Similar Frequency Of Adverse Events Research Articles

Comparing the safety and efficacy of nintedanib starting dose in patients with connective tissue disease-associated interstitial lung diseases

Objective This study aimed to analyse whether initiating nintedanib treatment at a reduced dose could improve the treatment continuation rate while maintaining efficacy in patients with connective tissue disease (CTD)-associated interstitial lung disease. Method In total, 51 patients (age 61.6 ± 13.2 years; 38 women, 13 men) were retrospectively analysed. The primary endpoint was the cumulative discontinuation rate due to adverse events. Secondary endpoints included changes in drug dosage, efficacy evaluated based on annual changes in forced vital capacity (FVC), and safety assessed based on the frequency of adverse events. Results Eighteen patients who started treatment at the standard dose of 300 mg (standard dosage group) were compared with 33 patients who started treatment at a reduced dose (reduced dosage group). Systemic sclerosis was the most common CTD (n = 32), followed by idiopathic inflammatory myopathies and, rarely, rheumatoid arthritis. Both groups exhibited comparable cumulative discontinuation rates due to adverse events and similar frequencies of adverse events. No significant differences were observed in maintenance doses between the two groups; however, patients in the reduced dosage group had a lower cumulative dose for up to 52 weeks than those in the standard dosage group. No significant differences were observed in changes in FVC between the two groups. Conclusion There was no evidence for a difference between the two groups in terms of discontinuation rates, efficacy, and safety. To provide further evidence, future studies using more precise dose-escalation protocols are warranted.

Hepatitis C Virus Infection in the Elderly in the Era of Direct-Acting Antivirals: Evidence from Clinical Trials and Real Life.

The introduction of direct-acting antiviral agents (DAAs) into clinical practice has revolutionized the therapeutic approach to patients with chronic hepatitis C virus (HCV) infection. According to the most recent guidelines, the first line of treatment for HCV infection involves the use of one of three pan-genotypic DAA combinations, sofosbuvir/velpatasvir (SOF/VEL), glecaprevir/pibrentasvir (GLE/PIB), and sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX). These drugs have been shown to be effective and safe in numerous clinical trials and real-world studies, but special populations have been neglected. Among the special populations to be treated are elderly patients, whose numbers are increasing in clinical practice. The management of these patients can be challenging, in particular due to multiple comorbidities, polypharmacotherapy, and potential drug-drug interactions. This narrative review aims to summarize the current scientific evidence on the efficacy and safety of DAAs in the elderly population, both in clinical trials and in real-life settings. Although there is still a paucity of real-world data and no clinical trials have yet been conducted in the population aged ≥ 75 years old, some considerations about the efficacy and safety of DAAs in the elderly can be made based on the results of these studies. The pan-genotypic associations of DAAs appear to be as efficacious and safe in the elderly population as in the general population; this is both in terms of similar sustained virologic response (SVR) rates and similar frequencies of adverse events (AEs). However, further studies specifically involving this patient population would be necessary to confirm this evidence.

Tdap booster to adolescents with juvenile idiopathic arthritis on and off anti-TNF agents is safe and immunogenic

Introduction: The response to vaccines in juvenile idiopathic arthritis (JIA) patients on and off anti-tumor necrosis factor (anti-TNF) agents remains highly discussed. There are no published studies on the immune response following a Tdap booster dose in JIA patients so far. ObjectiveTo evaluate the immune response and safety after a Tdap booster in JIA patients and in healthy adolescents. MethodsNineteen adolescents with JIA according to the ILAR criteria on anti-TNF medication, 19 adolescents with JIA off anti-TNF medication, and 27 healthy adolescents (control group) were compared after a Tdap booster. Adverse events and disease activity were evaluated. Lymphocyte immunophenotyping was performed by flow cytometry. Tetanus, diphtheria and pertussis toxin antibodies were assessed by ELISA; whole blood was stimulated with whole-cell pertussis, and supernatants were assessed for cytokines by xMAP. ResultsThe three groups showed a similar frequency of adverse events. There was no disease reactivation after the Tdap booster. Tetanus, diphtheria and pertussis antibodies showed a significant response when D0 and D14 concentrations were compared in both JIA groups and controls. Over time, a different pattern of response to the Tdap booster was observed among the groups for tetanus antibodies (p = 0.005) but not for diphtheria and pertussis antibodies. In contrast to the protection attained for tetanus and diphtheria, in the three groups, not all individuals showed pertussis seroconversion at either D14 or D28. In addition, the seroconversion of three subjects with JIA on anti-TNF medication was not maintained at D28. JIA patients off anti-TNF showed a higher percentage of naive CD8 + T cells (p = 0.007) and central memory CD8 + cells (p = 0.003) and a lower percentage of effector CD8 + T cells (p = 0.003) and NK cell numbers (p = 0.018) than the control group. The JIA group off anti-TNF medication had fewer B lymphocytes than both the JIA group on anti-TNF medication and the control group (p = 0.016). Cellular immunity to Bordetella pertussis showed that IFNγ levels were significantly lower in both JIA groups than in the control group (p = 0.003), IL10 levels were higher in the JIA off anti-TNF group (p = 0.009), IL17A and IL5 levels were lower in the JIA on anti-TNF group than in the control group (p = 0.018 and p = 0.016, respectively); however, an increase in IFNγ (p = 0.008), IL17A (p = 0.030) and TNFα (p = 0.041) levels was observed at D14 in both patient groups. Both JIA groups showed higher levels of IL21 than the control group (p = 0.023). ConclusionWe conclude that individuals with JIA on or off anti-TNF agents showed a good response to a booster dose for the three antigens studied in the absence of major adverse events and without the reactivation of the disease.

14‐day reverse hybrid therapy vs 7‐day concomitant therapy in the first‐line treatment of Helicobacter pylori infection

AbstractIncreasing antibiotics resistance poses a great challenge for the treatment of Helicobacter pylori (H. pylori) infection. The reported eradication rates of 7‐day standard triple therapy have fallen below 80% in most countries due to increasing clarithromycin resistance. Both 14‐day reverse hybrid therapy and 7‐day concomitant therapy have been reported to yield high eradication rates for the treatment of H. pylori infection. However, whether 14‐day reverse hybrid therapy can achieve a higher eradication rate than 7‐day concomitant therapy remains unanswered. The aim of this study is to compare the efficacies of 14‐day reverse hybrid and 7‐day concomitant therapies for the first‐line treatment of H. pylori infection in a primary care setting. From May 2016 to December 2019, 322 H. pylori‐infected patients receiving either 14‐day reverse hybrid therapy (a proton pump inhibitor [PPI] plus amoxicillin 1 g b.d. for 14 days, and clarithromycin 500 mg plus metronidazole 500 mg b.d. for the initial 7 days, n = 142) or 7‐day concomitant therapy (PPI plus amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg b.d. for 7 days, n = 180) in our clinic were included in the retrospective study. All the patients underwent a follow‐up endoscopy with a rapid urease test or a urea breath test at least 4 weeks after completion of anti‐H. pylori therapy and at least 2 weeks after discontinuation of PPI. Intention‐to‐treat analysis demonstrated a significantly higher eradication rate for the 14‐day reverse hybrid group than for the 7‐day concomitant group (95.8% vs 88.9%, P = .024). Per‐protocol analysis also yielded similar results (97.8% vs 90.3%, P = .009). Both groups had similar frequencies of adverse events (14.1% vs 13.9%, P = .990) and drug compliance (95.8% vs 97.2%, P = .478).ConclusionsFourteen‐day reverse hybrid therapy achieves a higher eradication rate than 7‐day concomitant therapy in the first‐line treatment of H. pylori infection.

Adequate tetanus but poor diphtheria and pertussis response to a Tdap booster in adolescents with juvenile systemic lupus erythematosus.

Reports on vaccine responses in immunocompromised patients, such as juvenile systemic lupus erythematosus (jSLE), have shown highly variable results. To compare the immune response and safety after a Tdap booster in 26 jSLE patients and 26 matched healthy adolescents.Methodology: Adverse events and disease activity were evaluated. Lymphocyte immunophenotyping was performed by flow cytometry. Tetanus, diphtheria and pertussis toxin antibodies were assessed by ELISA; whole blood was stimulated with whole cell pertussis and supernatants were assessed for cytokines by xMAP. Both groups showed a similar frequency of adverse events. There was no evidence of disease reactivation after Tdap booster in the jSLE cohort. Both groups showed a significant increase in antibody titers for all three antigens on D14 and D28 (p < 0.001). jSLE patients had a significantly lower increase in diphtheria titers than the control group (p = 0.007). jSLE patients had a distinct titer increase of tetanus and pertussis antibodies when compared to controls (p = 0.004 and p < 0.001, respectively). There was a lower frequency of pertussis seroconversion in the jSLE group on D14 (p = 0.009), D28 (p = 0.023), D12m (p = 0.015) and D24m (p = 0.004). Cellular immune response to Bordetella pertussis showed significantly lower levels of IFNγ (p < 0.001) and higher levels of IL10, IL12, IL21 and TNFα in jSLE patients than controls. jSLE patients had good response to Tdap booster dose for the tetanus antigen, but not for diphtheria and pertussis. This vaccine was safe in relation to adverse events and absence of disease reactivation.

Anti-cytokine targeted therapies for ANCA-associated vasculitis

Anti-cytokine targeted therapies for ANCA-associated vasculitis

Etifoxine impairs neither alertness nor cognitive functions of the elderly: A randomized, double-blind, placebo-controlled crossover study

Etifoxine hydrochloride (Stresam®), a treatment indicated for psychosomatic manifestations of anxiety, could be an alternative to benzodiazepines. While no impact on alertness and cognitive functions has been proven among youth, data on elderly are lacking. The primary objective of this study was to measure the impact of etifoxine, lorazepam or placebo on alertness in the elderly. The secondary objectives were to evaluate cognitive performances and adverse effects. In this randomized, placebo-controlled, double-blind, 3-way crossover design, 30 healthy volunteers aged 65 to 75 years underwent three one-day sessions. After treatment intake, standardized cognitive tests were conducted using the Cambridge Neuropsychological Test Automated Batteries and other psychological tests (Stroop, Rey Auditory Verbal Learning Test, Digit Span). The reaction time (RTI) as primary endpoint was analysed using a 3 × 3 latin square variance analysis. A 100-mg dose of etifoxine has no deleterious impact on alertness and causes no cognitive disorders as compared to placebo (RTI: 744 ± 146 ms versus 770 ± 153 ms; p = 1.00). As expected, a 2-mg dose of lorazepam impairs alertness (RTI: 957 ± 251 ms versus placebo; p < 0.0001) and cognitive functions. A similar frequency of adverse events was observed with etifoxine and placebo while their incidence was 3-fold higher with lorazepam, drowsiness being the most frequent adverse event. No serious adverse events were observed. This study demonstrates in the elderly that a single dose of etifoxine does neither impair alertness nor any of the cognitive parameters evaluated. Etifoxine may be a good option when anxiolytic treatment is required, especially in elderly people.

Update on Microinvasive Glaucoma Surgery.

Update on Microinvasive Glaucoma Surgery.

Safety and Efficacy of TachoSil (Absorbable Fibrin Sealant Patch) Compared With Current Practice for the Prevention of Cerebrospinal Fluid Leaks in Patients Undergoing Skull Base Surgery: A Randomized Controlled Trial.

Cerebrospinal fluid (CSF) leakage associated with incomplete sealing of the dura mater is a major complication of intradural procedures. To compare the efficacy and safety of adjunctive TachoSil (Takeda Pharma A/S, Roskilde, Denmark) with current practice for the prevention of postoperative CSF leaks in patients undergoing elective skull base surgery involving dura mater closure. Patients were intraoperatively randomized to TachoSil or current practice immediately before primary dura closure by suturing ± duraplasty. Choice of adjunctive treatment in the current practice group was at the surgeon's discretion. Primary efficacy endpoint was occurrence of clinically evident verified postoperative CSF leak or clinically evident pseudomeningocele within 7 weeks after surgery or treatment failure (third application of trial treatment or use of other treatment). A total of 726 patients were randomized to TachoSil (n = 361) or current practice (n = 365). More current practice patients had sutures plus duraplasty for primary dura closure compared with TachoSil (49.6% vs 35.7%) and fewer had sutures only (45.5% vs 63.2%). The primary endpoint of estimated leak rate favored TachoSil with events in 25 (6.9%) patients vs 30 (8.2%) current practice patients; however, this was not statistically significant (odds ratio: 0.82; 95% confidence interval: 0.47, 1.43; P = .485). Both treatments were well tolerated with similar frequency of adverse events. Very low rates of postoperative CSF leaks can be achieved in patients undergoing skull base surgery of various indications. Although the study did not meet its primary endpoint, TachoSil appears to be safe and effective for the prevention of CSF leaks and associated complications.

A Pilot Randomized Controlled Study of Dexlansoprazole MR-Based Triple Therapy for Helicobacter Pylori Infection

Dexlansoprazole MR is the R-enantiomer of lansoprazole that is delivered by a dual delayed release formulation. It is effective for symptom control of patients with gastroesophageal reflux disease. However, its efficacy in the treatment of Helicobacter pylori infection remains unclear. This pilot, randomized, controlled, head-to-head study was conducted to investigate whether the efficacy of single-dose dexlansoprazole MR-based triple therapy was noninferior to double-dose rabeprazole-based triple therapy in the treatment of H pylori infection.Consecutive H pylori-infected subjects were randomly allocated to either 7-day dexlansoprazole MR-based standard triple therapy (dexlansoprazole MR 60 mg once daily, clarithromycin 500 mg twice daily, and amoxicillin 1 g twice daily) or rabeprazole-based triple therapy (rabeprazole 20 mg twice daily, clarithromycin 500 mg twice daily, and amoxicillin 1 g twice daily). H pylori status was assessed 6 weeks after the end of treatment.A total of 177 H pylori-infected patients were randomized to receive dexlansoprazole MR-based (n = 90) or rabeprazole-based (n = 87) triple therapy. Intention-to-treat analysis demonstrated no differences between eradication rates of the 2 study groups (83.3% vs 81.6%; P = 0.736). Per-protocol analysis yielded comparable results (85.1% vs 81.2%; P = 0.497). Both groups exhibited similar frequencies of adverse events (7.8% vs 4.6%; P = 0.536) and drug compliance (98.9% vs 97.7%; P = 0.496). Multivariate analysis disclosed that the presence of clarithromycin resistance was the only independent factors predictive of treatment failure with an odds ratio of 6.8 (95% confidence interval: 1.2–37.6).This work demonstrates that single-dose dexlansoprazole MR-based triple therapy yields a similar eradication rate as double-dose rabeprazole-based therapy. Since the pharmaceutical cost of the single-dose dexlansoprazole MR regime is lower than that of the double-dose rabeprazole regimen, dexlansoprazole-based therapy can reasonably be recommended in the first-line treatment of H pylori infection.

Randomized controlled trial comparing 7-day triple, 10-day sequential, and 7-day concomitant therapies for Helicobacter pylori infection.

With the rising prevalence of antimicrobial resistance, the failure rate of the standard triple therapy for Helicobacter pylori infection is increasing. Sequential therapy and concomitant therapy have been recommended to replace standard triple therapy for H. pylori eradication in regions with high clarithromycin resistance. The aim of this prospective, randomized, and controlled study was to simultaneously assess the efficacies of 10-day sequential and 7-day concomitant therapies versus a 7-day standard triple therapy for treating H. pylori infection. Consecutive H. pylori-infected subjects were randomly assigned to a 7-day standard triple therapy (pantoprazole, clarithromycin, and amoxicillin for 7 days), a 10-day sequential therapy (pantoprazole and amoxicillin for 5 days, followed by pantoprazole, clarithromycin, and metronidazole for a further 5 days), or a 7-day quadruple therapy (pantoprazole, clarithromycin, amoxicillin, and metronidazole for 7 days). H. pylori status was confirmed 6 weeks after therapy. Three hundred seven H. pylori-infected participants were randomized to receive triple (n = 103), sequential (n = 102), or concomitant (n = 102) therapies. The eradication rates by an intention-to-treat analysis in the three treatment groups were 81.6% (95% confidence interval [CI], 74.1% to 89.0%), 89.2% (95% CI, 83.2% to 95.2%), and 94.1% (95% CI, 89.5% to 98.7%). The seven-day concomitant therapy had a higher eradication rate than did the 7-day triple therapy (difference, 12.5%; 95% CI, 3.7% to 21.3%). There were no significant differences in the eradication rates between the sequential and standard triple therapies. All three treatments exhibited similar frequencies of adverse events (8.7%, 8.8%, and 13.7%, respectively) and drug compliance (99.0%, 98.0%, and 100.0%, respectively). In conclusion, the seven-day concomitant therapy is superior to the 7-day standard triple therapy for H. pylori eradication. Additionally, it is less complex than the 10-day sequential therapy because the drugs are not changed halfway through the treatment course. (This study has been registered at ClinicalTrials.gov under registration no. NCT1769365.).

Sequential therapy achieves a higher eradication rate than standard triple therapy in Taiwan

Most clinical trials concerning sequential therapy have been conducted in Italy. The efficacy of sequential therapy for Helicobacter pylori (H. pylori) eradication in Asia remains unclear. The aim of this study was to compare the efficacy of sequential therapy with standard triple therapy in Taiwan. From January 2005 to December 2009, 233 H. pylori-infected patients receiving either a 10-day sequential therapy (40 mg pantoprazole and 1 g amoxicillin, twice daily, for the initial 5 days, followed by 40 mg pantoprazole, 500 mg clarithromycin, and 500 mg metronidazole, twice daily, for the subsequent 5 days, n = 118) or a 7-day standard triple therapy (40 mg pantoprazole, 500 mg clarithromycin, and 1 g amoxicillin twice daily for 7 days, n = 115) were included in the retrospective study. All the patients underwent a follow-up endoscopy with a rapid urease test and histological examination or a urea breath test at 8 weeks after the end of anti-H. pylori therapy to assess H. pylori status. Intention-to-treat analysis demonstrated a significantly higher eradication rate for the sequential group than for the triple group (93% vs 80%, respectively, P = 0.003). Per-protocol analysis also showed similar results (93% vs 80%, P = 0.005). Both groups had similar frequencies of adverse events (29% vs 22%) and drug compliance (98% vs 97%). Sequential therapy achieves a higher eradication rate than standard triple therapy in Taiwan. The novel treatment can be used as a first-line therapy for H. pylori infection for Taiwanese.

ACAM2000&amp;trade;: The new smallpox vaccine for United States Strategic National Stockpile

Smallpox was eradicated more than 30 years ago, but heightened concerns over bioterrorism have brought smallpox and smallpox vaccination back to the forefront. The previously licensed smallpox vaccine in the United States, Dryvax (Wyeth Laboratories, Inc.), was highly effective, but the supply was insufficient to vaccinate the entire current US population. Additionally, Dryvax had a questionable safety profile since it consisted of a pool of vaccinia virus strains with varying degrees of virulence, and was grown on the skin of calves, an outdated technique that poses an unnecessary risk of contamination. The US government has therefore recently supported development of an improved live vaccinia virus smallpox vaccine. This initiative has resulted in the development of ACAM2000 (Acambis, Inc.), a single plaque-purified vaccinia virus derivative of Dryvax, aseptically propagated in cell culture. Preclinical and clinical trials reported in 2008 demonstrated that ACAM2000 has comparable immunogenicity to that of Dryvax, and causes a similar frequency of adverse events. Furthermore, like Dryvax, ACAM2000 vaccination has been shown by careful cardiac screening to result in an unexpectedly high rate of myocarditis and pericarditis. ACAM2000 received US Food and Drug Administration (FDA) approval in August 2007, and replaced Dryvax for all smallpox vaccinations in February 2008. Currently, over 200 million doses of ACAM2000 have been produced for the US Strategic National Stockpile. This review of ACAM2000 addresses the production, characterization, clinical trials, and adverse events associated with this new smallpox vaccine.

High‐dose versus low‐dose esomeprazole‐based triple therapy for Helicobacter pylori infection

This prospective, randomized, controlled study was conducted to compare the efficacies of high-dose and low-dose esomeprazole-based triple therapies for Helicobacter pylori eradication in Taiwan. From January 2004 to June 2006, 240 H. pylori-infected patients were randomly assigned to undergo high-dose (40 mg b.d.) or low-dose (40 mg o.d.) esomeprazole combined with clarithromycin (500 mg b.d.) and amoxicillin (1 g b.d.) for one week. Follow-up endoscopy was performed at eight weeks after the end of treatment to evaluate the response to therapy. Intention-to-treat analysis demonstrated no differences between eradication rates of high-dose and low-dose groups (92% vs. 90%, respectively, P > 0.05). Per-protocol analysis yielded comparable results (95% vs. 93%). Both groups exhibited similar frequencies of adverse events (13% vs. 11%) and drug compliance (96% vs. 93%). Multivariate analysis indicated that only good compliance (odds ratio: 10.3, 95% CI, 3.0-35.7) was an independent predictor of treatment success. This work demonstrates that low-dose esomeprazole-based triple therapy yields a similar eradication rate as high-dose esomeprazole-based therapy in Taiwan. Since the cost of the low-dose regime is lower than that of the high-dose regime, low-dose esomeprazole-based triple therapy can reasonably be recommended for the first-line eradication of H. pylori for Taiwanese and probably most Asians.

Nebulized arformoterol in patients with COPD: A 12-week, multicenter, randomized, double-blind, double-dummy, placebo- and active-controlled trial

Objective: The aim of this study was to assess the efficacy and tolerability of nebulized arformoterol tartrate (a selective, long-acting β 2-adretlergic agonist that is the [ R,R] isomer of formoterol) and salmeterol xinafoate versus placebo in patients with chronic obstructive pulmonary disease (COPD). Methods: This 12-week, multicenter, randomized, double-blind, double-dummy, placebo- and active-controlled trial was conducted at 60 centers across the United States. Male and female patients aged ≥35 years with physician-diagnosed COPD received arformoterol (15 μg BID, 25 μg BID, or 50 μg QD via nebulizer), saleterol (42 μg BID via metered dose inhaler), or placebo. Pulmonary function was assessed by spirotnetry; dyspnea, by the Transitional Dyspnea Index (TDI); and health status, by the St. George's Respiratory Questionnaire (SGRQ). Adverse events (AEs) were assessed by site personnel at all clinic visits (screening, first dose at week 0, and at weeks 3, 6, 9, 12, and follow-up). COPD exacerbations were defined as worsening respiratory status requiring a change in medication or an unscheduled provider visit. Results: A total of 717 patients received study medication.The demographic composition of all treatment arms was similar. The mean age was 62.9 years, 58% were men, and mean baseline forced expiratory volume in 1 second (FEV 1) was 1.2 L (41% predicted). Mean improvement in trough FEV 1 over 12 weeks was significantly greater with all 3 arfortttoterol doses (15 μg BID, +16.9%; 25 μg BID, +18.9%;,50 μg QD, +14.9%) and for salmeterol (+17.4%) relative to placebo (+6.0%; P < 0.001). There were significantly greater improvements in the mean percentage change in FEV 1 AUC 0–12h from the predose value over 12 weeks (15 μg BID, 12.7%, 25 μg BID, 13.9%, 50 μg QD, 18.9%; salmeterol, 9.8%) versus placebo (2.7%; P ≤ 0.001); all doses of arfortnoterol were statistically different from salmeterol for this end point ( P ≤ 0.024). At week 12, TDI focal scores were significantly greater with all arformoterol doses compared with placebo (mean [95% CI]: 15 μg BID, 0.97 [0.25–1.69]; 25 μg BID, 1.08 [0.3–1.86]; 50 μg QD, 1.04 [0.32–1.771), suggesting treatment-associated improvement in dyspnea, however, the difference between salmeterol and placebo was not statistically significant (0.36 [-0.40 to 1.12]). Improvements in health status, as measured using SGRQ total scores, were -2.6 to -3.6 U in the arforinoterol groups, -4.4 U for saltneterol, and -1.2 U for placebo; 95% CI of differences versus placebo suggested significant improvement for the arfortnoterol 25 μg BID and salmeterol groups. There was a similar frequency of AEs and COPD exacerbations across all groups, including placebo. Conclusions: In this trial, patients with moderate tosevere COPD administered nebulized arformoterol over 12 weeks were observed to have significant and sustained improvements in airway function and dyspnea compared with placebo. The results also suggest that all doses of arforrnoterol, including the lowest dose (15 μg BID), were effective. Overall, nebulized arformoterol was well tolerated.

Safety of the selective costimulation modulator abatacept in rheumatoid arthritis patients receiving background biologic and nonbiologic disease‐modifying antirheumatic drugs: A one‐year randomized, placebo‐controlled study

To assess the safety of abatacept, a selective costimulation modulator, in patients with active rheumatoid arthritis (RA) who had been receiving > or =1 traditional nonbiologic and/or biologic disease-modifying antirheumatic drugs (DMARDs) approved for the treatment of RA for at least 3 months prior to entry into the study. This was a 1-year, multicenter, randomized, double-blind, placebo-controlled trial. Patients were randomized 2:1 to receive abatacept at a fixed dose approximating 10 mg/kg by weight range, or placebo. The abatacept and placebo groups exhibited similar frequencies of adverse events (90% and 87%, respectively), serious adverse events (13% and 12%, respectively), and discontinuations due to adverse events (5% and 4%, respectively). Five patients (0.5%) in the abatacept group and 4 patients (0.8%) in the placebo group died during the study. Serious infections were more frequent in the abatacept group than in the placebo group (2.9% versus 1.9%). Fewer than 4% of patients in either group experienced a severe or very severe infection. The incidence of neoplasms was 3.5% in both groups. When evaluated according to background therapy, serious adverse events occurred more frequently in the subgroup receiving abatacept plus a biologic agent (22.3%) than in the other subgroups (11.7-12.5%). Abatacept in combination with synthetic DMARDs was well tolerated and improved physical function and physician- and patient-reported disease outcomes. However, abatacept in combination with biologic background therapies was associated with an increase in the rate of serious adverse events. Therefore, abatacept is not recommended for use in combination with biologic therapy.

A Prospective Randomized Trial of Esomeprazole- versus Pantoprazole-Based Triple Therapy for Helicobacter pylori Eradication

This prospective, randomized, controlled, head-to-head study was conducted to compare the efficacies of esomeprazole- and pantoprazole-based triple therapies for Helicobacter pylori eradication. From January 2002 to October 2003, 200 H. pylori-infected patients were randomly assigned to undergo twice daily treatment with esomeprazole 40 mg (n = 100) or pantoprazole 40 mg (n = 100) combined with clarithromycin 500 mg and amoxicillin 1 g for 1 wk (ECA and PCA groups, respectively). Follow-up endoscopy was performed at 8 wks after the end of treatment to assess the treatment response. Intention-to-treat analysis demonstrated a significantly higher eradication rate for the ECA group than for the PCA group (94%vs 82%, respectively, p= 0.009). Per-protocol analysis also showed similar results (97%vs 84%, p= 0.003). Both groups had similar frequencies of adverse events (15%vs 24%) and drug compliance (97%vs 96%). Multivariate analysis disclosed that the use of esomeprazole (OR: 1.56, 95% CI, 1.11-2.19) and good compliance 7.39 (95% CI, 1.27-42.95) were independent predictors of treatment success. Alcohol drinking was an independent predictor of eradication failure (OR: 0.18; 95% CI, 0.06-0.54). Esomeprazole-based triple therapy demonstrated a higher eradication rate than pantoprazole-based regimen. The differences in eradiation efficacies between the two study groups may be related to the more powerful acid inhibition effect and stronger anti-H. pylori activity of esomeprazole compared to pantoprazole.

Safety and feasibility of using serial infusions of nesiritide for heart failure in an outpatient setting (from the FUSION I trial)

The Follow-Up Serial Infusions of Nesiritide pilot study was designed to assess the safety and tolerability of outpatient serial infusions of nesiritide in 210 patients with decompensated heart failure who were randomly assigned to usual care only or usual care plus weekly infusions of nesiritide at dosages of 0.005 or 0.01 microg/kg/min for 12 weeks. The mean age +/- SD of the entire population was 67 +/- 13 years; 70% were men, and 80% were white. Mean baseline serum creatinine levels were 1.8 +/- 0.7 mg/dl, and mean left ventricular ejection fraction was 0.28 +/- 0.15%. Diabetes mellitus was present in 106 patients (50%), and atrial arrhythmias were present in 100 patients (48%). A totalof 1,645 nesiritide infusions was administered; 11 (< 1%) were discontinued due to an adverse event. All treatment groups had a similar frequency of adverse events and experienced improvements in quality of life. Administration of nesiritide resulted in acute decreases in aldosterone and endothelin-1 concentrations. Although there were no statistically significant differences among groups by outcome, prospectively defined higher risk subgroups demonstrated significant decreases in cardiovascular events. These results demonstrate the safety and feasibility of administering nesiritide in an outpatient setting. Additional studies are needed to determine the effect of outpatient serial infusions of nesiritide on rates of morbidity and mortality in advanced heart failure.

Efeitos da titulação de doses no perfil de tolerabilidade de Tramadol de liberação prolongada&lt;a href="#back1"&gt;*&lt;/a&gt; em pacientes com dor crônica não-oncológica

Este estudo multicêntrico teve por objetivo comparar os efeitos de dois esquemas posológicos no perfil de tolerabilidade do tramadol de liberação prolongada em pacientes com dor crônica não-oncológica. A casuística envolveu 189 pacientes com idade entre 14 e 75 anos, divididos em 2 grupos aleatoriamente: grupo A com 96 e o grupo B com 93 pacientes que receberam a medicação do estudo por 15 dias. O grupo A utilizou uma dose inicial de tramadol de liberação prolongada de 50mg a cada 12 horas por 3 a 7 dias, passando para uma dose de manutenção de 100mg a cada 12 horas até o 15º dia. O grupo B fez uso de uma dose padronizada de 100mg a cada 12 horas de tramadol de liberação prolongada durante os 15 dias do estudo. Os aspectos analisados foram o tipo de dor crônica não-oncológica, a intensidade da dor através da escala visual analógica, a aderência ao tratamento prescrito, a necessidade do uso da medicação de resgate, os efeitos adversos, a avaliação global da eficácia pelo médico e pelo paciente, bem como a tolerabilidade global na opinião do médico e do paciente. A dor de origem músculo-esquelética, definida como dor muscular com suas inserções no osso, foi a mais freqüente com 45,8% dos casos no grupo A, enquanto a dor osteoarticular foi a mais observada no grupo B (47,3%). Verificou-se uma melhora altamente significante tanto intra grupos como entre grupos, quanto à intensidade da dor, com redução de 67% em ambos os grupos. No grupo A, 77,1% dos pacientes cumpriram adequadamente o tratamento prescrito e no grupo B, a proporção foi de 75,3%, não havendo diferença estatisticamente significativa entre os grupos. Os grupos foram semelhantes entre si quanto à utilização da medicação de resgate, onde apenas 9,7% dos pacientes do grupo A e 15,1% do grupo B necessitaram-na durante o período do estudo. Não houve diferença significante na freqüência de eventos adversos nos dois grupos ( 30,2% e 36,6% respectivamente). Nos pacientes cuja dose final foi de 200mg/dia, a avaliação global da eficácia foi considerada boa e excelente pelos investigadores no grupo A em 86,7% dos pacientes e no grupo B o resultado foi de 78,8%. Os pacientes do grupo A consideraram a avaliação global da eficácia como boa e excelente em 88,9% e no grupo B 78,8%. A tolerabilidade da droga foi considerada entre boa e excelente pelos investigadores no grupo A em 86% e no grupo B o resultado foi de 77,2%. Os pacientes consideraram a tolerabilidade da droga como boa e excelente no grupo A em 77,4% e no grupo B o resultado foi de 71,5%. Em conclusão, os dois grupos de tratamento foram estatisticamente semelhantes em relação a todos os parâmetros estudados, com exceção da intensidade da dor, a qual foi inicialmente maior no grupo B, sendo equivalente em ambos os grupos ao final do estudo. Houve uma tendência favorável, porém não significante, ao esquema terapêutico de titulação de doses.

New antiretroviral drugs and approaches to HIV treatment.

New antiretroviral drugs and approaches to HIV treatment.