Search

Objectives: This study explores the preferences and willingness-to-pay (WTP) of carers for Meeting Centres (MCs) attributes in assisting individuals with mild to moderate dementia., Method: Preferences from 108 carers, gathered through UK-wide MC networks, were collected using a Discrete Choice Experiment survey. The survey incorporated attributes derived from evidence synthesis and lay consultation. A regression model estimated preference weights and marginal WTP for a change in attributes one a time within the MC support 'package.', Results: Carers preferred MCs offering a balanced mix of practical activities and emotional support, along with flexibility without booking requirements and low costs. Social opportunities and the frequency of the meeting were not prioritised. Respondents expressed a WTP of £43 to stay with 'My MC,' the preferred option, compared to transitioning to an alternative in-person MC, all else being equal. Various factors, including attendance modality, the relationship with the supported person, age, and gender, influenced carers' choices., Conclusion: These findings offer valuable insights into carers' preferences, priorities, and WTP within MC support for those with mild to moderate dementia. Understanding these factors can guide the implementation and sustainability of MCs, ensuring alignment with carers' needs and preferences and, ultimately, enhancing support for individuals with dementia.

Background and Aim: Migraine is a common disabling conditions which, globally, affects 15.2% of the population. It is the second cause of health loss in terms of years lived with disability, the first among women. Despite being so common, it is poorly recognised and too often undertreated. Specialty centres and neurologists with specific expertise on headache disorders have the knowledge to provide specific care: however, those who do not regularly treat patients with migraine will benefit from a synopsis on the most relevant and updated information about this condition. This paper presents a comprehensive view on the hallmarks of migraine, from genetics and diagnostic markers, up to treatments and societal impact, and reports the elements that identify migraine specific features., Main Results: The most relevant hallmark of migraine is that it has common and individual features together. Besides the known clinical manifestations, migraine presentation is heterogeneous with regard to frequency of attacks, presence of aura, response to therapy, associated comorbidities or other symptoms, which likely reflect migraine heterogeneous genetic and molecular basis. The amount of therapies for acute and for prophylactic treatment is really wide, and one of the difficulties is with finding the best treatment for the single patient. In addition to this, patients carry out different daily life activities, and might show lifestyle habits which are not entirely adequate to manage migraine day by day. Education will be more and more important as a strategy of brain health promotion, because this will enable reducing the amount of subjects needing specialty care, thus leaving it to those who require it in reason of refractory condition or presence of comorbidities., Conclusions: Recognizing the hallmarks of migraine and the features of single patients enables prescribing specific pharmacological and non-pharmacological treatments. Medical research on headaches today particularly suffers from the syndrome of single-disease approach, but it is important to have a cross-sectional and joint vision with other close specialties, in order to treat our patients with a comprehensive approach that a heterogeneous condition like migraine requires., (© 2024. The Author(s).)

Objective: To compare the cost-effectiveness of different treatments for cervical intraepithelial neoplasia (CIN)., Design: A cost-effectiveness analysis based on data available in the literature and expert opinion., Setting: England., Population: Women treated for CIN., Methods: We developed a decision-analytic model to simulate the clinical course of 1000 women who received local treatment for CIN and were followed up for 10 years after treatment. In the model we considered surgical complications as well as oncological and reproductive outcomes over the 10-year period. The costs calculated were those incurred by the National Health Service (NHS) of England., Main Outcome Measures: Cost per one CIN2+ recurrence averted (oncological outcome); cost per one preterm birth averted (reproductive outcome); overall cost per one adverse oncological or reproductive outcome averted., Results: For young women of reproductive age, large loop excision of the transformation zone (LLETZ) was the most cost-effective treatment overall at all willingness-to-pay thresholds. For postmenopausal women, LLETZ remained the most cost-effective treatment up to a threshold of £31,500, but laser conisation became the most cost-effective treatment above that threshold., Conclusions: LLETZ is the most cost-effective treatment for both younger and older women. However, for older women, more radical excision with laser conisation could also be considered if the NHS is willing to spend more than £31,500 to avert one CIN2+ recurrence., (© 2024 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

We examine the cost-effectiveness of treating epilepsy with anti-epileptic medicines in autistic children, looking at impacts on healthcare providers (in England, Ireland, Italy and Spain) and children's families (in Ireland). We find carbamazepine to be the most cost-effective drug to try first in children with newly diagnosed focal seizures. For England and Spain, oxcarbazepine is the most cost-effective treatment when taken as additional treatment for those children whose response to monotherapy is suboptimal. In Ireland and Italy, gabapentin is the most cost-effective option. Our additional scenario analysis presents the aggregate cost to families with autistic children who are being treated for epilepsy: this cost is considerably higher than healthcare provider expenditure., (© 2023. The Author(s).)

Background: Globally, guidance recommends the integration of mental health into maternal and child healthcare to address common maternal mental health problems during the perinatal period. However, implementing this in the real-world requires substantial resource allocations., Objective: The aim of this study was to estimate the likely costs and consequences linked to scaling the delivery of treatment (in the form of psychosocial interventions) during the perinatal period., Design: Simulation modelling., Setting(s): England., Methods: Costs and consequences were modelled for three scenarios of assumed provision of services, whereby one referred to the projected provision under current government plans, with no additional scaling up of treatment. The other two scenarios referred to additional scaling of treatment: in one scenario, this referred to the provision of treatment by midwives and health visitors trained in the routine enquiry about mental health and delivery of psychosocial interventions; in the other scenario this referred to an expanded provision by primary mental health services. For each scenario and in yearly intervals (covering a ten-year period, 2015 to 2024), unit cots and outcomes were assigned to the activities women were assumed to receive (routine enquiry, assessment, treatment, care coordination). All costs were in 2020 pounds sterling. Data sources for the modelling included: published findings from randomised controlled trials; national unit cost source; national statistics; and expert consultation., Results: If the projected treatment gap was to be addressed, an estimated additional 111,154 (50,031) women would be accessing treatment in 2015 (2024). Estimated total costs (including cost offsets) in the scenario of projected provision under current government plans would be £73.5 million in 2015 and £95.2 million in 2024, whilst quality-adjusted life years gained would be 901 and 928 respectively. Addressing the treatment gap through provision by trained midwives and health visitors could mean additional costs of £7.3 million in 2015 but lower costs of £18.4 million in 2024. The additional quality-adjusted life years gained are estimated at 2096 in 2015 and 1418 in 2024. A scenario in which the treatment gap would be met by primary mental health services was likely to be more costly and delivered less health gains., Conclusions: Findings from this modelling study suggest that scaling the integration of mental health care into routinely delivered care for women during the perinatal period might be economically viable., Registration: N/A., Tweetable Abstract: Integrating mental health into maternal and child healthcare might generate economic benefits new study by @a_annettemaria and @knappem @CPEC_LSE finds #increasing access to treatment for women with perinatal mental health problems., Competing Interests: Declaration of Competing Interest Dr Alain Gregoire is founder and honorary president of the Maternal Mental Health Alliance, which funded the research. He was not involved in decisions concerning the funding of the research. The other authors have no conflict of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Treatment of lenalidomide refractory (Len-R) multiple myeloma (MM) patients still represents an unmet clinical need. In the last years, daratumumab-bortezomib-dexamethasone (D-VD) combination was extensively used in this setting, even though only a small fraction of Len-R patients was included in the pivotal trial. This real-life study aimed to evaluate the efficacy and safety of the D-VD regimen in a cohort that exclusively enrolled Len exposed or refractory MM patients. The study cohort included 57 patients affected by relapsed/refractory MM. All patients were previously exposed to Len, with 77.2% being refractory. The overall response rate (ORR) was 79.6% with 43% of cases obtaining at least a very good partial response (VGPR). The D-VD regimen showed a favorable safety profile, with low frequency of grade 3-4 adverse events, except for thrombocytopenia observed in 21.4% of patients. With a median follow-up of 13 months, median progression-free survival (PFS) was 17 months. No significant PFS differences were observed according to age, ISS, LDH levels, type of relapse, and high-risk FISH. Len exposed patients displayed a PFS advantage as compared to Len refractory patients (29 vs 16 months, p = 0.2876). Similarly, patients treated after Len maintenance showed a better outcome as compared to patients who had received a full-dose Len treatment (23 vs 13 months, p = 0.1728). In conclusion, our real-world data on D-VD combination showed remarkable efficacy in Len-R patients, placing this regimen as one of the standards of care to be properly taken into account in this MM setting., (© 2023. The Author(s).)

Background: Many autistic children experience difficulties in their communication and language skills development, with consequences for social development into adulthood, often resulting in challenges over the life-course and high economic impacts for individuals, families, and society. The Preschool Autism Communication Trial (PACT) intervention is effective in terms of improved social communication and some secondary outcomes. A previously published within-trial economic analysis found that results at 13 months did not support its cost-effectiveness. We modeled cost-effectiveness over 6 years and across four European countries., Methods: Using simulation modeling, we built on economic analyses in the original trial, exploring longer-term cost-effectiveness at 6 years (in England). We adapted our model to undertake an economic analysis of PACT in Ireland, Italy, and Spain. Data on resource use were taken from the original trial and a more recent Irish observational study., Results: PACT is cost-saving over time from a societal perspective, even though we confirmed that, at 13 months post-delivery, PACT is more expensive than usual treatment (across all countries) when given to preschool autistic children. After 6 years, we found that PACT has lower costs than usual treatment in terms of unpaid care provided by parents (in all countries). Also, if we consider only out-of-pocket expenses from an Irish study, PACT costs less than usual treatment., Discussion: PACT may be recommended as a cost-saving early intervention for families with an autistic child.

Background: Autism is a lifelong complex neurodevelopmental condition that affects brain development and behaviour with significant consequences for everyday life. Despite its personal, familial, and societal impact, Europe-wide harmonised guidelines are still lacking for early detection, diagnosis, and intervention, leading to an overall unsatisfactory autistic person and carer journey., Methods: The care pathway for autistic children and adolescents was analysed in Italy, Spain and the UK from the perspective of carers (using a survey aimed at caregivers of autistic children 0-18 years old), the autistic community, and professionals in order to identify major barriers (treatment gaps) preventing carers from receiving information, support, and timely screening/diagnosis and intervention., Results: Across all three countries, analysis of the current care pathway showed: long waits from the time carers raised their first concerns about a child's development and/or behaviour until screening and confirmed diagnosis; delayed or no access to intervention once a diagnosis was confirmed; limited information about autism and how to access early detection services; and deficient support for families throughout the journey., Conclusions: These findings call for policy harmonisation in Europe to shorten long wait times for diagnosis and intervention and therefore, improve autistic people and their families' journey experience and quality of life.

Ceftazidime-avibactam (CAZ-AVI) is an active antibiotic combination of a β-lactam-β-lactamase inhibitor against carbapenemase-producing Enterobacterales. Reports of resistance to CAZ-AVI other than metallo-β-lactamases have increased in recent years. The aim of this study was to analyze KPC- Klebsiella pneumoniae (KP) isolates resistant to CAZ-AVI from the intestinal carriage of hospitalized elderly patients in Italy, in February 2018-January 2020. Characterization of CAZ-AVI-resistant KP isolates, including MLST, resistome, virulome and plasmid content, was performed by WGS analysis. Out of six CAZ-AVI-resistant KP isolates, three belonged to ST101 and three to ST512; two isolates produced KPC-3 (both ST512), four had mutated KPC-3 (KPC-31, in ST101 and ST512, and KPC-46, both ST101). All CAZ-AVI-resistant KP isolates were multidrug-resistant and carried several resistance genes. The yersiniabactin ybt 9 gene cluster was present in all ST101 isolates, while, in ST512 isolates, no virulence genes were detected. Several plasmids were detected: IncF was present in all isolates, as well as IncR and Col440 in ST101 and IncX3 in ST512 isolates. In conclusion, it is important to monitor the circulation of K. pneumoniae resistant to CAZ-AVI to prevent the spread of clones causing difficult-to-treat infections. The presence of mutated KPC-3 in high-risk K. pneumoniae clones resistant to CAZ-AVI in hospitalized patients deserves attention.

Background: Autism and epilepsy often occur together. Epilepsy and other associated conditions have a substantial impact on the well-being of autistic people and their families, reduce quality of life, and increase premature mortality. Despite this, there is a lack of studies investigating the care pathway of autistic children with co-occurring epilepsy in Europe., Methods: We analyzed the care pathway for autistic children with associated epilepsy in Italy, Spain, and the United Kingdom from the perspective of caregivers (using a survey aimed at caregivers of autistic children 0-18 years old), the autistic community, and professionals, in order to identify major barriers preventing caregivers and autistic children from receiving timely screening and treatment of possible co-occurring epilepsy., Results: Across all three countries, an analysis of the current care pathway showed a lack of systematic screening of epilepsy in all autistic children, lack of treatment of co-occurring epilepsy, and inappropriate use of antiepileptic drugs. A major challenge is the lack of evidence-based harmonized guidelines for autism with co-occurring epilepsy in these countries., Conclusions: Our findings show both heterogeneity and major gaps in the care pathway for autism with associated epilepsy and the great efforts that caregivers must make for timely screening, diagnosis, and adequate management of epilepsy in autistic children. We call for policy harmonization in Europe in order to improve the experiences and quality of life of autistic people and their families.

Introduction: The effect of remdesivir on COVID-19 mortality remains conflicting. Elderly individuals are at risk for poor COVID-19 outcomes. We aimed to assess the effect of remdesivir on COVID-19 mortality among elderly individuals, using real-world data., Methods: Retrospective multinational cohort of individuals aged ≥65 years, hospitalized with COVID-19 in six medical centres between January 2020 and May 2021. Associations with in-hospital mortality were evaluated using a multivariable logistic regression model with propensity score adjustment for remdesivir therapy and while implementing generalized estimating equations to control for centre effect. Sensitivity analysis was performed by stratification according to the degree of respiratory support., Results: Of 3010 individuals included, 2788 individuals required either oxygen supplementation or non-invasive/invasive mechanical ventilation, 489 (16%) were treated with remdesivir, and 836 (28%) died. Median age was 77 (IQR 70-84) years and 42% were women. Remdesivir was the only therapeutic intervention associated with decreased mortality [adjusted OR (aOR) 0.49, 95% CI 0.37-0.66, P < 0.001]. This protective effect was shown for individuals requiring oxygen support and non-invasive mechanical ventilation, while no association was found among individuals necessitating invasive mechanical ventilation.Risk factors for mortality included invasive ventilation (aOR 5.18, 95% CI 2.46-10.91, P < 0.001), higher serum creatinine (aOR 1.25, 95% CI 1.09-1.43, P = 0.001) and dyspnoea (aOR 1.40, 95% CI 1.07-1.84, P = 0.015) on presentation, and other non-modifiable factors, such as comorbidities., Conclusions: Among elderly individuals hospitalized with COVID-19, remdesivir carries survival benefit for those with moderate to severe disease. Its role among individuals with critical illness should be further assessed., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Older adults and immunocompromised individulas are often excluded from vaccine trials., Aim: We hypothesised that during the coronavirus disease 2019 (COVID-19) pandemic, the proportion of trials excluding these patients decreased., Methods: Using the US Food and Drug Administration and and European Medicines Agency search engines, we identified all vaccines approved against pneumococcal disease, influenza (quadrivalent vaccines), and COVID-19 from 2011 to 2021. Study protocols were screened for direct and indirect age exclusion criteria and exclusion of immunocompromised individuals. In addition, we reviewed the studies with no explicit exclusion criteria and investigated the actual inclusion of those individuals., Results: We identified 2024 trial records; 1702 were excluded (e.g., use of other vaccine or risk group); and 322 studies were eligible for our review. Among the pneumococcal and influenza vaccine trials (n = 193), 81 (42%) had an explicit direct age exclusion, and 150 (78%) had an indirect age-related exclusion. In total, 163 trials (84%) trials were likely to exclude older adults. Among the COVID-19 vaccine trials (n = 129), 33 (26%) had direct age exclusion and 82 (64%) had indirect age exclusion; in total, 85 (66%) trials were likely to exclude older adults. Therefore was a 18% decrease in the proportion of trials with age-related exclusion between 2011 and 2021 (only influenza and pneumococcal vaccine trials) and 2020-2021 (only COVID-19 vaccine trials) (p = 0.014). In a sub-analysis assessing observational and randomised trials, the decrease was 25% and 9%, respectively. Immunocompromised individuals were included in 87 (45%) of the pneumococcal and influenza vaccine trials compared with 54 (42%) of the COVID-19 vaccine trials (p = 0.058)., Conclusions: During the COVID-19 pandemic, we found a decrease in the exclusion of older adults from vaccine trials but no significant change in the inclusion of immunocompromised individulas., (© 2023. The Author(s).)

Objective: To identify predictors of 30-day survival in elderly patients with coronavirus disease 2019 (COVID-19)., Methods: Retrospective cohort study including patients with COVID-19 aged ≥65 years hospitalized in six European sites (January 2020 to May 2021). Data on demographics, comorbidities, clinical characteristics, and outcomes were collected. A predictive score (FLAMINCOV) was developed using logistic regression. Regression coefficients were used to calculate the score. External validation was performed in a cohort including elderly patients from a major COVID-19 centre in Israel. Discrimination was evaluated using the area under the receiver operating characteristic curve (AUC) in the derivation and validation cohorts. Survival risk groups based on the score were derived and applied to the validation cohort., Results: Among 3010 patients included in the derivation cohort, 30-day survival was 74.5% (2242/3010). The intensive care unit admission rate was 7.6% (228/3010). The model predicting survival included independent functional status (OR, 4.87; 95% CI, 3.93-6.03), a oxygen saturation to fraction of inspired oxygen (SpO 2 /FiO 2 ) ratio of >235 (OR, 3.75; 95% CI, 3.04-4.63), a C-reactive protein level of <14 mg/dL (OR, 2.41; 95% CI, 1.91-3.04), a creatinine level of <1.3 (OR, 2.02; 95% CI, 1.62-2.52) mg/dL, and absence of fever (OR, 1.34; 95% CI, 1.09-1.66). The score was validated in 1174 patients. The FLAMINCOV score ranges from 0 to 15 and showed good discrimination in the derivation (AUC, 0.79; 95% CI, 0.77-0.81; p < 0.001) and validation cohorts (AUC, 0.79; 95% CI, 0.76-0.81; p < 0.001). Thirty-day survival ranged from 39.4% (203/515) to 95.3% (634/665) across four risk groups according to score quartiles in the derivation cohort. Similar proportions were observed in the validation set., Discussion: The FLAMINCOV score identifying elderly with higher or lower chances of survival may allow better triage and management, including intensive care unit admission/exclusion., (Copyright © 2022 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Introduction: Anterior shoulder dislocation is a common reason for consultation at the emergency department (ED). Hypnosis could be a safe and effective alternative therapy for pain relief during shoulder dislocation reduction but nowadays, evidence is not sufficient. The main objective of this study is to show that reduction under hypnosis is associated with a decrease in the use of analgesic compared with usual care., Methods and Analysis: We will conduct an interventional, controlled, multicentre, randomised study. A total of 44 patients with shoulder dislocation will be randomised in two groups: the hypnosis group (N=22) and the usual care group (N=22). The primary endpoint will be the comparison of morphine equivalent analgesic consumption during a shoulder dislocation reduction manoeuvre. Secondary endpoints will include haemodynamic parameters monitoring, patient and practitioner satisfaction using a Likert scale, use of coanalgesic or sedative drugs, number of reduction attempts and time spent at ED. Adverse events will be recorded. Statistical analysis will include parametric tests, multivariate linear regression and descriptive statistics., Ethics and Dissemination: This study has received ethics approval from the Comité de Protection des Personnes of Sud-Est IV on 03/11/2021 (ANSM informed on 19 November 2021). The results will be published in scientific articles and communicated in national and international conferences., Trial Registration Number: ClinicalTrial.gov: NCT04992598; National Clinical trial no ID RCB : 2021-A01382-39., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Self-neglect and hoarding are behaviours that are hard to define, measure and address. They are more prevalent among older people because of bio-psycho-social factors, which may be exacerbated by advancing age. This paper aims to further understandings of self-neglect and hoarding in England's Care Act 2014 context, drawing on a study involving qualitative interviews with local authority adult safeguarding managers who play an important role in determining interventions with individuals who self-neglect and/or hoard. Online interviews were conducted with adult safeguarding leads and managers from 31 English local authorities in 2021. Interview data were subject to thematic analysis. This paper explores the commonalities and differences in adult safeguarding managers' understandings of the causes and consequences of self-neglect and/or hoarding among older people, which are likely to have tangible impacts on service provision in their local authority, and influencing of wider changes to policies and procedures. Most participants understood these phenomena as caused by a range of bio-psycho-social factors, including chronic physical conditions, bereavement, isolation. A minority took a more clinical or psycho-medical perspective, focusing on mental ill-health, or referred to the social construction of norms of cleanliness and tidiness. Whatever their understanding, by the time such behaviours are brought to the attention of safeguarding professionals a crisis response may be all that is offered. The implications of the findings are that other agencies should be encouraged to provide more early help to older people at risk of self-neglect and/or of developing harmful hoarding behaviours, and that sustained engagement with those affected may help to understand some of the causes of these behaviours to enable effective support or practice interventions., (© 2022 The Authors. Health and Social Care in the Community published by John Wiley & Sons Ltd.)

There are long-standing concerns that people experiencing homelessness may not recover well if left unsupported after a hospital stay. This study reports on a study investigating the cost-effectiveness of three different 'in patient care coordination and discharge planning' configurations for adults experiencing homelessness who are discharged from hospitals in England. The first configuration provided a clinical and housing in-reach service during acute care and discharge coordination but with no 'step-down' care. The second configuration provided clinical and housing in-reach, discharge coordination and 'step-down' intermediate care. The third configuration consisted of housing support workers providing in-reach and discharge coordination as well as step-down care. These three configurations were each compared with 'standard care' (control, defined as one visit by the homelessness health nurse before discharge during which patients received an information leaflet on local services). Multiple sources of data and multi-outcome measures were adopted to assess the cost utility of hospital discharge service delivery for the NHS and broader public perspective. Details of 354 participants were collated on service delivery costs (salary, on-costs, capital, overheads and 'hotel' costs, advertising and other indirect costs), the economic consequences for different public services (e.g. NHS, social care, criminal justice, housing, etc.) and health utilities (quality-adjusted-life-years, QALYs). Findings were complex across the configurations, but, on the whole, there was promising evidence suggesting that, with delivery costs similar to those reported for bed-based intermediate care, step-down care secured better health outcomes and improved cost-effectiveness (compared with usual care) within NICE cost-effectiveness recommendations., (© 2022 The Authors. Health and Social Care in the Community published by John Wiley & Sons Ltd.)

Summary: Internationally there has been much interest in the impact of the COVID-19 pandemic on the care and support of older people including those with needs arising from self-neglect and/or hoarding. During the pandemic English local authorities' legal duties remained to respond to concerns about harm about people with care and support needs living in the community. This paper reports interviews with 44 participants working for adult safeguarding/adult protective services (APS) in 31 local authorities recruited from all English regions. Interviews took place online in November-December 2020 as the pandemic's second UK wave was emerging. Analytic induction methods were used to develop themes., Findings: Participants reported some of the variations in referrals to their services with more contact being received from community sources concerned about their neighbours' welfare. Participants provided accounts of the local organisation of adult safeguarding services during the pandemic, including in some areas the potential for offering early help to older people at risk of harm from self-neglect or hoarding behaviour. Online inter-agency meetings were positively received but were acknowledged to potentially exclude some older people., Applications: This article reports observations from adult safeguarding practitioners about their services which may be of interest internationally and in renewing services that can sustain public interest in the welfare of their older citizens and in developing early help. The findings reflect those from children's services where online meetings are also predicted to enhance professional communications post-pandemic but similarly need to ensure effective engagement with service users and their families., (© The Author(s) 2022.)

The spread of carbapenemase-producing (CP) Enterobacterales is currently a worldwide concern, especially in the elderly. Twelve CP- E. coli isolated from rectal swabs of colonized inpatients aged ≥65 years from four hospitals in two Italian cities (Milan and Rome) were analyzed by whole genome sequencing (WGS) to obtain multi-locus sequence typing (MLST), identification of carbapenemase-encoding genes, resistome, plasmid content, and virulence genes. MLST analysis showed the presence of 10 unrelated lineages: ST410 (three isolates from three different hospitals in two cities) and ST12, ST38, ST69, ST95, ST131, ST189, ST648, ST1288, and ST1598 (one isolate each). Most isolates (9/12, 75%) contained a serine-β-lactamase gene (5 bla KPC-3 , 2 bla KPC-2 , and 2 bla OXA-181 ), while three isolates harbored a metallo-β-lactamase gene (two bla NDM-5 and one bla VIM-1 ). In most CP- E. coli , the presence of more than one plasmid was observed, with the predominance of IncF. Several virulence genes were detected. All isolates contained genes enhancing the bacterial fitness, such as gad and ter C, and all isolates but one, fim H, encoding type 1 fimbriae. In conclusion, CP- E. coli clones colonizing elderly patients showed heterogeneous genetic backgrounds. We recommend strict surveillance to monitor and prevent the spread of successful, high-risk clones in healthcare settings.

Management of patients with infections caused by multidrug-resistant organisms is challenging and requires a multidisciplinary approach to achieve successful clinical outcomes. The aim of this paper is to provide recommendations for the diagnosis and optimal management of these infections, with a focus on targeted antibiotic therapy. The document was produced by a panel of experts nominated by the five endorsing Italian societies, namely the Italian Association of Clinical Microbiologists (AMCLI), the Italian Group for Antimicrobial Stewardship (GISA), the Italian Society of Microbiology (SIM), the Italian Society of Infectious and Tropical Diseases (SIMIT) and the Italian Society of Anti-Infective Therapy (SITA). Population, Intervention, Comparison and Outcomes (PICO) questions about microbiological diagnosis, pharmacological strategies and targeted antibiotic therapy were addressed for the following pathogens: carbapenem-resistant Enterobacterales; carbapenem-resistant Pseudomonas aeruginosa; carbapenem-resistant Acinetobacter baumannii; and methicillin-resistant Staphylococcus aureus. A systematic review of the literature published from January 2011 to November 2020 was guided by the PICO strategy. As data from randomised controlled trials (RCTs) were expected to be limited, observational studies were also reviewed. The certainty of evidence was classified using the GRADE approach. Recommendations were classified as strong or conditional. Detailed recommendations were formulated for each pathogen. The majority of available RCTs have serious risk of bias, and many observational studies have several limitations, including small sample size, retrospective design and presence of confounders. Thus, some recommendations are based on low or very-low certainty of evidence. Importantly, these recommendations should be continually updated to reflect emerging evidence from clinical studies and real-world experience., (Copyright © 2022. Published by Elsevier Ltd.)

Carbapenemase-producing Enterobacterales (CPE) represent a serious threat to public health worldwide. Elderly patients are at increased risk of colonisation/infection with CPE. This study aimed to evaluate the persistence of CPE colonisation and the genotypic characteristics of persistent strains in elderly people discharged from Italian hospitals. A longitudinal study was conducted in two Italian cities (March 2018 to September 2020) enrolling 137 patients aged ≥65 years with CPE intestinal colonisation at hospital discharge. CPE colonisation was evaluated after 4, 8 and 12 months. Competing risk analysis was used to explore the association between baseline characteristics and persistence at 4 months. For all isolates, carbapenemase typing and multilocus sequence typing were performed. Persistent isolates underwent whole-genome sequencing. Of 137 patients, 91% carried carbapenemase-producing Klebsiella pneumoniae (CP-KP) and 8.8% carried carbapenemase-producing Escherichia coli. Although a large number of patients were lost to follow-up owing to death or withdrawal, 28/65 patients (43.1%) remained colonised at Month 4; 16/42 (38.1%) and 5/28 (17.9%) were found colonised up to Months 8 and 12, respectively. Colonisation persistence was more frequent in patients with bacteraemia or complicated urinary tract infection while in hospital and in those staying in long-term care facilities (LTCFs). Clonal characteristics of CP-KP isolates did not appear to influence persistence. Isolates obtained from each persistent carrier were identical or highly related by SNP phylogenetic analysis. Identification of patients at higher risk of persistent intestinal carriage after hospital discharge can prompt control measures to limit the transmission of CPE in the community, especially in LTCF settings., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Introduction: Improving support for people with early to moderate dementia to live at home in their communities is a global public health goal. Community adult social care is not robust in many parts of the UK, however, with the pandemic increasing pressure on services for this population. Community-led interventions can play a key role in supporting people postdiagnosis, helping delay decline, but many interventions struggle to sustain beyond 1-2 years. Meeting Centres (MCs) are one such intervention, which many UK community groups find attractive and achievable. However, it is not understood how these communities can ensure they are putting in place strategies that will help them sustain in the longer term, beyond start-up phase., Methods and Analysis: This realist evaluation aims to understand the factors affecting sustainability of MCs in rural areas and learn lessons from MCs that have sustained beyond 3 years. Data will be collected using mixed methods: interviews and group discussions with stakeholders involved at every level in three case study locations in England and Wales, analysed with Soft Systems modelling; a Discrete Choice Experiment exploring what people across the UK value and are willing to pay for MCs, analysed with regression modelling. All data will be synthesised using a Realist logic of analysis to build a theoretical model of how, why, for whom, in what contexts and to what extent MCs can be successfully implemented for the long term., Ethics and Dissemination: As participants may lack capacity for informed consent, favourable ethical opinion was received from a Health Research Authority research ethics committee. Resulting recommendations will be of interest to stakeholders including those commissioning, planning, running, supporting or attending MCs, as well as policy-makers and healthcare professionals. Knowledge will be shared with emerging MCs to help accelerate scale up of this intervention., Competing Interests: Competing interests: GW is deputy chair of the National Institute for Health Research Health Technology Assessment Prioritisation Committee: Integrated Community Health and Social Care (A)., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

The purpose of this survey is to explore changes in the management of COVID-19 during the first versus the second wave, with particular emphasis on therapies, antibiotic prescriptions, and elderly care. An internet-based questionnaire survey was distributed to European Society of Clinical Microbiology and Infectious Diseases (ESCMID) members. Therapeutic approach to patients with mild-to-moderate (PiO 2 /FiO 2 200-350) and severe (PiO 2 /FiO 2  < 200) COVID-19, antibiotic use, and reasons for excluding patients from the intensive care unit (ICU) were investigated. A total of 463 from 21 countries participated in the study. Most representatives were infectious disease specialists (68.3%). During the second wave of pandemic, physicians abandoned the use of hydroxychloroquine, lopinavir/ritonavir, and azithromycin in favor of dexamethasone, low-molecular weight heparin (LMWH), and remdesivir in mild-to-moderate COVID-19. In critically ill patients, we detected an increased use of high-dose steroids (51%) and a decrease in tocilizumab use. The use of antibiotics at hospital admission decreased but remained high in the second wave. Age was reported to be a main consideration for exclusion of patients from ICU care by 25% of responders; a third reported that elderly were not candidates for ICU admission in their center. The decision to exclude patients from ICU care was based on the individual decision of an intensivist in 59.6% of cases. The approach of physicians to COVID-19 changed over time following evidence accumulation and guidelines. Antibiotic use at hospital admission and decision to exclude patients from ICU care remain critical aspects that should be better investigated and harmonized among clinicians., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Although rituximab is widely used off-label for complex pediatric diseases, safety reports are limited. We aimed to report evidence of its use in clinical practice, to describe the incidence of adverse drug reactions (ADR) to rituximab biosimilar Novex ® and innovator, and to identify risk factors for the development of ADR in a real-life follow-up cohort of pediatric patients with complex diseases. We conducted a prospective, longitudinal, observational, single-centre study in patients that received rituximab for any complex disease, and as part of an intensive pharmacovigilance program. Demographic, pharmacological, clinical, and drug-related data were collected for all patients. ADR-free survival, including infusion-related reactions (IRR) and delayed ADR (dADR), was estimated using Kaplan-Meier curves. Risk factors were evaluated by multivariable Cox regression models. In total, 77 patients (<19 y.o.) received 187 infusions of rituximab Novex ® ( n = 155) or innovator rituximab ( n = 32) for neurologic (Neu), immune-hematologic-rheumatic (IHR), oncologic (O) diseases, and hematopoietic stem-cell transplantation (HSCT) or solid-organ transplantation (SOT). We recorded 29 IRR and 58 dADR that occurred in 27 (35.1%) and 29 (37.7%) patients, respectively. The respiratory tract was the most affected during IRR (29.6%) and hypogammaglobulinemia (37.9 %) was the most frequent dADR. First versus subsequent infusions (HR 5.4, CI95% 2.4-12.1, p <0.05), sex (boys vs. girls, HR 0.3, CI95% 0.1-0.8, and p <0.05), and diagnosis (Neu-IHR diseases vs. O-HSCT-SOT, HR 2.3, CI95% 1.02-5.4, and p < 0.05) were significantly associated with the development of IRR. For dADR, risk factors were diagnosis (Neu-IHR diseases vs. O-HSCT-SOT, HR 0.4, CI95% 0.2-0.9, and p < 0.05) and cumulative body surface area-normalized dosage (HR 1.0003, CI95% 1.0001-1.0006, and p < 0.05). The present is the largest real-world safety assessment of rituximab in Latin-American children with complex diseases supporting its use based on the overall acceptable safety. Identification of risk factors may contribute to optimization of off-label rituximab treatment in pediatrics., Competing Interests: ES and MT were employed by the company Laboratorio Elea-Phoenix S.A. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Riva, Molina, Cornaló, Salvador, Savransky, Tenembaum, Katsicas, Monteverde, Cáceres Guido, Rousseau, Staciuk, González Correas, Zubizarreta, Imventarza, Lagomarsino, Spitzer, Tinelli and Schaiquevich.)

Multidrug-resistant pathogens constitute a serious global issue and, therefore, novel antimicrobials with new modes of action are urgently needed. Here, we investigated the effect of a phenothiazine derivative (JBC 1847) with high antimicrobial activity on Staphylococcus aureus , using a wide range of in vitro assays, flow cytometry, and RNA transcriptomics. The flow cytometry results showed that JBC 1847 rapidly caused depolarization of the cell membrane, while the macromolecule synthesis inhibition assay showed that the synthesis rates of DNA, RNA, cell wall, and proteins, respectively, were strongly decreased. Transcriptome analysis of S. aureus exposed to sub-inhibitory concentrations of JBC 1847 identified a total of 78 downregulated genes, whereas not a single gene was found to be significantly upregulated. Most importantly, there was downregulation of genes involved in adenosintrifosfat (ATP)-dependent pathways, including histidine biosynthesis, which is likely to correlate with the observed lower level of intracellular ATP in JBC 1847-treated cells. Furthermore, we showed that JBC 1847 is bactericidal against both exponentially growing cells and cells in a stationary growth phase. In conclusion, our results showed that the antimicrobial properties of JBC 1847 were primarily caused by depolarization of the cell membrane resulting in dissipation of the proton motive force (PMF), whereby many essential bacterial processes are affected. JBC 1847 resulted in lowered intracellular levels of ATP followed by decreased macromolecule synthesis rate and downregulation of genes essential for the amino acid metabolism in S. aureus . Bacterial compensatory mechanisms for this proposed multi-target activity of JBC 1847 seem to be limited based on the observed very low frequency of resistance toward the compound., Competing Interests: AP was employed by company Unibrains. LS and KH were employed by company Bioneer A/S. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ronco, Kappel, Aragao, Biagi, Svenningsen, Christensen, Permin, Saaby, Holmstrøm, Klitgaard, Sabat, Akkerboom, Monaco, Tinelli, Friedrich, Jana and Olsen.)

Background: Headache disorders are disabling, with major consequences for productivity, yet the literature is silent on the relationship between headache-attributed disability and lost productivity, often erroneously regarding the two as synonymous. We evaluated the relationship empirically, having earlier found that investment in structured headache services would be cost saving, not merely cost-effective, if reductions in headache-attributed disability led to > 20% pro rata recovery of lost productivity., Methods: We used individual participant data from Global Campaign population-based studies conducted in China, Ethiopia, India, Nepal, Pakistan and Russia, and from Eurolight in Lithuania, Luxembourg and Spain. We assessed relationships in migraine and probable medication-overuse headache (pMOH), the most disabling common headache disorders. Available symptom data included headache frequency, usual duration and usual intensity. We used frequency and duration to estimate proportion of time in ictal state (pTIS). Disability, in the sense used by the Global Burden of Disease study, was measured as the product of pTIS and disability weight for the ictal state. Impairment was measured as pTIS * intensity. Lost productivity was measured as lost days (absence or < 50% productivity) from paid work and corresponding losses from household work over the preceding 3 months. We used Spearman correlation and linear regression analyses., Results: For migraine, in a linear model, we found positive associations with lost paid worktime, significant (p < 0.05) in many countries and highly significant (p < 0.001) in some despite low values of R 2 (0-0.16) due to high variance. With lost household worktime and total lost productivity (paid + household), associations were highly significant in almost all countries, although still with low R 2 (0.04-0.22). Applying the regression equations for each country to the population mean migraine-attributed disability, we found pro rata recoveries of lost productivity in the range 16-56% (> 20% in all countries but Pakistan). Analysing impairment rather than disability increased variability. For pMOH, with smaller numbers, associations were generally weaker, occasionally negative and mostly not significant., Conclusion: Relief of disability through effective treatment of migraine is expected, in most countries, to recover > 20% pro rata of lost productivity, above the threshold for investment in structured headache services to be cost saving., (© 2021. The Author(s).)

Background: Failure to attend appointments places a huge strain on health care systems around the world, resulting in poorer care for the patients, waste of staff time and increased waiting times. This study looked at the impact of an Outpatient-Monitor-Service (OMS) on clinical, economic, patient safety and service improvement outcomes in gynaecology patients compared with care as usual (with no access to the OMS)., Methods: We conducted a retrospective match-pair controlled study at a London-based hospital. The cohort included adult women who received either (i) gynecological, (ii) hysteroscopy or (iii) vulval procedures. A cost-consequences analysis compared intervention (who received the OMS) with control (historical cases who did not receive the OMS. Main outcome measures were clinical-effectiveness, NHS-cost, patient safety, and service improvement., Results: The intervention had positive impacts spanning clinical, patient safety and service improvement areas and showed cost saving results for the healthcare in terms of reduced follow-up consultations and did-not-attend occurrences., Conclusions: The OMS offered by Message Dynamics appears to be a successful digital health technology to monitor gynecological patients' conditions and inform clinical decision making via remote channels, which is particularly relevant in coronavirus disease pandemic., (© 2021 John Wiley & Sons Ltd.)

Background and Purpose: The recent report on Value-of-Treatment (VoT) project highlights the need for early diagnosis-intervention, integrated, seamless care underpinning timely care pathways and access to best treatments. The VoT-multiple-sclerosis (MS) economic case study analysis aimed to estimate the effectiveness/cost-effectiveness of both early treatment and reducing MS risk factors (e.g. smoking and vitamin D insufficiency)., Methods: A series of decision analytical modellings were developed and applied to estimate the cost-effectiveness of: (1) reducing the conversion from clinically-isolated-syndrome (CIS) to clinically-definite-MS (CDMS); (2) smoking cessation and increase of 25 hydroxyvitamin D (25(OH)D) serum level. Both (1) and (2) considered socioeconomic impact on averted MS disability progression. Costs were reported for societal and healthcare provider perspectives (pending on data across nations; Euros). Effectiveness was expressed as Quality-Adjusted-Life-Years (QALYs) gains. Long term (25, 30, 40,50-years) and short (one-year) timelines were considered for (1) and (2), respectively., Results: Early treatment was cost-effective for the health care provider and both cost-effective/cost-saving for the society across time-horizons and nations. Smoking cessation and an increase of 25(OH)D in MS patients were both cost-effective/cost-saving across nations., Conclusions: To the best of our knowledge, our work provides the first economic evidence to base appropriate public health interventions to reduce the MS burden in Europe., (Copyright © 2021. Published by Elsevier B.V.)

Background: Health economic evaluations support health-care decision-making by providing information on the costs and consequences of health interventions. No universally accepted methodology exists for modelling effectiveness and cost-effectiveness of interventions designed to close treatment gaps for headache disorders in countries of Europe (or elsewhere). Our aim here, within the European Brain Council's Value-of-Treatment project, was to develop headache-type-specific analytical models to be applied to implementation of structured headache services in Europe as the health-care solution to headache., Methods: We developed three headache-type-specific decision-analytical models using the WHO-CHOICE framework and adapted these for three European Region country settings (Luxembourg, Russia and Spain), diverse in geographical location, population size, income level and health-care systems and for which we had population-based data. Each model compared current (suboptimal) care vs target care (delivered in accordance with the structured headache services model). Epidemiological and economic data were drawn from studies conducted by the Global Campaign against Headache; data on efficacy of treatments were taken from published randomized controlled trials; assumptions on uptake of treatments, and those made for Healthy Life Year (HLY) calculations and target-care benefits, were agreed with experts. We made annual and 5-year cost estimates from health-care provider (main analyses) and societal (secondary analyses) perspectives (2020 figures, euros)., Results: The analytical models were successfully developed and applied to each country setting. Headache-related costs (including use of health-care resources and lost productivity) and health outcomes (HLYs) were mapped across populations. The same calculations were repeated for each alternative (current vs target care). Analyses of the differences in costs and health outcomes between alternatives and the incremental cost-effectiveness ratios are presented elsewhere., Conclusions: This study presents the first headache-type-specific analytical models to evaluate effectiveness and cost-effectiveness of implementing structured headache services in countries in the European Region. The models are robust, and can assist policy makers in allocating health budgets between interventions to maximize the health of populations., (© 2021. The Author(s).)

Background: There have been several calls for estimations of costs and consequences of headache interventions to inform European public-health policies. In a previous paper, in the absence of universally accepted methodology, we developed headache-type-specific analytical models to be applied to implementation of structured headache services in Europe as the health-care solution to headache. Here we apply this methodology and present the findings., Methods: Data sources were published evidence and expert opinions, including those from an earlier economic evaluation framework using the WHO-CHOICE model. We used three headache-type-specific analytical models, for migraine, tension-type-headache (TTH) and medication-overuse-headache (MOH). We considered three European Region case studies, from Luxembourg, Russia and Spain to include a range of health-care systems, comparing current (suboptimal) care versus target care (structured services implemented, with provider-training and consumer-education). We made annual and 5-year cost estimates from health-care provider and societal perspectives (2020 figures, euros). We expressed effectiveness as healthy life years (HLYs) gained, and cost-effectiveness as incremental cost-effectiveness-ratios (ICERs; cost to be invested/HLY gained). We applied WHO thresholds for cost-effectiveness., Results: The models demonstrated increased effectiveness, and cost-effectiveness (migraine) or cost saving (TTH, MOH) from the provider perspective over one and 5 years and consistently across the health-care systems and settings. From the societal perspective, we found structured headache services would be economically successful, not only delivering increased effectiveness but also cost saving across headache types and over time. The predicted magnitude of cost saving correlated positively with country wage levels. Lost productivity had a major impact on these estimates, but sensitivity analyses showed the intervention remained cost-effective across all models when we assumed that remedying disability would recover only 20% of lost productivity., Conclusions: This is the first study to propose a health-care solution for headache, in the form of structured headache services, and evaluate it economically in multiple settings. Despite numerous challenges, we demonstrated that economic evaluation of headache services, in terms of outcomes and costs, is feasible as well as necessary. Furthermore, it is strongly supportive of the proposed intervention, while its framework is general enough to be easily adapted and implemented across Europe., (© 2021. The Author(s).)

In countries where headache services exist at all, their focus is usually on specialist (tertiary) care. This is clinically and economically inappropriate: most headache disorders can effectively and more efficiently (and at lower cost) be treated in educationally supported primary care. At the same time, compartmentalizing divisions between primary, secondary and tertiary care in many health-care systems create multiple inefficiencies, confronting patients attempting to navigate these levels (the "patient journey") with perplexing obstacles.High demand for headache care, estimated here in a needs-assessment exercise, is the biggest of the challenges to reform. It is also the principal reason why reform is necessary.The structured headache services model presented here by experts from all world regions on behalf of the Global Campaign against Headache is the suggested health-care solution to headache. It develops and refines previous proposals, responding to the challenge of high demand by basing headache services in primary care, with two supporting arguments. First, only primary care can deliver headache services equitably to the large numbers of people needing it. Second, with educational supports, they can do so effectively to most of these people. The model calls for vertical integration between care levels (primary, secondary and tertiary), and protection of the more advanced levels for the minority of patients who need them. At the same time, it is amenable to horizontal integration with other care services. It is adaptable according to the broader national or regional health services in which headache services should be embedded.It is, according to evidence and argument presented, an efficient and cost-effective model, but these are claims to be tested in formal economic analyses., (© 2021. The Author(s).)

Background: Inpatients experiencing homelessness are often discharged to unstable accommodation or the street, which may increase the risk of readmission., Methods: We conducted a cohort study of 2772 homeless patients discharged after an emergency admission at 78 hospitals across England between November 2013 and November 2016. For each individual, we selected a housed patient who lived in a socioeconomically deprived area, matched on age, sex, hospital, and year of discharge. Counts of emergency readmissions, planned readmissions, and Accident and Emergency (A&E) visits post-discharge were derived from national hospital databases, with a median of 2.8 years of follow-up. We estimated the cumulative incidence of readmission over 12 months, and used negative binomial regression to estimate rate ratios., Results: After adjusting for health measured at the index admission, homeless patients had 2.49 (95% CI 2.29 to 2.70) times the rate of emergency readmission, 0.60 (95% CI 0.53 to 0.68) times the rate of planned readmission and 2.57 (95% CI 2.41 to 2.73) times the rate of A&E visits compared with housed patients. The 12-month risk of emergency readmission was higher for homeless patients (61%, 95% CI 59% to 64%) than housed patients (33%, 95% CI 30% to 36%); and the risk of planned readmission was lower for homeless patients (17%, 95% CI 14% to 19%) than for housed patients (30%, 95% CI 28% to 32%). While the risk of emergency readmission varied with the reason for admission for housed patients, for example being higher for admissions due to cancers than for those due to accidents, the risk was high across all causes for homeless patients., Conclusions: Hospital patients experiencing homelessness have high rates of emergency readmission that are not explained by health. This highlights the need for discharge arrangements that address their health, housing and social care needs., Competing Interests: Competing interests: NH is medical director, and AH is a trustee of the charity ‘Pathway: Healthcare for homeless people’. AS is clinical lead and manager for the ‘Find and Treat’ service at University College London Hospitals., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Purpose: Arthrodesis of the knee joint is still a salvage procedure after recurrent prosthetic joint infections (PJI) of total knee arthroplasties (TKA) with substantial bone loss and seems to be a good solution to avoid amputation. Until now, intramedullary arthrodesis has increasingly been performed; no study has yet been published to compare these techniques after septic removal of TKA in terms of functional assessment and quality of daily life., Methods: In a single-centre retrospective setting, clinical and radiographic evaluation of consecutive patients after knee arthrodesis using intramedullary and external fixation for infected knee joints was performed. All patients were evaluated clinically, with x-ray and questionnaire including analysis regarding any complications at latest follow-up of a minimum 12 months postoperatively., Results: We included 152 patients (75 females, 77 males) in this study. The mean age of the patients at surgery was 63.6 years (range 12 to 90 years). The minimum follow-up was 12 months (mean 3.1 years, range 12 to 49 months). Arthrodesis with external fixator (83 patients, 52.2%) showed less blood loss and less peri-operative complications (1.6%) but a high rate of post-operative, pin-track infections (35.5%); loose pins (12.7%); and pin fractures (4.8%), and therefore risk factors for instability and nonunion (30.9%). Revision rate was 22.6% for arthrodesis with external fixator, and the primary union rate was 65.6%. Intramedullary arthrodesis (69 patients, 43.4%) showed a similar re-infection rate to external fixation (16.1% and 15.9%, respectively) but a significantly lower revision rate (5.4%, p < 0.001). Eighty percent of patients with intramedullary arthrodesis showed very good patient-related outcomes regarding pain, function and daily life activities in the questionnaire., Conclusion: Despite similar results regarding patient satisfaction and everyday competences in questionnaires, intramedullary arthrodesis of the knee is superior to the external fixator, as it results in fewer complications, lower revision rate, and union rates/loosening.

Aim: Clinical research nurses work at the fulcrum of clinical trials with clearly defined roles and responsibilities. In England, the National Institute for Health Research (the main funder of health research) has broadened its scope to encompass social care research. The expectation is that clinical research nurses will expand their skill set to support these new studies, many of which will employ qualitative and mixed methods. This discussion paper explores the challenges of facilitating this clinical academic workforce development through a case study of a homeless health and social care research project. This was one of the first studies to engage clinical research nurses in this new and expanded role., Background: Much of what is known about the research nurse workforce has been generated through studies of clinical trials in oncology. The 'caring-recruiting' dichotomy has been used as a heuristic device for identifying workforce issues that can impact on study delivery such as how intense pressure to recruit study participants leads to low job satisfaction., Design: This case study reflects on the authors' experiences of employing a clinical research nurse in a social care research project concerned with the discharge of homeless people from hospital. The 'caring-recruiting' dichotomy is used to generate new information about the relationship between workforce development and the successful delivery of social care research., Conclusion: The case study illuminates how social care research can generate different pressures and ethical challenges for research nurses. The time and skill it took to recruit study participants identified as 'hard to reach' was suggestive of the need to move beyond performance measures that prioritise recruitment metrics. The need for different types of staff supervision and training was also warranted as supporting study participants who were homeless was often distressing, leading to professional boundary issues., Relevance to Workforce Development: This study highlights that performance management, training and supervisory arrangements must be tailored to the characteristics of each new study coming onto the portfolio to ensure research nurses are fully supported in this new and expanded role., (© 2021 The Authors. Journal of Clinical Nursing published by John Wiley & Sons Ltd.)

Objective: Dorsal stabilization is a frequently used procedure in the treatment of acute traumatic vertebral body fractures. Besides the traditional open surgical procedure, the percutaneous positioning of pedicle screws is now widely used. The aim of the current study is to compare pedicle screw misplacement following open vs. percutaneous dorsal instrumentation after traumatic spinal fracture of the thoracic and lumbar spine and to assess possible risk factors associated with pedicle screw misplacement., Methods: All patients who suffered a traumatic spinal fracture that were treated with dorsal stabilization in our level I trauma center in the period from 01/2007 to 03/2014 were included in this retrospective therapeutic cohort study. From 01/2007 to 06/2009, an open surgical procedure was used, and from 06/2009 to 03/2014, the percutaneous procedure was used for all types of fractures. Retrospectively, the positioning of every single pedicle screw was evaluated in the post-operative computed tomography scan and classified. Epidemiological data were also documented to compare the two treatment groups., Results: A total of 491 patients with 681 vertebral body fractures were included. Of 733 pedicle screws placed during the open surgery procedure, 96.0% were within the safe zone. There was no significant difference compared with pedicle screws placed percutaneously (95.3% of 1884 screws). In all other categories, the number of misplaced pedicle screws also showed no differences between the two treatment groups. There is a positive correlation between pedicle screw misplacement and duration of the operation. Most pedicle screws are misplaced at the levels T12, L1 and T7, T8., Conclusion: The current study shows that percutaneous surgery using dorsal stabilization allows the positioning of pedicle screws in an equivalently safe manner compared with an open surgical procedure in the acute care of spinal trauma.

Scope: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has become pandemic, reaching almost one million death worldwide. At present standard treatment for coronavirus disease 2019 (COVID-19) is not well defined because the evidence, either from randomized or observational studies, with conflicting results, has led to rapid changes in treatment guidelines. Our aim was to narratively summarize the available literature on the management of COVID-19 in order to combine current evidence and interpretation of the data by experts who are treating patients in the frontline setting., Methods: The panel conducted a detailed review of the literature and eventual press releases from randomized clinical trials for each possible available treatment. Inductive PubMed search waws performed for publications relevant to the topic, including all clinical trials conducted. The result was a flowchart with treatment indications for patients with COVID-19., Implications: After 6 months of a pandemic situation and before a possible second coronavirus wave descends on Europe, it is important to evaluate which drugs proved to be effective while also considering that results from many randomized clinical trials are still awaited. Indeed, among treatments for COVID-19, only glucocorticoids have resulted in an association with a significant decrease in mortality in published randomized controlled trials. New therapeutic strategies are urgently needed., (Copyright © 2020. Published by Elsevier Ltd.)

The increase in the aged population led to a global rise in the demand for elderly healthcare services, such as long-term care facilities (LTCFs), nursing homes, residential homes. Unfortunately, the spread of multidrug-resistant organisms (MDROs) in these structures represent an urgent public health threat requiring immediate action. The aim of this review is to provide a practice guide for the prevention of infections in European LTCFs. A team of experts identify specific problems and proposed practical solutions for the management of colonized and infected patients residing in LTCFs. The heterogeneity of LTCF represents one of the main problems for the implementation of standardized surveillance and infection control programs. Crucial steps involved in the spread of infections among LTCF residents are represented by patient's accommodation, MDRO screening on admission, management of patients with rectal colonization by MDROs, management of patients at high risk of MDRO infections, MDRO transmission by staff and implementation of antimicrobial stewardship. Efforts to implement specific actions in each of these fields are required to reduce the infections in this setting.

Background: Parkinson's disease (PD) is a chronic progressive neurological disorder with a high psychosocial and economic burden. As part of the European Brain Council (EBC)-led Value of Treatment project, this study aimed to capture the economic benefit of timely, adequate, and adherence to PD treatment., Methods: The EBC Value of Treatment Initiative combined different stakeholders to identify unmet needs in the patients' journey according to Rotterdam methodology. The economic evaluation focused on three major topics identified as major gaps: start of treatment; best treatment for advanced disease; and adherence to treatment. Two separate healthcare systems (Germany and the UK) were chosen. Cost-effectiveness was determined by using decision-analytical modelling approaches. Effectiveness was expressed as quality-adjusted life-years (QALYs) gained and incremental cost-effectiveness ratio (ICER)., Results: Treatment intervention in PD was found to be cost-effective regardless of the initial health state of the patient receiving the treatment. Cost savings were between -€1000 and -€5400 with 0.10 QALY gain and -€1800 and -€7600 with 0.10 QALY gain for Germany and the UK, respectively. Treatment remains cost-effective within the National Institute for Health and Care Excellence thresholds. Availability of adequate treatment to more patients was also found to be cost-effective, with an ICER of €15,000-€32,600 across country settings. Achieving the target adherence to treatment would generate cost-savings of €239,000-€576,000 (Germany) and €917,000-€2,980.000 (UK) for every 1,000 patients treated adequately., Conclusions: The analyses confirmed that timely, adequate, and adherence to PD treatment will not only improve care of the patients but is also cost-effective across healthcare systems. Further studies with a distinct identification of gaps in care are necessary to develop better and affordable care., (© 2020 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Restless legs syndrome (RLS) is one of the most common neurological disorders. It describes an irresistible urge to move the legs, mostly manifested in the evening and at night, which can lead to severe sleep disturbance. As part of the European Brain Council (EBC)-led Value-of-Treatment project, this study aimed at capturing the socioeconomic impact of RLS related to the inadequate diagnosis and treatment across different European healthcare settings. The economic burden of RLS was estimated using the published EBC framework of analysis in three separate European Union healthcare systems (France, Germany, and Italy). The RLS care pathway was mapped to identify the unmet needs of patients. Based on specific patient stories, the economic impact of correctly diagnosing RLS and changing between inadequate and target treatment was calculated using appropriate scenario analysis. RLS proved to be a significant personal and social burden, when epidemiological data, high prevalence of RLS, and its need for treatment are combined. By looking at the savings emerging from the provision of optimal care management (timely and correct diagnosis, evidence-based therapy, avoidance of therapy-related complications such as augmentation), the authors foresee substantial economic savings with the achievement of adequate diagnosis and treatment of RLS. Education about RLS is urgently needed for all subspecialties involved in RLS patient care as well as the general public. Equally important, the search for new causal treatment strategies should be intensified to reduce suffering and substantial societal cost., (© 2020 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background and Purpose: Idiopathic normal-pressure hydrocephalus (iNPH) is a progressive, severe brain disorder, which mainly affects people above the age of 65 years. iNPH is characterized by the accumulation of excess cerebrospinal fluid in the brain's ventricles. In most cases, iNPH patients can be effectively treated with shunt surgery, which involves placing a tube into the brain to drain the excess fluid. As part of the European Brain Council-led Value of Treatment project, this study aimed to investigate the cost-effectiveness of delivering timely and adequate iNPH treatment in Germany., Methods: The study identified treatment gaps that prevent iNPH patients from receiving adequate and timely treatment. The cost-effectiveness of delivering shunt surgery to iNPH-prevalent patients aged ≥65 years in Germany was calculated using decision-analytical modelling. The model compared two alternatives, current care (shunt surgery in 25% of iNPH cases) and target care (shunt surgery in 90% of iNPH cases), and looked at healthcare costs (diagnosis, shunt intervention and follow-up care) from the public health insurance perspective, as well as effectiveness outcomes in terms of lives saved and quality-adjusted life-years (QALYs) gained., Results: Delivering timely and adequate iNPH treatment proved to be cost-effective. Cost per life saved varied between €27 921 at 5 years and €246 726 at 15 years. Cost-per-QALY estimates varied between €10 202 at 5 years and €35 128 at 15 years., Conclusions: Idiopathic normal-pressure hydrocephalus is a treatable but often not-treated disease, resulting in unnecessary and avoidable disease burden for the healthcare system. Actions required to close this treatment gap are straightforward and their implementation has been modelled with successful outcomes., (© 2020 European Academy of Neurology.)

Purpose The vasopressin analog desmopressin (dDAVP) is known to increase plasma levels of hemostatic factors, and preclinical studies in colorectal cancer models have demonstrated that it hampers tumor vascularization and metastatic progression. We evaluated safety and preliminary efficacy of dDAVP in rectal cancer patients with bleeding, before receiving specific oncologic treatment with surgery, chemotherapy and/or radiotherapy. Methods Patients with rectal cancer having moderate or severe rectal bleeding were enrolled in an open-label, dose-finding trial. Intravenous infusions of dDAVP were administered during two consecutive days in doses from 0.25 to 2.0 µg/kg, using single or twice daily regimen. Bleeding was graded using a score based on the Chutkan scale and tumor perfusion was evaluated by dynamic contrast-enhanced magnetic resonance imaging. Results The trial accrued a total of 32 patients. Dose-limiting toxicity occurred in patients receiving 1 µg/kg or higher. The most prominent treatment-related severe adverse event was hyponatremia. Most patients receiving the maximum tolerated dose of 0.5 µg/kg showed at least a partial hemostatic response and 58% developed a complete response with absence of bleeding at day 4 and/or at the last follow-up at day 14. Tumor perfusion was decreased in two-thirds of patients after dDAVP treatment. Conclusions dDAVP appeared as a promising hemostatic agent in rectal cancer patients with bleeding. Randomized clinical trials to confirm its effectiveness are warranted.Clinical trial registration www.clinicaltrials.gov NCT01623206.

Acute myeloid leukemia is characterized by the accumulation of clonal myeloid blast cells unable to differentiate into mature leukocytes. Chemotherapy induces remission in the majority of patients, but relapse rates are high and lead to poor clinical outcomes. Because this is primarily caused by chemotherapy-resistant leukemic stem cells (LSCs), it is essential to eradicate LSCs to improve patient survival. LSCs have predominantly been studied at the transcript level, thus information about posttranscriptionally regulated genes and associated networks is lacking. Here, we extend our previous report on LSC proteomes to healthy age-matched hematopoietic stem and progenitor cells (HSPCs) and correlate the proteomes to the corresponding transcriptomes. By comparing LSCs to leukemic blasts and healthy HSPCs, we validate candidate LSC markers and highlight novel and potentially targetable proteins that are absent or only lowly expressed in HSPCs. In addition, our data provide strong evidence that LSCs harbor a characteristic energy metabolism, adhesion molecule composition, as well as RNA-processing properties. Furthermore, correlating proteome and transcript data of the same individual samples highlights the strength of proteome analyses, which are particularly potent in detecting alterations in metabolic pathways. In summary, our study provides a comprehensive proteomic and transcriptomic characterization of functionally validated LSCs, blasts, and healthy HSPCs, representing a valuable resource helping to design LSC-directed therapies., (© 2020 by The American Society of Hematology.)

Objectives: To maximise efficacy and minimise toxicity, special considerations are required for antibiotic prescription in elderly patients. This review aims to provide practical suggestions for the optimal management of antibiotic therapy in elderly patients., Methods: This was a narrative review. A literature search of published articles in the last 15 years on antibiotics and elderly patients was performed using the Cochrane Library and PubMed electronic databases. The three priority areas were identified: (i) pharmacokinetics/pharmacodynamics (PK/PD) for optimising dosage regimens and route of administration; (ii) antibiotic dosages in some special subpopulations; and (iii) treatment considerations relating to different antibiotic classes and their adverse events., Results: Clinicians should understand the altered PK/PD of drugs in this population owing to co-morbid conditions and normal physiological changes associated with ageing. The body of evidence justifies the need for individualised dose selection, especially in patients with impaired renal and liver function. Clinicians should be aware of the major drug-drug interactions commonly observed in the elderly as well as potential side effects., Conclusion: Antibiotic therapy in the elderly requires a comprehensive approach, including strategies to improve appropriate antibiotic prescribing, limit their use for uncomplicated infections and ensure the attainment of an optimal PK/PD target. To this purpose, further studies involving the elderly are needed to better understand the PK of antibiotics. Moreover, it is necessary to assess the role therapeutic drug monitoring in guiding antibiotic therapy in elderly patients in order to evaluate its impact on clinical outcome., (Copyright © 2020. Published by Elsevier Ltd.)

Amyloidosis represents a heterogeneous group of pathologies characterized by the deposit, in the form of fibrils, in the various organs and tissues of the body, of abnormal proteins; the deposits made up of these fibrils are called amyloid or amyloid substance. AL amyloidosis, also called "light chains", is a primary form characterized by deposits of light chains of monoclonal immunoglobulins, proteins that are produced by the bone marrow with the aim of protecting the body from pathological processes; for unknown reasons, these immunoglobulins, once fulfilled their function, do not dissolve but, on the contrary, they transform into amyloid fibrils and accumulate progressively, transported by the bloodstream, in the various organs and tissues. Below we report the case of a 77-year-old Caucasian male patient hospitalized at our Operative Unit for nephrotic syndrome and creatinine increase in the last couple of months, compared to previous normal tests. The patient underwent a renal biopsy and a bone marrow smear with evidence of AL amyloidosis (or primary amyloidosis) and of the presence, at serum immunofixation, of small IgG multiple myeloma k. Treated with bortezomib (1 mg/m 2 ) and soldesam (10 mg) first and with lenalidomid after, the patient had a clinical course burdened by symptomatic hypotension, due to severe dysautonomia. He had to start replacement treatment with haemodiafiltration for terminal kidney disease two months after the onset of illness. He died 4 months after the first hospitalization for nephrotic syndrome., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)