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1.
Judy M. Bradley Paul Koker Qiqi Deng Petra Moroni-Zentgraf Felix Ratjen David E. Geller J. Stuart Elborn 《PloS one》2014,9(9)
Background
Tiotropium is a once-daily, long-acting anticholinergic bronchodilator with the potential to alleviate airway obstruction in cystic fibrosis. Our objective was to evaluate the efficacy and safety of 2.5 and 5 µg once-daily tiotropium delivered via the Respimat Soft Mist Inhaler vs. placebo in people with cystic fibrosis.Methods
This phase 2, 12-week, randomized, double-blind, placebo-controlled parallel-group study of tiotropium Respimat as add-on to usual cystic fibrosis maintenance therapy included people with cystic fibrosis with pre-bronchodilator forced expiratory volume in 1 second (FEV1) ≥25% predicted. Co-primary efficacy end points were change from baseline in percent-predicted FEV1 area under the curve from 0 to 4 hours (FEV1 AUC0–4h), and trough FEV1 at the end of week 12.Findings
A total of 510 subjects with cystic fibrosis aged 5–69 years were randomized. Both doses of tiotropium resulted in significant improvement compared with placebo in the co-primary efficacy end points at the end of week 12 (change from baseline in percent-predicted FEV1 AUC0–4h: 2.5 µg: 2.94%, 95% confidence interval 1.19–4.70, p = 0.001; 5 µg: 3.39%, 95% confidence interval 1.67–5.12, p = 0.0001; in percent-predicted trough FEV1∶2.5 µg: 2.24%, p = 0.2; 5 µg: 2.22%, p = 0.02). There was a greater benefit with tiotropium 5 vs. 2.5 µg. No treatment-related adverse events or unexpected safety findings were observed in patients taking tiotropium.Conclusions
Tiotropium significantly improved lung function in people with cystic fibrosis. The improvement was greater with the higher dose than the lower dose, with no difference in adverse events.Trial Registration
ClinicalTrials.gov NCT00737100 EudraCT 2008-001156-43. 相似文献2.
Anne Louise Bischoff Nilofar Vahman F?lsgaard Charlotte Giwercman Carson Jakob Stokholm Louise Pedersen Maria Holmberg Amalie Bisgaard Sune Birch Theodore F. Tsai Hans Bisgaard 《PloS one》2013,8(4)
Background
Pregnant women were suspected to be at particular risk when H1N1pnd09 influenza became pandemic in 2009. Our primary objective was to compare the immune responses conferred by MF59®-adjuvanted vaccine (Focetria®) in H1N1pnd09-naïve pregnant and non-pregnant women. The secondary aims were to compare influences of dose and adjuvant on the immune response.Methods
The study was nested in the Copenhagen Prospective Studies on Asthma in Childhood (COPSAC2010) pregnancy cohort in 2009-2010 and conducted as a single-blinded block-randomised [1∶1∶1] controlled clinical trial in pregnant women after gestational week 20: (1) 7.5 µg H1N1pnd09 antigen with MF59-adjuvant (Pa7.5 µg); (2) 3.75 µg antigen half MF59-adjuvanted (Pa3.75 µg); (3) 15 µg antigen unadjuvanted (P15 µg); and in non-pregnant women receiving (4) 7.5 µg antigen full adjuvanted (NPa7.5 µg). Blood samples were collected at baseline, 3 weeks, 3 and 10 months after vaccination, adverse events were recorded prospectively.Results
58 pregnant women were allocated to Pa7.5 µg and 149 non-pregnant women were recruited to NPa7.5 µg. The sero-conversion rate was significantly increased in non-pregnant (NPa7.5 µg) compared with pregnant (Pa7.5 µg) women (OR = 2.48 [1.03–5.95], p = 0.04) and geometric mean titers trended towards being higher, but this difference was not statistically significant (ratio 1.27 [0.85–1.93], p = 0.23). The significant titer increase rate showed no difference between pregnant (Pa7.5 µg) and non-pregnant (NPa7.5 µg) groups (OR = 0.49 [0.13–1.85], p = 0.29).Conclusion
Our study suggests the immune response to the 7.5 µg MF59-adjuvanted Focetria® H1N1pnd09 vaccine in pregnant women may be diminished compared with non-pregnant women.Trial Registration
ClinicalTrials.gov NCT01012557. 相似文献3.
Sahrai Saeed Ulrike Waje-Andreassen Annette Fromm Halvor ?ygarden Marina V. Kokorina Halvor Naess Eva Gerdts 《PloS one》2014,9(11)
Background
Ischemic stroke survivors have high risk of cardiovascular morbidity and mortality even at young age, suggesting that early arterial aging is common among such patients.Methods
We measured aortic stiffness by carotid-femoral pulse wave velocity (PWV) in 205 patients (69% men) aged 15–60 years with acute ischemic stroke in the prospective Norwegian Stroke in the Young Study. High for age carotid-femoral PWV was identified in the reference normogram.Results
Patients were on average 49±10 years old, 34% had a history of hypertension and 37% had metabolic syndrome (MetS). In the total study population, higher PWV was associated with history of hypertension (β = 0.18), higher age (β = 0.34), systolic blood pressure (BP) (β = 0.28) and serum creatinine (β = 0.18) and lower high-density lipoprotein (HDL) cholesterol (β = –0.10, all p<0.01) in multivariate linear regression analysis (multiple R2 = 0.42, p<0.001). High for age PWV was found in 18% of patients. In univariate analyses, known hypertension was associated with a 6-fold, MetS with a 4-fold and presence of carotid plaque with a 3.7-fold higher risk for high for age PWV (all p<0.01). In multiple logistic regression analysis higher systolic BP (odds ratio [OR] 1.04; 95% confidence interval [CI] 1.02–1.06; p<0.01), history of hypertension (OR 3.59; 95% CI 1.52–8.51; p<0.01), low HDL cholesterol (OR 3.03; 95% CI 1.00–9.09; p = 0.05) and higher serum creatinine (OR 1.04; 95% CI 1.01–1.06; p<0.01) were associated with high for age PWV.Conclusions
Higher PWV is common in younger and middle-aged ischemic stroke patients and associated with a clustering of classical cardiovascular risk factors.ClinicalTrials.gov NCT01597453 相似文献4.
Ping-Yen Liu Liang-Yu Lin Hung-Ju Lin Chien-Hsun Hsia Yi-Ren Hung Hung-I Yeh Tao-Cheng Wu Ju-Yi Chen Kuo-Liong Chien Jaw-Wen Chen 《PloS one》2013,8(10)
Background
Evidence about the efficacy and safety of statin treatment in high-risk patients with hypercholesterolemia is available for some populations, but not for ethnic Chinese. To test the hypothesis that treatment with pitavastatin (2 mg/day) is not inferior to treatment with atorvastatin (10 mg/day) for reducing low-density lipoprotein cholesterol (LDL-C), a 12-week multicenter collaborative randomized parallel-group comparative study of high-risk ethnic Chinese patients with hypercholesterolemia was conducted in Taiwan. In addition, the effects on other lipid parameters, inflammatory markers, insulin-resistance-associated biomarkers and safety were evaluated.Methods and Results
Between July 2011 and April 2012, 251 patients were screened, 225 (mean age: 58.7 ± 8.6; women 38.2% [86/225]) were randomized and treated with pitavastatin (n = 112) or atorvastatin (n = 113) for 12 weeks. Baseline characteristics in both groups were similar, but after 12 weeks of treatment, LDL-C levels were significantly lower: pitavastatin group = −35.0 ± 14.1% and atorvastatin group = −38.4 ± 12.8% (both: p < 0.001). For the subgroup with diabetes mellitus (DM) (n = 125), LDL-C levels (−37.1 ± 12.9% vs. −38.0 ± 13.1%, p = 0.62) were similarly lowered after either pitavastatin (n = 63) or atorvastatin (n = 62) treatment. Triglycerides, non-high density lipoprotein cholesterol, and apoprotein B were similarly and significantly lower in both treatment groups. In non-lipid profiles, HOMA-IR and insulin levels were higher to a similar degree in both statin groups. Hemoglobin A1C was significantly (p = 0.001) higher in the atorvastatin group but not in the pitavastatin group. Both statins were well tolerated, and both groups had a similar low incidence of treatment-emergent adverse events.Conclusion
Both pitavastatin (2 mg/day) and atorvastatin (10 mg/day) were well tolerated, lowered LDL-C, and improved the lipid profile to a comparable degree in high-risk Taiwanese patients with hypercholesterolemia.Trial Registration
ClinicalTrials.gov NCT01386853 http://clinicaltrials.gov/ct2/show/NCT01386853?term=NCT01386853&rank=1 相似文献5.
Background
Treatment remains uncertain for IgA nephropathy patients with mild to moderate proteinuria, for whom anti-hypertensive medication or the RAS blocker is not applicable due to low blood pressure.Trial design
A double blinded randomized trial.Methods
The anti-proteinuric effect of tacrolimus was explored for 40 biopsy-proven mild IgA nephropathies for 16 weeks. We randomly assigned patients either to receive tacrolimus or placebo with stratification by using a renin angiotensin system blocker. The primary outcome was the percentage change of final UACR compared to the baseline value (pcUACR).Results
The mean value of pcUACR at 12-week and 16-week visits (primary outcome) was decreased more in the Tac group compared to the control group (–52.0±26.4 vs –17.3±29.3%, p = 0.001). At each visit, pcUACR was also decreased more in the Tac group compared to the control group. In the Tac group, the pcUACRs were –60.2±28.2%, –62.2±33.9%, –48.5±29.8%, and –55.5±24.0%, and, in the control group, –6.8±32.2%, –2.5±35.9%, –12.7±34.2%, and –21.9±30.6%, at 4-week, 8-week, 12-week, and 16-week visits, respectively. The pre-defined secondary outcomes were better in the Tac group compared to the control group. The frequency of decrease in pcUACR and percentage change of UPCR (pcUPCR) ≥50% at 16 weeks were 65.0% (13/20) and 55.0% (11/20)in the Tac group, and 25.0% (5/20) and 15.0% (3/20), in the control group, respectively (p = 0.025 for pcUACR and p = 0.019 for pcUPCR). However, tacrolimus wasn''t effective with a dose of 0.05 mg/kg/day in patients taking ARB. The adverse events were tolerable.Conclusion
Tacrolimus effectively reduced proteinuria in IgA nephropathy with normal blood pressure. This suggested that tacrolimus could be an alternative to corticosteroid and RAS blocker for IgA nephropathy patients who cannot endure anti-hypertensive medication.Trial Registration
Clinicaltrial.gov NCT1224028 相似文献6.
Hanna Fernemark Christine Jaredsson Bekim Bunjaku Ulf Rosenqvist Fredrik H. Nystrom Hans Guldbrand 《PloS one》2013,8(11)
Background
In the clinic setting both fasting levels of glucose and the area under the curve (AUC) of glucose, by determination of HbA1c levels, are used for risk assessments, in type 2 diabetes (NIDDM). However little is known about postprandial levels, and hence AUC, regarding other traditional risk factors such as insulin and blood-lipids and how this is affected by different diets.Objective
To study postprandial effects of three diets, during a single day, in NIDDM.Methods
A low-fat diet (45–56 energy-% from carbohydrates), and a low-carbohydrate diet (16–24 energy-% from carbohydrates) was compared with a Mediterranean-style diet (black coffee for breakfast and the same total-caloric intake as the other two diets for lunch with red wine, 32–35 energy−% from carbohydrates) in a randomized cross-over design. Total-caloric intake/test-day at the clinic from food was 1025–1080 kCal in men and 905–984 kCal in women. The test meals were consumed at a diabetes ward under supervision.Results
Twenty-one participants were recruited and 19 completed the studies. The low-carbohydrate diet induced lower insulin and glucose excursions compared with the low-fat diet (p<0.0005 for both AUC). The insulin-response following the single Mediterranean-style lunch-meal was more pronounced than during the low-fat diet lunch (insulin increase-ratio of the low-fat diet: 4.35±2.2, of Mediterranean-style diet: 8.12±5.2, p = 0.001) while postprandial glucose levels were similar. The increase-ratio of insulin correlated with the elevation of the incretin glucose-dependent insulinotropic-polypeptide following the Mediterranean-style diet lunch (Spearman, r = 0.64, p = 0.003).Conclusions
The large Mediterranean-style lunch-meal induced similar postprandial glucose-elevations as the low-fat meal despite almost double amount of calories due to a pronounced insulin-increase. This suggests that accumulation of caloric intake from breakfast and lunch to a single large Mediterranean style lunch-meal in NIDDM might be advantageous from a metabolic perspective.Trial Registration
ClinicalTrials.gov NCT01522157 NCT01522157 相似文献7.
Objective
Copeptin, a marker for stress mirroring vasopressin concentrations, has been shown to increase upon insulin-induced hypoglycaemia in patients after transsphenoidal surgery of pituitary adenomas. Patients with type 1 diabetes mellitus are prone to hypoglycaemia, but no data about copeptin levels upon hypoglycaemia are available. Furthermore, the perception of hypoglycaemia can vary from total unawareness to disabling episodes. The aim of this study was to investigate whether copeptin increases upon hypoglycaemia in patients with type 1 diabetes mellitus and is associated with the degree of hypoglycaemia awareness.Materials and Methods
In this prospective observational study, 17 patients with type 1 diabetes underwent a standardized insulin infusion test. Blood sampling for glucose and copeptin was performed at baseline and after 60 minutes (min). To assess hypoglycaemia associated symptoms the Mood and Symptom Questionnaire (MSQ) was conducted at baseline and after 60 min.Results
During insulin infusion, blood glucose decreased from 5.1 (SD±0.2) to 3.0 (±0.5) mmol/L at 60 min (p<0.001). Copeptin concentrations increased from 3.2 (±1.7) to 3.8 (±1.9) pmol/L (p = 0.03). Mood and Symptoms Questionnaire scores increased from 14 (±3.0) to 18 (±5.8), (p = 0.006). Patients with good hypoglycaemia awareness had an increase in copeptin from 3.0 (±1.8) to 4.2 (±2.4) pmol/L (p = 0.03) in contrast to patients more unaware of hypoglycaemia who only showed an increase in copeptin from 3.3 (±1.6) to 3.6 (±1.4) pmol/L (p = 0.4). There was a trend to a larger copeptin increase in patients aware of hypoglycemia compared to patients unaware of hypoglycemia (p = 0.074).Conclusion
Copeptin increases in patients with type 1 diabetes upon insulin induced hypoglycaemia. Interestingly, the copeptin increase seems associated with the degree of hypoglycaemia awareness. This hypothesis warrants further verification.Trial Registration
ClinicalTrials.gov NCT00515801 相似文献8.
Carolyn O. Walsh Cara B. Ebbeling Janis F. Swain Robert L. Markowitz Henry A. Feldman David S. Ludwig 《PloS one》2013,8(3)
Background
The major circulating metabolic fuels regulate hunger, and each is affected by dietary composition. An integrated measure of postprandial energy availability from circulating metabolic fuels may help inform dietary recommendations for weight maintenance after weight loss.Aim
We examined the effect of low-fat (LF, 60% of energy from carbohydrate, 20% fat, 20% protein), low-glycemic index (LGI, 40%–40%-20%), and very low-carbohydrate (VLC, 10%–60%-30%) diets on total postprandial metabolic fuel energy availability (EA) during weight loss maintenance.Methods
Eight obese young adults were fed a standard hypocaloric diet to produce 10–15% weight loss. They were then provided isocaloric LF, LGI, and VLC diets in a randomized crossover design, each for a 4-week period of weight loss maintenance. At the end of each dietary period, a test meal representing the respective diet was provided, and blood samples were obtained every 30 minutes for 5 hours. The primary outcome was EA, defined as the combined energy density (circulating level×relative energy content) of glucose, free fatty acids, and β-hydroxybutyrate. Secondary outcomes were individual metabolic fuels, metabolic rate, insulin, glucagon, cortisol, epinephrine, and hunger ratings. Respiratory quotient was a process measure. Data were analyzed by repeated-measures analysis of variance, with outcomes compared in the early (30 to 150 min) and late (180 to 300 min) postprandial periods.Results
EA did not differ between the test meals during the early postprandial period (p = 0.99). However, EA in the late postprandial period was significantly lower after the LF test meal than the LGI (p<0.0001) and VLC (p<0.0001) test meals. Metabolic rate also differed in the late postprandial period (p = 0.0074), with higher values on the VLC than LF (p = 0.0064) and LGI (p = 0.0066) diets.Conclusion
These findings suggest that an LF diet may adversely affect postprandial EA and risk for weight regain during weight loss maintenance.Trial Registration
ClinicalTrials.gov NCT00315354 相似文献9.
10.
Azusa Hara Lutgarde Thijs Kei Asayama Lotte Jacobs Ji-Guang Wang Jan A. Staessen 《PloS one》2014,9(8)
Background
In the Systolic Hypertension in Europe trial (NCT02088450), we investigated whether systolic blood pressure variability determines prognosis over and beyond level.Methods
Using a computerised random function and a double-blind design, we randomly allocated 4695 patients (≥60 years) with isolated systolic hypertension (160–219/<95 mm Hg) to active treatment or matching placebo. Active treatment consisted of nitrendipine (10–40 mg/day) with possible addition of enalapril (5–20 mg/day) and/or hydrochlorothiazide (12.5–25.0 mg/day). We assessed whether on-treatment systolic blood pressure level (SBP), visit-to-visit variability independent of the mean (VIM) or within-visit variability (WVV) predicted total (n = 286) or cardiovascular (n = 150) mortality or cardiovascular (n = 347), cerebrovascular (n = 133) or cardiac (n = 217) endpoints.Findings
At 2 years, mean between-group differences were 10.5 mm Hg (p<0.0001) for SBP, 0.29 units (p = 0.20) for VIM, and 0.07 mm Hg (p = 0.47) for WVV. Active treatment reduced (p≤0.048) cardiovascular (−28%), cerebrovascular (−40%) and cardiac (−24%) endpoints. In analyses dichotomised by the median, patients with low vs. high VIM had similar event rates (p≥0.14). Low vs. high WVV was not associated with event rates (p≥0.095), except for total and cardiovascular mortality on active treatment, which were higher with low WVV (p≤0.0003). In multivariable-adjusted Cox models, SBP predicted all endpoints (p≤0.0043), whereas VIM did not predict any (p≥0.058). Except for an inverse association with total mortality (p = 0.042), WVV was not predictive (p≥0.15). Sensitivity analyses, from which we excluded blood pressure readings within 6 months after randomisation, 6 months prior to an event or both were confirmatory.Conclusions
The double-blind placebo-controlled Syst-Eur trial demonstrated that blood-pressure lowering treatment reduces cardiovascular complications by decreasing level but not variability of SBP. Higher blood pressure level, but not higher variability, predicted risk.Trial Registration
ClinicalTrials.gov NCT02088450 相似文献11.
Erica Maxine Lazarus Kennedy Otwombe Tania Adonis Elaine Sebastian Glenda Gray Nicole Grunenberg Surita Roux Gavin Churchyard Craig Innes Fatima Laher 《PloS one》2014,9(11)
Because sexual transmission of HIV occurs across mucosal membranes, understanding the immune responses of the genital mucosa to vaccines may contribute knowledge to finding an effective candidate HIV vaccine. We describe the uptake of rectal secretion, cervical secretion and seminal mucosal secretion sampling amongst volunteers in a Phase 1b HIV vaccine trial. Age at screening, gender, study site and the designation of the person conducting the informed consent procedure were collected for volunteers who screened for the HVTN 097 study. A total of 211 volunteers (54% female) were screened at three sites in South Africa: Soweto (n = 70, 33%), Cape Town (n = 68, 32%) and Klerksdorp (n = 73, 35%). Overall uptake of optional mucosal sampling amongst trial volunteers was 71% (n = 149). Compared to Cape Town, volunteers from Soweto and Klerksdorp were less likely to consent to sampling (Soweto OR 0.08 CI: 0.03–0.25 p<0.001 and Klerksdorp OR 0.13 CI: 0.04–0.41 p = 0.001). In contrast, volunteers over 25 years of age were 2.39 times more likely to consent than younger volunteers (CI: 1.13–5.08, p = 0.02). Further studies are required to better understand the cultural, demographic and sociobehavioral factors which influence willingness to participate in mucosal sampling in HIV prevention studies.
Trial Registration
ClinicalTrials.gov: NCT02109354 相似文献12.
Sunil Sazawal Usha Dhingra Pratibha Dhingra Girish Hiremath Archana Sarkar Arup Dutta Venugopal P. Menon Robert E. Black 《PloS one》2010,5(8)
Background
Multiple micronutrient deficiencies are highly prevalent among preschool children and often lead to anemia and growth faltering. Given the limited success of supplementation and health education programs, fortification of foods could be a viable and sustainable option. We report results from a community based double-masked, randomized trial among children 1–4 years evaluating the effects of micronutrients (especially of zinc and iron) delivered through fortified milk on growth, anemia and iron status markers as part of a four group study design, running two studies simultaneously.Methods and Findings
Enrolled children (n = 633) were randomly allocated to receive either micronutrients fortified milk (MN = 316) or control milk (Co = 317). Intervention of MN milk provided additional 7.8 mg zinc, 9.6 mg iron, 4.2 µg selenium, 0.27 mg copper, 156 µg vitamin A, 40.2 mg vitamin C, and 7.5 mg vitamin E per day (three serves) for one year. Anthropometry was recorded at baseline, mid- and end-study. Hematological parameters were estimated at baseline and end-study. Both groups were comparable at baseline. Compliance was over 85% and did not vary between groups. Compared to children consuming Co milk, children consuming MN milk showed significant improvement in weight gain (difference of mean: 0.21 kg/year; 95% confidence interval [CI] 0.12 to 0.31, p<0.001) and height gain (difference of mean: 0.51 cm/year; 95% CI 0.27 to 0.75, p<0.001). Mean hemoglobin (Hb) (difference of 13.6 g/L; 95% CI 11.1 to 16.0, p<0.001) and serum ferritin levels (difference of 7.9 µg/L; 95% CI 5.4 to 10.5, p<0.001) also improved. Children in MN group had 88% (odds ratio = 0.12, 95% CI 0.08 to 0.20, p<0.001) lower risk of iron deficiency anemia.Conclusions/Significance
Milk provides an acceptable and effective vehicle for delivery of specific micronutrients, especially zinc and iron. Micronutrient bundle improved growth and iron status and reduced anemia in children 1–4 years old.Trial Registration
ClinicalTrials.gov NCT00255385 相似文献13.
Louise Balfour Johanna N. Spaans Dean Fergusson Harold Huff Edward J. Mills Charles J. la Porte Sharon Walmsley Neera Singhal Ron Rosenes Nancy Tremblay M. John Gill Hugues Loemba Brian Conway Anita Rachlis Edward Ralph Mona Loutfy Ranjeeta Mallick Rika Moorhouse D. William Cameron 《PloS one》2014,9(1)
Introduction
The MAINTAIN study is an on-going RCT comparing high-dose micronutrient and anti-oxidant supplementation versus recommended daily allowance (RDA) vitamins in slowing HIV immune deficiency progression in ART-naïve people with HIV infection.Objective
We planned analysis of the first 127 participants to determine the baseline prevalence of serum micronutrient deficiencies and correlates, as well as tolerance and adherence to study interventions.Methods
Participants receive eight capsules twice daily of 1) high-dose or 2) RDA supplements for two years and are followed-up quarterly for measures of immune deficiency progression, safety and tolerability. Regression analysis was used to identify correlates of micronutrient levels at baseline. Adherence was measured by residual pill count, self-report using the General Treatment Scale (GTS) and short-term recall HIV Adherence Treatment Scale (HATS).Results
Prior micronutrient supplementation (within 30 days) was 27% at screening and 10% of study population, and was not correlated with baseline micronutrient levels. Low levels were frequent for carotene (24%<1 nmol/L), vitamin D (24%<40 nmol/L) and serum folate (20%<15 nmol/L). The proportion with B12 deficiency (<133 pmol/L) was 2.4%. Lower baseline levels of B12 correlated lower baseline CD4 count (r = 0.21, p = 0.02) with a 21 pmol/L reduction in B12 per 100 cells/µL CD4. Vitamin D levels were higher in men (p<0.001). After a median follow-up of 1.63 years, there were 19 (15%) early withdrawals from the study treatment. Mean treatment adherence using pill count was 88%. Subjective adherence by the GTS was 81% and was moderately but significantly correlated with pill count (r = 0.29, p<0.001). Adherence based on short-term recall (HATS) was >80% in 75% of participants.Conclusion
Micronutrient levels in asymptomatic HIV+ persons are in keeping with population norms, but micronutrient deficiencies are frequent. Adherence levels are high, and will permit a valid evaluation of treatment effects.Trial Registration
ClinicalTrials.gov NCT00798772 相似文献14.
Christian Trolle Kristian H. Mortensen Lisbeth N. Pedersen Agnethe Berglund Henrik K. Jensen Niels H. Andersen Claus H. Gravholt 《PloS one》2013,8(7)
Objectives
QT-interval prolongation of unknown aetiology is common in Turner syndrome. This study set out to explore the presence of known long QT mutations in Turner syndrome and to examine the corrected QT-interval (QTc) over time and relate the findings to the Turner syndrome phenotype.Methods
Adult women with Turner syndrome (n = 88) were examined thrice and 68 age-matched healthy controls were examined once. QTc was measured by one blinded reader (intra-reader variability: 0.7%), and adjusted for influence of heart rate by Bazett’s (bQTc) and Hodges’s formula (hQTc). The prevalence of mutations in genes related to Long QT syndrome was determined in women with Turner syndrome and a QTc >432.0 milliseconds (ms). Echocardiographic assessment of aortic valve morphology, 24-hour blood pressures and blood samples were done.Results
The mean hQTc in women with Turner syndrome (414.0±25.5 ms) compared to controls (390.4±17.8 ms) was prolonged (p<0.001) and did not change over time (416.9±22.6 vs. 415.6±25.5 ms; p = 0.4). 45,X karyotype was associated with increased hQTc prolongation compared to other Turner syndrome karyotypes (418.2±24.8 vs. 407.6±25.5 ms; p = 0.055). In women with Turner syndrome and a bQTc >432 ms, 7 had mutations in major Long QT syndrome genes (SCN5A and KCNH2) and one in a minor Long QT syndrome gene (KCNE2).Conclusion
There is a high prevalence of mutations in the major LQTS genes in women with TS and prolonged QTc. It remains to be settled, whether these findings are related to the unexplained excess mortality in Turner women.Clinical Trial Registration
NCT00624949. https://register.clinicaltrials.gov/prs/app/action/SelectProtocol/sid/S0001FLI/selectaction/View/ts/3/uid/U000099E. 相似文献15.
Kwablah Awadzi Nicholas O. Opoku Simon K. Attah Janis Lazdins-Helds Annette C. Kuesel 《PLoS neglected tropical diseases》2014,8(6)
Background
Control of onchocerciasis as a public health problem in Africa relies on annual mass ivermectin distribution. New tools are needed to achieve elimination of infection. This study determined in a small number of Onchocerca volvulus infected individuals whether moxidectin, a veterinary anthelminthic, is safe enough to administer it in a future large study to further characterize moxidectin''s safety and efficacy. Effects on the parasite were also assessed.Methodology/Principal Findings
Men and women from a forest area in South-eastern Ghana without ivermectin mass distribution received a single oral dose of 2 mg (N = 44), 4 mg (N = 45) or 8 mg (N = 38) moxidectin or 150 µg/kg ivermectin (N = 45) with 18 months follow up. All ivermectin and 97%–100% of moxidectin treated participants had Mazzotti reactions. Statistically significantly higher percentages of participants treated with 8 mg moxidectin than participants treated with ivermectin experienced pruritus (87% vs. 56%), rash (63% vs. 42%), increased pulse rate (61% vs. 36%) and decreased mean arterial pressure upon 2 minutes standing still after ≥5 minutes supine relative to pre-treatment (61% vs. 27%). These reactions resolved without treatment. In the 8 mg moxidectin and ivermectin arms, the mean±SD number of microfilariae/mg skin were 22.9±21.1 and 21.2±16.4 pre-treatment and 0.0±0.0 and 1.1±4.2 at nadir reached 1 and 3 months after treatment, respectively. At 6 months, values were 0.0±0.0 and 1.6±4.5, at 12 months 0.4±0.9 and 3.4±4.4 and at 18 months 1.8±3.3 and 4.0±4.8, respectively, in the 8 mg moxidectin and ivermectin arm. The reduction from pre-treatment values was significantly higher after 8 mg moxidectin than after ivermectin treatment throughout follow up (p<0.01).Conclusions/Significance
The 8 mg dose of moxidectin was safe enough to initiate the large study. Provided its results confirm those from this study, availability of moxidectin to control programmes could help them achieve onchocerciasis elimination objectives.Trial Registration
ClinicalTrails.gov NCT00300768 相似文献16.
Mark T. Gladwin Robyn J. Barst J. Simon R. Gibbs Mariana Hildesheim Vandana Sachdev Mehdi Nouraie Kathryn L. Hassell Jane A. Little Dean E. Schraufnagel Lakshmanan Krishnamurti Enrico Novelli Reda E. Girgis Claudia R. Morris Erika Berman Rosenzweig David B. Badesch Sophie Lanzkron Oswaldo L. Castro James G. Taylor VI Jonathan C. Goldsmith Gregory J. Kato Victor R. Gordeuk Roberto F. Machado 《PloS one》2014,9(7)
Background
The role of pulmonary hypertension as a cause of mortality in sickle cell disease (SCD) is controversial.Methods and Results
We evaluated the relationship between an elevated estimated pulmonary artery systolic pressure and mortality in patients with SCD. We followed patients from the walk-PHaSST screening cohort for a median of 29 months. A tricuspid regurgitation velocity (TRV)≥3.0 m/s cuttof, which has a 67–75% positive predictive value for mean pulmonary artery pressure ≥25 mm Hg was used. Among 572 subjects, 11.2% had TRV≥3.0 m/sec. Among 582 with a measured NT-proBNP, 24.1% had values ≥160 pg/mL. Of 22 deaths during follow-up, 50% had a TRV≥3.0 m/sec. At 24 months the cumulative survival was 83% with TRV≥3.0 m/sec and 98% with TRV<3.0 m/sec (p<0.0001). The hazard ratios for death were 11.1 (95% CI 4.1–30.1; p<0.0001) for TRV≥3.0 m/sec, 4.6 (1.8–11.3; p = 0.001) for NT-proBNP≥160 pg/mL, and 14.9 (5.5–39.9; p<0.0001) for both TRV≥3.0 m/sec and NT-proBNP≥160 pg/mL. Age >47 years, male gender, chronic transfusions, WHO class III–IV, increased hemolytic markers, ferritin and creatinine were also associated with increased risk of death.Conclusions
A TRV≥3.0 m/sec occurs in approximately 10% of individuals and has the highest risk for death of any measured variable.The study is registered in ClinicalTrials.gov with identifier
NCT00492531 相似文献17.
18.
Mikael Engman Suby Varghese Kristina Lagerstedt Robinson Helena Malmgren Anna Hammarsj? Birgitta Bystr?m Parameswaran Grace L Lalitkumar Kristina Gemzell-Danielsson 《PloS one》2013,8(12)
Progesterone receptor modulators, such as mifepristone are useful and well tolerated in reducing leiomyoma volume although with large individual variation. The objective of this study was to investigate the molecular basis for the observed leiomyoma volume reduction, in response to mifepristone treatment and explore a possible molecular marker for the selective usage of mifepristone in leiomyoma patients. Premenopausal women (N = 14) were treated with mifepristone 50 mg, every other day for 12 weeks prior to surgery. Women were arbitrarily sub-grouped as good (N = 4), poor (N = 4) responders to treatment or intermediate respondents (N = 3). Total RNA was extracted from leiomyoma tissue, after surgical removal of the tumour and the differential expression of genes were analysed by microarray. The results were analysed using Ingenuity Pathway Analysis software. The glutathione pathway was the most significantly altered canonical pathway in which the glutathione-s transferase mu 1 (GSTM1) gene was significantly over expressed (+8.03 folds) among the good responders compared to non responders. This was further confirmed by Real time PCR (p = 0.024). Correlation of immunoreactive scores (IRS) for GSTM1 accumulation in leiomyoma tissue was seen with base line volume change of leiomyoma R = −0.8 (p = 0.011). Furthermore the accumulation of protein GSTM1 analysed by Western Blot correlated significantly with the percentual leiomyoma volume change R = −0.82 (p = 0.004). Deletion of the GSTM1 gene in leiomyoma biopsies was found in 50% of the mifepristone treated cases, with lower presence of the GSTM1 protein. The findings support a significant role for GSTM1 in leiomyoma volume reduction induced by mifepristone and explain the observed individual variation in this response. Furthermore the finding could be useful to further explore GSTM1 as a biomarker for tailoring medical treatment of uterine leiomyomas for optimizing the response to treatment.
Clinical Trials identifier
www.clinicaltrials.gov: NCT00579475, Protocol date: November 2004. http://clinicaltrials.gov/ct2/show/NCT00579475 相似文献19.
Continuous renal replacement therapy (CRRT) is considered as an effective modality for renal replacement therapy in hemodynamically unstable patients within intensive care units (ICUs). However, the role of heparin anticoagulation, which is used to maintain circuit patency, is equivocal due to the risk of bleeding and morbidity. Among various alternative anticoagulants, nafamostat mesilate has been shown to be an effective anticoagulant in patients prone to bleeding. Hence, we conducted a prospective, randomized controlled study investigating the effect of nafamostat mesilate on mortality, CRRT filter life span and adverse events in patients with bleeding tendency. Seventy-three Patients were randomized into either the futhan or no-anticoagulation group. Thirty-six subjects in the futhan group received nafamostat mesilate, while thirty seven subjects in the no-anticoagulation group received no anticoagulants. Baseline characteristics and appropriate laboratory tests were taken from each group. The mortality between the two groups was not significantly different. Nevertheless, between the futhan group and the no-anticoagulation group, the overall number of filters used during CRRT (2.71±2.12 vs. 4.50±3.25; p = 0.042) and the number of filters changed due to clots per 24 hours (1.15±0.81 vs. 1.74±1.62; p = 0.040) were significantly different. When filter life span was subdivided into below and over 12 hours, the number of filters functioning over 12 hours was significantly higher in the futhan group than in the no-anticoagulation group (p = 0.037, odds ratio 1.84). There were no significant differences in transfusion, mortality, or survival between the two groups, and no adverse events related to nafamostat mesilate were noted. Hence, nafamostat mesilate may be used as an effective and safe anticoagulant, without increasing the risk of major bleeding complications, in patients prone to bleeding.
Trial Registration
Clinicaltrials.gov NCT01761994 相似文献20.
Lieke J. J. Klinkenberg Peter T. Res Guido R. Haenen Aalt Bast Luc J. C. van Loon Marja P. van Dieijen-Visser Steven J.R. Meex 《PloS one》2013,8(11)