2494 research outputs found
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Airway autoimmune responses in severe eosinophilic asthma following low-dose Mepolizumab therapy
No full textAbstract
Background
Anti-interleukin (IL)-5 monoclonal antibodies as an eosinophil-depleting strategy is well established, with Mepolizumab being the first biologic approved as an adjunct treatment for severe eosinophilic asthma.
Case presentation
A 62-year old woman diagnosed with severe eosinophilic asthma showed poor response to Mepolizumab therapy (100\ua0mg subcutaneous dose/monthly) and subsequent worsening of symptoms. The treatment response to Mepolizumab was monitored using both blood and sputum eosinophil counts. The latter\ua0was superior in assessing deterioration in symptoms, suggesting that normal blood eosinophil count may not always indicate amelioration or adequate control of the ongoing eosinophil-driven disease process. This perplexing situation of persistent airway eosinophilia and increased steroid insensitivity despite an anti-eosinophil therapy can be explained if the administered dose of the mAb was inadequate in comparison to the target antigen. The resultant immune complexes could act as \u2018cytokine depots\u2019, protecting the potency of the \u2018bound\u2019 IL-5, thereby sustaining the eosinophilic inflammation within the target tissue. Molecular analysis of the sputum indicated the development of a polyclonal autoimmune response as well as an increase in group 2 innate lymphoid cells, two novel observations in severe eosinophilic asthma, which were associated with indices of disease severity and progression. This case highlights the possibility of a previously unrecognised autoimmune-mediated worsening of asthma perhaps triggered by immune complexes formed due to inadequate dosing of administered monoclonal antibodies in the target tissue.
Conclusions
While anti-IL5 mAb therapy is an exciting novel option to treat patients with severe asthma, there is the rare possibility of worsening of asthma as observed in this case study, due to local autoimmune mechanisms precipitated by potential inadequate airway levels of the monoclonal antibody
Three-minute SPECT/CT is sufficient for the assessment of bone metastasis as add-on to planar bone scintigraphy: prospective head-to-head comparison to 11-min SPECT/CT
No full textAbstract
Background
The aim of this study is to assess whether ultra-fast acquisition SPECT/CT (UF-SPECT/CT) can replace standard SPECT/CT (std-SPECT/CT) as \u201cadd-on\u201d to whole-body bone scintigraphy (WB-BS) for the investigation of bone metastases.
Consecutive cancer patients referred for WB-BS who underwent SPECT/CT in addition to WB-BS were included. Std-SPECT, UF-SPECT, and low-dose CT were performed (std-SPECT: matrix 128\u2009\ud7\u2009128, zoom factor 1, 20\ua0s/view, 32 views; UF-SPECT: identical parameters except for 10\ua0s/view and 16 views, reducing the acquisition time from 11 to 3\ua0min). A consensus diagnosis was reached by two observers for each set of images (WB-BS + standard SPECT/CT or WB-BS + UF-SPECT/CT) using a three-category evaluation scale: M0: no bone metastases; M1: bone metastases; and Me: equivocal findings.
Results
Among the 104 included patients, most presented with prostate cancer ( n \u2009=\u200971) or breast cancer ( n \u2009=\u200928). Using WB-BS + std-SPECT/CT, 71 (68%) patients were classified as M0, 19 (18%) as M1, and 14 (14%) as Me. Excellent agreement was observed between WB-BS + std-SPECT/CT and WB-BS + UF-SPECT/CT using the three-category scale: kappa\u2009=\u20090.91 (95% CI 0.84\u20130.97). No difference in observer agreement between cancer types was detected. SPECT/CT provided a definitive classification in 90 of 104 cases in which WB-BS was not entirely diagnostic.
Conclusions
To investigate potential bone metastases, UF-SPECT/CT can be conducted as add-on to WB-BS to notably reduce the SPECT acquisition time without compromising diagnostic confidence
An algorithm based on logistic regression with data fusion in wireless sensor networks
No full textAbstract
A decision fusion rule using the total number of detections reported by the local sensors for hypothesis testing and the total number of detections that report \u201c1\u201d to the fusion center (FC) is studied for a wireless sensor network (WSN) with distributed sensors. A logistic regression fusion rule (LRFR) is formulated. We propose the logistic regression fusion algorithm (LRFA), in which we train the coefficients of the LRFR, and then use the LRFR to make a global decision about the presence/absence of the target. Both the fixed and variable numbers of decisions received by the FC are examined. The fusion rule of K out of N and the counting rule are compared with the LRFR. The LRFA does not depend on the signal model and the priori knowledge of the local sensors\u2019 detection probabilities and false alarm rate. The numerical simulations are conducted, and the results show that the LRFR improves the performance of the system with low computational complexity
Poisson-type inequalities for growth properties of positive superharmonic functions
No full textAbstract
In this paper, we present new Poisson-type inequalities for Poisson integrals with continuous data on the boundary. The obtained inequalities are used to obtain growth properties at infinity of positive superharmonic functions in a smooth cone
Fourier series of higher-order Bernoulli functions and their applications
No full textAbstract
In this paper, we study the Fourier series related to higher-order Bernoulli functions and give new identities for higher-order Bernoulli functions which are derived from the Fourier series of them.
MSC: 11B68, 42A16
Bacterial etiology of bloodstream infections and antimicrobial resistance in Dhaka, Bangladesh, 2005\u20132014
No full textAbstract
Background
Bloodstream infections due to bacterial pathogens are a major cause of morbidity and mortality in Bangladesh and other developing countries. In these countries, most patients are treated empirically based on their clinical symptoms. Therefore, up to date etiological data for major pathogens causing bloodstream infections may play a positive role in better healthcare management. The aim of this study was to identify the bacterial pathogens causing major bloodstream infections in Dhaka, Bangladesh and determine their antibiotic susceptibility pattern.
Methods
From January 2005 to December 2014, a total of 103,679 single bottle blood samples were collected from both hospitalized and domiciliary patients attending Dhaka hospital, icddrb, Bangladesh All the blood samples were processed for culture using a BACT/Alert blood culture machine. Further identification of bacterial pathogens and their antimicrobial susceptibility test were performed using standard microbiological procedures.
Results
Overall, 13.6% of the cultured blood samples were positive and Gram-negative (72.1%) bacteria were predominant throughout the study period. Salmonella Typhi was the most frequently isolated organism (36.9% of samples) in this study and a high percentage of those strains were multidrug-resistant (MDR). However, a decreasing trend in the S . Typhi isolation rate was observed and, noticeably, the percentage of MDR S. Typhi isolated declined sharply over the study period. An overall increase in the presence of Gram-positive bacteria was observed, but most significantly we observed the percentage of MDR Gram-positive bacteria to double over the study period. Overall, Gram positive bacteria were more resistant to most of the commonly used antibiotics than Gram-negative bacteria, but the MDR level was high in both groups.
Conclusions
This study identified the major bacterial pathogens involved with BSI in Dhaka, Bangladesh and also revealed their antibiotic susceptibility patterns. We expect our findings to help healthcare professionals to make informed decisions and provide better care for their patients. Also, we hope this study will assist researchers and policy makers to prioritize their research options to face the future challenges of infectious diseases
Shiga (Vero)-toxin producing Escherichia coli isolated from the hospital foods; virulence factors, o-serogroups and antimicrobial resistance properties
No full textAbstract
Background
According to the presence of the weak, diabetic and immunosuppressive patients in hospitals, hospital foods should have a high quality and safety. Cooking a lot of foods higher than daily requirement, storage of cooked foods in an inappropriate condition and presence of nurses and servants in distribution of food to patients are the main reasons caused contamination of hospital foods. Shiga toxigenic Escherichia coli is one of the common cause of food poisoning in hospitals. The present research was carried out to study the distribution of virulence factors, O-serogroups and antibiotic resistance properties in STEC strains recovered from Iranian hospital food samples.
Methods
Five-hundred and eighty raw and cooked food samples were collected and immediately transferred to the laboratory. E. coli -positive strains were subjected to PCR and disk diffusion method.
Results
Thirty-nine out of 580 (6.72%) hospital food samples were contaminated with E. coli . Raw (20%) and cooked meat (6%) were the most commonly contaminated samples. Raw samples had the higher prevalence of E. coli ( P <0.01). Samples which were collected in the summer season had the highest prevalence of bacteria (64.10%). Significant difference was seen between the prevalence of EHEC and AEEC subtypes ( P <0.01). The most commonly detected virulence factors in both EHEC and AEEC subtypes were stx 1 and eae . The most commonly detected serogroups were O26 (43.75%) and O157 (25%) and there were no positive results for O103, O145, O91, O113 and O128 serogroups. Aac ( 3 )- IV (100%), CITM (100%) and tetA (62.50%) were the most commonly detected antibiotic resistance genes. STEC strains harbored the highest levels of resistance against ampicillin (93.75%), gentamycin (93.75%), tetracycline (87.50%) and ciprofloxacin (81.25%). All of the STEC strains were resistant to at least 3 antibiotics, while the prevalence of resistance against more than 12 antibiotics were 12.50%.
Conclusions
High presence of O157 serogroups, EHEC strains and animal-based antibiotics in cooked foods showed insufficiency of cooking time and temperature in the kitchens of hospitals. Judicious prescription of antibiotics and attentions to the principles of food safety can reduce the risk of resistant and virulent strains of STEC in hospital foods
Deflazacort: therapeutic index, relative potency and equivalent doses versus other corticosteroids
No full textAbstract
Background
Deflazacort is a synthetic corticosteroid characterized by a favourable pharmacokinetic profile, peculiar pharmacodynamic properties and a good safety profile. However, to the best of our knowledge, no dose-conversion table based on direct comparison of relative potencies between deflazacort and other main corticosteroids is currently available in scientific literature.
Main body
This paper, while reporting a brief review of deflazacort pharmacological properties, its efficacy and tolerability in different clinical areas, has been designed with the specific aim of providing a new dose-conversion table of corticosteroids, including for the first time also deflazacort.
Short conclusion
We suggest that this new conversion table could be a useful tool for physicians who need to select the appropriate dose of deflazacort in their clinical practice
The efficacy and safety of co-administration of fimasartan and rosuvastatin to patients with hypertension and dyslipidemia
No full textAbstract
Background
Hypertension and dyslipidemia are major risk factors of cardiovascular disease (CVD) events. The objective of this study was to evaluate the efficacy and safety of the co-administration of fimasartan and rosuvastatin in patients with hypertension and hypercholesterolemia.
Methods
We conducted a randomized double-blind and parallel-group trial. Patients who met eligible criteria after 4\ua0weeks of therapeutic life change were randomly assigned to the following groups.
1) co-administration of fimasartan 120\ua0mg/rosuvastatin 20\ua0mg (FMS/RSV), 2) fimasartan 120\ua0mg (FMS) alone 3) rosuvastatin 20\ua0mg (RSV) alone. Drugs were administered once daily for 8\ua0weeks.
Results
Of 140 randomized patients, 135 for whom efficacy data were available were analyzed. After 8\ua0weeks of treatment, the FMS/RSV treatment group showed greater reductions in sitting systolic (siSBP) and diastolic (siDBP) blood pressures than those in the group receiving RSV alone (both p \u2009<\u20090.001). Reductions in siSBP and siDBP were not significantly different between the FMS/RSV and FMS alone groups ( p \u2009=\u20090.500 and p \u2009=\u20090.734, respectively). After 8\ua0weeks of treatment, FMS/RSV treatment showed greater efficacy in percentage reduction of low-density lipoprotein cholesterol (LDL-C) level from baseline than that shown by FMS alone treatment ( p \u2009<\u20090.001). The response rates of siSBP with FMS/RSV, FMS alone, and RSV alone treatments were 65.22, 55.56, and 34.09%, respectively (FMS/RSV vs. RSV, p \u2009=\u20090.006). The LDL-C goal attainment rates with FMS/RSV, RSV alone, and FMS alone treatments were 80.43%, 81.82%, and 15.56%, respectively (FMS/RSV vs. FMS, p \u2009<\u20090.001). Incidence of adverse drug reactions with FMS/RSV ..
Approval status and evidence for WHO essential medicines for children in the United States, United Kingdom, and Japan: a cross-sectional study
No full textAbstract
Background
The WHO Model List of Essential Medicines for Children (EMLc) covers medicines for globally high-burden diseases. Regulatory approval in high-income countries ensures evidence and dosage form but usually focuses on diseases common in those countries and not in low- and middle-income countries.
Methods
This cross-sectional study assessed supporting evidence for the 346 medicines in the 5th WHO EMLc and their approval data from the United States, United Kingdom, and Japan.
Results
Of the 346 EMLc medicines, 307 were approved in one or more of the three countries, 278 of which had supporting evidence of efficacy. The percentage of medicines approved in one or more of the three countries was lowest for antiparasitics (60%) whereas 100% for medicines for cancers and musculoskeletal and respiratory conditions were approved. Five of the 30 EMLc antineoplastics had no supporting paediatric evidence. Of the 39 EMLc medicines unapproved in all three countries, 26 were indicated for neglected infectious diseases (NIDs). Ten of the 26 had supporting paediatric evidence. Seventeen of the 39 unapproved medicines had no paediatric dosage form available, and all 17 were indicated for NIDs.
Conclusions
Most EMLc medicines for diseases common in the three countries had supporting evidence, which was closely associated with approval, whereas a substantial number of medicines for NIDs were unapproved in the three countries, regardless of whether they had supporting evidence. Because of the limited contribution to the EMLc from high income countries, appropriate incentive mechanisms for pharmaceutical companies are required to make paediatric development for NIDs feasible and effective