Model and Empirical Data-Based Cost-Utility Studies of Continuous Glucose Monitoring in Individuals with Type 1 Diabetes: A Protocol of a Systematic Review on Methodology and Quality.

INTRODUCTION: This review aims to critically appraise differences in methodology and quality of model-based and empirical-data-based cost-utility studies to address key limitations, opportunities, and challenges to inform future cost-utility analyses of continuous glucose monitoring (CGM) in type 1 diabetes. This protocol is registered at PROSPERO (CRD42023391284). METHODS: The review will be conducted in accordance with the PRISMA guideline for systematic reviews. Searches will be conducted in MEDLINE, Embase, Web of Science, Cochrane Library, and Econlit from 2000 to January 2023. Model and empirical data-based studies evaluating the cost-utility of any CGM system in type 1 diabetes will be considered for inclusion. Studies that only report on cost per life year or any other clinical outcome, or reporting only costs or only clinical outcomes studies in type 2 diabetes populations, and studies on bi-hormonal closed loops and do-it-yourself hybrid closed loop devices will be excluded. Two reviewers will independently screen each study for inclusion. Data on the intervention, population, model settings (such as perspective, time horizon), model type and structure, clinical outcomes used to populate the model, validation, and uncertainty will be extracted and qualitatively synthesised. Quality will be assessed using the Philips et al. 2006 (model-based studies) or Consensus Health Economic Criteria (empirical data-based studies) checklists. Model validation will be assessed using the AdViSHE checklist. DISCUSSION: Now that CGM is being used more broadly in practice, critical appraisal of existing cost-utility methodology and quality is important to inform future cost-utility analyses of CGM in type 1 diabetes in various settings.

Metabolic syndrome and cardiovascular disease after haematopoietic cell transplantation (HCT) in adults: an EBMT cross-sectional non-interventional study.

Metabolic syndrome (MetS) is associated with cardiovascular disease in the general population and is also a potential cardiovascular risk factor in survivors of haematopoietic cell transplantation (HCT). We report an EBMT cross-sectional, multi-centre, non-interventional study of 453 adult HCT patients surviving a minimum of 2 years post-transplant attending routine follow-up HCT and/or late effects clinics in 9 centres. The overall prevalence of MetS was 37.5% rising to 53% in patients >50 years of age at follow-up. There were no differences in rates of MetS between autologous and allogeneic HCT survivors, nor any association with graft-versus-host disease (GvHD) or current immunosuppressant therapy. Notably, there was a significantly higher occurrence of cardiovascular events (CVE, defined as cerebrovascular accident, coronary heart disease or peripheral vascular disease) in those with MetS than in those without MetS (26.7% versus 9%, p < 0.001, OR 3.69, 95% CI 2.09-6.54, p < 0.001), and, as expected, MetS and CVE were age-related. Unexpectedly, CVE were associated with occurrence of second malignancy. Screening for and management of MetS should be integrated within routine HCT long-term follow-up care for both allogeneic and autologous HCT survivors. Further research is warranted, including randomised controlled trials of interventional strategies and mechanistic studies of cardiovascular risk in HCT survivors.

COVA1-18 neutralizing antibody protects against SARS-CoV-2 in three preclinical models.

One year into the Coronavirus Disease 2019 (COVID-19) pandemic caused by Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), effective treatments are still needed 1-3 . Monoclonal antibodies, given alone or as part of a therapeutic cocktail, have shown promising results in patients, raising the hope that they could play an important role in preventing clinical deterioration in severely ill or in exposed, high risk individuals 4-6 . Here, we evaluated the prophylactic and therapeutic effect of COVA1-18 in vivo , a neutralizing antibody isolated from a convalescent patient 7 and highly potent against the B.1.1.7. isolate 8,9 . In both prophylactic and therapeutic settings, SARS-CoV-2 remained undetectable in the lungs of COVA1-18 treated hACE2 mice. Therapeutic treatment also caused a dramatic reduction in viral loads in the lungs of Syrian hamsters. When administered at 10 mg kg - 1 one day prior to a high dose SARS-CoV-2 challenge in cynomolgus macaques, COVA1-18 had a very strong antiviral activity in the upper respiratory compartments with an estimated reduction in viral infectivity of more than 95%, and prevented lymphopenia and extensive lung lesions. Modelling and experimental findings demonstrate that COVA1-18 has a strong antiviral activity in three different preclinical models and could be a valuable candidate for further clinical evaluation.

Baseline characteristics and clinical symptoms related to respiratory viruses identified among patients presenting with influenza-like illness in primary care.

OBJECTIVES: We aimed to identify patients' clinical characteristics associated with respiratory viruses identified among patients presenting with influenza-like illness (ILI). METHODS: A sample of patients of all ages presenting with ILI was included by physicians of the French Sentinelles network during two seasons (2015/16 and 2016/17). Nasopharyngeal samples were tested for the presence of influenza virus (IV), respiratory syncytial virus (RSV), human rhinovirus (HRV) and human metapneumovirus (HMPV). Patients' characteristics associated with each of the four virus classes were studied using multivariate logistic regressions. RESULTS: A total of 5859 individuals were included in the study: 48.0% tested positive for IV, 7.9% for HRV, 7.5% for RSV and 4.1% for HMPV. Cough was associated with IV (OR 2.14, 95% CI 1.81-2.52) RSV (OR 2.52, 95% CI 1.75-3.74) and HMPV detection (OR 2.15, 95% CI 1.40-3.45). Rhinorrhoea was associated mainly with HRV detection (OR 1.75, 95% CI 1.34-2.32). Headache was associated with IV detection (OR 1.75, 95% CI 1.34-2.32), whereas absence of headache was associated with RSV and HMPV detection. Dyspnoea was associated with RSV detection (OR 2.33, 95% CI 1.73-3.12) and absence of dyspnoea with IV detection. Conjunctivitis was associated with IV detection (OR 1.27, 95% CI 1.08-1.50). Some associations were observed only in children: dyspnoea and cough with RSV detection (age <5 years), conjunctivitis with IV detection (age <15 years). Period of onset of symptoms differed among aetiological diagnoses. Seasonal influenza vaccination decreased the risk of IV detection (OR, 0.67, 95% CI 0.51-0.86). CONCLUSIONS: This study allowed the identification of symptoms associated with several viral aetiologies in patients with ILI. A proper knowledge and understanding of these clinical signs may improve the medical management of patients.

Influenza B burden during seasonal influenza epidemics in France.

CONTEXT: Seasonal flu outbreaks are linked to the circulation of influenza virus type A or B. Special attention has always been paid to influenza A epidemics; but recently, several studies have investigated the impact of influenza B virus epidemics, particularly as, since the 1980s, two antigenically different influenza B lineages co-circulate, raising the issue of vaccine matching. OBJECTIVES: We present the results of influenza B burden during nine influenza seasons (2003-2013) and vaccine matching of the circulating lineages. PATIENTS AND METHODS: Clinical and virological influenza surveillance data, collected by the Regional Groups for Influenza Surveillance Network in France, allows for studying the burden of influenza in the practice of the population of ambulatory care physicians. RESULTS AND CONCLUSION: Our analysis is based on 37,801 samples, of which 12,036 were virologically confirmed influenza cases (31.8%), including 3576 cases of influenza B (29.7% of influenza cases). Influenza B viruses significantly circulated during six seasons. For each season, the influenza B epidemic peaked later than the influenza A epidemic. Influenza B is very common in children of school age but also affects other age groups. Finally, more than one-third of the analyzed influenza B viruses belonged to a different lineage than the one used in the composition of the trivalent vaccine. Our results are comparable to those described in other countries.

The EBMT-ELN working group recommendations on the prophylaxis and treatment of GvHD: a change-control analysis.

In 2013, recommendations for a standardized practice in the prophylaxis and treatment of GvHD were adopted and published by the European Society for Blood and Marrow Transplantation and the European LeukemiaNet. One year later, all 341 European Society for Blood and Marrow Transplantation centres performing allogeneic haematopoietic stem cell transplantation were contacted for a change-control analysis and asked to fill in a questionnaire; 111 centres (33%) responded. Of these, 83% had been aware of the recommendations. Paediatric centres (P=0.004), centres with shorter programme duration (P=0.049), not JACIE (the Joint Accreditation Committee of the International Society for Cellular Therapy and the European Society for Blood and Marrow Transplantation)-accredited centres (P=0.010) and centres from middle-income countries (P=0.033) were more likely to be unaware of the recommendations. Thirty-eight per cent of the centres regarded the recommendations as relevant guidelines affecting their policies, 61% as interesting information. Thirty per cent had decided to make changes in their institutional protocols based on the recommendations. More than 80% were willing to use the recommendations for a control arm in randomized studies. This survey shows that the published recommendations had some, though insufficient, impact on the strategies and methods of allogeneic haematopoietic stem cell transplantation applied by the centres. It also identified some of the weaknesses to be addressed when releasing recommendations in the future.

Allogeneic hematopoietic stem cell transplantation in solid organ transplant recipients: a retrospective, multicenter study of the EBMT.

We conducted a questionnaire survey of the 565 European Society for Blood and Marrow Transplantation centers to analyze the outcome of allogeneic hematopoietic stem cell transplantation (alloSCT) in recipients of solid organ transplantation (SOT). We investigated 28 patients with malignant (N = 22) or nonmalignant diseases (N = 6), who underwent 31 alloSCT procedures: 12 after kidney, 13 after liver and 3 after heart transplantation. The incidence of solid organ graft failure at 60 months after first alloSCT was 33% (95% confidence interval [CI], 16-51%) for all patients, 15% (95% CI, 2-40%) for liver recipients and 50% (95% CI, 19-75%) for kidney recipients (p = 0.06). The relapse rate after alloSCT (22%) was low following transplantation for malignant disorders, despite advanced stages of malignancy. Overall survival at 60 months after first alloSCT was 40% (95% CI, 19-60%) for all patients, 51% (95% CI, 16-86%) for liver recipients and 42% (95% CI, 14-70%) for kidney recipients (p = 0.39). In summary, we show that selected SOT recipients suffering from hematologic disorders may benefit from alloSCT and experience enhanced long-term survival without loss of organ function.

Kinetics and pattern of viral excretion in biological specimens of two MERS-CoV cases.

BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging coronavirus involved in severe acute respiratory distress syndrome (ARDS) and rapid renal failure. Hospital outbreak and nosocomial transmission were reported, however, several issues remain on the viral excretion course. OBJECTIVES: Describe the kinetics and pattern of viral excretion in two infected patients. STUDY DESIGN: After the initial diagnosis, blood, urine, rectal and respiratory samples were collected regularly, aliquoted and stored at -80°C. Real-time reverse transcriptase polymerase chain reaction assay targeted the UpE and Orf1a regions of the MERS-CoV genome. RESULTS: In patient 1, who died of refractory ARDS and renal failure, MERS-CoV RNA was detected in pharyngeal and tracheal swabs, as well blood samples and urine samples until the 30th day. Rectal swabs were negative. Patient 2 also developed multiple-organ failure, but survived, with persisting renal insufficiency (creatinine clearance at 30 mL/min) and persistent interstitial syndrome albeit weaned off mechanical ventilation and no longer requiring oxygen. Tracheal aspirations were positive until the 33rd day, while nasopharyngeal swabs were negative. All other biological samples were negative. DISCUSSION: Lower respiratory tract excretion of MERS-CoV could be observed for more than one month. The most severely ill patient presented an expression of the virus in blood and urine, consistent with a type-1 interferon mediated immunological response impaired in patient 1, but developed by patient 2. These results suggest that infection control precautions must be adequately evaluated in clinical wards and laboratories exposed to MERS-CoV.

Influenza at the animal-human interface: a review of the literature for virological evidence of human infection with swine or avian influenza viruses other than A(H5N1).

Factors that trigger human infection with animal influenza virus progressing into a pandemic are poorly understood. Within a project developing an evidence-based risk assessment framework for influenza viruses in animals, we conducted a review of the literature for evidence of human infection with animal influenza viruses by diagnostic methods used. The review covering Medline, Embase, SciSearch and CabAbstracts yielded 6,955 articles, of which we retained 89; for influenza A(H5N1) and A(H7N9), the official case counts of t he World Health Organization were used. An additional 30 studies were included by scanning the reference lists. Here, we present the findings for confirmed infections with virological evidence. We found reports of 1,419 naturally infected human cases, of which 648 were associated with avian influenza virus (AIV) A(H5N1), 375 with other AIV subtypes, and 396 with swine influenza virus (SIV). Human cases naturally infected with AIV spanned haemagglutinin subtypes H5, H6, H7, H9 and H10. SIV cases were associated with endemic SIV of H1 and H3 subtype descending from North American and Eurasian SIV lineages and various reassortants thereof. Direct exposure to birds or swine was the most likely source of infection for the cases with available information on exposure.

First cases of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infections in France, investigations and implications for the prevention of human-to-human transmission, France, May 2013.

In May 2013, Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection was diagnosed in an adult male in France with severe respiratory illness, who had travelled to the United Arab Emirates before symptom onset. Contact tracing identified a secondary case in a patient hospitalised in the same hospital room. No other cases of MERS-CoV infection were identified among the index case's 123 contacts, nor among 39 contacts of the secondary case, during the 10-day follow-up period.

Highly heterogeneous temperature sensitivity of 2009 pandemic influenza A(H1N1) viral isolates, northern France.

We assayed the temperature sensitivity of 2009 pandemic influenza A(H1N1) viral isolates (n=23) and seasonal influenza A(H1N1) viruses (n=18) isolated in northern France in 2007/08 and 2008/09. All isolates replicated with a similar efficiency at 34 °C and 37 °C, and with a lower efficiency at 40 °C. The pandemic viral isolates showed a stronger heterogeneity in their ability to grow at the highest temperature, as compared with the seasonal isolates. No statistically significant difference in temperature sensitivity was observed between the pandemic viral isolates from severe and mild cases of influenza. Our data point to the impact of temperature sensitivity on the genetic evolution and diversification of the pandemic influenza A(H1N1) virus since its introduction into the human population in April 2009, and call for close surveillance of this phenotypic marker related to host and tissue tropism.

Time course and risk factors of post-stroke fatigue: a prospective cohort study.

BACKGROUND: Post-stroke fatigue (PSF) often occurs after stroke and has a negative impact on the rehabilitation process. Several studies focused either on short- or on long-term PSF and their relations with stroke characteristics. However, possible pre-stroke risk factors such as history of depression, pre-existent white matter lesions or brain atrophy were usually not taken into account. Therefore, the precise mechanisms underlying PSF remain still unclear. This study was aimed at assessing the possible contributions of (pre-)stroke factors to both short-term PSF and its course over time. METHODS: This study pertains to 108 patients with an acute cerebral infarction. PSF was rated by the Checklist Individual Strength at 2 months and 1.5 year post-stroke. The relation between (pre-)stroke factors and PSF was assessed with multivariate regression analysis. RESULTS: The prevalence of baseline PSF was 35% and at follow-up 33%. Older age had a protective effect on PSF at baseline (OR 0.95; 95% CI 0.91-0.98), whereas post-stroke depressive symptoms and infratentorial infarctions were related to an increased risk for PSF (OR 1.40; 95% CI 1.21-1.63 and OR 4.69; 95% CI 1.03-21.47, respectively). Baseline fatigue was related to an increased risk of PSF at follow-up (OR 1.15; 95% CI 1.09-1.22). CONCLUSIONS: Predictors for baseline fatigue were younger age, post-stroke depressive symptoms, and infratentorial infarctions. Baseline fatigue did predict fatigue outcome over time, suggesting that early interventions might be useful to prevent deteriorated PSF.

S-OtrH3N2 viruses: use of sequence data for description of the molecular characteristics of the viruses and their relatedness to previously circulating H3N2 human viruses.

Emergence of influenza viruses from the animal reservoir is a permanent challenge. The rapid description and immediate sharing of information on these viruses is invaluable for influenza surveillance networks and for pandemic preparedness. With the help of data generated from the World Health Organization Collaborating Centre for Reference and Research on Influenza at the United States Centers for Disease Control and Prevention, we provide here information on the swine­origin triple reassortant influenza A(H3N2) viruses detected in human cases in the north-east of the United States.

Kinetics of nasopharyngeal shedding of novel H1N1 (swine-like) influenza A virus in an immunocompetent adult under oseltamivir therapy.

We describe a patient with confirmed novel H1N1 (swine-like) influenza A virus who had daily nasal swabs tested during oseltamivir therapy. Nasal shedding remained positive for 2 days and became negative on day 3. This report presents the first available data on the kinetics of shedding of this novel virus under antiviral therapy.

[A young woman from Cameroon with rectal blood loss, intestinal schistosomiasis and rectosigmoid carcinoma]. / Een jonge vrouw uit kameroen met rectaal bloedverlies, intestinale schistosomiasis en rectosigmoïdcarcinoom.

A 32-year-old woman from Cameroon presented with rectal blood loss due to a focally infiltrating adenocarcinoma of the rectosigmoid in the presence of an active intestinal schistosomiasis (Schistosoma intercalatum). A correlation between chronic intestinal schistosomiasis and the development of colorectal cancer has been suggested in the literature, but is not uniformly accepted. However, the case presented here reinforces this suggestion. In a patient with rectal blood loss who comes from an area where intestinal schistosomiasis is endemic, the possibility of a colorectal carcinoma should be considered in the diagnosis.

Early prediction of favourable recovery 6 months after mild traumatic brain injury.

BACKGROUND: Predicting outcome after mild traumatic brain injury (MTBI) is notoriously difficult. Although it is recognised that milder head injuries do not necessarily mean better outcomes, less is known about the factors that do enable early identification of patients who are likely to recover well. OBJECTIVE: To develop and internally validate two prediction rules for identifying patients who have the highest chance for good 6 month recovery. METHODS: A prospective cohort study was conducted among patients with MTBI admitted to the emergency department. Apart from MTBI severity indices, a range of pre-, peri- and early post-injury variables were considered as potential predictors, including emotional and physical functioning. Logistic regression modelling was used to predict the absence of postconcussional symptoms (PCS) and full return to work (RTW). RESULTS: At follow-up, 64% of the 201 participating patients reported full recovery. Based on our prediction rules, patients without premorbid physical problems, low levels of PCS and post-traumatic stress early after injury had a 90% chance of remaining free of PCS. Patients with over 11 years of education, without nausea or vomiting on admission, with no additional extracranial injuries and only low levels of pain early after injury had a 90% chance of full RTW. The discriminative ability of the prediction models was satisfactory, with an area under the curve >0.70 after correction for optimism. CONCLUSIONS: Early identification of patients with MTBI who are likely to have good 6 month recovery was feasible on the basis of relatively simple prognostic models. A score chart was derived from the models to facilitate clinical application.

Humoral and cellular responses to influenza vaccination in human recipients naturally tolerant to a kidney allograft.

Rare kidney allograft recipients enjoy unaltered graft function years after interruption of their immunosuppressive treatment. To assess the extent to which this state of 'operational tolerance' (TOL) is specific to the graft and not the result of a global immunodeficiency, we analyzed the response of such patients following influenza vaccination. Hemagglutination inhibition titers and frequency of IFNgamma-secreting T cells were measured before 1 and 3 months after vaccination. The proportion of healthy volunteers (HV) responding to vaccine was significantly higher than that of immunosuppressed (IS) patients. Three 'TOL' patients presented a humoral response similar to that of HV, whereas the two others had a poor response, like the IS recipients. Although the small number of patients does not allow for definitive conclusions to be made, these data suggest that the status of tolerance may be heterogeneous, with some patients with a global immunodeficiency and others with an adapted response to vaccination.