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1.
Laura W. Goff Nilay Thakkar Liping Du Emily Chan Benjamin R. Tan Dana B. Cardin Howard L. McLeod Jordan D. Berlin Barbara Zehnbauer Chloe Fournier Joel Picus Andrea Wang-Gillam Wooin Lee A. Craig Lockhart 《PloS one》2014,9(9)
Background
Retrospective studies indicate associations between TSER (thymidylate synthase enhancer region) genotypes and clinical outcomes in patients receiving 5-FU based chemotherapy, but well-controlled prospective validation has been lacking.Methods
In this phase II study (NCT00515216 registered through ClinicalTrials.gov, http://clinicaltrials.gov/show/NCT00515216), patients with “good risk” TSER genotypes (at least one TSER*2 allele) were treated with FOLFOX chemotherapy to determine whether prospective patient selection can improve overall response rates (ORR) in patients with gastric and gastroesophageal junction (GEJ) cancers, compared with historical outcomes in unselected patients (estimated 43%).Results
The ORR in genotype-selected patients was 39.1% (9 partial responses out of 23 evaluable patients, 95% CI, 22.2 to 59.2), not achieving the primary objective of improving ORR. An encouraging disease control rate (DCR, consisting of partial responses and stable diseases) of 95.7% was noted and patients with homozygous TSER*2 genotype showed better tumor response.Conclusions
In this first prospective, multi-institutional study in patients with gastric or GEJ cancers, selecting patients with at least one TSER*2 allele did not improve the ORR but led to an encouraging DCR. Further studies are needed to investigate the utility of selecting patients homozygous for the TSER*2 allele and additional genomic markers in improving clinical outcomes for patients with gastric and GEJ cancers.Trial Registration
ClinicalTrials.gov NCT00515216 相似文献2.
Walter P Maksymowych Anthony S Russell Peter Chiu Alex Yan Niall Jones Tracey Clare Robert GW Lambert 《Arthritis research & therapy》2012,14(5):1-7
Introduction
Inflammation associated with synovial expression of TNFα is a recognised feature of osteoarthritis (OA), although no studies have yet reported beneficial effects of anti-TNFα therapy on clinical manifestations of inflammation in OA.Methods
We conducted an open-label evaluation of adalimumab over 12 weeks in 20 patients with OA of the knee and evidence of effusion clinically. Inclusion criteria included daily knee pain for the month preceding study enrolment and a summed pain score of 125 to 400 mm visual analogue scale on the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) pain subscale. The primary outcome was the Osteoarthritis Research Society International/Outcome Measures in Rheumatology Clinical Trials (OARSI/OMERACT) response criterion at week 12. Secondary outcomes included the WOMAC pain score 20% and 50% improvement, WOMAC stiffness and function scores, patient and physician global visual analogue scale, as well as target joint swelling.Results
Treatment was well tolerated and completed by 17 patients with withdrawals unrelated to lack of efficacy or adverse events. By intention to treat, an OARSI/OMERACT response was recorded in 14 (70%) patients. WOMAC pain 20% and 50% responses were recorded in 14 (70%) patients and eight (40%) patients, respectively. Significant improvement was observed in mean WOMAC pain, stiffness, function, physician and patient global, as well as target joint swelling at 12 weeks (P < 0.0001 for all). After treatment discontinuation, 16 patients were available for assessment at 22 weeks and OARSI/OMERACT response compared with baseline was still evident in 10 (50%) patients.Conclusion
Targeting TNFα may be of therapeutic benefit in OA and requires further evaluation in controlled trials.Trial registration
ClinicalTrials.gov: NCT00686439. 相似文献3.
Background
Intense abdominal pain is the dominant feature of chronic pancreatitis. During the disease changes in central pain processing, e.g. central sensitization manifest as spreading hyperalgesia, can result from ongoing nociceptive input. The aim of the present study is to evaluate the effect of pregabalin on pain processing in chronic pancreatitis as assessed by quantitative sensory testing (QST).Methods
This randomized, double-blind, placebo-controlled trial evaluated effects of pregabalin on pain processing. QST was used to quantify pain processing by measuring thresholds to painful electrical and pressure stimulation in six body dermatomes. Descending endogenous pain modulation was quantified using the conditioned pain modulation (CPM) paradigm to elicit a DNIC (diffuse noxious inhibitory controls) response. The main effect parameter was the change in the sum of all body pain threshold values after three weeks of study treatment versus baseline values between both treatment groups.Results
64 patients were analyzed. No differences in change in sum of pain thresholds were present for pregabalin vs. placebo after three weeks of treatment. For individual dermatomes, change vs. baseline pain thresholds was significantly greater in pregabalin vs. placebo patients for electric pain detection threshold in C5 (P = 0.005), electric pain tolerance threshold in C5 (P = 0.04) and L1 (P = 0.05), and pressure pain tolerance threshold in T4 (P = 0.004). No differences were observed between pregabalin and placebo regarding conditioned pain modulation.Conclusion
Our study provides first evidence that pregabalin has moderate inhibitory effects on central sensitization manifest as spreading hyperalgesia in chronic pancreatitis patients. These findings suggest that QST can be of clinical use for monitoring pain treatments in the context of chronic pain.Trial Registration
ClinicalTrials.gov NCT00755573 相似文献4.
Background
By measuring very early changes in muscle strength and functional performance after fast-track total hip arthroplasty (THA), post-operative rehabilitation, introduced soon after surgery, can be designed to specifically target identified deficits.Objective(s)
Firstly, to quantify changes (compared to pre-operative values) in hip muscle strength, leg-press power, and functional performance in the first week after THA, and secondly, to explore relationships between the muscle strength changes, and changes in hip pain, systemic inflammation, and thigh swelling.Design
Prospective, cohort study.Setting
Convenience sample of patients receiving a THA at Copenhagen University Hospital, Hvidovre, Denmark, between March and December 2011.Participants
Thirty-five patients (65.9±7.2 years) undergoing THA.Main outcome measures
Hip muscle strength, leg-press power, performance-based function, and self-reported disability were determined prior to, and 2 and 8 days after, THA (Day 2 and 8, respectively). Hip pain, thigh swelling, and C-Reactive Protein were also determined.Results
Five patients were lost to follow-up. Hip muscle strength and leg press power were substantially reduced at Day 2 (range of reductions: 41–58%, P<0.001), but less pronounced at Day 8 (range of reductions: 23–31%, P<0.017). Self-reported symptoms and function (HOOS: Pain, Symptoms, and ADL) improved at Day 8 (P<0.014). Changes in hip pain, C-Reactive Protein, and thigh swelling were not related to the muscle strength and power losses.Conclusion(s)
Hip muscle strength and leg-press power decreased substantially in the first week after THA – especially at Day 2 – with some recovery at Day 8. The muscle strength loss and power loss were not related to changes in hip pain, systemic inflammation, or thigh swelling. In contrast, self-reported symptoms and function improved. These data on surgery-induced changes in muscle strength may help design impairment-directed, post-operative rehabilitation to be introduced soon after surgery.Trial Registration
ClinicalTrials.gov NCT01246674. 相似文献5.
Marina Chiara Garassino Sheila Piva Nicla La Verde Ilaria Spagnoletti Vittorio Iorno Claudia Carbone Antonio Febbraro Anna Bianchi Annalisa Bramati Anna Moretti Monica Ganzinelli Mirko Marabese Marta Gentili Valter Torri Gabriella Farina 《PloS one》2013,8(4)
Purpose
Neuropathic pain is commonly associated with cancer. Current treatments include combination opioid and adjuvant therapies, but no guidelines are available for dose escalation strategies. This phase II study compared the efficacy and tolerability of two dose escalation strategies for oxycodone and pregabalin combination therapy.Methods
Patients (N = 75) with oncological neuropathic pain, previously untreated with pregabalin, were recruited in 5 Italian institutions between 2007 and 2010. Patients were randomised to two different dose escalation strategies (arm A; N = 38) oxycodone at a fixed dose with increasing pregabalin doses; (arm B; N = 37) pregabalin at a fixed dose with increasing oxycodone doses. Patients were evaluated from daily diaries and follow-ups at 3, 7, 10, and 14 days after beginning treatment with a numerical rating scale (NRS), neuropathic pain scale (SDN), and well-being scale (ESAS). The primary endpoint was a ≥1/3 reduction in pain (NRS); secondary endpoints included the time to analgesia and adverse effects. The study had a 90% probability of detecting the best strategy for a true difference of at least 15%.Results
More patients in arm A (76%) than arm B (64%) achieved ≥1/3 overall pain reduction even after controlling for baseline factors (gender, baseline pain). Group A reported fewer side effects than group B; constipation 52.8% vs. 66.7%; nausea: 27.8% vs. 44.4%; drowsiness: 44.4% vs. 55.6%; confusion: 16.7% vs. 27.8%; itching: 8.3% vs. 19.4%.Conclusions
Both strategies effectively controlled neuropathic pain, but according to the adopted selection design arm A is preferable to arm B for pain control.Trial Registration
ClinicalTrials.gov NCT00637975 相似文献6.
Ishani Ganguli Jamie E. Collins William M. Reichmann Elena Losina Jeffrey N. Katz Christian Arbelaez Laurel A. Donnell-Fink Rochelle P. Walensky 《PloS one》2013,8(1)
Background
HIV infection remains a major US public health concern. While HIV-infected individuals now benefit from earlier diagnosis and improved treatment options, progress is tempered by large numbers of newly diagnosed patients who are lost to follow-up prior to disease confirmation and linkage to care.Methodology
In the randomized, controlled USHER trial, we offered rapid HIV tests to patients presenting to a Boston, MA emergency department. Separate written informed consent was required for confirmatory testing. In a secondary analysis, we compared participants with reactive results who did and did not complete confirmatory testing to identify factors associated with refusal to complete the confirmation protocol.Principal Findings
Thirteen of 62 (21.0%, 95% CI (11.7%, 33.2%)) participants with reactive rapid HIV tests refused confirmation; women, younger participants, African Americans, and those with fewer HIV risks, with lower income, and without primary care doctors were more likely to refuse. We projected that up to four true HIV cases were lost at the confirmation stage.Conclusions
These findings underscore the need to better understand the factors associated with refusal to confirm reactive HIV testing and to identify interventions that will facilitate confirmatory testing and linkage to care among these populations.Trial Registration
ClinicalTrials.gov NCT00502944; NCT01258582. 相似文献7.
Dominique Hubert Lucile Soubeiran Fabrice Gourmelon Dominique Grenet Rapha?l Serreau Elodie Perrodeau Rafael Zegarra-Parodi Isabelle Boutron 《PloS one》2014,9(7)
Background
Pain is a common complication in patients with cystic fibrosis (CF) and is associated with shorter survival. We evaluated the impact of osteopathic manipulative treatment (OMT) on pain in adults with CF.Methods
A pilot multicenter randomized controlled trial was conducted with three parallel arms: OMT (group A, 16 patients), sham OMT (sham treatment, group B, 8 patients) and no treatment (group C, 8 patients). Medical investigators and patients were double-blind to treatment for groups A and B, who received OMT or sham OMT monthly for 6 months. Pain was rated as a composite of its intensity and duration over the previous month. The evolution of chest/back pain after 6 months was compared between group A and groups B+C combined (control group). The evolution of cervical pain, headache and quality of life (QOL) were similarly evaluated.Results
There was no statistically significant difference between the treatment and control groups in the decrease of chest/back pain (difference = −2.20 IC95% [−4.81; 0.42], p = 0.098); also, group A did not differ from group B. However, chest/back pain decreased more in groups A (p = 0.002) and B (p = 0.006) than in group C. Cervical pain, headache and QOL scores did not differ between the treatment and control groups.Conclusion
This pilot study demonstrated the feasibility of evaluating the efficacy of OMT to treat the pain of patients with CF. The lack of difference between the group treated with OMT and the control group may be due to the small number of patients included in this trial, which also precludes any definitive conclusion about the greater decrease of pain in patients receiving OMT or sham OMT than in those with no intervention.Trial Registration
ClinicalTrials.gov NCT01293019 相似文献8.
Bego?a Comin-Anduix Hooman Sazegar Thinle Chodon Douglas Matsunaga Jason Jalil Erika von Euw Helena Escuin-Ordinas Robert Balderas Bartosz Chmielowski Jesus Gomez-Navarro Richard C. Koya Antoni Ribas 《PloS one》2010,5(9)
Background
The effects on cell signalling networks upon blockade of cytotoxic T lymphocyte-associated antigen-4 (CTLA4) using the monoclonal antibody tremelimumab were studied in peripheral blood mononuclear cell (PBMC) samples from patients with metastatic melanoma.Methodology/Principal
Findings Intracellular flow cytometry was used to detect phosphorylated (p) signaling molecules downstream of the T cell receptor (TCR) and cytokine receptors. PBMC from tremelimumab-treated patients were characterized by increase in pp38, pSTAT1 and pSTAT3, and decrease in pLck, pERK1/2 and pSTAT5 levels. These changes were noted in CD4 and CD8 T lymphocytes but also in CD14 monocytes. A divergent pattern of phosphorylation of Zap70, LAT, Akt and STAT6 was noted in patients with or without an objective tumor response.Conclusions/Significance
The administration of the CTLA4-blocking antibody tremelimumab to patients with metastatic melanoma influences signaling networks downstream of the TCR and cytokine receptors both in T cells and monocytes. The strong modulation of signaling networks in monocytes suggests that this cell subset may be involved in clinical responses to CTLA4 blockade.Clinical Trial Registration
clinicaltrials.gov; Registration numbers NCT00090896 and NCT00471887 相似文献9.
Background
The effectiveness of injection therapy for low-back pain is still debatable. We compared the efficacy of local injections of the homeopathic preparation Disci/Rhus toxicodendron compositum (verum) with placebo injections and with no treatment in patients with chronic low back pain.Methodology/Principal Findings
In a randomized controlled partly double blind multicenter trial patients with chronic low back pain from 9 German outpatient clinics were enrolled and randomly allocated in a 1∶1∶1 ratio to receive subcutaneous injections (verum or placebo) into painful sites on the lower back over 12 treatment sessions within eight weeks, or no treatment (rescue pain medication with paracetamol or NSAIDs). All trial personnel and participants were masked to treatment allocation. The primary outcome measure was the average pain intensity over the last seven days on a visual analogue scale (0–100 mm, 0 = no pain, 100 = worst imaginable pain) after eight weeks. Follow-up was 26 weeks. Primary analysis was by intention to treat. Between August 2007 and June 2008, 150 patients were randomly allocated to three groups (51 verum, 48 placebo and 51 no treatment). The mean baseline-adjusted low back pain intensity at week eight was: verum group 37.0 mm (97.5% CI 25.3;48.8), no treatment group 53.0 (41.8;64.2), and placebo group 41.8 (30.1;53.6). The verum was significantly superior to no treatment (P = 0.001), but not to placebo (P = 0.350). No significant side effects were reported.Conclusions/Significance
The homeopathic preparation was not superior to placebo. Compared to no treatment injections resulted in significant and clinical relevant chronic back pain relief.Trial Registration
ClinicalTrials.gov NCT00567736 相似文献10.
Chen Wang Zhenguo Zhai Yuanhua Yang Yadong Yuan Zhaozhong Cheng Lirong Liang Huaping Dai Kewu Huang Weixuan Lu Zhonghe Zhang Xiansheng Cheng Ying H Shen China Venous Thromboembolism Study Group 《Respiratory research》2009,10(1):128
Backgrounds
Urokinase (UK) 2 200 U/kg·h for 12 hours infusion(UK-12 h)is an ACCP recommended regimen in treating acute pulmonary embolism (PE). It is unclear whether this dose and time can be reduced further. We compared the efficacy and safety of 20, 000 U/kg for 2 hours (UK-2 h) with the UK-12 h regime in selected PE patients.Methods
A randomized trial involving 129 patients was conducted. Patients with acute PE were randomly assigned to receive either UK-12 h (n = 70), or UK-2 h (n = 59). The efficacy was determined by the improvement of right heart dysfunction and perfusion defect at 24 h and 14 d post UK treatment. The bleeding incidence, death rate and PE recurrence were also evaluated.Results
Similarly significant improvements in right heart dysfunction and lung perfusion defects were observed in both groups. Overall bleeding incidents were low in both groups. Major bleeding directly associated with UK infusion occurred in one patient in the UK-2 h group and one in the UK-12 h group. Mortality rates were low, with one reported fatal recurrent in the UK-12 h group and none in the UK-2 h group. When the rate of bleeding, death and PE recurrence were compared separately in the hemodynamic instability and the massive anatomic obstruction subgroups, no significant difference was found.Conclusions
The UK-2 h regimen exhibits similar efficacy and safety as the UK-12 h regimen for acute PE.Trial Registration
Clinical trial registered with http://clinicaltrials.gov/ct2/show/NCT00799968 (Identifier: NCT 00799968) 相似文献11.
Pascal H. Vuilleumier Marie Besson Jules Desmeules Lars Arendt-Nielsen Michele Curatolo 《PloS one》2013,8(3)
Background and Aims
Compounds that act on GABA-receptors produce anti-hyperalgesia in animal models, but little is known on their effects in humans. The aim of this study was to explore the potential usefulness of GABA-agonism for the control of pain in humans. Two agonists at the benzodiazepine-binding site of GABAA-receptors (clobazam and clonazepam) were studied using multiple experimental pain tests. Positive results would support further investigation of GABA agonism for the control of clinical pain.Methods
In a randomized double-blind crossover design, 16 healthy male volunteers received clobazam 20 mg, clonazepam 1 mg and tolterodine 1 mg (active placebo). The area of static hyperalgesia after intradermal capsaicin injection was the primary endpoint. Secondary endpoints were: area of dynamic hyperalgesia, response to von Frey hair stimulation, pressure pain thresholds, conditioned pain modulation, cutaneous and intramuscular electrical pain thresholds (1, 5 and 20 repeated stimulation), and pain during cuff algometry.Results
For the primary endpoint, an increase in the area of static hyperalgesia was observed after administration of placebo (p<0.001), but not after clobazam and clonazepam. Results suggestive for an anti-hyperalgesic effect of the benzodiazepines were obtained with all three intramuscular pain models and with cuff algometry. No effect could be detected with the other pain models employed.Conclusions
Collectively, the results are suggestive for a possible anti-hyperalgesic effect of drugs acting at the GABAA-receptors in humans, particularly in models of secondary hyperalgesia and deep pain. The findings are not conclusive, but support further clinical research on pain modulation by GABAergic drugs. Because of the partial results, future research should focus on compounds acting selectively on subunits of the GABA complex, which may allow the achievement of higher receptor occupancy than unselective drugs. Our data also provide information on the most suitable experimental models for future investigation of GABAergic compounds.Trial Registration
ClinicalTrials.gov NCT01011036 相似文献12.
Introduction
Iodine is essential for normal fetal and neonatal development. We studied the prevalence and impact on fetal thyroid development of iodine deficiency in pregnant women in the northern part of the Paris conurbation.Materials and Methods
110 patients underwent several determinations of urinary iodine excretion (UIE) and of serum FT4, FT3, and TSH. Fetal thyroid gland size was assessed using ultrasonography.Results
We found evidence of widespread iodine deficiency (mean UIE, 49.8 µg/L [standard deviation, 2.11]). Iodine deficiency did not correlate significantly with maternal thyroid parameters but showed a significant negative correlation with fetal thyroid gland size (rho = 0.25, P = 0.02).Conclusion
Iodine deficiency during pregnancy is still a problem in our geographical area and affects the fetal thyroid gland.Clinical Trials.gov NCT00162539 相似文献13.
Yulia Kundel Nicola J. Nasser Ofer Purim Rinat Yerushalmi Eyal Fenig Raphael M. Pfeffer Salomon M. Stemmer Shulamith Rizel Zvi Symon Bella Kaufman Aaron Sulkes Baruch Brenner 《PloS one》2013,8(7)
Background
Pain from bone metastases of breast cancer origin is treated with localized radiation. Modulating doses and schedules has shown little efficacy in improving results. Given the synergistic therapeutic effect reported for combined systemic chemotherapy with local radiation in anal, rectal, and head and neck malignancies, we sought to evaluate the tolerability and efficacy of combined capecitabine and radiation for palliation of pain due to bone metastases from breast cancer.Methodology/Principal Findings
Twenty-nine women with painful bone metastases from breast cancer were treated with external beam radiation in 10 fractions of 3 Gy, 5 fractions a week for 2 consecutive weeks. Oral capecitabine 700 mg/m2 twice daily was administered throughout radiation therapy. Rates of complete response, defined as a score of 0 on a 10-point pain scale and no increase in analgesic consumption, were 14% at 1 week, 38% at 2 weeks, 52% at 4 weeks, 52% at 8 weeks, and 48% at 12 weeks. Corresponding rates of partial response, defined as a reduction of at least 2 points in pain score without an increase in analgesics consumption, were 31%, 38%, 28%, 34% and 38%. The overall response rate (complete and partial) at 12 weeks was 86%. Side effects were of mild intensity (grade I or II) and included nausea (38% of patients), weakness (24%), diarrhea (24%), mucositis (10%), and hand and foot syndrome (7%).Conclusions/Significance
External beam radiation with concurrent capecitabine is safe and tolerable for the treatment of pain from bone metastases of breast cancer origin. The overall and complete response rates in our study are unusually high compared to those reported for radiation alone. Further evaluation of this approach, in a randomized study, is warranted.Trial Registration
ClinicalTrials.gov NCT01784393NCT01784393 相似文献14.
S Lambert-Niclot P Flandre MA Valantin C Soulie S Fourati M Wirden S Sayon S Pakianather L Bocket B Masquelier G Dos Santos C Katlama V Calvez AG Marcelin 《PloS one》2012,7(7):e41390
Background
A higher proportion of intermittent viremia (to have a HIV-1 RNA viral load>50 copies/mL not confirmed) was reported in the boosted protease inhibitor monotherapy arm in some studies including MONOI trial, and that could have an impact on the replenishment of the HIV-1 DNA reservoirs. The HIV-1 DNA level is an interesting marker which reflects the size of cellular HIV reservoir. Our objectives were to study the impact of 96 weeks of Darunavir/ritonavir monotherapy versus a triple standard combination on the HIV-1 blood reservoir and factors associated with HIV-1 plasma DNA at baseline in MONOI trial sub-study.Methodology/Principal Findings
This sub-study is focused on 160 patients (79 patients in monotherapy arm and 81 in tritherapy arm) for whom blood cells were available both at baseline and at week 96 (W96). Baseline HIV-1 plasma DNA was associated with CD4 nadir, pre therapeutic HIV-1 RNA viral load and baseline HIV-1 RNA measured by ultrasensitive assay. A similar median delta HIV-DNA was observed between D0 and W96 in both arms; 0.35 log copies/106 leucocytes in monotherapy arm versus 0.51 log copies/106 leucocytes in tritherapy arm.Conclusion/Significance
Despite a higher proportion of intermittent viremia in monotherapy arm, a similar evolution of cellular HIV-1 DNA level was observed between mono and triple therapy arm.Trial Registration
ClinicalTrials. gov NCT00421551 <NCT00421551> 相似文献15.
Gavin C Donaldson Hanna Müllerova Nicholas Locantore John R Hurst Peter MA Calverley Jorgen Vestbo Antonio Anzueto Jadwiga A Wedzicha 《Respiratory research》2013,14(1):79
Background
Patients with chronic obstructive pulmonary disease (COPD) can be categorized as having frequent (FE) or infrequent (IE) exacerbations depending on whether they respectively experience two or more, or one or zero exacerbations per year. Although most patients do not change category from year to year, some will, and the factors associated with this behaviour have not been examined.Methods
1832 patients completing two year follow-up in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE) study were examined at baseline and then yearly. Exacerbations were defined by health care utilisation. Patient characteristics compared between those patients who did or did not change exacerbation category from year 1 to year 2.Findings
Between years 1 and 2, 221 patients (17%) changed from IE to FE and 210 patients (39%) from FE to IE. More severe disease was associated with changing from IE to FE and less severe disease from FE to IE. Over the preceding year, small falls in FEV1 and 6-minute walking distance were associated with changing from IE to FE, and small falls in platelet count associated with changing from FE to IE.Conclusion
No parameter clearly predicts an imminent change in exacerbation frequency category.Trial registration
SCO104960, clinicaltrials.gov identifier NCT00292552 相似文献16.
Török ME Nguyen DB Tran TH Nguyen TB Thwaites GE Hoang TQ Nguyen HD Tran TH Nguyen TC Hoang HT Wolbers M Farrar JJ 《PloS one》2011,6(12):e27821
Background
Dexamethasone has been shown to reduce mortality in patients with tuberculous meningitis but the long-term outcome of the disease is unknown.Methods
Vietnamese adults and adolescents with tuberculous meningitis recruited to a randomised, double-blind, placebo-controlled trial of adjunctive dexamethasone were followed-up at five years, to determine the effect of dexamethasone on long-term survival and neurological disability.Results
545 patients were randomised to receive either dexamethasone (274 patients) or placebo (271 patients). 50 patients (9.2%) were lost to follow-up at five years. In all patients two-year survival, probabilities tended to be higher in the dexamethasone arm (0.63 versus 0.55; p = 0.07) but five-year survival rates were similar (0.54 versus 0.51, p = 0.51) in both groups. In patients with grade 1 TBM, but not with grade 2 or grade 3 TBM, the benefit of dexamethasone treatment tended to persist over time (five-year survival probabilities 0.69 versus 0.55, p = 0.07) but there was no conclusive evidence of treatment effect heterogeneity by TBM grade (p = 0.36). The dexamethasone group had a similar proportion of severely disabled patients among survivors at five years as the placebo group (17/128, 13.2% vs. 17/116, 14.7%) and there was no significant association between dexamethasone treatment and disability status at five years (p = 0.32).Conclusions
Adjunctive dexamethasone appears to improve the probability of survival in patients with TBM, until at least two years of follow-up. We could not demonstrate a five-year survival benefit of dexamethasone treatment which may be confined to patients with grade 1 TBM.Trial Registration
ClinicalTrials.gov NCT01317654 NCT01317654?term = tuberculous+meningitis&rank = 3 相似文献17.
Lennart Greiff Anders Cervin Cecilia Ahlstr?m-Emanuelsson Gun Almqvist Morgan Andersson Jan Dolata Leif Eriksson Edward H?gest?tt Anders K?llén Per Norlén Inga-Lisa Sj?lin Henrik Widegren 《Respiratory research》2012,13(1):53
Background
Interactions between Th1 and Th2 immune responses are of importance to the onset and development of allergic disorders. A Toll-like receptor 7 agonist such as AZD8848 may have potential as a treatment for allergic airway disease by skewing the immune system away from a Th2 profile.Objective
To evaluate the efficacy and safety of intranasal AZD8848.Methods
In a placebo-controlled single ascending dose study, AZD8848 (0.3-600 μg) was given intranasally to 48 healthy subjects and 12 patients with allergic rhinitis (NCT00688779). In a placebo-controlled repeat challenge/treatment study, AZD8848 (30 and 60 μg) was given once weekly for five weeks to 74 patients with allergic rhinitis out of season: starting 24 hours after the final dose, daily allergen challenges were given for seven days (NCT00770003). Safety, tolerability, pharmacokinetics, and biomarkers were monitored. During the allergen challenge series, nasal symptoms and lavage fluid levels of tryptase and α2-macroglobulin, reflecting mast cell activity and plasma exudation, were monitored.Results
AZD8848 produced reversible blood lymphocyte reductions and dose-dependent flu-like symptoms: 30–100 μg produced consistent yet tolerable effects. Plasma interleukin-1 receptor antagonist was elevated after administration of AZD8848, reflecting interferon production secondary to TLR7 stimulation. At repeat challenge/treatment, AZD8848 reduced nasal symptoms recorded ten minutes after allergen challenge up to eight days after the final dose. Tryptase and α2-macroglobulin were also reduced by AZD8848.Conclusions
Repeated intranasal stimulation of Toll-like receptor 7 by AZD8848 was safe and produced a sustained reduction in the responsiveness to allergen in allergic rhinitis.Trial registration
NCT00688779 and NCT00770003 as indicated above. 相似文献18.
Sandrine Roisin Christine Laurent Olivier Denis Michèle Dramaix Claire Nonhoff Marie Hallin Baudouin Byl Marc J. Struelens 《PloS one》2014,9(5)
Design
Cluster randomised crossover trial with seven wards randomly allocated to intervention or control arm.Setting
Medical and surgical wards of a university hospital with active MRSA control programme.Participants
All patients hospitalized >48 h in study wards and screened for MRSA on admission and discharge Intervention: Rapid PCR-based screening test for MRSA compared with control screening test by enrichment culture using chromogenic agar.Objective
We determined the benefit of PCR-detection versus culture-based detection of MRSA colonisation upon patient admission on early implementation of isolation precautions and reduction of hospital transmission of MRSA.Main outcome
Cumulative rate of MRSA hospital acquisition of in patients screened negative on admission.Randomization
The sequential order of inclusion of study wards in each arm was randomised by assigning a number to each ward and using a computer generated list of random numbers.Findings
Of 3704 eligible patients, 67.8% were evaluable for the study. Compared with culture, PCR-screening reduced the median test reporting time from admission from 88 to 11 hours (p<0.001) and the median time from admission to isolation from 96 to 25 hours (p<0.001). MRSA acquisition was detected in 36 patients (3.2%) in the control arm and 34 (3.2%) in the intervention arm. The incidence density rate of hospital acquired MRSA was 2.82 and 2.57/1,000 exposed patient-days in the control and intervention arm, respectively (risk ratio 0.91 (95% confidence interval, 0.60–1.39). Poisson regression model adjusted for colonisation pressure, compliance with hand hygiene and antibiotic use indicated a RR 0.99 (95% CI, 0.69 to 1.44).Interpretation
Universal PCR screening for MRSA on admission to medical and surgical wards in an endemic setting shortened the time to implement isolation precautions but did not reduce nosocomial acquisition of MRSA.Trial registration
clinicaltrials.gov NCT00846105 相似文献19.
S Perrin J Cremer P Roll O Faucher A Ménard J Reynes P Dellamonica A Naqvi J Micallef E Jouve C Tamalet C Solas C Pissier I Arnoux C Nicolino-Brunet L Espinosa N Lévy E Kaspi A Robaglia-Schlupp I Poizot-Martin P Cau 《PloS one》2012,7(7):e41129
Background
The ANRS EP45 “Aging” study investigates the cellular mechanisms involved in the accelerated aging of HIV-1 infected and treated patients. The data reported focus on mitochondria, organelles known to be involved in cell senescence.Methods
49 HIV-1 infected patients untreated with antiretroviral therapy, together with 49 seronegative age- and sex-matched control subjects and 81 HIV-1 infected and treated patients, were recruited by 3 AIDS centres (Marseille, Montpellier, Nice; France; http://clinicaltrials.gov/, NCT01038999). In more than 88% of treated patients, the viral load was <40 copies/ml and the CD4+ cell count was >500/mm3. ROS (reactive oxygen species) production and ΔΨm (inner membrane potential) were measured by flow cytometry in blood lymphocytes and monocytes (functional parameters). Three mitochondrial network quantitative morphological parameters were computed using confocal microscopy and image analysis. Three PBMC mitochondrial proteins (porin and subunits 2 and 4 of cytochrome C oxidase encoded by mtDNA or nuclear DNA, respectively) were analysed by western blotting.Results
Quantitative changes in PBMC mitochondrial proteins were not induced by either HIV-1 infection or ART. Discriminant analysis integrating functional (ROS production and ΔΨm) or morphological (network volume density, fragmentation and branching) parameters revealed HIV-1 infection and ART differential effects according to cell type. First line ART tended to rescue lymphocyte mitochondrial parameters altered by viral infection, but induced slight changes in monocytes. No statistical difference was found between the effects of three ART regimens on mitochondrial parameters. Correlations between functional parameters and viral load confirmed the damaging effects of HIV-1 in lymphocyte mitochondria.Conclusions
In patients considered to be clinically stable, mitochondria exhibited functional and morphological modifications in PBMCs resulting from either direct or indirect effects of HIV-1 infection (lymphocytes), or from first line ART (monocytes). Together with other tissue impairments, these changes may contribute to global aging.Trial Registration
ClinicalTrials.gov NCT01038999 NCT01038999 相似文献20.
Derek J. Hoare Nicolas Van Labeke Abby McCormack Magdalena Sereda Sandra Smith Hala Al Taher Victoria L. Kowalkowski Mike Sharples Deborah A. Hall 《PloS one》2014,9(9)