462 research outputs found
Long-term safety and efficacy of subcutaneous immunoglobulin IgPro20 in CIDP PATH extension study
Objective To investigate the long-term safety and efficacy of weekly subcutaneous IgPro20 (Hizentra, CSL Behring) in chronic inflammatory demyelinating polyneuropathy (CIDP). Methods In a 48-week open-label prospective extension study to the PATH study, patients were initially started on 0.2 g/kg or on 0.4 g/kg weekly and-if clinically stable-switched to 0.2 g/kg weekly after 24 weeks. Upon CIDP relapse on the 0.2 g/kg dose, 0.4 g/kg was (re)initiated. CIDP relapse was defined as a deterioration by at least 1 point in the total adjusted Inflammatory Neuropathy Cause and Treatment score. Results Eighty-two patients were enrolled. Sixty-two patients initially received 0.4 g/kg, 20 patients 0.2 g/kg weekly. Seventy-two received both doses during the study. Sixty-six patients (81%) completed the 48-week study duration. Overall relapse rates were 10% in 0.4 g/kg-treated patients and 48% in 0.2 g/kg-treated patients. After dose reduction from 0.4 to 0.2 g/kg, 51% (27/53) of patients relapsed, of whom 92% (24 of 26) improved after reinitiation of the 0.4 g/kg dose. Two-thirds of patients (19/28) who completed the PATH study without relapse remained relapse-free on the 0.2 g/kg dose after dose reduction in the extension study. Sixty-two patients had adverse events (AEs) (76%), of which most were mild or moderate with no related serious AEs. Conclusions Subcutaneous treatment with IgPro20 provided long-term benefit at both 0.4 and 0.2 g/kg weekly doses with lower relapse rates on the higher dose. Long-term dosing should be individualized to find the most appropriate dose in a given patient. Classification of evidence This study provides Class IV evidence that for patients with CIDP, long-term treatment with SCIG beyond 24 weeks is safe and efficacious.Peer reviewe
Simulations for designing and interpreting intervention trials in infectious diseases.
BACKGROUND: Interventions in infectious diseases can have both direct effects on individuals who receive the intervention as well as indirect effects in the population. In addition, intervention combinations can have complex interactions at the population level, which are often difficult to adequately assess with standard study designs and analytical methods.
DISCUSSION: Herein, we urge the adoption of a new paradigm for the design and interpretation of intervention trials in infectious diseases, particularly with regard to emerging infectious diseases, one that more accurately reflects the dynamics of the transmission process. In an increasingly complex world, simulations can explicitly represent transmission dynamics, which are critical for proper trial design and interpretation. Certain ethical aspects of a trial can also be quantified using simulations. Further, after a trial has been conducted, simulations can be used to explore the possible explanations for the observed effects.
CONCLUSION: Much is to be gained through a multidisciplinary approach that builds collaborations among experts in infectious disease dynamics, epidemiology, statistical science, economics, simulation methods, and the conduct of clinical trials
Revealing the True Incidence of Pandemic A (H1N1)pdm09 Influenza in Finland during the First Two Seasons - An Analysis Based on a Dynamic Transmission Model
The threat of the new pandemic influenza A(H1N1)pdm09 imposed a heavy burden on the public health system in Finland in 2009-2010. An extensive vaccination campaign was set up in the middle of the first pandemic season. However, the true number of infected individuals remains uncertain as the surveillance missed a large portion of mild infections. We constructed a transmission model to simulate the spread of influenza in the Finnish population. We used the model to analyse the two first years (2009-2011) of A(H1N1)pdm09 in Finland. Using data from the national surveillance of influenza and data on close person-to-person (social) contacts in the population, we estimated that 6% (90% credible interval 5.1 - 6.7%) of the population was infected with A(H1N1)pdm09 in the first pandemic season (2009/2010) and an additional 3% (2.5 - 3.5%) in the second season (2010/2011). Vaccination had a substantial impact in mitigating the second season. The dynamic approach allowed us to discover how the proportion of detected cases changed over the course of the epidemic. The role of time-varying reproduction number, capturing the effects of weather and changes in behaviour, was important in shaping the epidemic.</p
Probing the single-particle character of rotational states in F using a short-lived isomeric beam
A beam containing a substantial component of both the ,
ns isomeric state of F and its , 109.77-min ground
state has been utilized to study members of the ground-state rotational band in
F through the neutron transfer reaction , in inverse kinematics.
The resulting spectroscopic strengths confirm the single-particle nature of the
13/2 band-terminating state. The agreement between shell-model
calculations, using an interaction constructed within the shell, and our
experimental results reinforces the idea of a single-particle/collective
duality in the descriptions of the structure of atomic nuclei
Clinical Value of 18F-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Response Evaluation after Primary Treatment of Advanced Epithelial Ovarian Cancer
Aims: To prospectively evaluate the use of F-18-fluorodeoxyglucose positron emission tomography/computed tomography (F-18-FDG-PET/CT) in the definition of the treatment response after primary treatment of advanced epithelial ovarian cancer (EOC). Materials and methods: Forty-nine patients with advanced EOC had an F-18-FDG PET/CT scan before and after primary treatment. The treatment response was defined with the currently used radiological and serological Response Criteria in Solid Tumors (RECIST1.1/GCIC) criteria and the modified PET Response Criteria in Solid Tumors (PERCIST). The concordance of the two methods was analysed. If the patient had a complete response to primary treatment by conventional criteria, the end of treatment F-18-FDG PET/CT scan (etPET/CT) was not opened until retrospectively at the time of disease progression. The ability of etPET/CT to predict the time to disease recurrence was analysed. The recurrence patterns were observed with an F-18-FDG PET/CT at the first relapse. Results: The agreement of the RECIST1.1/GCIC and modified PERCIST criteria in defining the primary treatment response in the whole patient cohort was good (weighted kappa coefficient = 0.78 ). Of the complete responders (n = 28), 34% had metabolically active lesions present in the etPET/CT, most typically in the lymph nodes. The same anatomical sites tended to activate at disease relapse, but were seldom the only site of relapse. In patients with widespread intra-abdominal carsinosis at diagnosis, the definition of metabolic response was challenging due to problems in distinguishing the physiological FDG accumulation in the bowel loops from the residual tumour in the same area. The presence of metabolically active lesions in the etPET/CT did not predict earlier disease relapse in the complete responders. Conclusions: In the present study, etPET/CT revealed metabolically active lesions in complete responders after EOC primary therapy, but they were insignificant for the patient's prognosis. The current study does not favour routine use of F-18-FDG PET/CT after EOC primary treatment for complete responders. (C) 2018 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.Peer reviewe
Mathematical modelling long-term effects of replacing Prevnar7 with Prevnar13 on invasive pneumococcal diseases in England and Wales
England and Wales recently replaced the 7-valent pneumococcal conjugate vaccine (PCV7) with its 13-valent equivalent (PCV13), partly based on projections from mathematical models of the long-term impact of such a switch compared to ceasing pneumococcal conjugate vaccination altogether. A compartmental deterministic model was used to estimate parameters governing transmission of infection and competition between different groups of pneumococcal serotypes prior to the introduction of PCV13. The best-fitting parameters were used in an individual based model to describe pneumococcal transmission dynamics and effects of various options for the vaccination programme change in England and Wales. A number of scenarios were conducted using (i) different assumptions about the number of invasive pneumococcal disease cases adjusted for the increasing trend in disease incidence prior to PCV7 introduction in England and Wales, and (ii) a range of values representing serotype replacement induced by vaccination of the additional six serotypes in PCV13. Most of the scenarios considered suggest that ceasing pneumococcal conjugate vaccine use would cause an increase in invasive pneumococcal disease incidence, while replacing PCV7 with PCV13 would cause an overall decrease. However, the size of this reduction largely depends on the level of competition induced by the additional serotypes in PCV13. The model estimates that over 20 years of PCV13 vaccination, around 5000–62000 IPD cases could be prevented compared to stopping pneumococcal conjugate vaccination altogether. Despite inevitable uncertainty around serotype replacement effects following introduction of PCV13, the model suggests a reduction in overall invasive pneumococcal disease incidence in all cases. Our results provide useful evidence on the benefits of PCV13 to countries replacing or considering replacing PCV7 with PCV13, as well as data that can be used to evaluate the cost-effectiveness of such a switch
Clustering of serotypes in a longitudinal study of Streptococcus pneumoniae carriage in three day care centres
<p>Abstract</p> <p>Background</p> <p><it>Streptococcus pneumoniae </it>(pneumococcus) causes a wide range of clinical manifestations that together constitute a major burden of disease worldwide. The main route of pneumococcal transmission is through asymptomatic colonisation of the nasopharynx. Studies of transmission are currently of general interest because of the impact of the new conjugate-polysaccharide vaccines on nasopharyngeal colonisation (carriage). Here we report the first longitudinal study of pneumococcal carriage that records serotype specific exposure to pneumococci simultaneously within the two most important mixing groups, families and day care facilities.</p> <p>Methods</p> <p>We followed attendees (N = 59) with their family members (N = 117) and the employees (N = 37) in three Finnish day care centres for 9 months with monthly sampling of nasopharyngeal carriage. Pneumococci were cultured, identified and serotyped by standard methods.</p> <p>Results</p> <p>Children in day care constitute a core group of pneumococcal carriage: of the 36 acquisitions of carriage with documented exposure to homologous pneumococci, the attendee had been exposed in her/his day care centre in 35 cases and in the family in 9 cases. Day care children introduce pneumococci to the family: 66% of acquisitions of a new serotype in a family were associated with simultaneous or previous carriage of the same type in the child attending day care. Consequently, pneumococcal transmission was found to take place as micro-epidemics driven by the day care centres. Each of the three day care centres was dominated by a serotype of its own, accounting for 100% of the isolates of that serotype among all samples from the day care attendees.</p> <p>Conclusion</p> <p>The transmission of pneumococci is more intense within than across clusters defined by day care facilities. The ensuing micro-epidemic behaviour enhances pneumococcal transmission.</p
Behavior of FDG-avid supradiaphragmatic lymph nodes in PET/CT throughout primary therapy in advanced serous epithelial ovarian cancer: a prospective study
BackgroundEpithelial ovarian cancer (EOC) typically spreads intra-abdominally, but preoperative evaluation with FDG PET/CT often reveals metabolically active supradiaphragmatic lymph nodes (sdLNs). Their clinical significance and behavior during treatment has not been established.MethodsEOC patients with PET positive sdLNs at diagnosis were prospectively followed with PET/CT after primary chemotherapy and at the first recurrence. In each patient, 2 most active LNs in 5 different supradiaphramatic regions were evaluated and the size and changes in FDG uptake (SUVmax) were recorded. The patients overall response to primary treatment was defined with RECIST criteria. The behavior of sdLNs during chemotherapy were compared in treatment responders and non-responders. Recurrence patterns were monitored.ResultsForty-one patients with 127 PET/CT scans were systematically evaluated. In pretreatment scan, 76% (31/41) of patients had FDG-avid sdLNs in multiple anatomical sites. Only a minority (22/136) of the sdLNs were enlarged in size, but their histopathologic confirmation by biopsy was not possible. Only 6/41 patients had FDG-avid sdLNs in a single surgically approachable site. The sdLNs became inactive during primary chemotherapy more often in the RECIST responders compared to the non-responders (HR 1.46 (95%CI: 1.09-1.96), p=0.002). The size and SUVmax values did not predict treatment outcome. In 50% of the responders the same sdLNs reactivated when recurrence occurred. Persistent post-treatment metabolic activity did not predict earlier disease relapse (p=0.59).ConclusionThe behavior of metabolically active sdLNs during chemotherapy supports their metastatic nature. Due to their distribution to multiple regions, the benefit of removal of reachable sdLNS seems unlikely.Trial registration>NCT, NCT01276574. Registered 1 September 2010
Outbreaks of Streptococcus pneumoniae carriage in day care cohorts in Finland – implications for elimination of transmission
Diagnostic value of serum biomarkers FGF21 and GDF15 compared to muscle sample in mitochondrial disease
The aim of this study was to compare the value of serum biomarkers, fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15), with histological analysis of muscle in the diagnosis of mitochondrial disease. We collected 194 serum samples from patients with a suspected or known mitochondrial disease. Biomarkers were analyzed blinded using enzyme-labeled immunosorbent assay. Clinical data were collected using a structured questionnaire. Only 39% of patients with genetically verified mitochondrial disease had mitochondrial pathology in their muscle histology. In contrast, biomarkers were elevated in 62% of patients with genetically verified mitochondrial disease. Those with both biomarkers elevated had a muscle manifesting disorder and a defect affecting mitochondrial DNA expression. If at least one of the biomarkers was induced and the patient had a myopathic disease, a mitochondrial DNA expression disease was the cause with 94% probability. Among patients with biomarker analysis and muscle biopsy takenPeer reviewe
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