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Neoadjuvant systemic therapy has now become the the standard in early breast cancer management. Chemotherapy in combination with trastuzumab +/- pertuzumab targeted therapy can improve rates of pathologic complete response (pCR) in patients with HER2-positive breast cancer. Achieving a pCR is considered a good prognostic factor, in particular in patients with more aggressive breast cancer subtypes such as TNBC or HER2 positive cancers. Furthermore, most studies demonstrate that chemotherapy in combination with trastuzumab and pertuzumab is well tolerated. The retrospective analysis presented here concentrates on neoadjuvant therapy with the TCbH-P regimen, with a particular emphasis on patients over 60 years of age. We analysed the factors affecting the achievement of pCR and presented adverse effects of the applied therapies, which opened a discussion about optimizing the therapy of older patients with HER-2 positive breast cancer.

Neoadjuvant systemic therapy has now become the standard in early breast cancer management. Chemotherapy in combination with trastuzumab +/− pertuzumab targeted therapy can improve the rates of pathologic complete response (pCR) in patients with HER2-positive breast cancer. Achieving a pCR is considered a good prognostic factor, in particular, in patients with more aggressive breast cancer subtypes such as TNBC or HER2-positive cancers. Furthermore, most studies demonstrate that chemotherapy in combination with trastuzumab and pertuzumab is well tolerated. The retrospective analysis presented here concentrates on neoadjuvant therapy with the TCbH-P regimen, with a particular emphasis on patients over 60 years of age. We analysed the factors affecting the achievement of pCR and present the adverse effects of the applied therapies, opening discussion about optimizing the therapy of older patients with HER-2 positive breast cancer.

Stage IV melanoma patients develop melanoma brain metastases (MBM) in 50% of cases. Their prognosis is improving, and its understanding outside the context of clinical trials is relevant. We have retrospectively analyzed the clinical data, course of treatment, and outcomes of 531 subsequent stage IV melanoma patients with BM treated in five reference Italian and Polish melanoma centers between 2014 and 2021. Patients with MBM after 2017 had a better prognosis, with a significantly improved median of overall survival (OS) after 2017 in the worst mol-GPA prognostic groups (mol-GPA ≤ 2): a median OS >6 months and HR 0.76 vs. those treated before 2017 (CI: 0.60–0.97, p = 0.027). In our prognostic model, mol-GPA was highly predictive for survival, and symptoms without steroid use did not have prognostic significance. Local therapy significantly improved survival regardless of the year of diagnosis (treated before or after 2017), with median survival >12 months. Systemic therapy improved outcomes when it was combined with local therapy. Local surgery was associated with improved OS regardless of the timing related to treatment start (i.e., before or after 30 days from MBM diagnosis). Local and systemic treatment significantly prolong survival for the poorest mol-GPA prognosis. Use of modern treatment modalities is justified in all mol-GPA prognostic groups.

This paper presents data on selected indicators to show progress towards elimination goals and targets for hepatitis B and hepatitis C in the 31 countries of the European Union (EU) and European Economic Area (EEA). A monitoring system was developed by the European Centre for Disease Prevention and Control, which combined newly collected data from EU/EEA countries along with relevant data from existing sources. Data for 2017 were collected from the EU/EEA countries via an online survey. All countries provided responses. In 2017, most countries reporting data had not reached prevention targets for childhood hepatitis B vaccination and for harm reduction services targeting people who inject drugs (PWID). Four of 12 countries had met the target for proportion of people living with chronic HBV diagnosed and seven of 16 met this target for hepatitis C. Data on diagnosed cases treated were lacking for hepatitis B. Of 12 countries reporting treatment data for hepatitis B, only Iceland met the target. This first collection of data across the EU/EEA highlighted major issues with data completeness and quality and in the indicators that were used, which impairs a clear overview of progress towards the elimination of hepatitis. The available data, whilst incomplete, suggest that as of 2017, the majority of the EU/EEA countries were far from meeting most of the 2020 targets, in particular those relating to harm reduction and diagnosis. It is critical to improve the data collected in order to develop more effective services for hepatitis prevention, diagnosis, and treatment that are needed in order to meet the 2030 elimination targets.

BackgroundThe introduction of COVID-19 vaccination passes (VPs) by many countries coincided with the Delta variant fast becoming dominant across Europe. A thorough assessment of their impact on epidemic dynamics is still lacking.MethodsHere, we propose the VAP-SIRS model that considers possibly lower restrictions for the VP holders than for the rest of the population, imperfect vaccination effectiveness against infection, rates of (re-)vaccination and waning immunity, fraction of never-vaccinated, and the increased transmissibility of the Delta variant.ResultsSome predicted epidemic scenarios for realistic parameter values yield new COVID-19 infection waves within two years, and high daily case numbers in the endemic state, even without introducing VPs and granting more freedom to their holders. Still, suitable adaptive policies can avoid unfavorable outcomes.ConclusionsWhile VP holders could initially be allowed more freedom, the lack of full vaccine effectiveness and increased transmissibility will require accelerated (re-)vaccination, wide-spread immunity surveillance, and/or minimal long-term common restrictions.Plain language summaryAssessing the impact of vaccines, other public health measures, and declining immunity on SARS-CoV-2 control is challenging. This is particularly true in the context of vaccination passes, whereby vaccinated individuals have more freedom of making contacts than unvaccinated ones. Here, we use a mathematical model to simulate various scenarios and investigate the likelihood of containing COVID-19 outbreaks in example European countries. We demonstrate that both Alpha and Delta SARS-CoV-2 variants inevitably lead to recurring outbreaks when measures are lifted for vaccination pass holders. High revaccination rates and a lowered fraction of the unvaccinated population increase the benefit of vaccination passes. These observations are important for policy making, highlighting the need for continued vigilance, even where the epidemic is under control, especially when new variants of concern emerge.

BackgroundEstimating the actual number of COVID-19 infections is crucial for steering through the COVID-19 pandemic crisis. It is, however, notoriously difficult, as many cases have no or only mild symptoms. Surveillance data for in-household secondary infections offers unbiased samples for COVID-19 prevalence estimation.MethodsWe analyse 16 115 Polish surveillance records to obtain key figures of the COVID-19 pandemic. We propose conservative upper and lower bound estimators for the number of SARS-CoV-2 infections. Further, we estimate age-dependent bounds on the severe case rate, death rate, and the in-household attack rate.ResultsBy maximum likelihood estimates, the total number of COVID-19 cases in Poland as of July 22nd, 2020, is at most around 13 times larger and at least 1.6 times larger than the recorded number. The lower bound on the severeness rate ranges between 0.2% for the 0–39 year-old to 5.7% for older than 80, while the upper bound is between 2.6% and 34.1%. The lower bound on the death rate is between 0.04% for the age group 40–59 to 1.34% for the oldest. Overall, the severeness and death rates grow exponentially with age. The in-household attack ratio is 8.18% for the youngest group and 16.88% for the oldest.ConclusionsThe proposed approach derives highly relevant figures on the COVID-19 pandemic from routine surveillance data, under assumption that household members of detected infected are tested and all severe cases are diagnosed.MOCOSThe MOCOS (MOdellingCOronaSpread) international research group is an interdisciplinary scientific consortium. The following authors are MOCOS members: Barbara Adamik, Marek Bawiec, Viktor Bezborodov, Przemyslaw Biecek, Wolfgang Bock, Marcin Bodych, Jan Pablo Burgard, Tyll Krueger, Agata Migalska, Tomasz Ożański, Barbara Pabjan, Magdalena Rosińska, Piotr Sobczyk and Ewa Szczurek

The purpose of this article is to analyze the changes in the strategies of the internationalization of enterprises as a result of the evolution the global economy. An attempt is made to assess the impact of the progressive stages of the process of globalization on the models of functioning of enterprises, especially the rules of competitiveness building. The article is divided into four parts. The first part is an analysis of the evolution of the globalization processes. The second part refers to the impact of changes in the globalization process for businesses. The third part shows the implications of the current phase of globalization for the competitiveness system. The last part is an attempt to explain the methods of the implementation of these challenges using selected corporations as examples (Volkswagen, Siemens, British Petroleum).

Objectives: The burden of acute gastrointestinal infections (AGIs) on the society has not been well studied in Central European countries, which prevents the implementation of effective, targeted public health interventions. Methods: We investigated patients of 11 randomly selected general practices and 8 hospital units. Each patient meeting the international AGI case definition criteria was interviewed on costs incurred related to the use of health care resources. Follow-up interview with consenting patients was conducted 2 to 4 weeks after the general practitioner (GP) visit or discharge from hospital, collecting information on self-medication costs and indirect costs. Costs were recalculated to US dollars by using the purchasing power parity exchange rate for Poland. Results: Weighting the inpatient costs by age-specific probability of hospital referral by GPs, the societal cost of a medically attended AGI case was estimated to be US $168. The main cost drivers of direct medical costs were cost of hospital bed days (US $28), cost of outpatient pharmacotherapy (US $20), and cost of GP consultation (US $10). Patients covered only the cost of outpatient pharmacotherapy. Considering the AGI population GP consultation rate, the age-adjusted societal cost of medically attended AGI episodes was estimated at US $2222 million, of which 53% was attributable to indirect costs. Conclusions: Even though AGIs generate a low cost for individuals, they place a high burden on the society, attributed mostly to indirect costs. Higher resources could be allocated to the prevention and control of AGIs.

SUMMARYA prospective survey was conducted in patients admitted to 11 randomly selected general practices and eight hospitals located in six provinces of Poland. For each patient meeting the international acute gastrointestinal infection (AGI) case definition criteria, information was collected on healthcare resources used. Antibacterial drug consumption was assessed using defined daily doses (DDD) and extrapolated to the national level using results from a parallel study of AGI incidence in the community. Additionally, a logistic multivariable model was fitted assessing determinants of antibacterial drug administration. Valid questionnaires were collected from 385 general practitioner (GP) consultations and 504 hospital admissions. Antibacterials for systemic use were prescribed during 60 (16%) GP consultations and 179 (36%) hospital admissions. The estimated societal AGI-related consumption of antibacterials amounted to 5·48 million DDD (95% uncertainty interval 1·56–14·12 million DDD). Antibacterial prescription was associated with work in large practices [adjusted odds ratio (aOR) 3·16] and hospital wards (aOR 2·87), compared to small general practices, referral for microbiological testing (aOR 2·88), presence of fever (aOR 2·50), presence of mucus or blood in stool (aOR 1·94), age >65 yearsvs. vs. urban residence (aOR 1·53). Despite the fact that antibacterials were prescribed to a minority of consulted AGI patients, their consumption in society was not negligible due to the high prevalence of AGI symptoms. Prescription of antibacterial drugs should be restricted to cases with specific indications, preferably following microbiological investigation of AGI aetiology. To achieve this, clear national recommendations should be widely disseminated to physicians, and included in medical training curricula.

Background The impact of age on melanoma patient outcomes is uncertain. Objective The aim of the study was to analyze the characteristics and treatment outcomes in cutaneous melanoma patients ≥ 65 years of age with lymph node metastases. Methods We analyzed data from 849 consecutive patients with stage III cutaneous melanoma who were treated between 1994 and 2007 at one institution. Of these, 225 (26.5%) were ≥ 65 years of age. The characteristics and disease-specific survival (DSS) from lymph node dissection (LND) date of patients ≥ 65 years of age were compared with those of younger patients. Median follow-up time was 49 months (range: 6–140 months). Results In the ≥ 65 years group (51.6% men), the median Breslow thickness was 5.0 mm and 70% was ulcerated. The 5-year DSS rate was significantly lower in older patients (34%). Multivariate analysis identified older age as an independent prognostic factor for DSS in the overall group. Independent negative prognostic factors of DSS in the group of older stage III patients were identified as features of nodal metastases (extracapsular invasion, HR = 1.74, P = 0.009; and ≥ 4 involved lymph nodes, HR = 1.5; P = 0.008) and male sex (HR = 1.5; P = 0.039). Conclusions This analysis showed that melanoma patients ≥ 65 years of age are characterized by a higher primary tumor stage and worse prognosis in the presence of regional node metastases than younger patients. Additionally, the results indicate that the same radical surgical therapy is necessary for patients ≥ 65 years old as in younger patients.

The main thesis of the following article states that, due to the fact that competitive strategy is the determinant of the organizational structure changes, global business networks (GBN) are created in the course of adjustments to the requirements of multinational corporations to compete in the rapidly changing economy. GBN is a model created in the course of search for corporate organizational structure adequate to the challenges of globalization. The purpose of this article is to identify theoretical concepts at the source of creative compilation of a new model. The author analyzed the characteristics of processual, virtual, learning, intelligent, fractal, and modular organization as trends in which transnational corporations saw a number of valuable elements and through their flexible merging received “a new quality”. The developmental strategy of openness, convergence within organization based on knowledge transfer, cooperation based on partnership and trust, and strategic synergy are the pillars of global network Tezą niniejszego artykułu jest, że z uwagi na fakt, iż strategia konkurencyjna jest determinantą zmian struktur organizacyjnych to w toku dostosowań korporacji transnarodowych do wymogów konkurowania w dynamicznie zmieniającej się gospodarce jest kreowanie globalnych sieci biznesowych (GSB). GSB jest modelem powstałym w toku poszukiwań przez korporacje konstrukcji organizacyjnej adekwatnej do wyzwań globalizacji. Celem artykułu jest wskazanie koncepcji teoretycznych stanowiących źródła kreatywnej kompilacji nowego modelu. Dokonano zatem analizy cech organizacji procesowej, wirtualnej, uczącej się, inteligentnej, fraktalnej, modularnej jako nurtów, w których korporacje transnarodowe dostrzegły wiele cennych elementów a poprzez ich elastyczne scalenie uzyskały „nową jakość”. Filary globalnej sieci stanowią: strategia otwartości prorozwojowej, konwergencja oparta na wewnątrzorganizacyjnym dzieleniu się wiedzą, współpraca opartą na partnerstwie i zaufaniu oraz synergia strategiczna. Uniwersytet Łódzki, Wydział Ekonomiczno-Socjologiczny, Katedra MSG

Background Estimates of treatment failure, change and interruption are lacking for individuals treated in early HIV infection. Methods Using CASCADE data, we compared the effect of treatment in early infection (within 12 months of seroconversion) with that seen in chronic infection on risk of virological failure, change and interruption. Failure was defined as two subsequent measures of HIV RNA>1,000 copies/ml following suppression (500 copies/ml 6 months following initiation. Treatment change and interruption were defined as modification or interruption lasting >1 week. In multivariable competing risks proportional subdistribution hazards models, we adjusted for combination antiretroviral therapy (cART) class, sex, risk group, age, CD4+ T-cell count, HIV RNA and calendar period at treatment initiation. Results Of 1,627 individuals initiating cART early (median 1.8 months from seroconversion), 159, 395 and 692 failed, changed and interrupted therapy, respectively. For 2,710 individuals initiating cART in chronic infection (median 35.9 months from seroconversion), the corresponding values were 266, 569 and 597. Adjusted hazard ratios (HRs; 95% CIs) for treatment failure and change were similar between the two treatment groups (0.93 [0.72, 1.20] and 1.06 [0.91, 1.24], respectively). There was an increasing trend in rates of interruption over calendar time for those treated early, and a decreasing trend for those starting treatment in chronic infection. Consequently, compared with chronic infection, treatment interruption was similar for early starters in the early cART period, but the relative hazard increased over calendar time (1.54 [1.33, 1.79] in 2000). Conclusions Individuals initiating treatment in early HIV infection are more likely to interrupt treatment than those initiating later. However, rates of failure and treatment change were similar between the two groups.

BackgroundTick-borne encephalitis (TBE) is endemic to Europe and medically highly significant. This study, focused on Poland, investigated individual risk factors for TBE symptomatic infection.Methods and findingsIn a nation-wide population-based case-control study, of the 351 TBE cases reported to local health departments in Poland in 2009, 178 were included in the analysis. For controls, of 2704 subjects (matched to cases by age, sex, district of residence) selected at random from the national population register, two were interviewed for each case and a total of 327 were suitable for the analysis. Questionnaires yielded information on potential exposure to ticks during the six weeks (maximum incubation period) preceding disease onset in each case. Independent associations between disease and socio-economic factors and occupational or recreational exposure were assessed by conditional logistic regression, stratified according to residence in known endemic and non-endemic areas. Adjusted population attributable fractions (PAF) were computed for significant variables. In endemic areas, highest TBE risk was associated with spending ≥10 hours/week in mixed forests and harvesting forest foods (adjusted odds ratio 19.19 [95% CI: 1.72-214.32]; PAF 0.127 [0.064-0.193]), being unemployed (11.51 [2.84-46.59]; 0.109 [0.046-0.174]), or employed as a forester (8.96 [1.58-50.77]; 0.053 [0.011-0.100]) or non-specialized worker (5.39 [2.21-13.16]; 0.202 [0.090-0.282]). Other activities (swimming, camping and travel to non-endemic regions) reduced risk. Outside TBE endemic areas, risk was greater for those who spent ≥10 hours/week on recreation in mixed forests (7.18 [1.90-27.08]; 0.191 [0.065-0.304]) and visited known TBE endemic areas (4.65 [0.59-36.50]; 0.058 [-0.007-0.144]), while travel to other non-endemic areas reduced risk.ConclusionsThese socio-economic factors and associated human activities identified as risk factors for symptomatic TBE in Poland are consistent with results from previous correlational studies across eastern Europe, and allow public health interventions to be targeted at particularly vulnerable sections of the population.

The impact of age on melanoma patient outcomes is uncertain.The aim of the study was to analyze the characteristics and treatment outcomes in cutaneous melanoma patients ≥ 65 years of age with lymph node metastases.We analyzed data from 849 consecutive patients with stage III cutaneous melanoma who were treated between 1994 and 2007 at one institution. Of these, 225 (26.5%) were ≥ 65 years of age. The characteristics and disease-specific survival (DSS) from lymph node dissection (LND) date of patients ≥ 65 years of age were compared with those of younger patients. Median follow-up time was 49 months (range: 6-140 months).In the ≥ 65 years group (51.6% men), the median Breslow thickness was 5.0 mm and 70% was ulcerated. The 5-year DSS rate was significantly lower in older patients (34%). Multivariate analysis identified older age as an independent prognostic factor for DSS in the overall group. Independent negative prognostic factors of DSS in the group of older stage III patients were identified as features of nodal metastases (extracapsular invasion, HR = 1.74, P = 0.009; and ≥ 4 involved lymph nodes, HR = 1.5; P = 0.008) and male sex (HR = 1.5; P = 0.039).This analysis showed that melanoma patients ≥ 65 years of age are characterized by a higher primary tumor stage and worse prognosis in the presence of regional node metastases than younger patients. Additionally, the results indicate that the same radical surgical therapy is necessary for patients ≥ 65 years old as in younger patients.

BackgroundMathematical modelling of infectious diseases transmitted by the respiratory or close-contact route (e.g., pandemic influenza) is increasingly being used to determine the impact of possible interventions. Although mixing patterns are known to be crucial determinants for model outcome, researchers often rely on a priori contact assumptions with little or no empirical basis. We conducted a population-based prospective survey of mixing patterns in eight European countries using a common paper-diary methodology.Methods and findings7,290 participants recorded characteristics of 97,904 contacts with different individuals during one day, including age, sex, location, duration, frequency, and occurrence of physical contact. We found that mixing patterns and contact characteristics were remarkably similar across different European countries. Contact patterns were highly assortative with age: schoolchildren and young adults in particular tended to mix with people of the same age. Contacts lasting at least one hour or occurring on a daily basis mostly involved physical contact, while short duration and infrequent contacts tended to be nonphysical. Contacts at home, school, or leisure were more likely to be physical than contacts at the workplace or while travelling. Preliminary modelling indicates that 5- to 19-year-olds are expected to suffer the highest incidence during the initial epidemic phase of an emerging infection transmitted through social contacts measured here when the population is completely susceptible.ConclusionsTo our knowledge, our study provides the first large-scale quantitative approach to contact patterns relevant for infections transmitted by the respiratory or close-contact route, and the results should lead to improved parameterisation of mathematical models used to design control strategies.

maszynopis Celem pracy jest wykazanie, iż rola korporacji transnarodowych w procesach globalizacji polega przede wszystkim na przyspieszeniu tworzenia globalnej przestrzeni biznesowej, w której kształtowane są znormalizowane wzorce oceny globalnej efektywności stanowiące standard minimum konkurowania w otoczeniu międzynarodowym. Korporacje wybierając ścieżkę swojego rozwoju kierują się logiką „weryfikatora efektywności” w długim okresie. Dynamiczny rozwój przedsiębiorstw międzynarodowych jest wynikiem ewolucji systemu gospodarki światowej, która wywołała zmiany w sferze funkcjonowania przedsiębiorstw polegające na nieustannym pogłębianiu stopnia umiędzynarodowienia ich działalności. Fale globalizacji (wskazane przez J. Schumpetera) stanowiące nasilenie zjawiska uaktywniały mechanizmy koncentracji kapitału na rynku przedsiębiorstw, co potwierdza współzależność obu procesów. Silne oddziaływanie korporacji transnarodowych na gospodarkę światową szczególnie widoczne jest jednak dopiero od lat 70. XX w., kiedy to zyskały one rangę podmiotów gospodarki światowej. Zmiana płaszczyzny budowania relacji państwa-korporacje stanowi, bowiem jedno z najistotniejszych przewartościowań we współczesnej gospodarce. Elementy konstytuujące współcześnie strukturę podmiotową gospodarki światowej (państwa jak i przedsiębiorstwa międzynarodowe) rywalizując o strefy wpływów na poziomie gospodarki światowej konsolidują się. Angażują się we wszelkiego typu formy integracji tworząc „układy korporacyjne”. Wydaje się, iż w konsekwencji zachodzących zmian to jednak korporacje transnarodowe skuteczniej umacniają swoje pozycje. Potwierdzają one swój status pełnoprawnych podmiotów poziomu makroekonomicznego poprzez oddziaływania na kierunki rozwoju gospodarki światowej. Opracowanie składa się z pięciu rozdziałów, które mają za zadanie wykazanie, że to postępujące procesy globalizacji są czynnikiem o kapitalnym znaczeniu w wytyczaniu ścieżek rozwojowych wszystkich typów podmiotów. Istotą obecnie zachodzących zmian jest kreowanie sprzyjających warunków rozwoju organizacjom otwartym na systematyczne zacieśnianie współpracy. Budowanie wzajemnych powiązań stanowi w dobie globalizacji fundament przewagi konkurencyjnej zwłaszcza na arenie międzynarodowej. W konsekwencji należy zwrócić uwagę na konieczność kooperencji, czyli współpracy rywalizujących ze sobą podmiotów. Zdolność do konkurencji i równoczesnego kreowania systemu wzajemnych powiązań kooperacyjnych jest wyznacznikiem nowego spojrzenia na budowanie pozycji konkurencyjnej na forum współczesnej gospodarki światowej.