non-English articles, patients with cholesteatoma or specific inflammatory diseases, and ossiculoplasty cases were excluded. The protocol was registered on PROSPERO (registration number: CRD42021289240) and PRISMA reporting guideline was used. Risk of bias was evaluated with the QUIPS tool. A random effect model was used in the analyses. Primary outcome was the rate of closed tympanic cavities. RESULTS: After duplicate removal, 9454 articles were found, of which 39 cohort studies were included. Results of four analyses showed significant effects: age (OR: 0.62, CI 0.50; 0.78, p value: 0.0002), size of the perforation (OR: 0.52, CI 0.29; 0.94, p value: 0.033), opposite ear condition (OR: 0.32, CI 0.12; 0.85, p value: 0.028), and the surgeon's experience (OR: 0.42, CI 0.26; 0.67, p value: 0.005), while prior adenoid surgery, smoking, the site of the perforation, and discharge of the ear did not. Four factors: etiology, Eustachian tube function, concomitant allergic rhinitis, and duration of the ear discharge were analyzed qualitatively. CONCLUSIONS: The age of the patient, the size of the perforation, the opposite ear status, and the surgeon's experience have a significant effect on the success of tympanic membrane reconstruction. Further comprehensive studies are needed to analyze the interactions between the factors. LEVEL OF EVIDENCE: Not applicable.

Mastoid Obliteration Decreases the Recurrent and Residual Disease: Systematic Review and Meta-analysis.

OBJECTIVE: Our study aims to evaluate the effectiveness of mastoid obliteration compared to the canal wall up (CWU) technique in cholesteatoma surgery based on the systematic review of the literature and the meta-analysis of the data. METHODS: The systematic search was performed in four major databases (MEDLINE, Web of Science, Embase, and CENTRAL) on October 14, 2021. Studies comparing the CWU technique and mastoid obliteration were included. The exclusion criteria were less than 12 months follow-up, congenital cholesteatoma, indefinite description of the surgical method, and animal studies. The protocol was registered on Prospero (registration number: CRD42021282485). The risk of bias was evaluated with the ROBINS-I tool. Residual and recurrent disease proportions as primary outcomes, quality of life, ear discharge, infection rates, hearing results, and operation time as secondary outcomes were analyzed. In the quantitative synthesis, the random effect model was used, and heterogeneity was identified. RESULTS: A total of 11 articles with 2077 operations' data were found eligible. All the identified studies were retrospective cohorts. The odds of pooled residual and recurrent disease proportion were significantly lower in the obliteration group compared to CWU (OR = 0.45, CI:0.28;0.80, p = 0.014). However, when separated, the proportion of ears with recurrent (OR = 0.41, CI:0.11;1.57, p = 0.140) or residual (OR = 0.59, CI:0.23, 1.50, p = 0.207) disease did not show a significant difference, even though the odds were quite similar. The qualitative synthesis identified no significant difference in the secondary outcomes, but obliteration elongated the operation time. CONCLUSION: Mastoid obliteration significantly decreased the proportion of residual and recurrent cholesteatoma in pooled analyses compared to the CWU technique with low-quality of data. LEVEL OF EVIDENCE: NA Laryngoscope, 133:1297-1305, 2023.

Multibiomarker disease activity score: an objective tool for monitoring rheumatoid arthritis? A systematic review and meta-analysis.

OBJECTIVES: The multibiomarker disease activity (MBDA) score is an objective tool for monitoring disease activity in RA. Here we report a systematic review and meta-analysis of the clinical value of the MBDA score in RA. METHODS: We performed a systematic literature search in five medical databases-MEDLINE (via PubMed), Cochrane Library (CENTRAL), Embase, Scopus and Web of Science-from inception to 13 October 2021. Original articles reporting on the performance of the MBDA score's correlation with conventional disease activity measures or the predictive and discriminative values of the MBDA score for radiographic progression, therapy response, remission and relapse were included. RESULTS: Our systematic search provided a total of 1190 records. After selection and citation searches, we identified 32 eligible studies. We recorded moderate correlations between MBDA score and conventional disease activity measures at baseline [correlation (COR) 0.45 (CI 0.28, 0.59), I2 = 71.0% for the 28-joint DAS with CRP (DAS28-CRP) and COR 0.55 (CI 0.19, 0.78), I2 = 0.0% for DAS28 with ESR] and at follow-up [COR 0.44 (CI 0.28, 0.57, I2 = 70.0% for DAS28-CRP) and found that the odds of radiographic progression were significantly higher for patients with a high baseline MBDA score (>44) than for patients with a low baseline MBDA score (<30) [OR 1.03 (CI 1.02-1.05), I2 = 10.0%]. CONCLUSION: The MBDA score might be used as an objective disease activity marker. In addition, it is also a reliable prognostic marker of radiographic progression.

Safety and risks of CBD oils purchased online: unveiling uncertain quality and vague health claims.

Introduction: The unmet need for highly effective, naturally derived products with minimal side effects results in the over-popularity of ever-newer medicinal plants. In the middle of 2010, products containing cannabidiol (CBD), one of the special metabolites of Cannabis sativa, started to gain popularity. For consumers and healthcare providers alike, the legal context surrounding the marketing of CBD products is not entirely clear, and the safety of using some products is in doubt. Companies in the online medicinal product market profit from the confusion around CBD oils. Methods: In our study, we employed a complex method known as risk-based safety mapping of the online pharmaceutical market, which included health claim content analysis of online stores, test purchases, and labeling and quantitative analysis of the CBD content. Results: There were discovered 16 online retailers selling an average of 2-7 goods and CBD oils with a concentration of 3%-5% (30-50 mg/mL) CBD. The majority (n/N = 10/16, 62.5%) displayed potential health-related benefits indirectly on their website, and in the case of one web shop (n/N = 1/16, 6.3%), we detected COVID-19-related use. Altogether, 30 types of purported "indications" were collected. A total of 12 CBD oil products were test-purchased from online retailers in December 2020. Upon evaluating the packaging and product information, we noticed that three products (n/N = 3/12, 25%) lacked instructions on use, hence increasing the risk of inappropriate application and dosing. The cannabidiol content was quantified using UHPLC. The measured CBD concentrations of the products ranged from 19.58 mg/mL to 54.09 mg/mL (mean 35.51 mg/mL, median 30.63 mg/mL, and SD ± 12.57 mg/mL). One (8.33%) product was underlabeled, five (41.67%) were over-labeled, and only every second product (50%) was appropriately labeled based on the quantitative assessment of CBD concentration. Discussion: Further research and quality control are necessary to establish the regulatory context of the usage and classification of CBD and other cannabinoids in nonmedicinal products (e.g., food supplements), as authorities and policymakers worldwide struggle with the uncertainties surrounding CBD products.