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During the first year of the COVID-19 pandemic, healthcare facilities worldwide struggled to adequately care for the increasing number of COVID-19 patients while maintaining quality of care for all other patients. The aim of this study was to investigate the displacement and underuse of non-COVID-19 patient care in a medical department of a tertiary hospital in Switzerland. In this retrospective cross-sectional study, internal medicine admissions from 2017 to 2020, emergency outpatient visits from 2019 to 2020 and COVID-19 admissions in 2020 were analyzed and compared using a regression model. Internal medicine admissions were also stratified by diagnosis. A questionnaire was used to assess the pandemic experience of local general practitioners, referring hospitals, and nursing homes. The total number of admissions decreased during the 1st and 2nd waves of the pandemic but increased between the two waves. Elective admissions decreased in 2020 compared to pre-pandemic years: they represented 25% of total admissions in 2020 versus 30% of the total admissions during 2017-2019, p

During the first year of the COVID-19 pandemic, healthcare facilities worldwide struggled to adequately care for the increasing number of COVID-19 patients while maintaining quality of care for all other patients. The aim of this study was to investigate the displacement and underuse of non-COVID-19 patient care in a medical department of a tertiary hospital in Switzerland. In this retrospective cross-sectional study, internal medicine admissions from 2017 to 2020, emergency outpatient visits from 2019 to 2020 and COVID-19 admissions in 2020 were analyzed and compared using a regression model. Internal medicine admissions were also stratified by diagnosis. A questionnaire was used to assess the pandemic experience of local general practitioners, referring hospitals, and nursing homes. The total number of admissions decreased during the 1st and 2nd waves of the pandemic but increased between the two waves. Elective admissions decreased in 2020 compared to pre-pandemic years: they represented 25% of total admissions in 2020 versus 30% of the total admissions during 2017–2019, p

IntroductionIn Switzerland, a nationwide Swiss Diagnosis related Groups (Swiss DRG) system for hospital reimbursement was introduced in 2012. However, the impact of DRG systems on primary care is still unclear with respect to number of consultations and costs. The aim of this study was to investigate the effect of the implementation of DRG on costs and volumes in the primary care sector, on a nationwide basis in Switzerland.MethodsThe study retrospectively analysed yearly data, from 2008 to 2014, of almost 60 Swiss health insurers that covered almost all Swiss general practitioners, with a total number of patients which represented approximately 76% of the Swiss population. GP consultations, total numbers and rates, and the relative costs reimbursed (TARMED tariff values) in the Swiss federal states, cantons, which already introduced a DRG-like system before 2012 (AP-DRG), were compared to the GP consultations and costs reimbursed in the other cantons (DRG-naive). Regression discontinuity design analysis and mixed regression models, at cantonal level, were performed to evaluate the effect of the nationwide implementation of the Swiss DRG on health care demand and costs in the primary care setting. Change in outcome level and yearly trend pattern difference between groups (AP-DRG vs. DRG-naive) were examined.ResultsOverall, the total number of GP consultations and the relative TARMED values increased from 2008 to 2014. In the DRG naive, 15 cantons: in 2008, the number of GP consultations were 13,114,126, with a TARMED value of 1,194,957,157 CHF, and in 2014, the GP consultation were 13,752,511, with a TARMED value of 1,513,861,260 CHF. In the AP-DRG group, 11 cantons, the total number of GP consultations increased from 8,787,646, in 2008, to 9,347,168 in 2014 and the TARMED value increased from 896,673,657 CHF in 2008, to 1,100,203,508 CHF in 2014. The yearly trend pattern of GP consultations and TARMED values, in the AP-DRG group, were not significantly different from the respective trends in the DRG- naive and, overall, no significant change was detected in consultations and costs trends before and after 2012.Discussion/conclusionThis study found no evidence of any effect of the introduction of the SwissDRG on the yearly trend of primary care consultations and costs. Nevertheless, potential negative impacts on vulnerable patients, as chronically ill patients, could not be excluded and further investigation is required.

This study examined the relationship of weather conditions, together with sex and country of origin, with running performance in the Boston Marathon from 1972 to 2018. A total of 580,990 observations from 382,209 different finishers were analyzed using Generalized Additive Mixed Models. Different groups and subgroups were considered such as all runners, near elite 101:200 finishers, near elite 21:100, annual top ten finishers and annual winners. Weather conditions, over the hours of the event, were average air temperature (°C), total precipitations (mm), wet-bulb globe temperature (WBGT) (°C), wind speed (km/h), wind direction (head wind, side wind, tail wind) and barometric pressure (hPa). These effects were examined in a multi-variable model, together with: sex, country of origin, calendar year, an interaction term country:sex and a spline smooth term in function of calendar year and sex. The average temperature, when increasing by 1°C, was related to worsened performance (by 00:01:47 h:min:sec for all finishers and by 00:00:20 h:min:sec for annual winners). Also, the pressure and wet-bulb globe temperature, when increasing, were related to worsened performances. Tail wind improved performances of all groups. Increasing precipitation was significantly (p

IntroductionFollowing years of controversy regarding screening for prostate cancer using prostate-specific antigen, evidence evolves towards a more restrained and preference-based use. This study reports the impact of landmark trials and updated recommendations on the incidence rate of prostate cancer screening by Swiss general practitioners.MethodsWe performed a retrospective analysis of primary care data, separated in 3 time periods based on dates of publications of important prostate-specific antigen screening recommendations. 1: 2010-mid 2012 including 2 updates; 2: mid 2012-mid 2014 including a Smarter Medicine recommendation; 3: mid-2014-mid-2017 maintenance period. Period 2 including the Smarter Medicine recommendation was defined as reference period. We further assessed the influence of patient's age and the number of prostate-specific-antigen (PSA) tests, by the patient and within each time period, on the mean PSA concentration. Uni- and multivariable analyses were used as needed.Results36,800 men aged 55 to 75 years were included. 14.6% had ≥ 2 chronic conditions, 11.7% had ≥ 1 prostate-specific antigen test, (mean 2.60 ng/ml [SD 12.3]). 113,921 patient-years were covered. Data derived from 221 general practitioners, 33.5% of GP were women, mean age was 49.4 years (SD 10.0), 67.9% used prostate-specific antigen testing. Adjusted incidence rate-ratio (95%-CI) dropped significantly over time periods: Reference Period 2: incidence rate-ratio 1.00; Period 1: incidence rate-ratio 1.74 (1.59-1.90); Period 3: incidence rate-ratio 0.61 (0.56-0.67). A higher number of chronic conditions and a patient age between 60-69 years were significantly associated with higher screening rate. Increasing numbers of PSA testing per patient, as well as increasing age, were independently and significantly associated with an increase in the PSA value.ConclusionSwiss general practitioners adapted screening behavior as early as evidence of a limited health benefit evolved, while using a risk-adapted approach whenever performing multiple testing. Updated recommendations might have helped to maintain this decrease. Further recommendations and campaigns should aimed at older patients with multimorbidity, to sustain a further decline in prostate-specific antigen screening practices.

The aim of the present study was to compare swimming performances of successful finishers of the 'Triple Crown of Open Water Swimming' from 1875 to 2017, assessing the effects of sex, the place of event and the nationality of swimmers. Data from 535 finishers in 'Catalina Channel Swim', 1,606 finishers in 'English Channel Swim' and 774 finishers in 'Manhattan Island Marathon Swim' were analysed. We performed different analyses and regression model fittings for all swimmers and annual top-5 finishers. Effects (sex, event, time, nationality) and interaction terms (event-time) were examined through a multi-variable spline mixed regression model. Considering all swimmers, we found that (i) women were approximately 0.06 km/h faster than men (p = 0.011) and (ii) Australians were 0.13 km/h faster than Americans (p = 0.004) and Americans were 0.19 km/h faster than British (p

[This corrects the article DOI: 10.1371/journal.pone.0164745.].

T cell maturation takes place within the thymus, a primary lymphoid organ that is commonly targeted during infections. Previous studies showed that acute infection with Paracoccidioides brasiliensis (Pb), the causative agent of paracoccidioidomycosis (PCM), promotes thymic atrophy that is associated with the presence of yeast cells in the organ. However, as human PCM is a chronic infection, it is imperative to investigate the consequences of Pb infection over the thymic structure and function in chronic infection. In this sense, we developed a new experimental model where Pb yeast cells are injected through the intraperitoneal route and mice are evaluated over 120 days of infection. Thymuses were analyzed in chronically infected mice and we found that the thymus underwent extensive morphological alterations and severe infiltration of P. brasiliensis yeast cells. Further analyses showed an altered phenotype and function of thymocytes that are commonly found in peripheral mature T lymphocytes. We also observed activation of the NLRP3 inflammasome in the thymus. Our data provide new information on the severe changes observed in the thymic microenvironment in a model of PCM that more closely mimics the human infection.

This study aimed to evaluate the diagnostic accuracy of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), midregional proatrial natriuretic peptide (MR-proANP) and midregional proadrenomedullin (MR-proADM) to distinguish bacterial from viral community-acquired pneumonia (CAP) and to identify severe cases in children hospitalized for radiologically confirmed CAP. Index test results were compared with those derived from routine diagnostic tests, i.e., white blood cell (WBC) counts, neutrophil percentages, and serum C-reactive protein (CRP) and procalcitonin (PCT) levels.This prospective, multicenter study was carried out in the most important children's hospitals (n = 11) in Italy and 433 otherwise healthy children hospitalized for radiologically confirmed CAP were enrolled. Among cases for whom etiology could be determined, CAP was ascribed to bacteria in 235 (54.3%) children and to one or more viruses in 111 (25.6%) children. A total of 312 (72.2%) children had severe disease.CRP and PCT had the best performances for both bacterial and viral CAP identification. The cut-off values with the highest combined sensitivity and specificity for the identification of bacterial and viral infections using CRP were ≥7.98 mg/L and ≤7.5 mg/L, respectively. When PCT was considered, the cut-off values with the highest combined sensitivity and specificity were ≥0.188 ng/mL for bacterial CAP and ≤0.07 ng/mL for viral CAP. For the identification of severe cases, the best results were obtained with evaluations of PCT and MR-proANP. However, in both cases, the biomarker cut-off with the highest combined sensitivity and specificity (≥0.093 ng/mL for PCT and ≥33.8 pmol/L for proANP) had a relatively good sensitivity (higher than 70%) but a limited specificity (of approximately 55%).This study indicates that in children with CAP, sTREM-1, MR-proANP, and MR-proADM blood levels have poor abilities to differentiate bacterial from viral diseases or to identify severe cases, highlighting that PCT maintains the main role at this regard.

The choice of the type of abdominal incision performed in caesarean delivery is made chiefly on the basis of the individual surgeon's experience and preference. A general consensus on the most appropriate surgical technique has not yet been reached. The aim of this systematic review of the literature is to compare the two most commonly used transverse abdominal incisions for caesarean delivery, the Pfannenstiel incision and the modified Joel-Cohen incision, in terms of acute and chronic post-surgical pain and their subsequent influence in terms of quality of life. Electronic database searches formed the basis of the literature search and the following databases were searched in the time frame between January 1997 and December 2013: MEDLINE, EMBASE Sciencedirect and the Cochrane Library. Key search terms included: "acute pain", "chronic pain", "Pfannenstiel incision", "Misgav-Ladach", "Joel Cohen incision", in combination with "Caesarean Section", "abdominal incision", "numbness", "neuropathic pain" and "nerve entrapment". Data on 4771 patients who underwent caesarean section (CS) was collected with regards to the relation between surgical techniques and postoperative outcomes defined as acute or chronic pain and future pregnancy desire. The Misgav-Ladach incision was associated with a significant advantage in terms of reduction of post-surgical acute and chronic pain. It was indicated as the optimal technique in view of its characteristic of reducing lower pelvic discomfort and pain, thus improving quality of life and future fertility desire. Further studies which are not subject to important bias like pre-existing chronic pain, non-standardized analgesia administration, variable length of skin incision and previous abdominal surgery are required.

Inflammation is a necessary process to control infection. However, exacerbated inflammation, acute or chronic, promotes deleterious effects in the organism. Violacein (viola), a quorum sensing metabolite from the Gram-negative bacterium Chromobacterium violaceum, has been shown to protect mice from malaria and to have beneficial effects on tumors. However, it is not known whether this drug possesses anti-inflammatory activity. In this study, we investigated whether viola administration is able to reduce acute and chronic autoimmune inflammation. For that purpose, C57BL/6 mice were intraperitoneally injected with 1 μg of LPS and were treated with viola (3.5mg/kg) via i.p. at the same time-point. Three hours later, the levels of inflammatory cytokines in the sera and phenotypical characterization of leukocytes were determined. Mice treated with viola presented a significant reduction in the production of inflammatory cytokines compared with untreated mice. Interestingly, although viola is a compound derived from bacteria, it did not induce inflammation upon administration to naïve mice. To test whether viola would protect mice from an autoimmune inflammation, Experimental Autoimmune Encephalomyelitis (EAE)-inflicted mice were given viola i.p. at disease onset, at the 10th day from immunization. Viola-treated mice developed mild EAE disease in contrast with placebo-treated mice. The frequencies of dendritic cells and macrophages were unaltered in EAE mice treated with viola. However, the sole administration of viola augmented the levels of splenic regulatory T cells (CD4+Foxp3+). We also found that adoptive transfer of viola-elicited regulatory T cells significantly reduced EAE. Our study shows, for the first time, that violacein is able to modulate acute and chronic inflammation. Amelioration relied in suppression of cytokine production (in acute inflammation) and stimulation of regulatory T cells (in chronic inflammation). New studies must be conducted in order to assess the possible use of viola in therapeutic approaches in human autoimmune diseases.

The thymus plays an important role shaping the T cell repertoire in the periphery, partly, through the elimination of inflammatory auto-reactive cells. It has been shown that, during Plasmodium berghei infection, the thymus is rendered atrophic by the premature egress of CD4+CD8+ double-positive (DP) T cells to the periphery. To investigate whether autoimmune diseases are affected after Plasmodium berghei NK65 infection, we immunized C57BL/6 mice, which was previously infected with P. berghei NK65 and treated with chloroquine (CQ), with MOG35-55 peptide and the clinical course of Experimental Autoimmune Encephalomyelitis (EAE) was evaluated. Our results showed that NK65+CQ+EAE mice developed a more severe disease than control EAE mice. The same pattern of disease severity was observed in MOG35-55-immunized mice after adoptive transfer of P. berghei-elicited splenic DP-T cells. The higher frequency of IL-17+- and IFN-γ+-producing DP lymphocytes in the Central Nervous System of these mice suggests that immature lymphocytes contribute to disease worsening. To our knowledge, this is the first study to integrate the possible relationship between malaria and multiple sclerosis through the contribution of the thymus. Notwithstanding, further studies must be conducted to assert the relevance of malaria-induced thymic atrophy in the susceptibility and clinical course of other inflammatory autoimmune diseases.

BACKGROUND: The modulation of inflammatory processes is a necessary step, mostly orchestrated by regulatory T (Treg) cells and suppressive Dendritic Cells (DCs), to prevent the development of deleterious responses and autoimmune diseases. Therapies that focused on adoptive transfer of Treg cells or their expansion in vivo achieved great success in controlling inflammation in several experimental models. Chloroquine (CQ), an anti-malarial drug, was shown to reduce inflammation, although the mechanisms are still obscure. In this context, we aimed to access whether chloroquine treatment alters the frequency of Treg cells and DCs in normal mice. In addition, the effects of the prophylactic and therapeutic treatment with CQ on Experimental Autoimmune Encephalomyelitis (EAE), an experimental model for human Multiple Sclerosis, was investigated as well. METHODOLOGY/PRINCIPAL FINDINGS: EAE was induced in C57BL/6 mice by immunization with myelin oligodendrocyte glycoprotein (MOG35-55) peptide. C57BL/6 mice were intraperitoneally treated with chloroquine. Results show that the CQ treatment provoked an increase in Treg cells frequency as well as a decrease in DCs. We next evaluated whether prophylactic CQ administration is capable of reducing the clinical and histopathological signs of EAE. Our results demonstrated that CQ-treated mice developed mild EAE compared to controls that was associated with lower infiltration of inflammatory cells in the central nervous system CNS) and increased frequency of Treg cells. Also, proliferation of MOG35-55-reactive T cells was significantly inhibited by chloroquine treatment. Similar results were observed when chloroquine was administrated after disease onset. CONCLUSION: We show for the first time that CQ treatment promotes the expansion of Treg cells, corroborating previous reports indicating that chloroquine has immunomodulatory properties. Our results also show that CQ treatment suppress the inflammation in the CNS of EAE-inflicted mice, both in prophylactic and therapeutic approaches. We hypothesized that the increased number of regulatory T cells induced by the CQ treatment is involved in the reduction of the clinical signs of EAE.

In recent years, the preservation of biodiversity has become an important issue. Despite much public discussion, however, current practices in the food industry seldom take account of its potential economic importance: on the contrary, the introduction of industrialized agriculture practices over large areas has often resulted in a dramatic reduction in biodiversity.In this paper, we report on the remarkable degree of biodiversity in the wine yeast populations naturally present in a small area of Sicily (Italy) where traditional (non-industrial) winery practices are still in place. Out of more than 900 Saccharomyces yeast isolates recovered from late spontaneous fermentations, we detected at least 209 strains. Most interestingly, when evaluated at the fermentation and technological level, a number of isolates were found to be superior to industrial yeast strains. Out of a selected group, isolates from two strains were used for experimental fermentations in a winery environment and the quality of the wines produced was assessed at the technological, quality and sensory levels. Given that the characteristics of the wines produced were found to be industrially appealing, the study demonstrated the economic potential of preserving the patrimony of Sicilian yeast biodiversity and highlighted the importance of maintaining traditional wine making practices.

Herpesvirus infection of placenta may be harmful in pregnancy leading to disorders in fetal growth, premature delivery, miscarriage, or major congenital abnormalities. Although a correlation between human herpesvirus 8 (HHV-8) infection and abortion or low birth weight in children has been suggested, and rare cases of in utero or perinatal HHV-8 transmission have been documented, no direct evidence of HHV-8 infection of placenta has yet been reported. The aim of this study was to evaluate the in vitro and in vivo susceptibility of placental cells to HHV-8 infection. Short-term infection assays were performed on placental chorionic villi isolated from term placentae. Qualitative and quantitative HHV-8 detection were performed by PCR and real-time PCR, and HHV-8 proteins were analyzed by immunohistochemistry. Term placenta samples from HHV-8-seropositive women were analyzed for the presence of HHV-8 DNA and antigens. In vitro infected histocultures showed increasing amounts of HHV-8 DNA in tissues and supernatants; cyto- and syncitiotrophoblasts, as well as endothelial cells, expressed latent and lytic viral antigens. Increased apoptotic phenomena were visualized by the terminal deoxynucleotidyl transferase-mediated deoxyuridine nick end-labeling method in infected histocultures. Ex vivo, HHV-8 DNA and a latent viral antigen were detected in placenta samples from HHV-8-seropositive women. These findings demonstrate that HHV-8, like other human herpesviruses, may infect placental cells in vitro and in vivo, thus providing evidence that this phenomenon might influence vertical transmission and pregnancy outcome in HHV-8-infected women.