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1.
Luisa?Pastò Emilio?Portaccio Angelo?Ghezzi Bahia?Hakiki Marta?Giannini Lorenzo?Razzolini Elisa?Piscolla Laura?De Giglio Carlo?Pozzilli Damiano?Paolicelli Maria?Trojano Maria?Giovanna?Marrosu Francesco?Patti Loredana?La Mantia Gian?Luigi?Mancardi Claudio?Solaro Rocco?Totaro Maria?Rosaria?Tola Valeria?Di Tommaso Alessandra?Lugaresi Lucia?Moiola Vittorio?Martinelli Giancarlo?Comi Maria?Pia?Amato
Background
Few studies have systematically addressed the role of epidural analgesia and caesarean delivery in predicting the post-partum disease activity in women with Multiple Sclerosis (MS).The objective of this study was to assess the impact of epidural analgesia (EA) and caesarean delivery (CD) on the risk of post-partum relapses and disability in women with MS.Methods
In the context of an Italian prospective study on the safety of immunomodulators in pregnancy, we included pregnancies occurred between 2002 and 2008 in women with MS regularly followed-up in 21 Italian MS centers. Data were gathered through a standardized, semi-structured interview, dealing with pregnancy outcomes, breastfeeding, type of delivery (vaginal or caesarean) and EA. The risk of post-partum relapses and disability progression (1 point on the Expanded Disability Status Sclae, EDSS, point, confirmed after six months) was assessed through a logistic multivariate regression analysis.Results
We collected data on 423 pregnancies in 415 women. Among these, 349 pregnancies resulted in full term deliveries, with a post-partum follow-up of at least one year (mean follow-up period 5.5±3.1 years). One hundred and fifty-five patients (44.4%) underwent CD and 65 (18.5%) EA. In the multivariate analysis neither CD, nor EA were associated with a higher risk of post-partum relapses. Post-partum relapses were related to a higher EDSS score at conception (OR=1.42; 95% CI 1.11-1.82; p=0.005), a higher number of relapses in the year before pregnancy (OR=1.62; 95% CI 1.15-2.29; p=0.006) and during pregnancy (OR=3.07; 95% CI 1.40-6.72; p=0.005). Likewise, CD and EA were not associated with disability progression on the EDSS after delivery. The only significant predictor of disability progression was the occurrence of relapses in the year after delivery (disability progression in the year after delivery: OR= 4.00; 95% CI 2.0-8.2; p<0.001; disability progression over the whole follow-up period: OR= 2.0; 95% CI 1.2-3.3; p=0.005).Conclusions
Our findings, show no correlation between EA, CD and postpartum relapses and disability. Therefore these procedures can safely be applied in MS patients. On the other hand, post-partum relapses are significantly associated with increased disability, which calls for the need of preventive therapies after delivery.2.
Serena Bugatti Antonio Manzo Francesca Benaglio Catherine Klersy Barbara Vitolo Monica Todoerti Garifallia Sakellariou Carlomaurizio Montecucco Roberto Caporali 《Arthritis research & therapy》2012,14(1):R34-9
Introduction
Biological markers specifically reflecting pathological processes may add value in the assessment of inter-individual variations in the course of rheumatoid arthritis (RA). The current study was undertaken to investigate whether baseline serum levels of the chemokine CXCL13 might predict clinical and ultrasonographic (US) outcomes in patients with recent-onset RA.Methods
The study included 161 early RA patients (disease duration < 12 months) treated according to a disease activity score (DAS) driven step-up protocol aiming at DAS < 2.4. Clinical disease activity measures were collected at baseline, 2, 4, 6, 9 and 12 months, and US examination of the hands was performed at baseline, 6 and 12 months. Grey-Scale (GS) and Power Doppler (PD) synovitis were scored (0 to 3), with overall scores as the sum of each joint score. CXCL13 levels were measured at baseline by enzyme-linked immunosorbent assay and evaluated in relation to the achievement of low disease activity (LDA, DAS < 2.4) and US residual inflammation (PD ≤ 1) at 12 months.Results
Baseline levels of CXCL13 were significantly higher in RA compared to healthy controls (n = 19) (P = 0.03) and correlated with measures of synovitis, such as the swollen joint count (R 0.28, P < 0.001), the US-GS (R 0.27, P = 0.003) and US-PD (R 0.26, P = 0.005) score. Although CXCL13 did not predict the likelihood of achieving clinical LDA at 12 months within a structured treat-to-target protocol, elevated levels of CXCL13 were associated with more frequent increases of methotrexate dosage (P < 0.001). Using adjusted analyses, the highest levels of CXCL13 (> 100 pg/ml) were the only independent predictor of residual imaging inflammation (P = 0.005), irrespective of initial US-PD scores, disease activity status, acute phase reactants and autoantibodies. Among the patients in clinical LDA at 12 months, US-PD scores ≤ 1 were less frequently achieved in the high baseline CXCL13 (> 100 pg/ml) group, with an adjusted OR = 0.06 (95% CI 0.01 to 0.55, P = 0.01).Conclusions
CXCL13 emerges as a new biological marker in early RA, accurate in assessing the severity of synovitis and the persistence of US-PD activity over time in response to conventional treatments. 相似文献3.
Philipp Hildebrand Armin Besirevic Markus Kleemann Stefan Schlichting Volker Martens Achim Schweikard Hans-Peter Bruch 《Annals of surgical innovation and research》2007,1(1):1-6
Background
Psychological factors play a role in a variety of gastrointestinal illness, including gastroesophageal reflux disease (GERD). Their impact on the surgical outcomes of antireflux surgery is unknown.Methods
This is a single institution prospective controlled trial, comparing patients undergoing a laparoscopic Nissen fundoplication for GERD (LNF Group, n = 17) to patients undergoing an elective laparoscopic cholecystectomy for biliary colic (Control Group, n = 10). All patients had a psychological assessment before surgery, at 3 months and 6 months after surgery (i.e. Symptom CheckList-90-R somatization subset (SCL-90-R), Depression Anxiety Stress Scales, Anxiety sensitivity index, Illness attitude scale and Beck Depression Inventory II). GERD symptoms were recorded in the LNF Group using a standardized questionnaire (score 0–60). Patients with post-operative GERD symptoms score above 12 at 6 months were evaluated specifically. Statistical analysis was performed using a Student T test, and statistical significance was set at 0.05.Results
There was no significant difference in preoperative and postoperative psychological assessment between the two groups. In the LNF Group, 7 patients had persisting GERD symptoms at 6 months (GERD score greater than 12). The preoperative SCL-90-R score was also significantly higher in this subgroup, when compared to the rest of the LNF Group (18.2 versus 8.3, p < 0.05) and to the Control Group (18.2 versus 7.9, p < 0.05). There was no significant difference for the other psychological tests.Conclusion
The SCL-90-R Somatization Subset, reflecting the level of somatization in a patient, may be useful to predict poor outcomes after antireflux surgery. Cognisance of psychological disorders could improve the selection of an optimal treatment for GERD and help reduce the rate of ongoing symptoms after LNF. 相似文献4.
Bernard Cosyns Steven Droogmans Sophie Hernot Céline Degaillier Christian Garbar Caroline Weytjens Bram Roosens Danny Schoors Tony Lahoutte Philippe R Franken Guy Van Camp 《Cardiovascular diabetology》2008,7(1):1-10
Background
Hypertension and type 2 diabetes are common co-morbidities. Preliminary studies suggest that thiazolidinediones reduce blood pressure (BP). We therefore used ambulatory BP to quantify BP lowering at 6–12 months with rosiglitazone used in combination with metformin or sulfonylureas compared to metformin and sulfonylureas in people with type 2 diabetes.Methods
Participants (n = 759) in the multicentre RECORD study were studied. Those taking metformin were randomized (open label) to add-on rosiglitazone or sulfonylureas, and those on sulfonylurea to add-on rosiglitazone or metformin.Results
24-Hour ambulatory BP was measured at baseline, 6 months and 12 months. At 6 and 12 months, reductions in 24-hour ambulatory systolic BP (sBP) were greater with rosiglitazone versus metformin (difference at 6 months 2.7 [95% CI 0.5–4.9] mmHg, p = 0.015; 12 months 2.5 [95% CI 0.2–4.8] mmHg, p = 0.031). Corresponding changes for ambulatory diastolic BP (dBP) were comparable (6 months 2.7 [95% CI 1.4–4.0] mmHg, p < 0.001; 12 months 3.1 [95% CI 1.8–4.5] mmHg, p < 0.001). Similar differences were observed for rosiglitazone versus sulfonylureas at 12 months (sBP 2.7 [95% CI 0.5–4.9] mmHg, p = 0.016; dBP 2.1 [95% CI 0.7–3.4] mmHg, p = 0.003), but differences were smaller and/or not statistically significant at 6 months (sBP 1.5 [95% CI -0.6 to 3.6] mmHg, p = NS; dBP 1.3 [95% CI 0.0–2.5] mmHg, p = 0.049). Changes in BP were not accompanied by compensatory increases in heart rate, did not correlate with basal insulin sensitivity estimates and were not explained by changes in antihypertensive therapy between the various strata.Conclusion
When added to metformin or a sulfonylurea, 12-month treatment with rosiglitazone reduces ambulatory BP to a greater extent than when metformin and a sulfonylurea are combined.Trial registration
NCT00379769 http://clinicaltrials.gov/ 相似文献5.
Cécile Tolédano Murielle Gain Adrien Kettaneh Bruno Baudin Catherine Johanet Patrick Chérin Sébastien Rivière Jean Cabane Kiet Phong Tiev 《Arthritis research & therapy》2012,14(3):1-9
Introduction
In early rheumatoid arthritis (RA), low-dose oral prednisone (PDN) co-medication yields better clinical results than monotherapy with disease-modifying anti-rheumatic drugs (DMARDs). In addition, ultrasonography (US) evaluation reveals rapid and significant effects of glucocorticosteroids on subclinical synovitis. No data currently exist that examine the clinical and US results offered by glucocorticoid co-medication over DMARD monotherapy in early RA patients.Methods
Two hundred and twenty patients with early RA (< 1 year from clinical onset) were treated according to a low disease activity (LDA) targeted step-up protocol including methotrexate (MTX) and, in the active treatment arm, low-dose (6.25 mg/day) oral PDN over 12 months. Clinical disease activity measures were collected at baseline, 2, 4, 6, 9 and 12 months, and US examination of hands was performed at baseline, 6 and 12 months. Grey-scale and power Doppler (PD) synovitis were scored (0 to 3) for each joint. At 12 months, clinical remission according to the disease activity score among 28 joints was defined as the clinical outcome, and a total joint PD score of 0 (PD negativity) as the imaging outcome.Results
Each group included 110 patients with comparable demographic, clinical, laboratory and US characteristics. At 12 months, the LDA rate was similar in the two groups, whilst the clinical remission rate (risk ratio = 1.61 (95% confidence interval = 1.08, 2.04)) and PD negativity rate (risk ratio = 1.31 (95% confidence interval = 1.04, 1.64)) were significantly higher in the MTX+PDN group.Conclusion
In early RA, despite a similar response rate in terms of LDA, low-dose oral PDN co-medication led to a higher proportion of clinical remission and PD negativity compared with MTX monotherapy, thus ensuring a better disease activity control.Trial registration number
Current Controlled Trials ISRCTN2486111 相似文献6.
Background and Aims
The association between allergic bronchopulmonary aspergillosis (ABPA) and aspergilloma has been proposed as a severe form of ABPA. However, this conclusion is based on single-patient case reports. In this study, we describe the clinical details and immunological findings of this association and compare patients of ABPA with aspergilloma and those without.Methods
This is a retrospective analysis of data of patients with ABPA managed in the Chest Clinic. We compared the clinical, radiological and immunological profile of patients with ABPA and central bronchiectasis, with and without the presence of aspergilloma on HRCT scan.Results
There were 98 men and 81 women with a mean (SD) age of 33.6 (12.2) years. Eight patients were diagnosed to have aspergilloma. Sputum cultures grew Aspergillus fumigatus in all these eight patients. The aspergilloma was solitary in six patients, and two each in two patients. Patients with aspergilloma had higher IgE levels (both total and A. fumigatus specific) than those without aspergilloma. Bronchiectasis was also more extensive in patients with aspergilloma. Overall, 70?% of the ABPA patients experienced relapse during the median (interquartile range) follow-up of 27 (19?C39) months. The number of relapses was significantly higher in patients with aspergilloma (p?=?0.0001). On a multivariate linear regression analysis, high-attenuation mucus and aspergilloma were independent predictors of relapse frequency.Conclusions
The concurrent presentation of ABPA and aspergilloma is associated with an immunologically severe disease and risk of recurrent relapses. 相似文献7.
Ester Simeone Giusy Gentilcore Diana Giannarelli Antonio M. Grimaldi Corrado Caracò Marcello Curvietto Assunta Esposito Miriam Paone Marco Palla Ernesta Cavalcanti Fabio Sandomenico Antonella Petrillo Gerardo Botti Franco Fulciniti Giuseppe Palmieri Paola Queirolo Paolo Marchetti Virginia Ferraresi Gaetana Rinaldi Maria Pia Pistillo Gennaro Ciliberto Nicola Mozzillo Paolo A. Ascierto 《Cancer immunology, immunotherapy : CII》2014,63(7):675-683
Background
Ipilimumab can induce durable disease control and long-term survival in patients with metastatic melanoma. Identification of a biomarker that correlates with clinical benefit and potentially provides an early marker of response is an active area of research.Patients and methods
Ipilimumab was available upon physician request for patients aged ≥16 years with stage III (unresectable) or IV cutaneous, ocular or mucosal melanoma, who had failed or did not tolerate previous treatments and had no other therapeutic option available. Patients received ipilimumab 3 mg/kg every 3 weeks for four doses. Tumour assessments were conducted at baseline, Week 12 and Week 24 using immune-related response criteria. Patients were monitored continuously for adverse events (AEs), including immune-related AEs. Candidate immunological markers were evaluated in peripheral blood and sera samples collected at baseline and Weeks 4, 7, 10 and 12.Results
Among 95 patients treated with ipilimumab 3 mg/kg, the immune-related disease control rate at Week 24 was 38 %. With a median follow-up of 24 months, median overall survival was 9.6 months. Both disease control and survival were significantly associated with decreasing levels of lactate dehydrogenase, C-reactive protein and FoxP3/regulatory T cells, and increasing absolute lymphocyte count, between baseline and the end of dosing (Week 12).Conclusion
Ipilimumab is a feasible treatment option for heavily pretreated patients with metastatic melanoma. Changes in some immunological markers between baseline and the fourth ipilimumab infusion appear to be associated with disease control and survival, but verification in prospective clinical trials is required. 相似文献8.
Introduction
The purpose of the present study was to systematically review the effect of cyclophosphamide treatment on pulmonary function in patients with systemic sclerosis and interstitial lung disease.Methods
The primary outcomes were the mean change in forced vital capacity and in diffusing capacity for carbon monoxide after 12 months of therapy in patients treated with cyclophosphamide.Results
Three randomized clinical trials and six prospective observational studies were included for analysis. In the pooled analysis, the forced vital capacity and the diffusing capacity for carbon monoxide predicted values after 12 months of therapy were essentially unchanged, with mean changes of 2.83% (95% confidence interval = 0.35 to 5.31) and 4.56% (95% confidence interval = -0.21 to 9.33), respectively.Conclusions
Cyclophosphamide treatment in patients with systemic sclerosis-related interstitial lung disease does not result in clinically significant improvement of pulmonary function. 相似文献9.
José Inciarte-Mundo Julio Ramirez Maria Victoria Hernández Virginia Ruiz-Esquide Andrea Cuervo Sonia Raquel Cabrera-Villalba Mariona Pascal Jordi Yagüe Juan D. Cañete Raimon Sanmarti 《Arthritis research & therapy》2018,20(1):275
Background
Calprotectin is a biomarker of disease activity in rheumatoid arthritis (RA) and psoriatic arthritis (PsA) and predicts relapse in juvenile idiopathic arthritis. Higher drug trough serum levels are associated with a good response in patients treated with tumor necrosis factor inhibitors (TNFi). Power Doppler ultrasound synovitis is predictive of relapse and structural damage progression in patients in clinical remission. The purpose of this study was to analyze the accuracy of serum calprotectin levels, drug trough serum levels (TSL), and power Doppler (PD) activity as predictors of relapse in RA and PsA patients in remission or with low disease activity receiving TNFi.Methods
This was a longitudinal, prospective, 1-year single-center study of 103 patients (47 RA, 56 PsA) receiving TNFi in remission or with low disease activity (28-joint Disease Activity Score (DAS28)?≤?3.2). The predictive value of serum calprotectin, TNFi TSL, and PD were assessed using receiver operating characteristic (ROC) analyses. To illustrate the predictive performance of calprotectin, TNFi TSL, and PD score, Kaplan-Meier curves were constructed from baseline to relapse. Associations between baseline factors and relapse were determined using Cox regression models. Multivariate models were constructed to analyze the effect of covariates and to fully adjust the association between calprotectin, TNFi TSL, and PD score with relapse. A generalized estimating equation model with an identity link for longitudinal continuous outcomes was used to assess the effect of covariates on TNFi TSL.Results
Ninety-five patients completed 1 year of follow-up, of whom 12 experienced a relapse. At baseline, relapsers had higher calprotectin levels, lower TNFi TSL, and higher PD activity than nonrelapsers. ROC analysis showed calprotectin fully predicted relapse (area under the curve (AUC)?=?1.00). TNFi TSL and PD had an AUC of 0.790 (95% confidence interval (CI) 0.691–0.889) and 0.877 (95% CI 0.772–0.981), respectively. Survival analyses and log rank tests showed significant differences between groups according to calprotectin serum levels (p?<?0.001), TNFi TSL (p?=?0.004), and PD score (p?<?0.001). Univariate Cox regression models showed that time-to-remission/low disease activity (hazard ratio (HR)?=?1.17, p?<?0.001), calprotectin levels (HR?=?2.38, p?<?0.001), TNFi TSL (HR?=?0.47, p?=?0.018), and PD score (HR?=?1.31, p?<?0.001) were significantly associated with disease relapse. In the multivariate analysis, only baseline calprotectin levels independently predicted disease relapse (HR?=?2.41, p?=?0.002). The generalized estimating equation analysis showed that only disease activity by DAS28-erythrocyte sedimentation rate (ESR) was significantly associated with longitudinal changes in TNFi TSL (regression coefficient 0.26 (0.0676 to 0.0036), p?=?0.001).Conclusion
Time-to-remission/low disease activity, calprotectin serum levels, TNFi TSL, and PD score were significantly associated with disease relapse. However, only baseline calprotectin serum levels independently predicted disease relapse in RA and PsA patients under TNFi therapy.10.
Masanori Kobayashi Shigetaka Shimodaira Kazuhiro Nagai Masahiro Ogasawara Hidenori Takahashi Hirofumi Abe Mitsugu Tanii Masato Okamoto Sun-ichi Tsujitani Seiichi Yusa Takefumi Ishidao Junji Kishimoto Yuta Shibamoto Masaki Nagaya Yoshikazu Yonemitsu 《Cancer immunology, immunotherapy : CII》2014,63(8):797-806
Objective
Dendritic cell (DC)-based cancer vaccines may have a significant benefit to patients with advanced pancreatic cancer. However, variations among clinical studies make it difficult to compare clinical outcomes. Here, we identified factors that determined the clinical benefits by analyzing data obtained at seven Japanese institutions that employed the same DC preparation and treatment regimens.Methods
Of 354 patients who met the inclusion criteria, 255 patients who received standard chemotherapy combined with peptide-pulsed DC vaccines were analyzed.Results
The mean survival time from diagnosis was 16.5 months (95 % CI 14.4–18.5) and that from the first vaccination was 9.9 months (95 % CI 8.0–12.9). Known prognostic baseline factors related to advanced pancreatic cancer, namely ECOG-PS, peritoneal metastasis, liver metastasis, and the prognostic nutrition index, were also representative. Importantly, we found that erythema reaction after vaccination was an independent and treatment-related prognostic factor for better survival and that OK-432 might be a good adjuvant enhancing the antitumor immunity during DC vaccination.Conclusions
This is the first report of a multicenter clinical study suggesting the feasibility and possible clinical benefit of an add-on DC vaccine in patients with advanced pancreatic cancer who are undergoing chemotherapy. These findings need to be addressed in well-controlled prospective randomized trials. 相似文献11.
Laxmaiah Manchikanti Mark V Boswell Jose J Rivera Vidya Sagar Pampati Kim S Damron Carla D McManus Doris E Brandon Sue R Wilson 《BMC anesthesiology》2005,5(1):1-14
Background
Postoperative epidural fibrosis may contribute to between 5% to 60% of the poor surgical outcomes following decompressive surgery. Correlations have been reported between epidural scarring and radicular pain, poor surgical outcomes, and a lack of any form of surgical treatment. The use of spinal endoscopic adhesiolysis in recent years in the management of chronic refractory low back and lower extremity pain has been described.Methods
A prospective, randomized, double-blind trial was conducted to determine the outcome of spinal endoscopic adhesiolysis to reduce pain and improve function and psychological status in patients with chronic refractory low back and lower extremity pain. A total of 83 patients were evaluated, with 33 patients in Group I and 50 patients in Group II. Group I served as the control, with endoscopy into the sacral level without adhesiolysis, followed by injection of local anesthetic and steroid. Group II received spinal endoscopic adhesiolysis, followed by injection of local anesthetic and steroid.Results
Among the 50 patients in the treatment group receiving spinal endoscopic adhesiolysis, significant improvement without adverse effects was shown in 80% at 3 months, 56% at 6 months, and 48% at 12 months. The control group showed improvement in 33% of the patients at one month and none thereafter. Based on the definition that less than 6 months of relief is considered short-term and longer than 6 months of relief is considered long-term, a significant number of patients obtained long-term relief with improvement in pain, functional status, and psychological status.Conclusion
Spinal endoscopic adhesiolysis with targeted delivery of local anesthetic and steroid is an effective treatment in a significant number of patients with chronic low back and lower extremity pain without major adverse effects. 相似文献12.
Brian A Haluska Leanne Jeffriess Phillip M Mottram Stephane G Carlier Thomas H Marwick 《Cardiovascular ultrasound》2007,5(1):1-11
Background
Arterial diameters enlarge in response to wall thickening, plaques, and many atherosclerotic risk factors. We hypothesized that right common carotid artery (RCCA) diameter would be independently associated with cardiac disease and improve risk discrimination.Methods
In a middle-aged, biracial population (baseline n = 11225), we examined associations between 1 standard deviation increments of baseline RCCA diameter with prevalent myocardial infarction (MI) and incident cardiac events (MI or cardiac death) using logistic regression and Cox proportional hazards models, respectively. Areas under the receiver operator characteristic curve (AUC) were used to estimate model discrimination.Results
MI was present in 451 (4%) participants at baseline (1987–89), and incident cardiac events occurred among 646 (6%) others through 1999. Adjusting for IMT, RCCA diameter was associated with prevalent MI (female OR = 2.0, 95%CI = 1.61–2.49; male OR = 1.16, 95% CI = 1.04–1.30) and incident cardiac events (female HR = 1.75, 95% CI = 1.51–2.02; male HR = 1.27, 95% CI = 1.15–1.40). Associations were attenuated but persisted after adjustment for risk factors (not including IMT) (prevalent MI: female OR = 1.73, 95% CI = 1.40–2.14; male OR = 1.14, 95% CI = 1.02–1.28, and incident cardiac events: female HR = 1.26, 95% CI = 1.08–1.48; male HR = 1.19, 95% CI = 1.08–1.32). After additional adjustment for IMT, diameter was associated with incident cardiac events in women (HR = 1.18, 95% CI = 1.00–1.40) and men (HR = 1.17, 95% CI = 1.06–1.29), and with prevalent MI only in women (OR = 1.73; 95% CI = 1.37–2.17). In women, when adjustment was limited, diameter models had larger AUC than other models.Conclusion
RCCA diameter is an important correlate of cardiac events, independent of IMT, but adds little to overall risk discrimination after risk factor adjustment. 相似文献13.
Karim H Shalaby Leslie G Gold Thomas F Schuessler James G Martin Annette Robichaud 《Respiratory research》2010,11(1):1-13
Background
Acute exacerbations contribute to the morbidity and mortality associated with chronic obstructive pulmonary disease (COPD). This proof-of-concept study evaluates whether intermittent pulsed moxifloxacin treatment could reduce the frequency of these exacerbations.Methods
Stable patients with COPD were randomized in a double-blind, placebo-controlled trial to receive moxifloxacin 400 mg PO once daily (N = 573) or placebo (N = 584) once a day for 5 days. Treatment was repeated every 8 weeks for a total of six courses. Patients were repeatedly assessed clinically and microbiologically during the 48-week treatment period, and for a further 24 weeks' follow-up.Results
At 48 weeks the odds ratio (OR) for suffering an exacerbation favoured moxifloxacin: per-protocol (PP) population (N = 738, OR 0.75, 95% confidence interval (CI) 0.565-0.994, p = 0.046), intent-to-treat (ITT) population (N = 1149, OR 0.81, 95% CI 0.645-1.008, p = 0.059), and a post-hoc analysis of per-protocol (PP) patients with purulent/mucopurulent sputum production at baseline (N = 323, OR 0.55, 95% CI 0.36-0.84, p = 0.006). There were no significant differences between moxifloxacin and placebo in any pre-specified efficacy subgroup analyses or in hospitalization rates, mortality rates, lung function or changes in St George's Respiratory Questionnaire (SGRQ) total scores. There was, however, a significant difference in favour of moxifloxacin in the SGRQ symptom domain (ITT: -8.2 vs -3.8, p = 0.009; PP: -8.8 vs -4.4, p = 0.006). Moxifloxacin treatment was not associated with consistent changes in moxifloxacin susceptibility. There were more treatment-emergent, drug related adverse events with moxifloxacin vs placebo (p < 0.001) largely due to gastrointestinal events (4.7% vs 0.7%).Conclusions
Intermittent pulsed therapy with moxifloxacin reduced the odds of exacerbation by 20% in the ITT population, by 25% among the PP population and by 45% in PP patients with purulent/mucopurulent sputum at baseline. There were no unexpected adverse events and there was no evidence of resistance development.Trial registration
ClinicalTrials.gov number, NCT00473460 (ClincalTrials.gov). 相似文献14.
Emiliano Lucero Simon M. Collin Sujit Gomes Fatima Akter Asaduzzam Asad Asish Kumar Das Koert Ritmeijer 《PLoS neglected tropical diseases》2015,9(4)
Background
Bangladesh is one of the endemic countries for Visceral Leishmaniasis (VL). Médecins Sans Frontières (MSF) ran a VL treatment clinic in the most endemic district (Fulbaria) between 2010 and 2013 using a semi-ambulatory regimen for primary VL of 15mg/kg Liposomal Amphotericin-B (AmBisome) in three equal doses of 5mg/kg. The main objective of this study was to analyze the effectiveness and safety of this regimen after a 12 month follow-up period by retrospective analysis of routinely collected program data. A secondary objective was to explore risk factors for relapse.Methods and Principal Findings
Our analysis included 1521 patients who were initially cured, of whom 1278 (84%) and 1179 (77.5%) were followed-up at 6 and 12 months, respectively. Cure rates at 6 and 12 months were 98.7% (1262/1278) and 96.4% (1137/1179), respectively. Most relapses (26/39) occurred between 6 and 12 months after treatment. Serious adverse events (SAE) were recorded for 7 patients (0.5%). Odds of relapse at 12 months were highest in the youngest and oldest age groups. There was some evidence that spleen size measured on discharge (one month after initiation of treatment) was associated with risk of relapse: OR=1.25 (95% CI 1.01 to 1.55) per cm below lower costal margin (P=0.04).Conclusions
Our study demonstrates that 15mg/kg AmBisome in three doses of 5mg/kg is an effective (>95% cure rate) and safe (<1% SAE) treatment for primary VL in Bangladesh. The majority of relapses occurred between 6 and 12 months, justifying the use of a longer follow-up period when feasible. Assessment of risk of relapse based on easily measured clinical parameters such as spleen size could be incorporated in VL treatment protocols in resource-poor settings where test-of-cure is not always feasible. 相似文献15.
Ann W Morgan James I Robinson Philip G Conaghan Stephen G Martin Elizabeth MA Hensor Michael D Morgan Lori Steiner Henry A Erlich Hock-Chye Gooi Anne Barton Jane Worthington Paul Emery 《Arthritis research & therapy》2010,12(2):1-10
Introduction
The purpose of this study was to investigate the effectiveness of adalimumab in enthesitis and peripheral arthritis in patients with ankylosing spondylitis (AS).Methods
Adults with active AS (Bath ankylosing spondylitis disease activity index [BASDAI] ≥ 4) received adalimumab 40 mg every other week with standard antirheumatic therapies in a 12-week, open-label study. Effectiveness in enthesitis was assessed using the Maastricht ankylosing spondylitis enthesitis score (MASES, 0-13) and by examining the plantar fascia in patients with enthesitis (≥ 1 inflamed enthesis) at baseline; effectiveness in peripheral arthritis was evaluated using tender and swollen joint counts (TJC, 0-46; SJC, 0-44) in patients with peripheral arthritis (≥ 1 swollen joint) at baseline. Overall effectiveness measures included Assessment of SpondyloArthritis International Society 20% response (ASAS20).Results
Of 1,250 patients enrolled, 686 had enthesitis and 281 had peripheral arthritis. In 667 patients with MASES ≥ 1 at baseline, the median MASES was reduced from 5 at baseline to 1 at week 12. At week 12, inflammation of the plantar fascia ceased in 122 of 173 patients with inflammation at baseline. The median TJC in 281 patients with SJC ≥ 1 at baseline was reduced from 5 at baseline to 1 at week 12; the median SJC improved from 2 to 0. ASAS20 responses were achieved by 70.5% of 457 patients with no enthesitis and no arthritis; 71.0% of 512 patients with only enthesitis; 68.0% of 107 patients with only arthritis; and 66.7% of 174 patients with both.Conclusions
Treatment with adalimumab improved enthesitis and peripheral arthritis in patients with active AS.Trial registration
ClinicalTrials.gov NCT00478660. 相似文献16.
Purpose
Normal myocardial perfusion imaging (MPI) is associated with excellent prognosis. However, in patients with persisting symptoms, it may be difficult to determine the patients in whom invasive angiography is justified to rule out false negative MPI. We evaluated predictors for severe stenosis at invasive angiography in patients with persisting symptoms after normal MPI.Methods
229 consecutive patients with normal MPI, without previous bypass surgery, underwent invasive angiography within 6 months. Older age was defined as >65 years. Multivariable analyses were performed to adjust for differences in baseline variables.Results
Mean age was 62?±?11 years, 48% were women. Severe stenosis was observed in 34%, and of these patients 60% had single-vessel disease (not left main coronary artery disease). After adjusting for several variables, including diabetes, smoking status, hypertension and hypercholesterolaemia, predictors of severe stenosis were male gender, odds ratio (OR) 2.7 (95% confidence interval (CI) 1.5–4.9), older age, OR 1.9 (95% CI 1.02–3.54) previous PCI, OR 2.0 (95% CI 1.0–4.3) and typical angina, OR 2.5 (95% CI 1.4–4.6).Conclusions
Increasing age, male gender, previous PCI and typical symptoms are predictors of severe stenosis at invasive coronary angiography in patients with normal MPI. The majority of these patients have single-vessel disease.17.
M Hassan Murad Ahmad Hazem Fernando Coto-Yglesias Svitlana Dzyubak Shabnum Gupta Irina Bancos Melanie A Lane Patricia J Erwin Lars Berglund Tarig Elraiyah Victor M Montori 《BMC endocrine disorders》2012,12(1):1-18
Background
Hypertriglyceridemia may be associated with important complications. The aim of this study is to estimate the magnitude of association and quality of supporting evidence linking hypertriglyceridemia to cardiovascular events and pancreatitis.Methods
We conducted a systematic review of multiple electronic bibliographic databases and subsequent meta-analysis using a random effects model. Studies eligible for this review followed patients longitudinally and evaluated quantitatively the association of fasting hypertriglyceridemia with the outcomes of interest. Reviewers working independently and in duplicate reviewed studies and extracted data.Results
35 studies provided data sufficient for meta-analysis. The quality of these observational studies was moderate to low with fair level of multivariable adjustments and adequate exposure and outcome ascertainment. Fasting hypertriglyceridemia was significantly associated with cardiovascular death (odds ratios (OR) 1.80; 95% confidence interval (CI) 1.31-2.49), cardiovascular events (OR, 1.37; 95% CI, 1.23-1.53), myocardial infarction (OR, 1.31; 95% CI, 1.15-1.49), and pancreatitis (OR, 3.96; 95% CI, 1.27-12.34, in one study only). The association with all-cause mortality was not statistically significant.Conclusions
The current evidence suggests that fasting hypertriglyceridemia is associated with increased risk of cardiovascular death, MI, cardiovascular events, and possibly acute pancreatitis. Précis: hypertriglyceridemia is associated with increased risk of cardiovascular death, MI, cardiovascular events, and possibly acute pancreatitis 相似文献18.
Que Liu Christen Anderson Anatoly Broyde Clara Polizzi Rayne Fernandez Alain Baron David G Parkes 《Cardiovascular diabetology》2010,9(1):1-14
Background
Patients with type 2 diabetes are at an increased risk for disease and treatment related complications after the initial approach of oral mono/dual antidiabetic therapy has failed. Data from clinical practice with respect to this patient group are however scarce. Therefore we set up a registry in primary care documenting the course and outcomes of this patient group.Methods
Diabetes Treatment Patterns and Goal Achievement in Primary Diabetes Care (DiaRegis) is a prospective, observational, German, multicenter registry including patients with type-2 diabetes in which oral mono/dual antidiabetic therapy has failed. Data were recorded at baseline and will be prospectively documented during visits at 6 ± 1, 12 ± 2 and 24 ± 2 months. The primary objective is to estimate the proportion of patients with at least 1 episode of severe hypoglycemia within one year.Results
313 primary care offices included 4,048 patients between June 2009 and March 2010 of which 3,810 patients fulfilled the in- and exclusion criteria. 46.7% of patients were female; patients had a median diabetes duration of 5.5 years and most were obese with respect to BMI or waist circumference. HbA1c at baseline was 7.4%, fasting plasma glucose 142 mg/dl and postprandial glucose 185 mg/dl. Co-morbidity in this patient population was substantial with 17.9% having coronary artery disease, 14.4% peripheral neuropathy, 9.9% heart failure and 6.0% peripheral arterial disease. 68.6% of patients received oral monotherapy, 31.4% dual oral combination therapy. The most frequent antidiabetic agent used as monotherapy was metformin (79.0%) followed by sulfonylureas (14.8%).Conclusions
DiaRegis is a large, prospective registry in primary diabetes care to document the course and outcomes of patients with type-2 diabetes in which the initial approach of oral mono/dual antidiabetic therapy has failed. The two year follow-up will allow for a prospective evaluation of these patients during multiple adjustments of therapy. 相似文献19.
Background
There is a paucity of surrogate lung-specific biological markers that can be used to track disease progression and predict clinical outcomes in chronic obstructive pulmonary disease (COPD). The principal aim of this pilot study was to determine whether circulating surfactant protein D (SPD) or Clara Cell protein-16 (CC16) levels are associated with lung function or health status in patients with severe COPD.Methods
We studied 23 patients with advanced COPD. Lung function measurements, Chronic Respiratory Disease Questionnaire (CRQ) scores, and serum levels of SPD, CC16, and C-reactive protein (CRP) were determined at baseline and at 3 months.Results
At baseline, FEV1 was inversely associated with serum SPD levels (P = 0.045) but not with CC16 (P = 0.675) or CRP levels (P = 0.549). Over a 3 month period, changes in SPD levels correlated significantly with changes in CRQ scores (adjusted P = 0.008) such that patients who had the largest declines in serum SPD levels experienced the largest gains in health status. The association was particularly notable between circulating SPD level and the dyspnea domain of the CRQ score (P = 0.018). Changes in CC16 or CRP levels did not correlate with changes in CRQ scores.Conclusion
Changes in serum SPD levels tracked well with changes in health status over a 3 month period in patients with severe COPD. These data suggest that circulating SPD levels may be useful biomarkers to track health outcomes of COPD patients. 相似文献20.
Sander Kelderman Bianca Heemskerk Harm van Tinteren Rob R. H. van den Brom Geke A. P. Hospers Alfonsus J. M. van den Eertwegh Ellen W. Kapiteijn Jan Willem B. de Groot Patricia Soetekouw Rob L. Jansen Edward Fiets Andrew J. S. Furness Alexandra Renn Marcin Krzystanek Zoltan Szallasi Paul Lorigan Martin E. Gore Ton N. M. Schumacher John B. A. G. Haanen James M. G. Larkin Christian U. Blank 《Cancer immunology, immunotherapy : CII》2014,63(5):449-458