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1.
Real‐world comparative analysis of bleeding complications and health‐related quality of life in patients with haemophilia A and haemophilia B 下载免费PDF全文
Jason Booth Abiola Oladapo Shaun Walsh Jamie O'Hara Liz Carroll Daniel‐Anibal Garcia Diego Brian O'Mahony 《Haemophilia》2018,24(5):e322-e327
Introduction
Clinical severity and impact of haemophilia on quality of life have been generally considered to be lower for haemophilia B (HB) compared with haemophilia A (HA) patients.Aims
To compare annual bleeding rate (ABR), target joint development and health‐related quality of life (HRQoL) between adult (≥18 years) severe HA and HB patients using recent data from the Cost of Haemophilia in Europe: a Socioeconomic Survey (CHESS) study.Methods
Multivariate generalized linear models (GLM) were constructed to assess the relationship between haemophilia type, ABR, HRQoL (derived from EQ‐5D index scores) and the presence of target joints while controlling for covariates.Results
Of the 1225 patients included, 77% (n = 949) had HA and 23% (n = 278) had HB. Of the 514 patients who completed the EQ‐5D, 78% (n = 405) had HA, and 22% (n = 110) had HB. Unadjusted mean ABR was 3.79 in HA and 4.60 in HB. The presence of ≥1 target joint was reported in 59% and 54% of patients with HA and HB, respectively. Unadjusted mean EQ‐5D index score was 0.78 in HA and 0.76 in HB. Haemophilia type was not a significant predictor of ABR, target joints or HRQoL when adjusted for confounding factors such as BMI, age and replacement therapy regimen.Conclusion
Data suggest comparable ABR, incidence of target joints and HRQoL between patients with HB and HA indicating comparable clinical severity and disease impact on patient quality of life. 相似文献2.
Udo F. Wehmeier Valerie Orth Vanessa Höppe Leonard A. Valentino Thomas Hilberg 《Haemophilia》2023,29(6):1539-1546
Introduction
People with haemophilia (PwH) suffer from haemophilic arthropathy which is accompanied by acute and chronic inflammation. The aim of this study was to examine the neuroinflammatory network operative in PwH and to compare it to healthy controls.Material and Methods
Blood samples were collected from 41 PwH (age 54.7 ± 11.7 years) and 33 healthy controls (age 50.9 ± 10.5 years) and the levels of 13 neuroinflammatory markers were analyzed by applying an antibody-based detection kit in a flow cytometer.Results
From 13 analyzed markers, three—ß-nerve growth factor (ß-NGF), soluble receptor for advanced glycation endproducts (sRAGE) and Interleukin-18 (IL-18) differed significantly between the groups (ß-NGF p = .045; sRAGE p = .003; IL-18 p = .007). While ß-NGF was downregulated in PwH, sRAGE and IL-18 were upregulated. None of the analyzed markers corelated to the joint status of PwH while CCL2 (C-C motif ligand 2 chemokine) correlated to HIV infections in PwH (r = .313, p = .007). Correlation analyses of the markers studied also revealed many differences between PwH and controls suggesting a number of deregulations in PwH.Conclusion
The altered levels of sRAGE and ß-NGF in PwH, which have not been analyzed in PwH before, may help to understand the neuroinflammatory network operative in PwH. The general inflammatory processes in PwH and the involved biomarkers in PwH remain poorly understood. PwH could benefit from new therapies against neuroinflammation which may help to reduce inflammation or also chronic pain. 相似文献3.
Long‐term tolerability,immunogenicity and efficacy of Nuwiq® (human‐cl rhFVIII) in children with severe haemophilia A 下载免费PDF全文
A. Klukowska T. Szczepański V. Vdovin S. Knaub J. Bichler M. Jansen I. Dzhunova R. J. Liesner 《Haemophilia》2018,24(4):595-603
Introduction
Nuwiq® (human‐cl rhFVIII, simoctocog alfa) is a 4th generation recombinant human FVIII, without chemical modification or fusion with any other protein, produced in a human cell line.Aim/Methods
This study (GENA‐13) was an extension of the GENA‐03 study in which previously treated children aged 2‐12 years with severe haemophilia A received Nuwiq® prophylaxis for ≥6 months. GENA‐13 examined long‐term tolerability, immunogenicity and efficacy of Nuwiq® prophylaxis in children.Results
Of 59 patients enrolled in GENA‐03, 49 continued Nuwiq® prophylaxis in GENA‐13 for a median (range) of 30.0 (9.5‐52.0) months. No patient withdrew due to drug‐related adverse events or developed inhibitors. Only 2 of 20 518 infusions were associated with possibly related adverse events (dyspnoea, fever). The estimated annualized bleeding rate (ABR) was 0.67 (95% CI: 0.44, 1.02) for spontaneous and 2.88 (95% CI: 1.86, 4.46) for all bleeds. Younger children (2‐5 years) had lower ABRs than children aged 6‐12 years. Annualized bleeding rates were reduced in GENA‐13 vs GENA‐03, especially for spontaneous bleeds in younger children (71% reduction; ABR ratio 0.29 [95% CI: 0.11, 0.74]). Nuwiq® efficacy was rated as excellent/good in the treatment of 83.0% of 305 evaluated breakthrough bleeds. Surgical prophylaxis with Nuwiq® was rated as excellent for all 17 assessed procedures.Conclusion
Long‐term treatment with Nuwiq® for the prevention of bleeds in children with severe haemophilia A was well tolerated, effective and reduced spontaneous bleeding by up to 70% compared with GENA‐03. 相似文献4.
Introduction
Patients with haemophilia (PwH) suffer from an enhanced pain sensitivity due to repetitive joint bleedings. A comprehensive, quantitative examination of the somatosensory system has not been performed in this population to date.Material and methods
Thirty patients with moderate or severe haemophilia A or B and 30 healthy controls were examined by means of Quantitative Sensory Testing to assess the function of the somatosensory system. Detection (DT) and pain thresholds (PT) were determined, amounting to a total of 13 parameters. Both knee joints and the hand as reference were examined in order to assess both joint‐specific as well as general changes in the somatosensory profile.Results
Analysing DT and PT, a significant main effect was found for group × stimulus interaction (P ≤ .001). Post hoc tests revealed significant differences in DT between PwH and controls for thermal stimuli across both knees (cold DT: P < .001; warm DT: P < .01) and the hand (cold DT: P < .01; warm DT: P < .05). Mechanical DT was increased in PwH at both knee joints (left knee: P ≤ .05; right knee: P ≤ .01). Furthermore, pressure PT was decreased in PwH at both knees (P ≤ .001).Conclusion
Haemophilic arthropathy leads to alterations of the somatosensory profile in PwH. Our results reveal initial evidence of a combination of peripheral sensitization, indicated by decreased pressure PT and mechanical DT at the knee joints, as well as general changes of the somatosensory system, shown by reduced thermal DT at affected sites and remote from these. Therefore, both mechanisms have to be considered regarding the pain management in PwH. 相似文献5.
Development of a short course on management of critically ill patients with acute respiratory infection and impact on clinician knowledge in resource‐limited intensive care units 下载免费PDF全文
Janet V. Diaz Justin R. Ortiz Paula Lister Nahoko Shindo Neill K.J. Adhikari WHO Critical Care Training Short Course collaborators 《Influenza and other respiratory viruses》2018,12(5):649-655
Background
The 2009 influenza A (H1N1) pandemic caused surges of patients in intensive care units (ICUs) in resource‐limited settings. Several Ministries of Health requested clinical management guidance from the World Health Organization (WHO), which had not previously developed guidance regarding critically ill patients.Objective
To assess the acceptability and impact on knowledge of a short course about the management of critically ill patients with acute respiratory infections complicated by sepsis or acute respiratory distress syndrome delivered to clinicians in resource‐limited ICUs.Methods
Over 4 years (2009‐2013), WHO led the development, piloting, implementation and preliminary evaluation of a 3‐day course that emphasized patient management based on evidence‐based guidelines and used interactive adult‐learner teaching methodology. International content experts (n = 35) and instructional designers contributed to development. We assessed participants’ satisfaction and content knowledge before and after the course.Results
The course was piloted among clinicians in Trinidad and Tobago (n = 29), Indonesia (n = 38) and Vietnam (n = 86); feedback from these courses contributed to the final version. In 2013, inaugural national courses were delivered in Tajikistan (n = 28), Uzbekistan (n = 39) and Azerbaijan (n = 30). Participants rated the course highly and demonstrated increased immediate content knowledge after (vs before) course completion (P < .001).Conclusions
We found that it was feasible to create and deliver a focused critical care short course to clinicians in low‐ and middle‐income countries. Collaboration between WHO, clinical experts, instructional designers, Ministries of Health and local clinician‐leaders facilitated course delivery. Future work should assess its impact on longer‐term knowledge retention and on processes and outcomes of care. 相似文献6.
Clinical experience with moroctocog alfa (AF‐CC) in younger paediatric patients with severe haemophilia A: Two open‐label studies 下载免费PDF全文
L. Rusen K. Kavakli J. Korth‐Bradley P. Rendo J. Fuiman J. A. Baumann L. Smith C. Alvey J. Rupon 《Haemophilia》2018,24(4):604-610
Introduction
The pharmacokinetics (PK), efficacy and safety of moroctocog alfa (AF‐CC) have been demonstrated in haemophilia A patients aged ≥6 years.Aim
These studies aimed to further describe moroctocog alfa (AF‐CC) experience in paediatric patients (<12 years) with severe haemophilia A (FVIII:C < 1%).Methods
Two prospective, open‐label studies enrolled patients aged <12 years: one study with 37 previously treated patients (PTPs) and another with 23 previously untreated patients (PUPs). All patients initially received 50 IU/kg of moroctocog alfa (AF‐CC) to evaluate either recovery alone, or with other PK parameters (6 to <12 years) before continuing treatment for 100 exposure days (EDs) or 24 months.Results
At baseline, mean (±SD) recovery ranged between 1.32 ± 0.65 (PUPs aged <2 years) and 2.13 ± 0.82 (PTPs aged 6 to <12 years). The mean (±SD) half‐life was 9.12 ± 1.94 hours in PTPs aged 6 to <12 years. No new safety signals were detected in either study, 2 transient lower titre inhibitors occurred in PTPs while 8 inhibitors (3 low and 5 high titre) were detected in PUPs. Most bleeding episodes resolved with one infusion (94% [893/954]). The annualised bleeding rate (ABR) in the PTP study was 27.5 and 4.2 for patients reporting an on‐demand and routine prophylaxis regimen at baseline, respectively. In the PUP study, the overall ABR was 5.9.Conclusion
Moroctocog alfa (AF‐CC) had expected PK findings (lower recovery in young children compared with older children) along with being safe and efficacious in a population of young severe haemophilia A patients. 相似文献7.
Long‐term follow‐up of clinical trial patients treated for chronic HCV infection with daclatasvir‐based regimens 下载免费PDF全文
K. Rajender Reddy Stanislas Pol Paul J. Thuluvath Hiromitsu Kumada Joji Toyota Kazuaki Chayama James Levin Eric J. Lawitz Adrian Gadano Wayne Ghesquiere Guido Gerken Maurizia R. Brunetto Cheng‐Yuan Peng Marcelo Silva Simone I. Strasser Jeong Heo Fiona McPhee Zhaohui Liu Rong Yang Misti Linaberry Stephanie Noviello 《Liver international》2018,38(5):821-833
Background & Aims
Daclatasvir has achieved high sustained virologic response (SVR) rates in diverse hepatitis C virus (HCV) populations. This study evaluated the long‐term efficacy and safety of daclatasvir‐based regimens administered during clinical studies.Methods
Patients enrolled within 6 months of parent study completion or protocol availability at the study sites. The primary objective was durability of SVR at follow‐up Week 12 (SVR12). Secondary objectives included analysing HCV sequences in non‐responders or responders who relapsed, and characterization of liver disease progression.Results
Between 24 February 2012 and 17 July 2015, this study enrolled and began following 1503 recipients of daclatasvir‐based regimens (follow‐up cut‐off, 13 October 2015); 60% were male, 18% aged ≥65 years, 87% had genotype‐1a (42%) or ‐1b (45%) infection, and 18% had cirrhosis. Median follow‐up from parent study follow‐up Week 12 was 111 (range, 11‐246) weeks. 1329/1489 evaluable patients were SVR12 responders; 1316/1329 maintained SVR until their latest visit. Twelve responders relapsed by (n = 9) or after (n = 3) parent study follow‐up Week 24; one was reinfected. Relapse occurred in 3/842 (0.4%) and 9/487 (2%) responders treated with interferon‐free or interferon‐containing regimens, respectively. Hepatic disease progression and new hepatocellular carcinoma were diagnosed in 15 and 23 patients, respectively. Among non‐responders, emergent non‐structural protein‐5A (NS5A) and ‐3 (NS3) substitutions were replaced by wild‐type sequences in 27/157 (17%) and 35/47 (74%) patients, respectively.Conclusions
SVR12 was durable in 99% of recipients of daclatasvir‐based regimens. Hepatic disease progression and new hepatocellular carcinoma were infrequent. Emergent NS5A substitutions persisted longer than NS3 substitutions among non‐responders. 相似文献8.
《European journal of haematology》2018,101(2):208-215
Objectives
Erythropoiesis‐stimulating agents (ESAs) remain first‐choice to treat symptomatic anemia and delay transfusion dependence in most patients with lower‐risk myelodysplastic syndromes (MDS) without del(5q). Deferasirox increased erythroid responses in some lower‐risk MDS patients in clinical trials, and adding low‐dose deferasirox to ESA treatment may further improve erythroid response.Methods
KALLISTO ( NCT01868477 ) was a randomized, open‐label, multicenter, phase II study. Lower‐risk MDS patients received deferasirox at 10 mg/kg/d (dispersible tablets) or 7 mg/kg/d (film‐coated tablets) plus erythropoietin (n = 11), or erythropoietin alone (n = 12) for 24 weeks. The primary endpoint was the between‐group difference in erythroid response within 12 weeks.Results
Erythroid response occurred in 27.3% of patients receiving deferasirox plus erythropoietin vs 41.7% of patients receiving erythropoietin alone within 12 weeks (difference 14.4%; 95% CI −24.0, 48.16). Within 24 weeks, the hematologic response rate was 27.3% with deferasirox plus erythropoietin vs 50% with erythropoietin alone, and hematologic improvement rates were 45.5% vs 100%. Deferasirox plus erythropoietin was generally well tolerated.Conclusions
In this small pilot study, combining low‐dose deferasirox with erythropoietin did not improve erythroid response. It remains of interest to investigate early chelation approaches with even lower deferasirox doses plus erythropoietin in lower‐risk MDS patients before the onset of transfusion dependence.9.
In Belgium, where haemophilia affects approximately 1:7000 people (2011), data on patients' quality of life (QoL) is scarce. This project aims to assess physical and mental QoL (P‐QoL and M‐QoL) simultaneously, and to analyse the influence of different variables on these two aspects of QoL. After Ethics Committee approval, we contacted 84 adult haemophilia A (HA) and haemophilia B (HB) patients, without current inhibitors, on replacement therapy (on‐demand or secondary prophylaxis), regularly followed up at our comprehensive treatment centre. Seventy‐one (n = 59 HA, n = 12 HB) replied to our questionnaire, which included the SF36v2 QoL assessment forms. We analysed two groups of variables: one including variables previously associated with decreased QoL, and another including variables with unclear impact on QoL (e.g. patients' understanding of haemophilia‐related issues, economical concerns). In our population (mean ± SD age: 45.2 ± 14.7 years old), P‐QoL appeared more reduced than M‐QoL. P‐QoL was strongly influenced by the number of arthropathies while M‐QoL was primarily affected by patients' concern of personal costs due to haemophilia. Among this latter group, having knowledge of insurance coverage had a positive impact on M‐QoL. Scores did not depend on haemophilia type. QoL was impaired in our haemophilia patients. A simultaneous assessment of P‐QoL and M‐QoL confirmed the benefit of primary prophylaxis in P‐QoL, while originally pointing out the major burden of patients' concerns and poor understanding of haemophilia‐related economical issues on their M‐QoL. This might become a particularly challenging issue in times of financial crisis. 相似文献
10.
11.
MONITOR‐GCSF DLBCL subanalysis: Treatment patterns/outcomes with biosimilar filgrastim for chemotherapy‐induced/febrile neutropenia prophylaxis 下载免费PDF全文
Pere Gascón Andriy Krendyukov Nadja Höbel Matti Aapro 《European journal of haematology》2018,100(3):241-246
Objective
Prospective data on the use of granulocyte‐colony‐stimulating factor (G‐CSF) in non‐Hodgkin's lymphoma and its aggressive subtypes, including diffuse large B‐cell lymphoma (DLBCL), are limited. MONITOR‐GCSF is a pan‐European, multicenter, prospective, observational study aiming to describe treatment patterns and clinical outcomes in patients receiving biosimilar filgrastim in the prophylaxis of chemotherapy‐induced neutropenia (CIN) and febrile neutropenia (FN).Methods
This analysis describes patient characteristics, treatment patterns, and outcomes for 245 patients with stage 3 or 4 DLBCL receiving ≤6 chemotherapy cycles as part of MONITOR‐GCSF study, including patients aged ≥65 years and ≥70 years. Outcomes of interest included the incidence of CIN and FN, antibiotic prophylaxis, biosimilar filgrastim prophylaxis, and adverse events (AEs).Results
MONITOR‐GCSF included 245 patients with DLBCL. Of these patients, 87 (35.5%) experienced one or more CIN (any grade) episode and 24 (9.8%) experienced FN (any grade). The most frequent AE reported was bone pain (n = 7, 2.9%), followed by arthralgia (n = 2, 0.8%) and back pain (n = 2, 0.8%).Conclusion
In real‐life practice, biosimilar filgrastim demonstrated clinical effectiveness and safety in patients with DLBCL. The large percentage of patients aged ≥65 years adds to the evidence on how to best treat older patients with DLBCL receiving myelosuppressive chemotherapy. 相似文献12.
Oestradiol level,oestrogen receptors,and mortality in elderly men: The three‐city cohort study 下载免费PDF全文
Nasser Laouali Sylvie Brailly‐Tabard Catherine Helmer Marie‐Laure Ancelin Christophe Tzourio Alexis Elbaz Anne Guiochon‐Mantel Marianne Canonico 《Clinical endocrinology》2018,89(4):514-525
Context
Although endogenous oestradiol, generally considered as the female hormone, has been little investigated in men, it could play a role in men's health, mortality in particular. The influence of oestrogen receptors (ER) genetic polymorphisms on this relationship has never been studied.Design and Participants
The Three‐City cohort study included (1999‐2001) 3650 men ≥65 years who were followed for mortality over 12 years. At baseline, total oestradiol (tE2) was measured and ER genotyped in a random subsample of 472 men without hormonal treatment. Free oestradiol (fE2) was estimated using Vermeulen and Södergard algorithms.Main Outcome
Mortality data were obtained from death certificates. We used inverse probability weighted Cox models to examine the association of oestradiol with all‐cause and cause‐specific mortality and its interaction with ER genetic polymorphisms.Results
A total of 183 men died over the follow‐up (cardiovascular disease (CVD), n = 44; cancer, n = 57; other causes, n = 82). After adjustment, there was a quadratic relationship of all‐cause mortality with tE2 and fE2 (P‐quadratic = 0.04 and 0.05, respectively), with higher mortality for the top and bottom tertiles compared to the middle one. These associations were stronger for CVD mortality (P‐quadratic = 0.01 and 0.02 for tE2 and fE2, respectively) and disappeared for cancer mortality. There was no evidence of an interaction of oestradiol with any ER polymorphisms on all‐cause mortality.Conclusion
In elderly men, we showed a nonlinear association of tE2 and fE2 with all‐cause mortality. These quadratic relationships were stronger for CVD mortality and did not exist for cancer mortality. ER genetic polymorphisms did not modify this association. 相似文献13.
《The Canadian journal of cardiology》2022,38(8):1235-1243
BackgroundTwelve-week high-intensity interval training (HIIT), moderate-to-vigorousintensity continuous training (MICT), and Nordic walking (NW) have been shown to improve functional capacity, quality of life (QoL), and depression symptoms in patients with coronary artery disease. However, their prolonged effects or whether the improvements can be sustained remains unknown. In this study we compared the effects of 12 weeks of HIIT, MICT, and NW on functional capacity, QoL, and depression symptoms at week 26.MethodsPatients with coronary artery disease were randomized to a 12-week HIIT, MICT, or NW program followed by a 14-week observation phase. At baseline, and at weeks 12 and 26, functional capacity was measured with a 6-minute walk test (6MWT); QoL was assessed using the HeartQoL and Short Form-36; and depression severity using the Beck Depression Inventory-II. Prolonged (between baseline and week 26) and sustained (between weeks 12 and 26) effects were assessed using linear mixed models with repeated measures.ResultsOf 130 participants randomized, 86 (HIIT: n = 29; MICT: n = 27; NW: n = 30) completed week 26 assessments. There were significant improvements in 6MWT distance, QoL, and depression symptoms from baseline to week 26 (P < 0.05); NW increased 6MWT distance (+94.2 ± 65.4 m) more than HIIT (+59.9 ± 52.6 m; interaction effect P = 0.025) or MICT (+55.6 ± 48.5 m; interaction effect P = 0.010). Between weeks 12 and 26, 6MWT distance and physical QoL increased significantly (P < 0.05).ConclusionsTwelve weeks of HIIT, MICT, and NW have positive prolonged effects on functional capacity, QoL, and depression symptoms. However, NW conferred additional benefits in increasing functional capacity. The effects of the 12-week exercise programs were sustained at week 26. 相似文献
14.
Preoperative Lund‐Mackay computed tomography score is associated with preoperative symptom severity and predicts quality‐of‐life outcome trajectories after sinus surgery 下载免费PDF全文
Steven G. Brooks MPH Michal Trope MD Mariel Blasetti BS Laurel Doghramji RN Arjun Parasher MD Jordan T. Glicksman MD MPH David W. Kennedy MD Erica R. Thaler MD Noam A. Cohen MD PhD James N. Palmer MD Nithin D. Adappa MD 《International forum of allergy & rhinology》2018,8(6):668-675
Background
Disagreement exists about the relationship between Lund‐Mackay CT scores (LMCTS) and quality‐of‐life outcome (QoL) measures. We investigated whether preoperative LMCTS are associated with preoperative QoL, and whether LMCTS is predictive of postoperative QoL outcomes in chronic rhinosinusitis (CRS) patients.Methods
Adult patients with medically recalcitrant CRS (n = 665) were enrolled in a prospective, observational cohort study. Preoperative LMCTS and pre‐ and postoperative self‐reported QoL outcomes (22‐item Sino‐Nasal Outcomes Test [SNOT‐22]) were collected and evaluated over 12 months. Five hundred sixty‐eight patients met the inclusion criteria. Longitudinal linear mixed‐effects modeling was used to investigate the effect of LMCTS on QoL after functional endoscopic sinus surgery (FESS).Results
Preoperative LMCTS were significantly associated with preoperative SNOT‐22 scores (p < 0.01) and postoperative SNOT‐22 scores (p < 0.001), driven by Extranasal and Rhinologic subdomains of the QoL questionaire. Patients in the lowest preoperative LMCTS quartile had the lowest mean change in SNOT‐22 scores at 12 months (16.8 points; 95% confidence interval [CI], 12.2‐21.3). Patients in the second and third lowest preoperative LMCTS quartiles had mean changes at 12 months of 21.1 points (95% CI, 16.7‐25.4) and 23.1 points (95% CI, 18.3‐27.9). Patients in the highest preoperative LMCTS quartile had the greatest improvement in SNOT‐22 scores after FESS (29.9 points; 95% CI, 24.9‐34.8). The difference in QoL change at 12 months between the highest and lowest preoperative LMCTS quartiles was 13.1 points (95% CI, 6.0‐20.2; p < 0.001).Conclusion
Our study demonstrates that preoperative LMCTS correlate with preoperative extranasal and rhinologic symptom severity and that the LMCTS is an indicator of postsurgical QoL outcomes for medically recalcitrant chronic rhinosinusitis patients in a large tertiary otolaryngology setting.15.
Molecular genetic characteristics of influenza A virus clinically isolated during 2011‐2016 influenza seasons in Korea 下载免费PDF全文
Han Sol Lee Ji Yun Noh Joon Young Song Hee Jin Cheong Won Suk Choi Hye Won Jeong Seong‐Heon Wie Woo Joo Kim 《Influenza and other respiratory viruses》2018,12(4):497-507
Background
The influenza virus is reportedly associated with 3‐5 million cases of severe illness and 250 000‐500 000 deaths annually worldwide.Objectives
We investigated the variation of influenza A virus in Korea and examined the association with death.Methods
A total of 13 620 cases were enrolled in the Hospital‐based Influenza Morbidity & Mortality surveillance system in Korea during 2011‐2016. Among these cases, a total of 4725 were diagnosed with influenza using RT‐PCR (influenza A; n = 3696, influenza B; n = 928, co‐infection; n = 101). We used 254 viral sequences from the 3696 influenza A cases for phylogenetic analysis using the BioEdit and MEGA 6.06 programs.Results
We found that the sequences of A/H3N2 in the 2011‐2012 season belong to subgroup 3C.1, whereas the sequences in the 2012‐2013 season pertain to subgroup 3C.2. The sequences in the 2013‐2014 and 2014‐2015 seasons involve subgroups 3C.3a and 3C.2a. The A/H1N1pdm09 subtype belongs to subgroup 6 and contains two clusters. In addition, sequence analysis confirmed the several substitutions of internal genes and gene substitutions associated with drug resistance (I222V in NA and S31N in M2) in the fatal cases. While statistical analysis found no significant associations between genetic differences in the viruses and mortality, mortality was associated with certain host factors, such as chronic lung disease.Conclusions
In conclusion, influenza A virus clade changes occurred in Korea during the 2011‐2016 seasons. These data, along with antigenic analysis, can aid in selecting effective vaccine strains. We confirmed that fatality in influenza A cases was related to underlying patient diseases, such as chronic lung disease, and further studies are needed to confirm associations between mortality and viral genetic substitutions. 相似文献16.
O. Stasyshyn S. Antunes V. Mamonov X. Ye J. Epstein Y. Xiong S. Tangada 《Haemophilia》2014,20(5):644-650
The Pro‐FEIBA study reported health‐related quality of life (HRQoL) improved following 6‐month of Factor Eight Inhibitor Bypassing Activity (FEIBA) prophylaxis. This study investigates whether 12‐month of FEIBA prophylaxis improved HRQoL in haemophilia patients with inhibitors. Thirty‐six subjects in a 1‐year prospective, randomized, open‐label, parallel‐design study were randomized to prophylaxis (85 ± 15 U kg?1 every other day) or on‐demand treatment. HRQoL was assessed at screening, 6 and 12‐month termination using the EQ‐5D, Haem‐A‐QoL, Haemo‐QoL and a general pain visual analog scale (VAS). To evaluate changes, paired t‐tests and criteria for minimally important differences were applied. Repeated measures regression tested the association between annualized bleeding rate (ABR) and physical HRQoL. At 6 and 12 months, prophylaxis subjects reported clinically meaningful improvement in EQ‐5D index (mean improvement, 0.10 and 0.08, respectively) and both clinically meaningful and statistically significant improvements in EQ‐VAS scores (16.9 and 15.7, respectively; P < 0.05) vs. baseline. General pain was significantly reduced during prophylaxis at each follow‐up (mean improvement, 20.3 and 23.2, respectively; both P <0.05). At 12 months, prophylaxis subjects achieved significant improvements in Haem‐A‐QoL Total Score and in four domains: Physical Health, Feeling, View, and Work and School (all P < 0.05). No statistically significant changes, except for Haem‐A‐QoL Physical Health at 6 months, were observed with on‐demand treatment. ABR was decreased by 72.5% with prophylaxis vs. on‐demand treatment (P = 0.0003) and reduced ABR was associated with better physical HRQoL (P < 0.05). FEIBA prophylaxis significantly reduced ABR and improved HRQoL in inhibitor patients. Subjects with lower ABR reported better physical HRQoL. 相似文献
17.
S. A. Mughal R. Park N. Nowak A. L. Gloyn F. Karpe H. Matile M. T. Malecki M. I. McCarthy M. Stoffel K. R. Owen 《Diabetic medicine》2013,30(2):246-250
Aims
Missed diagnosis of maturity‐onset diabetes of the young (MODY) has led to an interest in biomarkers that enable efficient prioritization of patients for definitive molecular testing. Apolipoprotein M (apoM) was suggested as a biomarker for hepatocyte nuclear factor 1 alpha (HNF1A)‐MODY because of its reduced expression in Hnf1a–/– mice. However, subsequent human studies examining apoM as a biomarker have yielded conflicting results. We aimed to evaluate apoM as a biomarker for HNF1A‐MODY using a highly specific and sensitive ELISA.Methods
ApoM concentration was measured in subjects with HNF1A‐MODY (n = 69), Type 1 diabetes (n = 50), Type 2 diabetes (n = 120) and healthy control subjects (n = 100). The discriminative accuracy of apoM and of the apoM/HDL ratio for diabetes aetiology was evaluated.Results
Mean (standard deviation) serum apoM concentration (μmol/l) was significantly lower for subjects with HNF1A‐MODY [0.86 (0.29)], than for those with Type 1 diabetes [1.37 (0.26), P = 3.1 × 10–18) and control subjects [1.34 (0.22), P = 7.2 × 10–19). There was no significant difference in apoM concentration between subjects with HNF1A‐MODY and Type 2 diabetes [0.89 (0.28), P = 0.13]. The C‐statistic measure of discriminative accuracy for apoM was 0.91 for HNF1A‐MODY vs. Type 1 diabetes, indicating high discriminative accuracy. The apoM/HDL ratio was significantly lower in HNF1A‐MODY than other study groups. However, this ratio did not perform well in discriminating HNF1A‐MODY from either Type 1 diabetes (C‐statistic = 0.79) or Type 2 diabetes (C‐statistic = 0.68).Conclusions
We confirm an earlier report that serum apoM levels are lower in HNF1A‐MODY than in controls. Serum apoM provides good discrimination between HNF1A‐MODY and Type 1 diabetes and warrants further investigation for clinical utility in diabetes diagnostics. 相似文献18.
Sergii V. Fedorchenko Tatiana Martynovych Zhanna Klimenko Vitaliy Yanchenko Iryna Solianyk 《Journal of viral hepatitis》2020,27(5):548-551
The use of direct‐acting antiviral agents (DAAs) in patients with chronic HCV genotype 1 infection results in sustained virologic response (SVR) rates of 95%‐97%, but 3%‐5% of patients experience virologic failure. We observed 17 patients infected with HCV subtype 1b who failed previous treatment with DAA, including 13 subjects (76.5%) with liver cirrhosis. Twelve subjects (70.6%) previously received NS5A inhibitors of the first generation (ledipasvir or daclatasvir) and five subjects (29.4%) – the second generation (velpatasvir). All patients were retreated with a combination of ombitasvir/paritaprevir/ritonavir and dasabuvir (3D) with sofosbuvir (SOF) and ribavirin (RBV). We compared SVR12 rates depending on fibrosis stage, presence of just single or double NS5A mutations (L31M/V/I and/or Y93H), and on the generation of previously used NS5A inhibitor. Observed SVR12 rates were as follows: 94.1% (16/17 patients) overall; 100% in patients without cirrhosis (n = 4) vs 92.3% in those with cirrhosis (n = 13); 100% with single L31M/V/I or Y93H mutation (n = 7) vs 88.9% with double mutations (n = 9); 100% in patients who previously failed first generation (n = 12) vs 80.0% in those failed second‐generation NS5A inhibitors (n = 5). Retreatment with 3D + 0SOF + RBV was highly effective and safe in patients with chronic HCV GT1b infection who failed previous use of NS5A inhibitors. Fibrosis stage, baseline presence of NS5A RAS mutations and the generation of previously used NS5A inhibitors may impact the probability of achieving SVR12, but statistical significance was not demonstrated in our small retrospective cohort. Further studies in a larger population are needed to confirm or not the predictive value of these baseline factors. 相似文献
19.
The influence of baseline characteristics and disease stage on health‐related quality of life in multiple myeloma: findings from six randomized controlled trials 下载免费PDF全文
Don Robinson Jr Dixie‐Lee Esseltine Antoine Regnault Juliette Meunier Kevin Liu Helgi van de Velde 《British journal of haematology》2016,174(3):368-381
20.
Association of circulating proinflammatory marker,leucine‐rich‐α2‐glycoprotein (LRG1), following metabolic/bariatric surgery 下载免费PDF全文
Sharon Li Ting Pek Anton Kui Sing Cheng Michelle Xueqin Lin Moh Sim Wong Eric Zit Liang Chan Angela Mei Chung Moh Chee Fang Sum Su Chi Lim Subramaniam Tavintharan 《Diabetes/metabolism research and reviews》2018,34(7)