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Urinary tract infections (UTIs) make up a significant proportion of the global burden of disease in vulnerable groups and tend to substantially impair the quality of life of those affected, making timely detection of UTIs a priority for public health. However, economic and societal barriers drastically reduce accessibility of traditional lab-based testing methods for critical patient groups in low-resource areas, negatively affecting their overall healthcare outcomes. As a result, cellulose-based materials such as paper and thread have garnered significant interest among researchers as substrates for so-called frugal analytical devices which leverage the material’s portability and adaptability for facile and reproducible diagnoses of UTIs. Although the field may be only in its infancy, strategies aimed at commercial penetration can appreciably increase access to more healthcare options for at-risk people. In this review, we catalogue recent advances in devices that use cellulose-based materials as the primary housing or medium for UTI detection and chart out trends in the field. We also explore different modalities employed for detection, with particular emphasis on their ability to be ported onto discreet casings such as sanitary products. Graphical abstract

The acute and long-lasting side effects of modern multimodal tumour therapy significantly impair quality of life and survival of patients afflicted with malignancies. The key components of this therapy include radiotherapy, conventional chemotherapy, immunotherapy and targeted therapies. In addition to established tumour therapy strategies, up to 30 new therapies are approved each year with only incompletely characterised side effects. This consensus paper discusses the risk factors that contribute to the development of a potentially adverse reaction to tumour therapy and, in addition, defines specific side effect profiles for different treatment groups. The focus is on novel therapeutics and recommendations for the surveillance and treatment of specific patient groups.

Introduction In adults with a suspicion of peripheral bone infection, evidence-based guidelines in choosing the most accurate diagnostic strategy are lacking. Aim and methods To provide an evidence-based, multidisciplinary consensus document on the diagnostic management of adult patients with PBIs, we performed a systematic review of relevant infectious, microbiological, orthopedic, radiological, and nuclear medicine literature. Delegates from four European societies (European Bone and Joint Infection Society, European Society of Microbiology and Infectious Diseases, European Society or Radiology, and European Association of Nuclear Medicine) defined clinical questions to be addressed, thoroughly reviewed the literature pertinent to each of the questions, and thereby evaluated the diagnostic accuracy of each diagnostic technique. Inclusion of the papers per statement was based on a PICO (Population/problem – Intervention/indicator – Comparator – Outcome) question following the strategy reported by the Oxford Centre for Evidence-based Medicine. For each statement, the level of evidence was graded according to the 2011 review of the Oxford Centre for Evidence-based Medicine. All approved statements were addressed taking into consideration the available diagnostic procedures, patient acceptance, tolerability, complications, and costs in Europe. Finally, a commonly agreed-upon diagnostic flowchart was developed. Electronic supplementary material The online version of this article (10.1007/s00259-019-4262-x) contains supplementary material, which is available to authorized users.

Lysosomal storage disorders (LSDs) are a very heterogeneous group of hereditary disorders. The diagnostic process usually involves complex sampling, processing, testing, and validation procedures, performed by specialized laboratories only, which causes great limitations in reaching a diagnosis for patients affected by these diseases.There are few studies about LSDs in Colombia. The diagnostic limitations often make medical practitioners disregard the possibility of these disorders while diagnosing their patients. The current study documents the results of a 7-year screening in high-risk patients, aimed to detect LSDs using dried blood spots (DBS) collected on filter paper, with a micromethodology that facilitates diagnosis even with a large number of samples.The activities of α-galactosidase A, α glucosidase, α-L-iduronidase, arylsulfatase B, β-galactosidase, β-glucosidase, total hexosaminidase, iduronate sulfatase, and chitotriosidase were analyzed in high-risk patients for lysosomal disease. The catalytic activity was evaluated with fluorometric micromethods using artificial substrates marked with 4-methylumbelliferone.The reference values for a control population were established for the enzymes listed above, and 242 patients were found to have an enzyme deficiency, guiding to the following diagnoses: Fabry disease (n = 31), Pompe disease (n = 16), Hurler Syndrome (n = 15), Maroteaux-Lamy Syndrome (n = 34), GM1 Gangliosidosis (n = 10), Morquio B (n = 1), Gaucher disease (n = 101), Sandhoff disease (n = 1), Mucolipidosis (n = 2), and Hunter Syndrome (n = 31). In conclusion, this protocol provides a comprehensive diagnostic approach which could be carried out in Colombia and made it available to medical services spread around the country, enabling the identification of a large number of patients affected by LSDs, which could potentially benefit from the therapeutic tools already available for many of these diseases.

Within the elderly population, psychogeriatric patients may be particularly susceptible to negative mental health effects of the coronavirus crisis. Detailed information about the psychosocial well-being of psychogeriatric patients during the pandemic is still sparse. Here we examined which aspects of subjective experience of the COVID-19 pandemic especially affect levels of depression, anxiety and quality of life in psychogeriatric patients with and without cognitive impairment. A cross-sectional paper survey was conducted during the first German lockdown among patients with a diagnosed psychiatric disorder (≥ 60 years) or a diagnosed neurodegenerative disease (regardless of their age) from the department for neurodegenerative diseases and geriatric psychiatry at the University of Bonn. The WHO-5-, GAD-7- and WHOQOL-old score were used to determine levels of depression, anxiety and quality of life. The second part obtained information about the subjective experience of the COVID-19 pandemic. Statistical analysis included among others principal component analysis and multiple linear regression analysis. COVID-19-related, immediate distress was a strong predictor of elevated symptoms of depression, anxiety and a reduced quality of life. COVID-19-related concerns regarding health and financial security, however, were not significantly associated with negative mental health outcomes. The overall prevalence of symptoms of depression (50.8% [95% CI 43.8–57.6%]) and anxiety (32.7% [95% CI 26.4–39.2%]) among psychogeriatric patients was high. Our findings indicate that psychogeriatric patients are not significantly affected by COVID-19-related concerns but are primarily suffering from emotional consequences resulting from changed living conditions due to the pandemic. Supplementary Information The online version contains supplementary material available at 10.1007/s00406-021-01340-1.

In this paper, we examine the variation in the outbreak of COVID-19 across departments in continental France. We use information on the cumulated number of deaths, discharged patients and infections from COVID-19 at the department level, and study how these relate to income inequality, controlling for other factors. We find that unfortunately, inequality kills: departments with higher income inequality face more deaths, more discharged (gravely ill) patients and more infections. While other papers have studied the impact of the level of income on the severity of COVID-19, we find that it is in fact the dispersion across incomes within the same department that drives the results. Our results suggest that individuals in relatively more precarious conditions deserve dedicated policies, to avoid that temporary shocks such as COVID-19 lead to permanent increases in inequality.

The COVID-19 has been a worldwide pandemic and it needs for studies related to effect on people's demand for insurance during the pandemic which is an important way to transfer risk. However, there is a lack of research linking COVID-19 and people's demand for insurance. The objective of this paper is to investigate the impact of COVID-19 pandemic on issuance demand, using data covering 241 cities on confirmed COVID-19 cases and insurance company revenue in China. The empirical results show that more confirmed COVID-19 cases are associated with greater per capita insurance revenue and the results are robust when considering endogeneity concern. Economically, the per capita insurance revenue increases by 0.896 Yuan for each more confirmed case. In terms of insurance type, the greatest increased insurance revenue is for life insurance, followed by health insurance. We further consider the heterogeneity of regions and find that the impact of COVID-19 on insurance revenue only exists in regions with worse medical treatment conditions or higher medical burden.

This paper asks whether marriage decisions of unmarried mature couples are driven by the prospect of financial advantages for the later widowed after one partner has suffered a serious health shock. We hypothesize that, in contrast to traditional marriage models, such health shocks may induce unmarried couples to obtain economic benefits, such as survivors’ pensions in particular, through marriage in advance of one partner’s death. This question has not yet been studied empirically. Hazard models capturing unobserved effects are applied to longitudinal data of the German Socioeconomic Panel. It turns out that the probability of marriage after male partners’ health shocks can increase significantly depending on the amount of expected survivors’ pensions for the (likely) surviving female partners. In contrast, an increased probability of marriage after health shocks to women (depending on the expected financial benefits to men) was not found. These findings are supported by various robustness checks. Economic and political implications are discussed and the results are placed in an international context.

COVID-19 is an acronym for coronavirus disease 2019. Initially, it was called 2019-nCoV, and later International Committee on Taxonomy of Viruses (ICTV) termed it SARS-CoV-2. On 30th January 2020, the World Health Organization (WHO) declared it a pandemic. With an increasing number of COVID-19 cases, the available medical infrastructure is essential to detect the suspected cases. Medical imaging techniques such as Computed Tomography (CT), chest radiography can play an important role in the early screening and detection of COVID-19 cases. It is important to identify and separate the cases to stop the further spread of the virus. Artificial Intelligence can play an important role in COVID-19 detection and decreases the workload on collapsing medical infrastructure. In this paper, a deep convolutional neural network-based architecture is proposed for the COVID-19 detection using chest radiographs. The dataset used to train and test the model is available on different public repositories. Despite having the high accuracy of the model, the decision on COVID-19 should be made in consultation with the trained medical clinician.

This paper analyses how recent trends in heat waves impact heat warning systems. We performed a retrospective analysis of the challenges faced by the French heat prevention plan since 2004. We described trends based on the environmental and health data collected each summer by the French heat warning system and prevention plan. Major evolutions of the system were tracked based on the evaluations organized each autumn with the stakeholders of the prevention plan. Excess deaths numbering 8000 were observed during heat waves between 2004 and 2019, 71% of these between 2015 and 2019. We observed major changes in the characteristics, frequency and the geographical spread of heat waves since 2015. Feedbacks led to several updates of the warning system such as the extension of the surveillance period. They also revealed that risk perception remained limited among the population and the stakeholders. The sharp increase in the number of heat warnings issued per year since 2015 challenges the acceptability of the heat warnings. Recent heat waves without historical equivalent interfere with the development of evidence-based prevention strategies. The growing public health impacts heat waves emphasize the urgent need to act to adapt the population, at different levels of intervention, from individual comportments to structural modifications. A specific attention should be given to increase the resources allocated to the evaluation and the management of heat-related risks, especially considering the needs to catch with the rapid rhythm of the changing climate. Supplementary Information The online version contains supplementary material available at 10.1007/s00484-021-02123-y.

There is currently little systematic knowledge about the contribution of different factors to the increase in health care spending in high-income countries such as Switzerland. The aim of this paper is to decompose inpatient care costs in the Swiss canton of Zurich by 100 diseases and 42 age/sex groups and to assess the contribution of six factors to the change in aggregate costs between 2013 and 2017. These six factors are population size, age and sex structure, inpatient treated prevalence, utilization in terms of stays per patient, length of stay per case, and costs per treatment day. Using detailed inpatient cost data at the case level, we find that the most important contributor to the change in disease-specific costs was a rise in costs per treatment day. For most conditions, this effect was partly offset by a reduction in the average length of stay. Changes in population size accounted for one third of the total increase, but population structure had only a small positive association with costs. The most expensive cases accounted for the largest part of the increase in costs, but the magnitude of this effect differed across diseases. A better understanding of the factors related to cost changes at the disease level over time is essential for the design of targeted health policies aiming at an affordable health care system.

Purpose We aimed to estimate the structure of internalizing and externalizing symptoms and potential time dynamics in their association. This is understudied among adolescents, despite increasing internalizing and decreasing externalizing symptoms in recent years. Methods We analyzed data from US Monitoring the Future cross-sectional surveys (1991–2018) representative of school-attending adolescents (N = 304,542). Exploratory factor analysis using maximum likelihood estimation method and promax rotation resulted in a two-factor solution (factor correlation r = 0.24) that differentiated eight internalizing and seven conduct-related externalizing symptoms. Time-varying effect modification linear regression models estimated the association between standardized internalizing and externalizing symptoms factor scores over time overall and by gender. Results In 2012, trends in average factor scores diverged for internalizing and externalizing factors. The average standardized internalizing factor score increased from − 0.03 in 2012 to 0.06 in 2013 and the average externalizing factor score decreased from − 0.06 in 2011 to − 0.13 in 2012. We found that for every one-unit increase in standardized internalizing factor score, standardized externalizing factor score increased by 0.224 units in 2010 (95% CI: 0.215, 0.233); the magnitude of this increase was 22.3% lower in 2018 (i.e., 0.174 units; 95% CI: 0.160, 0.188). Decoupling of internalizing and externalizing symptoms began earlier among boys (~ 1995) than among girls (~ 2010). Conclusion The decoupling of internalizing and externalizing symptoms among adolescents suggests that changes in the prevalence of shared risk factors for adolescent psychiatric symptoms affect these dimensions in opposing directions, raising the importance of considering symptoms and their risk factors together in prevention and intervention efforts. Supplementary Information The online version contains supplementary material available at 10.1007/s00127-021-02189-4.

Macracanthorhynchus hirudinaceus is a zoonotic parasite affecting suids worldwide which are the definitive hosts for this helminth species. Macracanthorhynchus hirudinaceus is of significant economic and management concern due to its pathogenicity, causing intestinal obstruction and perforation in the definitive hosts. Current study is the preliminary investigation from Sardinia, Italy, reporting the pathomorphological findings and molecular characterization of M. hirudinaceus in the wild boars (Sus scrofa meridionalis). A total of 59 wild boars were examined showing acanthocephalan infection in 8 (13.6%) animals. In total, 49 parasites were collected with a mean intensity of 6.1. Comparatively higher infection levels were observed for males (16.7%) and young boars (14.3%); however, these epidemiological differences were statistically non-significant. Histopathological examination revealed the presence of a variable number of nodules (∼5 mm) in the intestine of M. hirudinaceus infested animals surrounded by a hyperemic-hemorrhagic halo. Several parasites were recovered from the intestinal lumen attached by the means of characteristic hooks showing necrosis in muscle layers. A moderate number of plump reactive fibroblasts and lesser numbers of fibrocytes were embedded with and at the borders of the inflammatory nodules in a moderate amount of homogeneous intensely eosinophilic fibrillary material rupturing the cell membrane. For molecular characterization, six isolated worms were amplified for the partial mitochondrial cox1 gene showing distinct interindividual variations. This first pathological and molecular description from southern Europe provided new knowledge about the diffusion of M. hirudinaceus in wild boars, furthering the research into the origin and transmission status of M. hirudinaceus in endemic localities.

Little is known about the relationship of COVID-19 outcomes with onychomycosis. We investigated the relationship of onychomycosis with COVID-19 outcomes. A retrospective cohort study was performed on SARS-CoV-2 positive adult outpatients or inpatients who had onychomycosis and other skin diseases. Overall, 430 adults were identified with SARS-CoV-2 and a skin disease, including 98 with diagnosed onychomycosis. In bivariable logistic regression models, onychomycosis was associated with increased hospitalization {odds ratio(OR) [95% confidence interval (CI)]: 3.56 [2.18-5.80]}, initial inpatient vs. outpatient visits (OR [95% CI]: 2.24 [1.35-3.74]), use of oxygen therapy (OR [95% CI]: 2.77 [1.60-4.79]), severe-critical vs. asymptomatic-mild severity (OR [95% CI]: 2.28 [1.32-3.94]), and death (OR [95% CI]: 7.48 [1.83-30.47]) from COVID-19, but not prolonged hospitalization (OR [95% CI]: 1.03 [0.47-2.25]). In multivariable models adjusting for socio-demographics, comorbidities, and immunosuppressant medication use, the associations with onychomycosis remained significant for hospitalization, inpatient visits, oxygen therapy, severe-critical COVID-19. Onychomycosis was a significant independent risk factor for COVID-19 severity, hospitalization, and receiving supplemental oxygen therapy.

Purpose Multiple names within the literature refer to a clinical picture affecting infants and consisting of a large or fast growing head circumference with enlarged cortical subarachnoid spaces (CSAS) while cranial sutures are open. This myriad of terms demonstrates the confusion about the entity, that may even group together different etiological processes. In this review, we aim to shed light on this matter in an effort to restate the defining features of the clinical picture and sum the evidence and current understanding of its pathophysiology and related imaging findings. Methods Extensive and updated review of the literature with special focus on defining features, clinical history with long term evaluation and pathophysiological process. Results Functional and molecular CSF studies as well as clinical evidence challenges the common pathophysiological theory based on non-functional arachnoid villi. Conversely, there is increasing evidence supporting cerebro-venous system abnormalities as the main pathophysiological factor. Additionally, long term cohorts studies show that it may have subtle but irreversible neurodevelopmental consequences. Conclusion Subarachnomegaly is an age-related condition of the infancy with radiological enlargement of CSAS and often self limiting course. However, considering the evidence on pathophysiology as outlined herein and long term outcome reports, further research effort is needed to assess the consequences of venous outflow impairment and enlarged CSAS and how this relates to imaging findings and neurodevelopment test results later in life

Temperature has been studied in relation to many health outcomes. However, few studies have explored its effect on the risk of hospital admission for rheumatoid arthritis (RA). A distributed lag non-linear model (DLNM) was used to analyze associations between mean temperature, diurnal temperature range (DTR), temperature change between neighboring days (TCN), and daily admissions for RA from 2015 to 2019 in Anqing, China. Subgroup analyses based on age, gender, rheumatoid factors, and admission route were performed. In total, 1456 patients with RA were hospitalized. Regarding the cumulative-lag effects of extreme cold temperature (5th percentile = 3℃), the risks of admissions for RA were increased and highest at lag 0–11 (RR = 2.68, 95% CI: 1.23–5.86). Exposing to low (5th percentile = 1.9℃) and high (95th percentile = 14.2℃) DTRs both had increased risks of RA admission, with highest RRs of 1.40 (95% CI: 1.03–1.91) and 1.24 (95% CI: 1.0–1.53) at lag 0 day, respectively. As for TCN, the marginal risk of admission in RA patients was found when exposed to high TCN (95th percentile = 2.9℃) with the largest single-day effect at lag 10 (RR = 1.11, 95% CI: 1.01–1.23). In subgroup analyses, females were more susceptible to extreme cold temperature, low and high DTRs, and high TCN. In regard to extreme cold temperature, significant risk of hospital admission in females only appeared at lag 2 (RR = 1.48, 95% CI: 1.02–2.15) and lag 0–2 (RR = 2.35, 95% CI: 1.11–4.95). It is clear that RA patients exposed to changing temperature may increase risks of admission. Supplementary Information The online version contains supplementary material available at 10.1007/s00484-021-02207-9.

The intersection of technological changes and societal evolution has transformed every aspect of human life. Technological advancements are transforming how healthcare knowledge is expanding and accelerating the outreach of critical medical services delivery (Jamal et al. in Health Information Management Journal 38(3):26–37, 2009). While this transformation facilitates new opportunities simultaneously it also introduces challenges (Jacobzone and Oxley, 2001). Appropriate Health Technology (HT) is vital to new and existing global health care programs. Therefore, qualified professionals who can safely guide the development, evaluation, installation, integration, performance assurance, and risk mitigation of HT must be in position to lead. Trained Clinical Engineers (CE) and Biomedical Engineers (BE) have been recognized by the World Health Organization (WHO) as the essential practitioners to providing this critically needed guidance. Over the past four years, a senior professional group participated in an international project that seeks evidence for the hypothesis - that the engagement of CE and BE in guiding HT - impacts positively on patient outcomes, while the alternative is that there is no difference. The group collected published data that was subjected to peer review screening; additional data qualification conditions are described in this paper. The project was initiated at the Global CE Summit during the first International Clinical Engineering and Health Technology Management Congress (ICEHTMC) in Hangzhou, China in October 2015 (Global Clinical Engineering Summit at the First International Clinical Engineering and Health Technology Management Congress, 2015). Following the adoption of a resolution to investigate CE contributions to the improvement of world health status, an international survey and literature survey were initiated. During the first two years of this project 150 case studies from 90 countries were identified covering the previous ten years. The results of this survey were presented to health leaders at the World Health Organization (WHO) World Health Assembly in 2016. Last year, 250 case studies were added including 35 more countries covering the 2016–2017 period. The combined project contains 400 qualified submissions from 125 countries. The conclusion was that engagement of CE and BME is critical for successful investment in HT and for achieving intended patient outcomes. This paper describes the project’s plan, the results of the literature review performed, and the evidence identified during the process.

Purpose To review the use of different valve types in infants with hydrocephalus, in doing so, determining whether an optimal valve choice exists for this patient cohort. Methods We conducted (1) a literature review for all studies describing valve types used (programmable vs. non-programmable, valve size, pressure) in infants (≤ 2 years) with hydrocephalus, (2) a review of data from the pivotal BASICS trial for infant patients and (3) a separate, institutional cohort study from Alder Hey Children’s Hospital NHS Foundation Trust. The primary outcome was any revision not due to infection. Results The search identified 19 studies that were included in the review. Most did not identify a superior valve choice between programmable and non-programmable, small compared to ultra-small, and differential pressure compared to flow-regulating valves. Five studies investigated a single-valve type without a comparator group. The BASICS data identified 391 infants, with no statistically significant difference between gravitational and programmable subgroups. The institutional data from our tertiary referral centre did not reveal any significant difference in failure rate between valve subtypes. Conclusion Our review highlights the challenges of valve selection in infant hydrocephalus, reiterating that the concept of an optimal valve choice in this group remains a controversial one. While the infant-hydrocephalic population is at high risk of valve failure, heterogeneity and a lack of direct comparison between valves in the literature limit our ability to draw meaningful conclusions. Data that does exist suggests at present that there is no difference in non-infective failure rate are increasing in number, with the British valve subtypes in infant hydrocephalus, supported by both the randomised trial and institutional data in this study.

Assessing the current Artificial intelligence (AI) situation is a crucial step towards its implementation into radiology practice. The study aimed to assess radiographer willingness to accept AI in radiology work practice and the impact of AI in work performance. An exploratory cross-sectional online survey conducted for radiographers working within the Middle East and India was conducted from May–August 2020. A previously validated survey used to obtain radiographer's demographics, knowledge, perceptions, organization readiness, and challenges of integrating AI into radiology. The survey was accessible for radiographers and distributed through the societies page. The survey was completed by 549 radiographers distributed as (77.6%, n = 426) from the Middle East while (22.4%, n = 123) from India. A majority (86%, n = 773) agreed that AI currently plays an important role in radiology and (88.0%, n = 483) expected that AI would play a role in radiology practice and image production. The challenges for AI implementation in practice were developing AI skills (42.8%, n = 235) and AI knowledge development (37.0%, n = 203). Participants showed high interest to integrate AI in under and postgraduate curriculum. There is excitement about what AI could offer, but education input is a requirement. Fears are expressed about job security and how radiology may work across all ages and educational backgrounds. Radiographers become aware of AI role and challenges, which can be improved by education and training.

APOE4 is a strong genetic risk factor for Alzheimer’s disease and Dementia with Lewy bodies; however, how its expression impacts pathogenic pathways in a human-relevant system is not clear. Here using human iPSC-derived cerebral organoid models, we find that APOE deletion increases α-synuclein (αSyn) accumulation accompanied with synaptic loss, reduction of GBA levels, lipid droplet accumulation and dysregulation of intracellular organelles. These phenotypes are partially rescued by exogenous apoE2 and apoE3, but not apoE4. Lipidomics analysis detects the increased fatty acid utilization and cholesterol ester accumulation in apoE-deficient cerebral organoids. Furthermore, APOE4 cerebral organoids have increased αSyn accumulation compared to those with APOE3. Carrying APOE4 also increases apoE association with Lewy bodies in postmortem brains from patients with Lewy body disease. Our findings reveal the predominant role of apoE in lipid metabolism and αSyn pathology in iPSC-derived cerebral organoids, providing mechanistic insights into how APOE4 drives the risk for synucleinopathies.

Purpose Rapid antigen-detecting tests (Ag-RDTs) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can transform pandemic control. Thus far, sensitivity (≤ 85%) of lateral-flow assays has limited scale-up. Conceivably, microfluidic immunofluorescence Ag-RDTs could increase sensitivity for SARS-CoV-2 detection. Methods This multi-centre diagnostic accuracy study investigated performance of the microfluidic immunofluorescence LumiraDx™ assay, enrolling symptomatic and asymptomatic participants with suspected SARS-CoV-2 infection. Participants collected a supervised nasal mid-turbinate (NMT) self-swab for Ag-RDT testing, in addition to a professionally collected nasopharyngeal (NP) swab for routine testing with reverse transcriptase polymerase chain reaction (RT-PCR). Results were compared to calculate sensitivity and specificity. Sub-analyses investigated the results by viral load, symptom presence and duration. An analytical study assessed exclusivity and limit-of-detection (LOD). In addition, we evaluated ease-of-use. Results The study was conducted between November 2nd 2020 and 4th of December 2020. 761 participants were enrolled, with 486 participants reporting symptoms on testing day. 120 out of 146 RT-PCR positive cases were detected positive by LumiraDx™, resulting in a sensitivity of 82.2% (95% CI 75.2–87.5%). Specificity was 99.3% (CI 98.3–99.7%). Sensitivity was increased in individuals with viral load ≥ 7 log10 SARS-CoV2 RNA copies/ml (93.8%; CI 86.2–97.3%). Testing against common respiratory commensals and pathogens showed no cross-reactivity and LOD was estimated to be 2–56 PFU/mL. The ease-of-use-assessment was favourable for lower throughput settings. Conclusion The LumiraDx™ assay showed excellent analytical sensitivity, exclusivity and clinical specificity with good clinical sensitivity using supervised NMT self-sampling. Trial registration number and registration date DRKS00021220 and 01.04.2020

Purpose The risk psychological distress (PD) confers on mortality due to specific chronic diseases compared to suicide is unclear. Using the National Health Interview Survey (NHIS), we investigated the association between PD levels and risk of all-cause and chronic disease-specific mortality and compared the contribution of chronic disease-related mortality to that of suicide. Methods Data from 195, 531 adults, who participated in the NHIS between 1997 and 2004, were linked to the National Death Index records through to 2006. Multivariable Cox regression models were used to estimate hazard ratios (HRs) and their 95% confidence intervals (CIs) across four levels of PD, measured using the Kessler-6 scale. Outcomes included all-cause mortality, and mortality due to all CVDs and subtypes, all cancers and subtypes, diabetes mellitus, alcoholic liver disease and suicide. Results During a mean follow-up time of 5.9 years, 7665 deaths occurred. We found a dose–response association between levels of PD and all-cause mortality, with the adjusted HRs (95% CI) elevated for all levels of PD, when compared to asymptomatic levels: subclinical 1.10 (1.03–1.16), symptomatic 1.36 (1.26–1.46) and highly symptomatic 1.57 (1.37–1.81). A similar association was found for all CVDs and certain CVD subtypes, but not for cancers, cerebrovascular diseases diabetes mellitus. Excess mortality attributable to suicide and alcoholic liver disease was evident among those with levels of PD only. Conclusion PD symptoms, of all levels, were associated with an increased risk of all-cause and CVD-specific mortality while higher PD only was associated with suicide. These findings emphasise the need for lifestyle interventions targeted towards improving physical health disparities among those with PD. Supplementary Information The online version contains supplementary material available at 10.1007/s00127-021-02116-7.

Background A small aortic annulus is associated with increased risk of prosthesis–patient mismatch (PPM) after transcatheter aortic valve implantation (TAVI). Whether specific transcatheter heart valve (THV) designs yield superior hemodynamic performance in these small anatomies remains unclear. Methods Data from 8411 consecutive patients treated with TAVI from May 2012 to April 2019 at four German centers were retrospectively evaluated. A small aortic annulus was defined as multidetector computed tomography-derived annulus area 2. TAVI was performed with a balloon-expanding intra-annular (Sapien-3, n = 288), self-expanding intra-annular (Portico, n = 110), self-expanding supra-annular (Evolut, n = 179 and Acurate-Neo, n = 428) and mechanically expanding infra-annular (Lotus, n = 64) THV according to local practice. PPM was defined as indexed effective orifice area ≤ 0.85cm2/m2. Results A small annulus was found in 1069 (12.7%) patients. PPM was detected in 38.3% overall with a higher prevalence after implantation of a balloon-expanding intra-annular or mechanically expanding infra-annular THV compared to self-expanding intra- and supra-annular THV. Multivariable analysis linked self-expanding THV (Evolut: Odds ratio [OR] 0.341, Acurate-Neo: OR 0.436, Portico: OR 0.291), postdilatation (OR 0.648) and age (OR 0.968) to lower rates of PPM, while aortic valve calcification was associated with an increased risk (OR 1.001). Paravalvular regurgitation > mild was more frequent after TAVI with self-expanding THV (p = 0.04). Conclusion In this large contemporary multicenter patient population, a substantial number of patients with a small aortic anatomy were left with PPM after TAVI. Self-expanding supra- and intra-annular THV demonstrated superior hemodynamics in these patients at risk, however at the cost of higher rates of residual paravalvular regurgitation. Graphic abstract

Purpose The incidence of bone and joint infections is increasing while their treatment remains a challenge. Although guidelines and recommendations exist, evidence is often lacking and treatment complicated by complex clinical presentations and therapeutic options. Interdisciplinary boards shown to improve management of other diseases, seem potentially helpful. We describe the establishment of an osteomyelitis board to show the existing demand for such a platform. Methods All patients discussed in the board for bone and joint infections between October 2014 and September 2020 were included in this retrospective study. Data were extracted from patient records and analyzed descriptively. Results A total of 851 requests related to 563 patients were discussed in the board during the study period. After a run-in period of 3 years, a stable number of cases (> 170/year) were discussed, submitted by nearly all hospital departments (22 of 25). Recommendations were mainly related to antibiotic treatment (43%) and to diagnostics (24%). Periprosthetic joint infections were the most frequent entity (33%), followed by native vertebral osteomyelitis and other osteomyelitis. In 3% of requests, suspected infection could be excluded, in 7% further diagnostics were recommended to confirm or rule out infection. Conclusions A multidisciplinary board for bone and joint infections was successfully established, potentially serving as a template for further boards. Recommendations were mainly related to antibiotic treatment and further diagnostics, highlighting the need for interdisciplinary discussion to individualize and optimize treatment plans based on guidelines. Further research in needed to evaluate impact on morbidity, mortality and costs.

Purpose Migrant children underutilize mental health services (MHS), but differences according to age, reason for migration, type of problem, and time have not been thoroughly analyzed. We aimed to explore utilization of MHS among migrant children and youth and to study if the hypothesized lower utilization could be explained by fewer neurodevelopmental assessments. Methods A cohort of the population aged 0–24 years in Stockholm, comprising 472,129 individuals were followed for maximum 10 years, between January 1, 2006 and December 31, 2015. We categorized individuals as accompanied refugee migrants, unaccompanied refugee migrants and non-refugee migrants, or Swedish-born. We used survival and logistic analyses to estimate rates of utilization of MHS. Results Migrant children and youth utilized less MHS than the majority population, with hazard ratios ranging from 0.62 (95% CI: 0.57; 0.67) to 0.72 (95% CI: 0.69; 0.76). Refugee and non-refugee children utilized less mental health care than their Swedish peers, apart from the youngest refugees (0–10 years) who had similar utilization as Swedish-born. The lower rates were partly explained by all migrant youths’ lower risk of being diagnosed with a neurodevelopmental condition. Time in Sweden had a major impact, such that unaccompanied refugee minors had a higher utilization in their first 2 years in Sweden (OR: 3.39, 95% CI: 2.96; 3.85). Conclusion Migrant youth use less MHS compared with native-born peers, and this is partly explained by fewer neurodevelopmental diagnoses. Strengthening the awareness about unmet needs, and the referring capacity by professionals in contact with migrant children could help reduce barriers to care.

Purpose Recently discovered molecular classifications for urothelial bladder cancer appeared to be promising prognostic and predictive biomarkers. The present study was conducted to evaluate the prognostic impact of molecular subtypes assessed by two different methodologies (gene and protein expression), to compare these two approaches and to correlate molecular with histological subtypes in a consecutively collected, mono-institutional muscle-invasive bladder cancer (MIBC) cohort. Methods 193 MIBC were pathologically re-evaluated and molecular subtypes were assessed on mRNA (NanoString technology, modified 21-gene-containing MDACC approach) and protein levels (immuno-histochemical [IHC] analysis of CK5, CK14, CD44, CK20, GATA3 and FOXA1). Descriptive statistical methods and uni-/multi-variable survival models were employed to analyze derived data. Results Neither gene expression nor protein-based subtyping showed significant associations with disease-specific (DSS) or recurrence-free survival (RFS). Agreement between mRNA (reference) and protein-based subtyping amounted 68.6% for basal, 76.1% for luminal and 50.0% for double-negative tumors. Histological subtypes associated with RFS in uni-variable (P = 0.03), but not in multivariable survival analyses. Tumors with variant histology predominantly showed luminal subtypes (gene expression subtyping: 36/55 cases, 65.5%; protein subtyping: 44/55 cases, 80.0%). Squamous differentiation significantly associated with basal subtypes (gene expression subtyping: 44/45 squamous cases, 97.8%; protein subtyping: 36/45 cases, 80.0%). Conclusion In our consecutive cystectomy cohort, neither gene, protein expression-based subtyping, nor histological subtypes associated with DSS or RFS in multi-variably adjusted survival analyses. Application of a limited IHC subtyping marker panel showed high concordance of 83.9% with gene expression-based subtyping, thus underlining the utility for subtyping in pathological routine diagnostics. In addition, histological MIBC subtypes are strong indicators for intrinsic subtypes.

A cross-sectional study was carried out to determine the seroprevalence of Toxoplasma gondii and associated risk factors in pigs in the largest pork-producing region in Cuba. Serum samples from 420 pigs, including 210 sows and 210 post-weaning pigs, were tested for antibodies against T. gondii using a commercial indirect enzyme-linked immunosorbent assay. Anti-T. gondii antibodies were detected in 56 animals (13.3%, 95% CI: 10.1–16.6). A generalized estimating equations model revealed that the risk factors associated with higher seropositivity in pigs were altitude (higher in farm’s location T. gondii transmission worldwide. Control measures should be implemented to reduce the risk of exposure to T. gondii in pigs in Cuba.

Background Heyde syndrome (HS) is known as the association of severe aortic stenosis (AS) and recurrent gastrointestinal bleeding (GIB) from angiodysplasia. Data on the prevalence of HS and results after TAVI remain scarce. Methods 2548 consecutive patients who underwent TAVI for the treatment of AS from 2008 to 2017 were evaluated for a history of GIB and the presence of HS. The diagnosis of HS was defined as a clinical triad of severe AS, a history of recurrent GIB, and an endoscopic diagnosis of angiodysplasia. These patients (Heyde) were followed to investigate clinical outcomes, bleeding complications and the recurrence of GIB and were compared to patients with GIB unrelated to HS (Non-Heyde). Results A history of GIB prior to TAVI was detected in 190 patients (7.5%). Among them, 47 patients were diagnosed with HS (1.8%). Heyde patients required blood transfusions more frequently compared to Non-Heyde patients during index hospitalization (50.0% vs. 31.9%, p = 0.03). Recurrent GIB was detected in 39.8% of Heyde compared to 21.2% of Non-Heyde patients one year after TAVI (p = 0.03). In patients diagnosed with HS and recurrent GIB after TAVI, the rate of residual ≥ mild paravalvular leakage (PVL) was higher compared to those without recurrent bleeding (73.3% vs. 38.1%, p = 0.05). Conclusion A relevant number of patients undergoing TAVI were diagnosed with HS. Recurrent GIB was detected in a significant number of Heyde patients during follow-up. A possible association with residual PVL requires further investigation to improve treatment options and outcomes in patients with HS. Graphic abstract

Aims Immunocompromised patients have been excluded from studies of SARS-CoV-2 messenger RNA vaccines. The immune response to vaccines against other infectious agents has been shown to be blunted in such patients. We aimed to analyse the humoral and cellular response to prime-boost vaccination with the BNT162b2 vaccine (Pfizer-BioNTech) in cardiothoracic transplant recipients. Methods and results A total of 50 transplant patients [1–3 years post heart (42), lung (7), or heart–lung (1) transplant, mean age 55 ± 10 years] and a control group of 50 healthy staff members were included. Blood samples were analysed 21 days after the prime and the boosting dose, respectively, to quantify anti-SARS-CoV-2 spike protein (S) immunoglobulin titres (tested by Abbott, Euroimmun and RocheElecsys Immunoassays, each) and the functional inhibitory capacity of neutralizing antibodies (Genscript). To test for a specific T-cell response, heparinized whole blood was stimulated with SARS-CoV-2 specific peptides, covering domains of the viral spike, nucleocapsid and membrane protein, and the interferon-γ release was measured (QuantiFERON Monitor ELISA, Qiagen). The vast majority of transplant patients (90%) showed neither a detectable humoral nor a T-cell response three weeks after the completed two-dose BNT162b2 vaccination; these results are in sharp contrast to the robust immunogenicity seen in the control group: 98% exhibited seroconversion after the prime dose already, with a further significant increase of IgG titres after the booster dose (average > tenfold increase), a more than 90% inhibition capability of neutralizing antibodies as well as evidence of a T-cell responsiveness. Conclusions The findings of poor immune responses to a two-dose BNT162b2 vaccination in cardiothoracic transplant patients have a significant impact for organ transplant recipients specifically and possibly for immunocompromised patients in general. It urges for a review of future vaccine strategies in these patients.

Background Equity in access to scheduled surgery has been a topic of attention of researchers and decision-makers on healthcare. Most studies analyse the number of days that patients wait before undergoing surgery, and ignore patients that have been on the waiting list but have not benefited from surgery. This study contributes to the existing literature on waiting lists by analysing cancellations along with surgery episodes. Methods We use a database comprising all patients that entered the waiting list for scheduled surgeries in the Portuguese National Health Service from 2011 to 2015 (around 3 million observations) and estimate survival models to explain waiting times, where cancellations are introduced as censored data. Results The cancellation rate is significant (around 14%), and has a considerable impact on results: ignoring cancellations biases estimates, in particular for gender differences (that are overestimated without cancelations), and for the age effect (that is underestimated). Conclusion Thus, our approach provides a more accurate understanding of the impact that several factors have on overall access to scheduled surgery.

The COVID-19 pandemic is an inherently stressful situation, which may lead to adverse psychosocial outcomes in various populations. Yet, individuals may not be affected equally by stressors posed by the pandemic and those with pre-existing mental disorders could be particularly vulnerable. To test this hypothesis, we assessed the psychological response to the pandemic in a case–control design. We used an age-, sex- and employment status-matched case–control sample (n = 216) of psychiatric inpatients, recruited from the LMU Psychiatry Biobank Munich study and non-clinical individuals from the general population. Participants completed validated self-report measures on stress, anxiety, depression, paranoia, rumination, loneliness, well-being, resilience, and a newly developed index of stressors associated with the COVID-19 pandemic. Multiple linear regression analyses were conducted to assess the effects of group, COVID-19-specific stressors, and their interaction on the different psychosocial outcomes. While psychiatric inpatients reported larger mental health difficulties overall, the impact of COVID-19-specific stressors was lower in patients and not associated with worse psychological functioning compared to non-clinical individuals. In contrast, depressive symptoms, rumination, loneliness, and well-being were more strongly associated with COVID-19-specific stressors in non-clinical individuals and similar to the severity of inpatients for those who experienced the greatest COVID-19-specific stressor impact Contrary to expectations, the psychological response to the pandemic may not be worse in psychiatric inpatients compared to non-clinical individuals. Yet, individuals from the general population, who were hit hardest by the pandemic, should be monitored and may be in need of mental health prevention and treatment efforts. Supplementary Information The online version contains supplementary material available at 10.1007/s00406-021-01291-7.

Purpose This executive summary of a national living guideline aims to provide rapid evidence based recommendations on the role of drug interventions in the treatment of hospitalized patients with COVID-19. Methods The guideline makes use of a systematic assessment and decision process using an evidence to decision framework (GRADE) as recommended standard WHO (2021). Recommendations are consented by an interdisciplinary panel. Evidence analysis and interpretation is supported by the CEOsys project providing extensive literature searches and living (meta-) analyses. For this executive summary, selected key recommendations on drug therapy are presented including the quality of the evidence and rationale for the level of recommendation. Results The guideline contains 11 key recommendations for COVID-19 drug therapy, eight of which are based on systematic review and/or meta-analysis, while three recommendations represent consensus expert opinion. Based on current evidence, the panel makes strong recommendations for corticosteroids (WHO scale 5–9) and prophylactic anticoagulation (all hospitalized patients with COVID-19) as standard of care. Intensified anticoagulation may be considered for patients with additional risk factors for venous thromboembolisms (VTE) and a low bleeding risk. The IL-6 antagonist tocilizumab may be added in case of high supplemental oxygen requirement and progressive disease (WHO scale 5–6). Treatment with nMABs may be considered for selected inpatients with an early SARS-CoV-2 infection that are not hospitalized for COVID-19. Convalescent plasma, azithromycin, ivermectin or vitamin D3 should not be used in COVID-19 routine care. Conclusion For COVID-19 drug therapy, there are several options that are sufficiently supported by evidence. The living guidance will be updated as new evidence emerges.

Graphical abstract Ovarian cancer remains the most lethal gynaecological malignancy, as its timely detection at early stages remains elusive. Attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy of biofluids has been previously applied in pilot studies for ovarian cancer diagnosis, with promising results. Herein, these initial findings were further investigated by application of ATR-FTIR spectroscopy in a large patient cohort. Spectra were obtained by measurements of blood plasma and serum, as well as urine, from 116 patients with ovarian cancer and 307 patients with benign gynaecological conditions. A preliminary chemometric analysis revealed significant spectral differences in ovarian cancer patients without previous chemotherapy (n = 71) and those who had received neo-adjuvant chemotherapy—NACT (n = 45), so these groups were compared separately with benign controls. Classification algorithms with blind predictive model validation demonstrated that serum was the best biofluid, achieving 76% sensitivity and 98% specificity for ovarian cancer detection, whereas urine exhibited poor performance. A drop in sensitivities for the NACT ovarian cancer group in plasma and serum indicates the potential of ATR-FTIR spectroscopy to identify chemotherapy-related spectral changes. Comparisons of regression coefficient plots for identification of biomarkers suggest that glycoproteins (such as CA125) are the main classifiers for ovarian cancer detection and responsible for smaller differences in spectra between NACT patients and benign controls. This study confirms the capacity of biofluids’ ATR-FTIR spectroscopy (mainly blood serum) to diagnose ovarian cancer with high accuracy and demonstrates its potential in monitoring response to chemotherapy, which is reported for the first time. ATR-FTIR spectroscopy of blood serum achieves good segregation of ovarian cancers from benign controls, with attenuation of differences following neo-adjuvant chemotherapy. Supplementary Information The online version contains supplementary material available at 10.1007/s00216-021-03472-8.

This paper examines the behaviour of mental health care providers in response to marginal payment incentives induced by a discontinuous per diem reimbursement schedule with varying tariff rates over the length of stay. The analyses use administrative data on 12,627 cases treated in 82 psychiatric hospitals and wards in Germany. We investigate whether substantial reductions in marginal reimbursement per inpatient day led to strategic discharge behaviour once a certain length of stay threshold is exceeded. The data do not show gaps and bunches at the duration of treatment when marginal reimbursement decreases. Using logistic regression models, we find that providers did not react to discontinuities in marginal reimbursement by significantly reducing inpatient length of stay around the threshold. These findings are robust in terms of different model specifications and subsamples. The results indicate that if regulators aim to set incentives to decrease LOS, this might not be achieved by cuts in reimbursement over LOS. Electronic supplementary material The online version of this article (10.1007/s10198-020-01241-5) contains supplementary material, which is available to authorized users.

Unwarranted variation in the quality of care challenges the sustainability of healthcare systems. Especially in decentralised healthcare systems, it is crucial to understand the drivers behind regional differences in hospital qualities such as unplanned readmissions. This paper examines the factors that influence the risk of unplanned hospital readmission and the geographic disparity of readmission rate in Italy. We use hospital discharge data from 2010 to 2015 for patients above 65 years old admitted with Acute Myocardial Infarction. Employing hierarchical models, we identified the patient and hospital-level determinants for unplanned readmission. In line with the literature, the risk of readmission increases with age and being male, while hospitals with higher patient volume and capacity tend to have lower unplanned readmission. In particular, we find that after patient risk-adjustments, there are differential effects of hospitalisation length-of-stay on the probability of readmission across the hospitals that are governed by different payment systems. For hospitals under a prospective payment system, the effect of length-of-stay in reducing the probability of readmission is weaker than hospitals under an ex-post global budget, but the overall readmission rates are the lowest. Moreover, there are substantial geographic variations in readmission rate across Local Health Authority and regions, and these variations of unplanned readmission are explained by differences in hospital length-of-stay and surgical procedures used. Our results demonstrate that differential hospital behaviours can be one of the potential mechanisms that drive geographic quality disparities.

Background During the COVID-19 pandemic, compulsory masks became an integral part of outdoor sports such as jogging in crowded areas (e.g. city parks) as well as indoor sports in gyms and sports centers. This study, therefore, aimed to investigate the effects of medical face masks on performance and cardiorespiratory parameters in athletes. Methods In a randomized, cross-over design, 16 well-trained athletes (age 27 ± 7 years, peak oxygen consumption 56.2 ± 5.6 ml kg−1 min−1, maximum performance 5.1 ± 0.5 Watt kg−1) underwent three stepwise incremental exercise tests to exhaustion without mask (NM), with surgical mask (SM) and FFP2 mask (FFP2). Cardiorespiratory and metabolic responses were monitored by spiroergometry and blood lactate (BLa) testing throughout the tests. Results There was a large effect of masks on performance with a significant reduction of maximum performance with SM (355 ± 41 Watt) and FFP2 (364 ± 43 Watt) compared to NM (377 ± 40 Watt), respectively (p ηp2 = 0.50). A large interaction effect with a reduction of both oxygen consumption (p ηp2 = 0.34) and minute ventilation (p ηp2 = 0.39) was observed. At the termination of the test with SM 11 of 16 subjects reported acute dyspnea from the suction of the wet and deformed mask. No difference in performance was observed at the individual anaerobic threshold (p = 0.90). Conclusion Both SM and to a lesser extent FFP2 were associated with reduced maximum performance, minute ventilation, and oxygen consumption. For strenuous anaerobic exercise, an FFP2 mask may be preferred over an SM.

Purpose To evaluate the available tibial fracture non-union prediction scores and to analyse their strengths, weaknesses, and limitations. Methods The first part consisted of a systematic method of locating the currently available clinico-radiological non-union prediction scores. The second part of the investigation consisted of comparing the validity of the non-union prediction scores in 15 patients with tibial shaft fractures randomly selected from a Level I trauma centre prospectively collected database who were treated with intramedullary nailing. Results Four scoring systems identified: The Leeds-Genoa Non-Union Index (LEG-NUI), the Non-Union Determination Score (NURD), the FRACTING score, and the Tibial Fracture Healing Score (TFHS). Patients demographics: Non-union group: five male patients, mean age 36.4 years (18–50); Union group: ten patients (8 males) with mean age 39.8 years (20–66). The following score thresholds were used to calculate positive and negative predictive values for non-union: FRACTING score ≥ 7 at the immediate post-operative period, LEG-NUI score ≥ 5 within 12 weeks, NURD score ≥ 9 at the immediate post-operative period, and TFHS Conclusion The LEG-NUI had the best combination of positive and negative predictive values for early identification of non-union. Based on this study, all currently available scores have inherent strengths and limitations. Several recommendations to improve future score designs are outlined herein to better tackle this devastating, and yet, unsolved problem.

Objectives Optimizing valve implantation depth (ID) plays a crucial role in minimizing conduction disturbances and achieving optimal functional integrity. Until now, the impact of intraprocedural fast (FP) or rapid ventricular pacing (RP) on the implantation depth has not been investigated. Therefore, we aimed to (1) evaluate the impact of different pacing maneuvers on ID, and (2) identify the independent predictors of deep ID. Methods 473 TAVR patients with newer-generation self-expanding devices were retrospectively enrolled and one-to-one propensity-score-matching was performed, resulting in a matching of 189 FP and RP patients in each cohort. The final ID was analyzed, and the underlying functional, anatomical, and procedural conditions were evaluated by univariate and multivariate analysis. Results The highest ID was reached under RP in severe aortic valve calcification and valve size 26 mm. Multivariate analysis identified left ventricular outflow (LVOT) calcification [OR 0.50 (0.31–0.81) p = 0.005*], a “flare” aortic root [OR 0.42 (0.25–0.71), p = 0.001*], and RP (OR 0.49 [0.30–0.79], p = 0.004*) as independent highly preventable predictors of a deep ID. In a model of protective factors, ID was significantly reduced with the number of protective criteria (0–2 criteria: − 5.7 mm ± 2.6 vs. 3–4 criteria − 4.3 mm ± 2.0; p Conclusion Data from this retrospective analysis indicate that RP is an independent predictor to reach a higher implantation depth using self-expanding devices. Randomized studies should prove for validation compared to fast and non-pacing maneuvers during valve delivery and their impact on implantation depth. Trail registration Clinical Trial registration: NCT01805739. Graphic abstract Study design: Evaluation of the impact of different pacing maneuvers (fast ventricular pacing—FP vs. rapid ventricular pacing—RP) on implantation depth (ID). After one-to-one-propensity-score-matching, independent protective and risk factors for a very deep ID beneath 6 mm toward the LVOT (®. AVC aortic valve calcification.

Background Recent epidemiological studies on bloodstream infection (BSI) that include the proportion, species distribution and dynamic changes are scarce in China. This study was performed to understand these epidemiological data of BSI over the past 10 years in China. Methods Using a prospective nosocomial infection surveillance system, this study was retrospectively performed in one of the largest hospitals in China. The time trend was tested using the Cochran–Armitage trend test in R Programming Language. Results From 2010 to 2019, there were totally 9381 episodes of BSI cases out of 1,437,927 adult-hospitalized patients in the hospital, the total proportion of BSI cases was 6.50‰ (6.50 episodes per 1000 adult-hospitalized patients) and the proportion had significantly decreased (8.24–6.07‰, time trend P staphylococcus (25.6–32.5%), Escherichia coli (9.8–13.6%) and Klebsiella pneumoniae (5.3–10.4%) had been dynamically increased (all time trends P Pseudomonas aeruginosa had decreased (4.0–2.4%, time trend P = 0.032). However, Staphylococcus aureus (3.3–3.1%) and Acinetobacter baumannii (4.4–4.2%) had not changed significantly (P > 0.05). These common species were consistent with China Antimicrobial Surveillance Network reported in 2018 (2018 CHINET report), but their composition ratios were different. In addition, among bacteremia, the proportion of multidrug-resistant bacteria gradually increased from 52.9 to 68.4% (time trend P Conclusion The proportion and species distribution of BSI were dynamically changing along certain trends. These trends deserved more attention from clinicians and researchers.

Purpose Limited mechanical ventilators (MV) during the Coronavirus disease (COVID-19) pandemic have led to the use of non-invasive ventilation (NIV) in hypoxemic patients, which has not been studied well. We aimed to assess the association of NIV versus MV with mortality and morbidity during respiratory intervention among hypoxemic patients admitted with COVID-19. Methods We performed a retrospective multi-center cohort study across 5 hospitals during March–April 2020. Outcomes included mortality, severe COVID-19-related symptoms, time to discharge, and final oxygen saturation (SpO2) at the conclusion of the respiratory intervention. Multivariable regression of outcomes was conducted in all hypoxemic participants, 4 subgroups, and propensity-matched analysis. Results Of 2381 participants with laboratory-confirmed SARS-CoV-2, 688 were included in the study who were hypoxemic upon initiation of respiratory intervention. During the study period, 299 participants died (43%), 163 were admitted to the ICU (24%), and 121 experienced severe COVID-19-related symptoms (18%). Participants on MV had increased mortality than those on NIV (128/154 [83%] versus 171/534 [32%], OR = 30, 95% CI 16–60) with a mean survival of 6 versus 15 days, respectively. The MV group experienced more severe COVID-19-related symptoms [55/154 (36%) versus 66/534 (12%), OR = 4.3, 95% CI 2.7–6.8], longer time to discharge (mean 17 versus 7.1 days), and lower final SpO2 (92 versus 94%). Across all subgroups and propensity-matched analysis, MV was associated with a greater OR of death than NIV. Conclusions NIV was associated with lower respiratory intervention mortality and morbidity than MV. However, findings may be liable to unmeasured confounding and further study from randomized controlled trials is needed to definitively determine the role of NIV in hypoxemic patients with COVID-19. Supplementary Information The online version contains supplementary material available at 10.1007/s15010-021-01633-6.

Purpose Stability of the dorsal pelvic ring is important for patient mobilisation and can be restored using several surgical procedures after fracture. Placement of percutaneous iliosacral screws is a reliable and minimal-invasive technique to achieve stabilisation of the dorsal pelvic ring by placement of two screws in the first sacral vertebra. Aim of this study was to evaluate 3D CT scans regarding the anatomical possibility to place two 7.3 mm iliosacral screws for fixation of the dorsal pelvic ring. Methods 3D CT datasets of 500 consecutive trauma patients with 1000 hemipelves of a mid-european level I trauma centre with or without pelvic injury were evaluated and measured bilaterally in this retrospective study. Results One thousand hemipelvic datasets of 500 patients (157 females, 343 males) with a mean age of 49.7 years (18 to 95) were included in this study. Only 16 hemipelves (1.6%, 11 in females, 5 in males) in 14 patients (2.8%, 9 females = 5.73%, 5 males = 1.5%) showed too narrow corridors so that 7.3 mm screw placement would not be possible (p = 0.001). In women, too narrow corridors occurred 3.9 times as often as in men. Only two females showed this bilaterally. Conclusion The evaluation of 3D CT scans of the pelvis showed the importance of planning iliosacral screw placement, especially if two 7.3 mm screws are intended to be placed in the first sacral vertebra.

Background Transcatheter aortic valve implantation (TAVI) has become standard treatment for elderly patients with symptomatic severe aortic valve stenosis. The ACURATE neo AS study evaluates 30-day and 1-year clinical and hemodynamic outcomes in patients treated with the ACURATE neo2 valve. Methods The primary endpoint of this single-arm multicenter study is 30-day all-cause mortality. Other key endpoints include device performance, echocardiographic measures assessed by an independent core laboratory, and VARC-2 clinical efficacy and safety endpoints through 12 months. Results The study enrolled 120 patients (mean age 82.1 ± 4.0 years; 67.5% female, mean baseline STS score 4.8 ± 3.8%). The VARC-2 composite safety endpoint at 30 days occurred in 13.3% of patients. All-cause mortality was 3.3% at 30 days and 11.9% at 1 year. The 30-day stroke rate was 2.5% (disabling stroke 1.7%); there were no new strokes between 30 days and 12 months. The rate of permanent pacemaker implantation was 15.0% (18/120) at 30 days and 17.8% (21/120) at 1 year. No patients required re-intervention for valve-related dysfunction and there were no cases of valve thrombosis or endocarditis. Patients demonstrated significant improvement in mean aortic valve gradient (baseline 38.9 ± 13.1 mmHg, 1 year 7.8 ± 3.5 mmHg; P Conclusions One-year outcomes from the ACURATE neo AS study support the safety and performance of TAVI with the ACURATE neo2 valve. Graphic Abstract

Abdominal aortic aneurysm refers to abnormal, asymmetric distension of the infrarenal aortic wall due to pathological remodelling of the extracellular matrix. The distribution of enzymes remodelling the extracellular matrix and their expression patterns in the affected tissue are largely unknown. The goal of this work was to investigate the expression profiles of 20 selected genes coding for metalloproteinases and their inhibitors in the proximal to the distal direction of the abdominal aortic aneurysm. RNA samples were purified from four lengthwise fragments of aneurysm and border tissue obtained from 29 patients. The quantities of selected mRNAs were determined by real-time PCR to reveal the expression patterns. The genes of interest encode collagenases (MMP1, MMP8, MMP13), gelatinases (MMP2, MMP9), stromelysins (MMP3, MMP7, MMP10, MMP11, MMP12), membrane-type MMPs (MMP14, MMP15, MMP16), tissue inhibitors of metalloproteinases (TIMP1, TIMP2, TIMP3, TIMP4), and ADAMTS proteinases (ADAMTS1, ADAMTS8, and ADAMTS13). It was found that MMP, TIMP, and ADAMTS are expressed in all parts of the aneurysm with different patterns. A developed aneurysm has such a disturbed expression of the main participants in extracellular matrix remodelling that it is difficult to infer the causes of the disorder development. MMP12 secreted by macrophages at the onset of inflammation may initiate extracellular matrix remodelling, which, if not controlled, initiates a feedback loop leading to aneurysm formation.

Introduction The objective of this study was to estimate the lifetime risk of hospitalization associated with all major human papillomavirus (HPV)-related diseases in Italy. Moreover, a preliminary vaccination effect was also performed. Methods A retrospective, nonrandomized, observational study was developed based on patients hospitalized between 2006 and 2018 in Italy. All hospitalizations were identified through administrative archives, according to the International Classification of Diseases (ICD-9 CM). Information related to the hospital discharges of all accredited public and private hospitals, both for ordinary and day care regimes, was taken into account. We included hospitalizations related to resident patients presenting one of the ICD-9-CM codes as primary or secondary diagnosis: genital warts (GW); ‘cervical intraepithelial neoplasia (CIN)’ (067.32–067.33); ‘condyloma acuminatum’ (078.11); ‘anal cancers’ (AC) (154.2–154.8); oropharyngeal cancers (OC): ‘oropharyngeal cancer’(146.0–146.9) and ‘head, face and neck cancers’ (171.0); genital cancers (GC): ‘penis cancer’ (187.1–187.9) and ‘cervical cancer’ (180.0–180.9). Data were stratified by birth year and divided into two groups: (a) cohort born before 1996 (not vaccinable) and (b) cohort born after 1997 (vaccinable—first cohort that could be vaccinated at the beginning of immunization schedule in girls since 2008 in Italy). Disease-specific hospitalization risks for both groups were estimated by sex, year and age. Results Epidemiological data demonstrate that the peak hospitalization risk occurred at 24–26 years of age for GW (both male and female); 33–41 and 47–54 years for AC males and females, respectively; 53–59 and 52–58 years for OC males and females, respectively; and 54–60 and 39–46 years for GC males and females, respectively. Focusing on GW and GC, vaccinable females demonstrate a significant reduction in hospitalization risks (− 54% on average) compared to nonvaccinable females until 21 years of age (maximum follow-up available for girls born after 1997). Comparing the same birth cohort of males, no differences in hospitalization risk were found. Conclusions These results support the importance of primary prevention strategies in Italy and suggest that increased VCRs and time of observation (genital cancers for which vaccination is highly effective, have a latency of some decades) will provide useful information for decision-makers.

Repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex (dlPFC) is currently evolving as an effective and safe therapeutic tool in the treatment of major depressive disorder (MDD). However, already established rTMS treatment paradigms are rather time-consuming. With theta burst stimulation (TBS), a patterned form of rTMS, treatment time can be substantially reduced. Pilot studies and a randomized controlled trial (RCT) demonstrate non-inferiority of TBS to 10 Hz rTMS and support a wider use in MDD. Still, data from placebo-controlled multicenter RCTs are lacking. In this placebo-controlled multicenter study, 236 patients with MDD will be randomized to either intermittent TBS (iTBS) to the left and continuous TBS (cTBS) to the right dlPFC or bilateral sham stimulation (1:1 ratio). The treatment will be performed with 80% resting motor threshold intensity over six consecutive weeks (30 sessions). The primary outcome is the treatment response rate (Montgomery-Asberg Depression Rating Scale reduction ≥ 50%). The aim of the study is to confirm the superiority of active bilateral TBS compared to placebo treatment. In two satellite studies, we intend to identify possible MRI-based and (epi-)genetic predictors of responsiveness to TBS therapy. Positive results will support the clinical use of bilateral TBS as an advantageous, efficient, and well-tolerated treatment and pave the way for further individualization of MDD therapy.Trial registration: ClinicalTrials.gov (NCT04392947).

Background and purpose Total hip arthroplasty (THA) is a successful approach to treat unilateral symptomatic neglected hip dislocation (NHD). However, the extensive leg length discrepancy (LLD) can hereby only be partially corrected. In case of residual LLD of more than 2 cm, subsequent femoral lengthening can be considered. Patients/material/methods Retrospective analysis of clinical data and radiographs of five patients (age 38.1 (28–51) years) with unilateral NHD who underwent THA with (n = 3) or without (n = 2) subtrochanteric shortening osteotomy (SSO) and secondary intramedullary femoral lengthening through a retrograde magnetically-driven lengthening nail (follow-up 18.4 (15–27) months). Results LLD was 51.0 (45–60) mm before and 37.0 (30–45) mm after THA. Delayed bone union at one SSO site healed after revision with autologous bone grafting and plate fixation. Subsequent lengthening led to leg length equalisation in all patients. Complete consolidation was documented in all lengthened segments. Conclusion Staged reconstruction via THA and secondary femoral lengthening can successfully be used to reconstruct the hip joint and equalise LLD. The specific anatomical conditions have to be taken into consideration when planning treatment, and patients ought to be closely monitored.

Leishmania major and Leishmania tropica cause cutaneous leishmaniasis in humans and dogs in several parts of the world, with a large number of cases recorded in the Middle East. However, when they occur in sympatry, the role of each species of Leishmania in the epidemiology of cutaneous leishmaniasis (CL) is not clear. To assess the frequency and to identify the species of Leishmania that infect humans and stray dogs in Riyadh and Al-Qaseem (Saudi Arabia), 311 stray dogs and 27 human patients who were suspected for Leishmania infection were examined for CL by a nested polymerase chain reaction (nPCR). Seven (25.9%) out of 27 human patients scored positive for Leishmania spp. (i.e., L. major in five patients from Riyadh and L. tropica in two patients from Al-Qaseem). Out of 311 dogs, five (1.6%) were infected by L. tropica. Data herein presented demonstrate the occurrence of L. tropica in dogs and humans in Saudi Arabia, as well as the occurrence of L. major in humans.

Objectives To assess the cost-effectiveness (CE) of transcatheter aortic valve implantation (TAVI) in Italy, considering patient groups with different surgical risk. Methods A Markov model with a 1-month cycle length, comprising eight different health states, defined by the New York Heart Association functional classes (NYHA I–IV), with and without stroke plus death, was used to estimate the CE of TAVI for intermediate-, high-risk and inoperable patients considering surgical aortic valve replacement or medical treatment as comparators according to the patient group. The Italian National Health System perspective and 15-year time horizon were considered. In the base-case analysis, effectiveness data were retrieved from published efficacy data and total direct costs (euros) were estimated from national tariffs. A scenario analysis considering a micro-costing approach to estimate procedural costs was also considered. The incremental cost-effectiveness ratio (ICER) was expressed both in terms of costs per life years gained (LYG) and costs per quality adjusted life years (QALY). All outcomes and costs were discounted at 3% per annum. Univariate and probabilistic sensitivity analyses (PSA) were performed to assess robustness of results. Results Over a 15-year time horizon, the higher acquisition costs for TAVI were partially offset in all risk groups because of its effectiveness and safety profile. ICERs were €8338/QALY, €11,209/QALY and €10,133/QALY, respectively, for intermediate-, high-risk and inoperable patients. ICER values were slightly higher in the scenario analysis. PSA suggested consistency of results. Conclusions TAVI would be considered cost-effective at frequently cited willingness-to-pay thresholds; further studies could clarify the CE of TAVI in real-life scenarios.

Reports on metronidazole resistance of Trichomonas vaginalis strains have been on the increase. This study investigated the in vitro metronidazole resistance patterns in T. vaginalis isolates obtained from South African pregnant women and the genotypes of these isolates. This study included 362 pregnant women recruited from a hospital in Durban, South Africa. The women provided self-collected vaginal swabs for the detection of T. vaginalis by culture in Diamonds media. Cultured isolates were then subjected to anaerobic susceptibility assays to metronidazole. For the genotyping assays, the actin gene was digested by HindII, MseI, and RsaI. The banding patterns obtained after digestion was used to determine the genotypes. A total of 21/362 (5.8%) pregnant women tested positive for T. vaginalis infection. Of the 21 T. vaginalis isolates tested for metronidazole susceptibility, 9.5% (2/21) had a minimum inhibitory concentration (MIC) of 4 μg/ml (resistant), 38.1% (8/21) had a MIC of 2 μg/ml (intermediate), and 52.4% (11/21) had a MIC ≤ 1 μg/ml (susceptible). The dominant genotype that was identified across the isolates was genotype G. There was no correlation between genotype harboured and metronidazole susceptibility patterns. In this study, resistance to metronidazole was observed in clinical isolates of T. vaginalis. This study did not find a correlation between genotype harboured and metronidazole susceptibility patterns. Despite the lack of association, our study provides data on an area of research that is currently lacking in our setting.

The main objective of this survey is to study the published articles to determine the most favorite data mining methods and gap of knowledge. Since the threat of pandemics has raised concerns for public health, data mining techniques were applied by researchers to reveal the hidden knowledge. Web of Science, Scopus, and PubMed databases were selected for systematic searches. Then, all of the retrieved articles were screened in the stepwise process according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist to select appropriate articles. All of the results were analyzed and summarized based on some classifications. Out of 335 citations were retrieved, 50 articles were determined as eligible articles through a scoping review. The review results showed that the most favorite DM belonged to Natural language processing (22%) and the most commonly proposed approach was revealing disease characteristics (22%). Regarding diseases, the most addressed disease was COVID-19. The studies show a predominance of applying supervised learning techniques (90%). Concerning healthcare scopes, we found that infectious disease (36%) to be the most frequent, closely followed by epidemiology discipline. The most common software used in the studies was SPSS (22%) and R (20%). The results revealed that some valuable researches conducted by employing the capabilities of knowledge discovery methods to understand the unknown dimensions of diseases in pandemics. But most researches will need in terms of treatment and disease control.