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Cost-benefit analysis (CBA) is the universally applied tool to assess economic viability in assisting decisions on transport investments. Its framework is heavily influenced by the numerous variables it considers through estimating and valuing the intervention’s effects. This paper – utilising the authors’ previously implemented CBA test environment – comprehensively analyses the sensitivity of significant variables of three typical CBA models for transport interventions (road, rail and urban) to understand the prevailing appraisal approach better and to help focus on further methodological improvements. Morris and Sobol methods were selected to study the global sensitivity of and the relations between the input parameters of the models. The sensitivity test of the three analysed models provided similar results regarding which variables are most influential in CBAs. Input variables such as the investment cost, the economic discount rate, forecasted GDP changes and specific elasticities to these GDP changes often have a firm but mostly linear effect. Value of time, vehicle operating cost and mode choice-related parameters such as car availability, car occupancy rate, level of service indicators (e.g. frequency of service) and potential to induce travel demand (proxied by a ‘no travel’ parameter) are inputs with considerable linear effects and greater interactive effects.

Background: Combining antegrade stenting (AGS) and hepaticogastrostomy (HGS) is an increasingly used endoscopic ultrasound-guided intervention when stenting by endoscopic retrograde cholangiopancreatography is impossible. Objectives: We comprehensively assessed the benefits and downsides of combined AGS and HGS (HGS procedure with AGS, HGAS). Data sources and methods: From 788 HGS and 295 HGAS cases, a random-effects meta-analysis was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol. Five electronic databases were searched for studies on HGS with or without AGS from inception until May 2024. The odds ratio (OR) and pooled rates were used for single and two-arm comparisons with 95% confidence intervals (CI). Results: From 26 eligible studies. The pooled technical and clinical success was 94% (CI: 92%–96%) and 88% (CI: 84%–91%) for HGS and 89% (CI: 83%–93%) and 94% (CI: 89%–97%) for HGAS, respectively. Pooled OR of HGAS and HGS showed an OR = 0.38 (CI: 0.07–2.00) for technical success and an OR = 1.02 (CI: 0.50–2.06) for clinical success. The pooled adverse event rates were 20% (CI: 16%–25%) for HGS and 14% (CI: 9%–20%) for HGAS, whereas pooled OR showed an OR = 1.09 (CI: 0.30–3.94). For re-intervention, an OR = 0.37 (CI: 0.27–0.52) was found. Time to stent dysfunction increased, HGAS 333 (CI: 280–Not reached) and HGS 209 (CI: 120–325) with no change in overall survival HGS 117 (CI: 94–147) and 140 (CI: 105–170). Conclusion: The use of HGAS appears to increase clinical success and reduce the need for re-intervention. Overall adverse event rates were similar but bile leakage prevalence was decreased. Time to stent dysfunction seems to increase with no change in overall survival. Trial registration: Our protocol was prospectively registered with PROSPERO (CRD42024509412).

Background: Aldosterone-producing adenomas cause hypertension in 5–10 % of cases. Laparoscopic adrenalectomy is the gold standard treatment for early-stage adrenal gland tumors, but minimally invasive procedures, such as ablative techniques can also be applied. Therefore, we aimed to compare laparoscopic adrenalectomy and ablation techniques in terms of efficacy and safety in the treatment of benign adrenal gland tumors. Materials and methods: We conducted a systematic search in five databases and included studies comparing the efficacy and safety of ablation techniques and laparoscopic adrenalectomy. We calculated odds ratios (ORs) for eligible studies with binary outcomes, and mean differences (MD) with 95 % confidence intervals (CI) for continuous outcomes. Results: Five studies focusing on aldosterone-producing adenomas were included in our review. A total of 119 patients at 14 centers underwent ablation, and 161 patients had laparoscopic adrenalectomy. The complication rates (OR: 0.98, CI: 0.35–2.69) were similar in both groups, but among complications, hypertensive crisis (OR: 8.13; CI: 1.14–58.11) was more frequent in the ablative group, and even the success rate of interventions - the resolution of hypertension (OR: 0.30, CI: 0.16–0.56) - was lower in this group. On the other hand, the advantage of ablation was shorter intervention time (MD: 75.64 min; CI: 6.33–144.95), shorter hospital stay (MD: 1.6 days; CI: 0.88–2.31), and less perioperative blood loss (MD: 43.55 ml; CI: 12.07–75.04) compared to laparoscopy. Conclusion: Laparoscopic adrenalectomy is still the best therapeutic approach, but ablation can be an appropriate alternative option for the treatment of aldosterone-producing adrenal gland tumors.

Background: Endoscopic retrograde cholangiopancreatography (ERCP) is essential for the minimally invasive management of biliary and pancreatic disorders. Under certain indications, performing ERCP without delay during the weekend can be important for improving outcomes. Objectives: To compare the outcomes of ERCP performed on weekends and holidays with those of regular weekday ERCPs. Design: Propensity score match analysis of the data from the Hungarian ERCP Registry. Methods: A total of 116 ERCPs were performed during weekends or holidays, and 3144 during weekday working hours. The analyses were performed on 1:2 propensity-matched groups (116 weekend and 232 weekday cases). Results: Weekend ERCPs were mostly performed for acute cholangitis and acute biliary pancreatitis (70% of cases), whereas in the weekday group, only 32% of cases were performed for these indications. No significant difference was found between weekday and weekend ERCPs in terms of the rates of successful (91.38% vs 93.1%, p = 0.565) and difficult (33.62% vs 36.64%, p = 0.511) biliary cannulations. We found no significant differences in the number of adverse events (bleeding, post-ERCP pancreatitis, and 30-day mortality) in ERCPs performed during weekends or weekdays. Moreover, no significant differences in the aforementioned outcomes were detected between the propensity-matched groups. Conclusion: In this propensity-matched study, no significant differences were found in the outcomes of weekend and weekday ERCPs.

Abstract Objective Methods of cognitive measurements in multiple sclerosis (MS) are not standardized. We aimed to identify the prevalence of cognitive domain‐specific impairment (DSI) in MS by using subtests of the Brief Repeatable Battery of Neuropsychological Tests (BRB‐N) with analyzing different cutoff values. Methods The systematic review and meta‐analysis were registered on PROSPERO (ID: CRD42021287004). The systematic literature search was performed via PubMed, Embase, and CENTRAL on 24 October 2021. Inclusion criteria were adults of different MS subtypes (CIS, RRMS, PPMS, and SPMS) with the condition of distinct DSI measured by BRB‐N. Pediatric MS, computerized versions of BRB‐N, and patients receiving steroids were excluded. Primary outcome was pooled prevalence rates of impaired patients within each cutoff and MS subtype, with 95% confidence interval, I‐squared statistics for heterogeneity, and chi‐squared test for subgroup differences. Risk of bias was assessed using the “JBI Quality Assessment Tool for Prevalence Studies.” Results In 48 eligible observational studies (n = 3431 patients), the three most prevalent thresholds were the 2.0 SD and 1.5 SD below the mean of normative values, and the score below the fifth percentile of the normative values. A progressively increasing worsening of the overall DSI was observed from CIS, moving toward RRMS, PPMS, and SPMS. Interpretation Cognitive impairment is observed in all MS phenotypes, with varying degrees. Due to several potential influencing factors, our comprehensive literature review has not revealed consistent findings, and we, therefore, recommend considering a more sophisticated, “individual referencing” approach, acknowledging the diverse clinical and sociodemographic characteristics among populations and disparities in cognitive testing.

The PowerPlex Fusion 6C PCR™ amplification kit provides a strong discriminatory power for human identification. We have validated the kit with a reduced volume (12.5 µL) and as part of the validation we compared the efficiency of the polymerase chain reaction (PCR) prepared manually and on Hamilton Microlab® Autolys STAR Biorobot. Three years of casework data has been also included in the validation. Optimisation was carried out on different types of samples (blood, saliva, semen) and DNA was extracted robotically. Tests were conducted at two different cycle numbers (30;32), followed by analysis on both the Applied BiosystemsTM 3500 and 3500 xL Genetic Analyzer instruments (Applied Biosystems®, Foster City, CA, USA). When the PCR was prepared manually, no allele dropout was observed over 0.15 ng input DNA. Whereas when the PCR was prepared robotically, dropout already appeared at the level of 0.15 ng input DNA. In cases when increased cycle number was utilised, an increasing number of dropouts started to arise from 0.075 ng total input DNA. Despite the fact that robotically prepared PCR produced more missing alleles than the manually prepared PCR, using the optimal 0.5 ng input DNA, both methods proved to be reliable. Based on the results, our half-volume protocol is robust, and after three years of application it has proven to be effective with respect to a large number of casework samples.

Lean leadership is often cited in the practitioner literature as an important factor in successful lean transformation. More and more companies are creating full-time lean manager position and dedicated lean teams. There is a lack of research in the literature on whether the integration of a full-time lean manager into the organisational structure improves the effectiveness of lean, and what are the duties and responsibilities of the lean manager. The research has demonstrated that the effectiveness of lean transformation is significantly higher in organisations with a full-time lean team. A dynamic relationship exists between the roles of the full-time lean manager and the company-wide change management framework. A model job description has been developed for the full-time lean manager position, in the context of the organisational change framework for lean manufacturing implementation. The model would serve as the basis for further empirical research and a recommendation for business leaders on how to design a full-time lean manager position in their company.

Abstract This is the first large‐scale cross‐country analysis of patients with chronic lymphocytic leukemia (CLL) aimed to evaluate the incidence, types, and key prognostic factors of secondary malignancies, and to assess the impact on overall survival based on retrospective claims data from three Central European countries. We analyzed 25,814 newly diagnosed CLL patients from Czechia, Hungary, and Poland; 10,312 (39.9%) patients were treated for CLL in study periods between 2004 and 2016. Out of the treated patients, 1986 (19.3%) received the FCR therapy in the first line and 779 (7.6%) received FCR in subsequent lines. We observed that 33.7% of treated patients developed secondary malignancies during the study. Based on country estimates, the probability to develop a secondary malignancy within 4 years since starting the first‐line FCR therapy ranged between 28.0% and 36.8%. We found the age at diagnosis, male gender, any malignancy prior to the CLL diagnosis, and the CLL treatment to be the key risk factors for developing secondary malignancies. Specifically, the FCR therapy was a statistically significant (p

Aim: Demand for nipple- and skin- sparing mastectomy (NSM/SSM) with immediate breast reconstruction (BR) has increased at the same time as indications for post-mastectomy radiation therapy (PMRT) have broadened. The aim of the Oncoplastic Breast Consortium initiative was to address relevant questions arising with this clinically challenging scenario. Methods: A large global panel of oncologic, oncoplastic and reconstructive breast surgeons, patient advocates and radiation oncologists developed recommendations for clinical practice in an iterative process based on the principles of Delphi methodology. Results: The panel agreed that surgical technique for NSM/SSM should not be formally modified when PMRT is planned with preference for autologous over implant-based BR due to lower risk of long-term complications and support for immediate and delayed-immediate reconstructive approaches. Nevertheless, it was strongly believed that PMRT is not an absolute contraindication for implant-based or other types of BR, but no specific recommendations regarding implant positioning, use of mesh or timing were made due to absence of high-quality evidence. The panel endorsed use of patient-reported outcomes in clinical practice. It was acknowledged that the shape and size of reconstructed breasts can hinder radiotherapy planning and attention to details of PMRT techniques is important in determining aesthetic outcomes after immediate BR. Conclusions: The panel endorsed the need for prospective, ideally randomised phase III studies and for surgical and radiation oncology teams to work together for determination of optimal sequencing and techniques for PMRT for each patient in the context of BR

BackgroundThere were more than 1 million new cases of stomach cancer concerning oesophageal cancer, there were more than 600,000 new cases of oesophageal cancer in 2020. After a successful resection in these cases, the role of early oral feeding (EOF) was questionable, due to the possibility of fatal anastomosis leakage. It is still debated whether EOF is more advantageous compared to late oral feeding. Our study aimed to compare the effect of early postoperative oral feeding and late oral feeding after upper gastrointestinal resections due to malignancy.MethodsTwo authors performed an extensive search and selection of articles independently to identify randomized control trials (RCT) of the question of interest. Statistical analyses were performed including mean difference, odds ratio with 95% confidence intervals, statistical heterogeneity, and statistical publication bias, to identify potential significant differences. The Risk of Bias and the quality of evidence were estimated.ResultsWe identified 6 relevant RCTs, which included 703 patients. The appearance of the first gas (MD = −1.16; p = 0.009), first defecation (MD = −0.91; p

Nonchromosomal congenital anomalies (NCAs) are the most common cause of infant mortality and morbidity. The role of maternal age is well known, although the specifics are not thoroughly elucidated in the literature. To evaluate the role of maternal age in the incidence of NCAs and to pinpoint age groups at higher risk to refine screening protocols. A systematic review and meta-analysis were conducted following the PRISMA 2020 guidelines and Cochrane Handbook. Searches were performed on October 19, 2021, across MEDLINE (via PubMed), Cochrane Library (CENTRAL), and Embase. Population-based studies assessing the impact of maternal age on the incidence of NCAs in pregnant women were included, without restrictions on age range, country, or comorbidities. A random-effects model was used for pooling effect sizes, considering the heterogeneity across studies. From 15,547 studies, 72 were synthesized. Maternal age >35 showed an increased NCA risk (risk ratio [RR]: 1.31, confidence interval [CI]: 1.07 -1.61), rising notably after>40 (RR: 1.44, CI: 1.25 -1.66). The latter changes to 1.25 (CI: 1.08 -1.46) if the co-occurrence of chromosomal aberrations is excluded. Specific anomalies like cleft lip/palate (>40, RR: 1.57, CI: 1.11 -2.20) and circulatory system defects (>40, RR: 1.94, CI: 1.28 -2.93) were significantly associated with advanced maternal age. Conversely, gastroschisis was linked to mothers <20 (RR: 3.08, CI: 2.74 -3.47). The study confirms that both very young and advanced maternal ages significantly increase the risk of NCAs. There is a pressing need for age-specific prenatal screening protocols to better detect these anomalies, especially considering the current trend of delayed childbearing. Further research is required to fully understand the impact of maternal age on the prevalence of rarer NCAs. [Display omitted] [ABSTRACT FROM AUTHOR]

The negative cardiovascular effects of polycystic ovary syndrome (PCOS) and vitamin D deficiency (VDD) have been discussed previously; however, the sex differences between PCOS females and males are not yet known. Our aim was to investigate the effect of PCOS and VDD in the carotid artery of male and female Wistar rats. Females were treated with transdermal testosterone (Androgel) for 8 weeks, which caused PCOS. VDD and vitamin D supplementation were accomplished via diet. The carotid arteries’ contraction and relaxation were examined using myography. Receptor density was investigated using immunohistochemistry. In PCOS females, angiotensin receptor density, angiotensin II-induced contraction, androgen receptor optical density, and testosterone-induced relaxation increased. The increased contractile response may increase cardiovascular vulnerability in women with PCOS. As an effect of VDD, estrogen receptor density increased in all our groups, which probably compensated for the reduced relaxation caused by VDD. Testosterone-induced relaxation was decreased as a result of VDD in males and non-PCOS females, whereas this reduction was absent in PCOS females. Male sex is associated with increased contraction ability compared with non-PCOS and PCOS females. VDD and Androgel treatment show significant gender differences in their effects on carotid artery reactivity. Both VDD and PCOS result in a dysfunctional vascular response, which can contribute to cardiovascular diseases.

Hypertension and andropause both accelerate age–related vascular deterioration. We aimed to evaluate the effects of angiotensin-II induced hypertension and deficiency of testosterone combined regarding the resistance coronaries found intramurally.Four male groups were formed from the animals: control group (Co, n = 10); the group that underwenr orchidectomy (ORC, n = 13), those that received an infusion of angiotensin-II (AII, n = 10) and a grous that received AII infusion and were also surgically orchidectomized (AII + ORC, n = 8). AII and AII + ORC animals were infused with infusing angiotensin-II (100 ng/min/kg) using osmotic minipumps. Orchidectomy was perfomed in the ORC and the AII + ORC groupsto establish deficiency regarding testosterone. Following four weeks of treatment, pressure-arteriography was performed in vitro, and the tone induced by administration of thromboxane-agonist (U46619) and bradykinin during analysis of the intramural coronaries (well-known to be resistance arterioles) was studied.U46619-induced vasoconstriction poved to be significantly decreased in the ORC and AII + ORC groups when compared with Co and AII animals. In ORC and AII + ORC groups, the bradykinin-induced relaxation was also significantly reduced to a greater extent compared to Co and AII rats. Following orchidectomy, the vasocontraction and vasodilatation capacity of blood vessels is reduced. The effect of testosterone deficiency on constrictor tone and relaxation remains pronounced even in AII hypertension: testosterone deficiency further narrows adaptation range in the double noxa (AII + ORC) group. Our studies suggest that vascular changes caused by high blood pressure and testosterone deficiency together may significantly increase age-related cardiovascular risk.

This text is based on the recommendations accepted by the 4th Hungarian Consensus Conference on Breast Cancer, modified on the basis of the international consultation and conference within the frames of the Central-Eastern European Academy of Oncology. The recommendations cover non-operative, intraoperative and postoperative diagnostics, determination of prognostic and predictive markers and the content of cytology and histology reports. Furthermore, they address some specific issues such as the current status of multigene molecular markers, the role of pathologists in clinical trials and prerequisites for their involvement, and some remarks about the future.

The current review paper was written in collaboration with breast cancer surgeons from the European Breast Cancer Research Association of Surgical Trialists (EUBREAST), a breast pathologist from the Danish Breast Cancer Group (DBCG), and representatives from the European SocieTy for Radiotherapy & Oncology (ESTRO) breast cancer course. Herein we summarize the different mastectomies and reconstruction procedures and define high-risk anatomical areas for breast cancer recurrences, to further specify the challenges in the surgical procedure, histopathological evaluation, and target volumes in case of postmastectomy irradiation, as recommended by the ESTRO guidelines according to the surgical procedure. The paper has original figures and illustrations for all disciplines for in-depth understanding of the differences between the procedures.

Abstract Chronic pancreatitis (CP) is an end-stage disease with no specific therapy; therefore, an early diagnosis is of crucial importance. In this study, data from 1315 and 318 patients were analysed from acute pancreatitis (AP) and CP registries, respectively. The population from the AP registry was divided into AP (n = 983), recurrent AP (RAP, n = 270) and CP (n = 62) groups. The prevalence of CP in combination with AP, RAP2, RAP3, RAP4 and RAP5 + was 0%, 1%, 16%, 50% and 47%, respectively, suggesting that three or more episodes of AP is a strong risk factor for CP. Laboratory, imaging and clinical biomarkers highlighted that patients with RAP3 + do not show a significant difference between RAPs and CP. Data from CP registries showed 98% of patients had at least one AP and the average number of episodes was four. We mimicked the human RAPs in a mouse model and found that three or more episodes of AP cause early chronic-like morphological changes in the pancreas. We concluded that three or more attacks of AP with no morphological changes to the pancreas could be considered as early CP (ECP).The new diagnostic criteria for ECP allow the majority of CP patients to be diagnosed earlier. They can be used in hospitals with no additional costs in healthcare.

Abstract Mobility as a Service (MaaS) is a new transport concept which integrates, manages, and distributes private and public mobility alternatives by using intelligent digital technologies. Recently, research and implementations have been widely conducted. In order to reveal future implications, it is crucial to analyze the available MaaS services by using systematic methodology. Cluster analysis was applied to create typical groups of MaaS services and to define the common features of the systems, which may highlight future trends. In order to identify the most relevant MaaS initiatives, the typical parameters of the services were taken into account and a dataset was developed. More than 30 MaaS services from 14 countries were investigated, and the features and the functionalities of these services were analyzed. The findings demonstrate that there is potential for the development of the applications in terms of their payment features, their personalization, and the provision of all attainable elements of MaaS. The number of operators is constantly increasing. However, it is uncertain whether public or private MaaS operators will be dominant on the market. Three cluster groups were created with specific features and directions of development. The Route planners group involves a few modes of transport, but it provides an extensive service. While the Third parties group has primarily private MaaS operators, the Public systems group usually includes public MaaS operators. This comprehensive study might be useful to MaaS operators and regulators for understanding the typical features and the development directions of the market.

Ibrutinib, a Bruton tyrosine kinase inhibitor, provides effective treatment for chronic lymphocytic leukemia (CLL). Here, the authors describe time-dependent molecular changes to malignant cells and to the immune system in patients undergoing ibrutinib therapy, with can be used for therapy monitoring.

Fluid therapy is the cornerstone of early supportive therapy in acute pancreatitis (AP). Regrettably, the type of fluid is still debated among clinicians, despite recent evidence from randomized controlled trials (RCTs). We aimed to incorporate all evidence from RCTs comparing lactated Ringer’s solution (LR) with normal saline (NS) in adult and pediatric AP patients, with particular emphasis on clinically relevant outcomes. We evaluated RCTs comparing intravenous fluid resuscitation with LR to NS in adult or pediatric AP patients according to a prospectively registered protocol (CRD42021224542). Moderate-to-severe AP (MSAP), mortality, length of hospitalization (LoH), need for intensive care, the incidence of systemic (organ failure, OF) and local complications (in total), necrosis and pseudocyst formation were analyzed separately. Risk ratio (RR) and median difference (MD) were calculated with 95% confidence intervals (CI) using a random effect model. Risk of bias and quality of evidence were assessed. Altogether, 8 eligible RCTs were found, including 557 patients (LR: 278; NS: 279). LR reduced the risk of MSAP by 31% (RR: 0.59, 95% CI: 0.36–0.97, high quality) and the risk of death by 62% (RR: 0.48; 95% CI: 0.24–0.98, very low quality). LR was associated with a significantly lower risk of need for intensive care (RR: 0.50, 95% CI: 0.33–0.77), OF (RR: 0.78, 95% CI: 0.61–0.99) and local complications (RR: 0.64, 95% CI: 0.46–0.89). No significant risk reduction was observed for LoH (MD: −0.57 days, CI: −1.33–0.19), necrosis, pseudocyst and inflammatory parameters by LR compared to NS. LR reduces severity, mortality, need of intensive care and systemic and local complications in AP.

Viral infections during pregnancy raise several clinical challenges, including birth defects in the offspring. Thus, this systematic review and meta-analysis aims to prove and highlight the risk of birth defects after first-trimester maternal influenza infection. Our systematic search was performed on 21 November 2022. Studies that reported maternal influenza infection in the first trimester and non-chromosomal congenital abnormalities were considered eligible. We used odds ratios (OR) with 95% confidence intervals (CIs) to measure the effect size. Pooled ORs were calculated with a random effects model. Heterogeneity was measured with I² and Cochran’s Q tests. We found that first-trimester maternal influenza was associated with increased odds of developing any type of birth defects (OR: 1.5, CI: 1.30–1.70). Moreover, newborns were more than twice as likely to be diagnosed with neural tube defects (OR: 2.48, CI: 1.95–3.14) or cleft lip and palate (OR: 2.48, CI: 1.87–3.28). We also found increased odds of developing congenital heart defects (OR: 1.63, CI: 1.27–2.09). In conclusion, influenza increases the odds of non-chromosomal birth defects in the first trimester. The aim of the present study was to estimate the risk of CAs in the offspring of mothers affected by first-trimester influenza infection.

Introduction: At the initial part of the gastrointestinal tract, multiple tissues serve the normal function of food delivery. Periodontal structures are integral elements of these. When they deteriorate, it is extremely challenging to regenerate and reconstruct them. The conventional intervention for periodontal disease is scaling and root planning with the aim of reducing pathogenic bacteria. However, periodontal pathogens can rapidly recolonize treated areas. Probiotics have been proposed as novel tools for managing oral health by suppressing pathogenic bacteria through their anti-inflammatory effect, but the available data are controversial.Aim: Therefore, we performed a meta-analysis to study the effect of probiotics on periodontal pathogenic bacteria.Methods: The study was registered in PROSPERO under registration number CRD42018094903. A comprehensive literature search from four electronic databases (PubMed, Cochrane CENTRAL, Embase, and Web of Science) yielded nine eligible records for statistical analysis. Studies measuring bacterial counts in saliva and supra- and subgingival plaque were included. Bacterial counts were analyzed using standard mean difference (SMD) and by a random effects model with the DerSimonian–Laird estimation.Results: The results showed a significant decrease in the overall count of Aggregatibacter actinomycetemcomitans in the probiotic-treated group compared to the control at 4 weeks (SMD: −0.28; 95% CI: −0.56–−0.01; p = 0.045) but not later. Analyzing the bacterial counts in subgroups, namely, in saliva and supra- and subgingival plaque, separately, yielded no significant difference. Probiotics had no significant effect on the overall count of Porphyromonas gingivalis at 4 weeks (SMD: −0.02; 95% CI: −0.35−0.31; p = 0.914) or later. Subgroup analysis also revealed no significant difference between treatment and control groups nor did probiotics significantly decrease the overall and subgroup bacterial counts of Prevotella intermedia, Tannerella forsythia, and Fusobacterium nucleatum.Conclusion: Our data support the beneficial effect of probiotics in reducing A. actinomycetemcomitans counts, but not of other key periodontal pathogenic bacteria in periodontal disease patients. However, due to the complex mechanism associated with periodontal disease and the limitations of the available studies, there is a further need for well-designed randomized clinical trials to assess the efficacy of probiotics.

Abstract Background Juvenile Idiopathic arthritis (JIA) is the most common chronic rheumatic disease in childhood. The diagnosis is based on the underlying symptoms of arthritis with an exclusion of other diseases Biologic agents are increasingly used on the side of disease-modifying anti-rheumatic drugs (DMARD) in JIA treatment. Main body The aim of this meta-analysis was to investigate the observed infections in JIA children during tumor necrosis factor (TNF)-alpha inhibitor therapy. A systematic search of three databases (Medline via PubMed, Embase, Cochrane Library) was carried out up to May 2018. Published trials that evaluated the infectious adverse events in patients receiving TNF-alpha inhibitor vs. a control group were included in the analysis. Full-text data extraction was carried out independently by the investigators from ten relevant publications. 1434 patients received TNF-alpha inhibitor therapy; the control group consisted of 696 subjects. The analysis presented the risk of infection in the active treatment group (OR = 1.13; 95% CI: 0.76–1.69; p = 0.543). The majority of infections were upper respiratory tract infections (URTIs). Furthermore, the subgroup analysis demonstrated a higher infection rate in the observed localization. Conclusion Anti-TNF therapy slightly but not significantly increases the incidence of infection in JIA children compared to other therapies (GRADE: moderate evidence). The most common infections reported were mild URTIs. Further studies with larger patients number with a strong evidence level are crucially needed to finalize the answer whether anti-TNF therapy elevates and if yes on what extent the incidence of infection in JIA children. Trial registration Prospero: CRD42017067873.

Abstract Background Complete lymph node removal through conventional axillary dissection (ALND) has been standard treatment for breast cancer patients for almost a century. In the 1990s, however, and in parallel with the advent of the sentinel lymph node (SLN) procedure, ALND came under increasing scrutiny due to its association with significant patient morbidity. Several studies have since provided evidence to suggest omission of ALND, often in favor of axillary radiation, in selected clinically node-negative, SLN-positive patients, thus supporting the current trend in clinical practice. Clinically node-positive patients, by contrast, continue to undergo ALND in many cases, if only for the lack of studies re-assessing the indication for ALND in these patients. Hence, there is a need for a clinical trial to evaluate the optimal treatment for clinically node-positive breast cancer patients in terms of surgery and radiotherapy. The TAXIS trial is designed to fill this gap by examining in particular the value of tailored axillary surgery (TAS), a new technique for selectively removing positive lymph nodes. Methods In this international, multicenter, phase-III, non-inferiority, randomized controlled trial (RCT), including 34 study sites from four different countries, we plan to randomize 1500 patients to either receive TAS followed by ALND and regional nodal irradiation excluding the dissected axilla, or receive TAS followed by regional nodal irradiation including the full axilla. All patients undergo adjuvant whole-breast irradiation after breast-conserving surgery and chest-wall irradiation after mastectomy. The main objective of the trial is to test the hypothesis that treatment with TAS and axillary radiotherapy is non-inferior to ALND in terms of disease-free survival of clinically node-positive breast cancer patients in the era of effective systemic therapy and extended regional nodal irradiation. The trial was activated on 31 July 2018 and the first patient was randomized on 7 August 2018. Discussion Designed to test the hypothesis that TAS is non-inferior to ALND in terms of curing patients and preventing recurrences, yet is significantly superior in reducing patient morbidity, this trial may establish a new worldwide treatment standard in breast cancer surgery. If found to be non-inferior to standard treatment, TAS may significantly contribute to reduce morbidity in breast cancer patients by avoiding surgical overtreatment. Trial registration ClinicalTrials.gov, ID: NCT03513614. Registered on 1 May 2018. www.kofam.ch, ID: NCT03513614. Registered on 17 June 2018. EudraCT No.: 2018–000372-14.

A lean transzformáció jellemzőinek vizsgálata a szakirodalomban széles körű. Kutatások fókuszát képezi a lean transzformációt elősegítő és gátló tényezők vizsgálata és a lean szemléletű vezetői tulajdonságok, magatartásformák elemzése. A publikált kutatások többsége nem foglalkozik a lean transzformáció és a vállalatok életciklusa közötti összefüggésekkel és a főállású lean vezető / lean csoport szerepének vizsgálatával. A cikkben ezeknek az összefüggéseknek a fontosságára szeretnénk felhívni a figyelmet és a témában további kutatásokat kívánunk ösztönözni.

Abstract Background Aging sarcopenia characterized by low muscle mass with low muscle strength affects men and women differently. The contribution of interleukin-6 (IL-6) to sarcopenia has been suggested based on a negative correlation between plasma IL-6 and muscle function described by some studies. However, no consensus regarding clinically relevant cut-off criteria has been reached. Another question arises whether pooling male and female data is an accurate way to determine the predictive value of IL-6 in sarcopenia. The present meta-analysis was designed to assess: (1) whether plasma IL-6 in aged populations in fact correlates negatively to muscle strength; (2) whether such a correlation exists both in men and in women; and (3) whether plasma IL-6 shows a gender difference in old age. Methods We applied the preferred reporting items for systematic review and meta-analysis protocols (PRISMA). We searched PubMed and Embase for papers that reported data on individuals over 65 without inflammatory diseases. We extracted either separate male and female data on plasma IL-6 along with at least one muscle parameter or correlation coefficient between plasma IL-6 and these parameters. Random effect models calculated with DerSimonian and Laird weighting methods were applied to analyze correlation coefficients and gender difference in plasma IL-6. Egger’s test was used to assess the small study effect. Results Twenty articles out of 468 records identified were suitable for analyses. Plasma IL-6 correlates negatively with grip strength in mixed populations and also separately in men [− 0.25 with 95% confidence interval (CI): − 0.48, − 0.02] and in women (− 0.14 with 95% CI: − 0.24, − 0.03). However, contrary to expectations, men with better muscle condition have higher plasma IL-6 than women of similar age with worse muscle condition (plasma IL-6 male–female difference: 0.25 pg/mL with 95% CI: 0.15, 0.35). Conclusion This is the first study to demonstrate that a higher predictive IL-6 cut-off level should be determined for aging sarcopenia in men than in women.

Assessment of travel time reliability as a fundamental factor in travel behaviour has become a very important aspect in both transport modelling and economic appraisal. Improved reliability could provide a significant economic benefit if it is adequately calculated in cost-benefit analyses for which the theoretical background has already been set. However, methods to forecast travel time reliability as well as travel behaviour models including its effects are rather scarce and there is a need for development in this field. Another important aspect could be the influencing factor of reliability in travel demand management and related policy-making. Therefore, this paper intends to further analyse reliability focusing exclusively on urban road transport based on automatic measurements of journey times and traffic volumes from a dataset of the city of Budapest. The main finding and the novelty of the study is a model which can forecast the standard deviation of travel times based on the volume-capacity ratio and the free-flow travel time. The paper also provides a real-life numerical experiment in which the proposed model has been compared with other, existing ones. It proves that besides existing mean-delay-based models, travel time reliability can be forecasted based on the volume-capacity ratio with an adequate accuracy.

Mobility management centres play a significant role in urban transport, taking into account several factors that have an effect on the flow of vehicles. In the present paper a mobility management centre equipped with necessary information and information technologies for travellers is presented that can provide route plans. A route guidance methodology is described that combines current transportation demands with the results of the traditional four-step model.

Background: The management of the moderate and severe forms of acute pancreatitis (AP) with necrosis and multiorgan failure remains a challenge. To predict the severity and mortality of AP multiple clinical, laboratory-, and imaging-based scoring systems are available.Aim: To investigate, if the computed tomography severity index (CTSI) can predict the outcomes of AP better than other scoring systems.Methods: A systematic search was performed in three databases: Pubmed, Embase, and the Cochrane Library. Eligible records provided data from consecutive AP cases and used CTSI or modified CTSI (mCTSI) alone or in combination with other prognostic scores [Ranson, bedside index of severity in acute pancreatitis (BISAP), Acute Physiology, and Chronic Health Examination II (APACHE II), C-reactive protein (CRP)] for the evaluation of severity or mortality of AP. Area under the curves (AUCs) with 95% confidence intervals (CIs) were calculated and aggregated with STATA 14 software using the metandi module.Results: Altogether, 30 studies were included in our meta-analysis, which contained the data of 5,988 AP cases. The pooled AUC for the prediction of mortality was 0.79 (CI 0.73–0.86) for CTSI; 0.87 (CI 0.83–0.90) for BISAP; 0.80 (CI 0.72–0.89) for mCTSI; 0.73 (CI 0.66–0.81) for CRP level; 0.87 (CI 0.81–0.92) for the Ranson score; and 0.91 (CI 0.88–0.93) for the APACHE II score. The APACHE II scoring system had significantly higher predictive value for mortality than CTSI and CRP (p = 0.001 and p < 0.001, respectively), while the predictive value of CTSI was not statistically different from that of BISAP, mCTSI, CRP, or Ranson criteria. The AUC for the prediction of severity of AP were 0.80 (CI 0.76–0.85) for CTSI; 0.79, (CI 0.72–0.86) for BISAP; 0.83 (CI 0.75–0.91) for mCTSI; 0.73 (CI 0.64–0.83) for CRP level; 0.81 (CI 0.75–0.87) for Ranson score and 0.80 (CI 0.77–0.83) for APACHE II score. Regarding severity, all tools performed equally.Conclusion: Though APACHE II is the most accurate predictor of mortality, CTSI is a good predictor of both mortality and AP severity. When the CT scan has been performed, CTSI is an easily calculable and informative tool, which should be used more often in routine clinical practice.

Background: The Baveno VI Consensus Workshop defined criteria (liver stiffness measured by transient elastography 150 × 109 cells/L) to identify those patients with compensated advanced chronic liver diseases (cACLD) who are unlikely to have varices needing treatment (VNTs) and can safely avoid variceal screening endoscopy. This meta-analysis aimed to quantify the safety and efficacy of these criteria in suspected cACLD with liver stiffness >10 kPa and in compensated chronic liver diseases (cCLD) irrespective of liver stiffness.Methods: A systematic search was conducted in nine databases for studies discussed cACLD or cCLD and tested Baveno criteria against variceal screening endoscopy. The main safety and efficacy endpoints were missed VNT rate and spared endoscopy rate (SER), respectively; calculated with the random effect model. Pooled sensitivity, specificity, and area under the curve (AUC) were calculated with the hierarchical summary receiver operating characteristic model. For all outcome measures, 95% confidence intervals were computed. Heterogeneity was tested with I2-statistics.Results: The search yielded 13 studies including 4,464 patients which reported on suspected cACLD. Pooled missed VNT rate was 0.3% (0.1–0.6%; I2 = 45.5%), pooled SER was 32.8% (24.8–41.4%; I2 = 97.0%). Sensitivity, specificity, and AUC of Baveno criteria were 97% (95–98%), 41% (27–57%), and 96% (94–97%), respectively. In the subgroups of cACLD from hepatitis C and B viruses, non-alcoholic fatty liver disease/steatohepatitis, or alcohol, missed VNT rates were 0.0% (0.0–0.3%), 1.2% (0.4–2.2%), 0.0% (0.0–1.3%), or 0.0% (0.0–0.4%), while SERs were 24.2% (20.5–28.1%), 24.9% (21.7–28.4%), 38.6% (10.9–70.8%), or 27.0% (16.9–38.4%), respectively. If we expanded the study population to cCLD, 27 studies included 7,534 patients. Missed VNT rate was 0.2% (0.1–0.5%; I2 = 39.8%) with a SER of 30.5% (25.2–36.2%; I2 = 96.1%) while Se, Sp, and AUC were 97% (93–99%), 35% (27–44%), and 80% (77–84%), respectively.Conclusions: The application of Baveno criteria significantly reduces the number of unnecessary variceal screening endoscopies while being safe: cACLD patients with liver stiffness 150 × 109 cells/L carry a very low chance (i.e., 0.3%) of having VNTs. The criteria preserve low missed VNT rate with lower diagnostic performance among cCLD patients.

Background: Acute pancreatitis (AP) is one of the most common cause of hospitalization among gastrointestinal diseases worldwide. Although most of the cases are mild, approximately 10–20% of patients develop a severe course of disease with higher mortality rate. Scoring systems consider age as a risk factor of mortality and severity (BISAP; >60 years, JPN>70 years, RANSON; >55 years, APACHE II >45 years). If there is a correlation between aging and the clinical features of AP, how does age influence mortality and severity?Aim: This study aimed to systematically review the effects of aging on AP.Methods: A comprehensive systematic literature search was conducted in the Embase, Cochrane, and Pubmed databases. A meta-analysis was performed using the preferred reporting items for systematic review and meta-analysis statement (PRISMA). A total of 1,100 articles were found. After removing duplicates and articles containing insufficient or irrelevant data, 33 publications involving 194,702 AP patients were analyzed. Seven age categories were determined and several mathematical models, including conventional mathematical methods (linear regression), meta-analyses (random effect model and heterogeneity tests), meta-regression, funnel plot and Egger's test for publication bias were performed. Quality assessment was conducted using the modified Newcastle–Ottawa scale. The meta-analysis was registered in the PROSPERO database (CRD42017079253).Results: Aging greatly influences the outcome of AP. There was a low severe AP incidence in patients under 30 (1.6%); however, the incidence of severe AP showed a continuous, linear increase between 20 and 70 (0.193%/year) of up to 9.6%. The mortality rate was 0.9% in patients under 20 and demonstrated a continuous linear elevation until 59, however from this age the mortality rate started elevating with 9 times higher rate until the age of 70. The mortality rate between 20 and 59 grew 0.086%/year and 0.765%/year between 59 and 70. Overall, patients above 70 had a 19 times higher mortality rate than patients under 20. The mortality rate rising with age was confirmed by meta-regression (coefficient: 0.037 CI: 0.006–0.068, p = 0.022; adjusted r2: 13.8%), and severity also (coefficient: 0.035 CI: 0.019–0.052, p < 0.001; adjusted r2: 31.6%).Conclusion: Our analysis shows a likelihood of severe pancreatitis, as well as, pancreatitis-associated mortality is more common with advanced age. Importantly, the rapid elevation of mortality above the age of 59 suggests the involvement of additional deteriorating factors such as co-morbidity in elderly.