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Serious Adverse Reactions (serious + adverse_reaction)
Selected AbstractsDyspnoea after antiplatelet agents: the AZD6140 controversyINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 3 2007V. L. Serebruany Summary Recent randomised studies suggest that experimental oral reversible platelet P2Y12 receptor inhibitor, AZD6140, causes dyspnoea. This also raises similar concerns about the parent compound, and another adenosine triphosphate (ATP) analogue (AR-69931MX or cangrelor), which is currently in Phase 3 trial in patients undergoing coronary interventions. We analysed package inserts, and available clinical trials safety data for antiplatelet agents with regard to the incidence of dyspnoea. We found that dyspnoea is a very rare complication of the presently approved platelet inhibitors, mostly caused by underlying disease, rather than antiplatelet therapy per se. The main reasons for respiratory distress after oral (AZD6140), and intravenous (cangrelor) agents may be the development of mild asymptomatic thrombotic thrombocytopenic purpura, fluid retention and dyspnoea because of the reversible nature of these drugs. Also, these agents are ATP analogues, which rapidly metabolise to adenosine, a well-known bronchoprovocator causing dyspnoea as well. In summary, dyspnoea is seldom considered, there are no treatment algorithms when it does occur, plausible mechanisms exist and despite these plausible mechanisms, the true cause of dyspnoea in these exposed individuals is unknown. Additional pulmonary function testing, immunological investigations and platelet receptor studies are urgently needed to determine the cause of dyspnoea after AZD6140, and to point out how such serious adverse reactions can be prevented, or at least minimised, raising potential concerns about this drug. [source] Effect of Nonsteroidal Anti-Inflammatory Drug Use on the Rate of Gastrointestinal Hospitalizations Among People Living in Long-Term CareJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 5 2001Kate L. Lapane PhD OBJECTIVES: Gastrointestinal (GI) complications are the most-common serious adverse reactions associated with nonsteroidal anti-inflammatory drugs (NSAIDs). We quantified the effect of specific NSAIDs on the rate of GI hospitalizations among older people living in long-term care. DESIGN: Retrospective cohort study. SETTING: All Medicare/Medicaid certified nursing homes in four states (Maine, Minnesota, New York, and South Dakota). PARTICIPANTS: We identified 125,516 newly admitted residents from a database of all residents (1992,1996) of all Medicare/Medicaid certified nursing homes in four states. Using the federally mandated Minimum Data Set, which includes information on all drugs received (prescription and over-the-counter), we identified patients who received at least one prescription for aspirin (n = 19,101) or NSAIDs (n = 9,777). The control population consisted of all institutionalized persons who did not receive these drugs. MEASUREMENTS: From Health Care Financing Administration inpatient claims, we identified the first hospitalization for GI perforation, ulcer, or hemorrhage that occurred during the year of follow up (ICD9-CM discharge codes: 531,534, 578). Cox proportional hazards models provided adjusted estimates of rate ratios. RESULTS: NSAID exposure increased the GI-event-related hospitalization rate in both men (rate ratios (RR) = 2.64; 95% confidence interval (CI) = 1.17,5.99) and women (RR = 3.23; 95% CI = 1.85,5.65). The rate of GI hospitalizations for both men and women taking sulindac, naproxen, or indomethacin was higher than for nonusers. The risk of GI-event-related hospitalizations was greatest among women exposed to diflunisal (RR = 6.08; 95% CI = 2.27,16.26) or oxaprozin (RR = 6.03; 95% CI = 2.49,14.58). CONCLUSIONS: Despite the high background rate of GI events, most NSAIDs increased the risk of GI hospitalization. Careful attention to choice of agent and dosing is needed in prescribing NSAIDs in this frail, older population. [source] Adverse reactions of anti-tuberculosis drugs in hospitalized patients: incidence, severity and risk factors,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 10 2007Mohammad Reza Javadi Abstract Background Tuberculosis (TB) has been a common chronic infectious disease in human communities. Besides disease-related complications, there could be serious adverse reactions due to anti-tuberculosis (anti-TB) drug therapy. Objectives To assess the incidence and severity of adverse drug reactions (ADRs) induced by anti-TB drugs. To determine possible covariates associated with detected ADRs. Methods All patients with respiratory TB admitted to a teaching hospital who received anti-TB drugs during the research period entered the study and were monitored for ADRs. Socio-demographic and medical history of patients were used as independent covariates. The relationship between independent covariates with frequency and severity of ADRs was analysed using multivariate logistic regression. Preliminary analyses of the Mann,Whitney, Chi-square, Kruskal,Wallis and the Fisher's exact tests were applied to determine factors unlikely associated with the independent variables. Results Among 204 patients admitted, there were 92 patients (45.1%) with ADRs induced by anti-TB drugs. Patients with a previous history of anti-TB drugs usage (OR,=,5.81, 95% confidence interval [95%CI]: 1.31,25.2), patients with a history of drug allergy (OR,=,6.68, CI: 1.28,36.2), those from Afghani ethnic (OR,=,4.91, 95%CI: 1.28,18.30) as well as smoker patients with concurrent diseases (OR,=,19.67, CI: 1.24,341.51) had a higher rate of ADR incidence. Being female (OR,=,1.63, 95%CI: 1.96,36.40) and having previous history of ADR (OR,=,17.46, 95%CI: 1.96,20.42) were identified as risk factors. Conclusion Anti-TB drugs could cause severe and frequent adverse effects. Females, those with a previous history of ADRs to anti-TB drugs and Afghani patients, should be considered as high-risk groups. Copyright © 2007 John Wiley & Sons, Ltd. [source] Randomized sequential trial of valproic acid in amyotrophic lateral sclerosis,ANNALS OF NEUROLOGY, Issue 2 2009Sanne Piepers MD Objective To determine whether valproic acid (VPA), a histone deacetylase inhibitor that showed antioxidative and antiapoptotic properties and reduced glutamate toxicity in preclinical studies, is safe and effective in amyotrophic lateral sclerosis (ALS) using a sequential trial design. Methods Between April 2005 and January 2007, 163 ALS patients received VPA 1,500mg or placebo daily. Primary end point was survival. Secondary outcome measure was decline of functional status measured by the revised ALS Functional Rating Scale. Analysis was by intention to treat and according to a sequential trial design. This trial was registered with ClinicalTrials.gov (number NCT00136110). Results VPA did not affect survival (cumulative survival probability of 0.72 in the VPA group [standard error (SE), 0.06] vs 0.88 in the placebo group [SE, 0.04] at 12 months, and 0.59 in the VPA group [SE, 0.07] vs 0.68 in the placebo group [SE, 0.08] at 16 months) or the rate of decline of functional status. VPA intake did not cause serious adverse reactions. Interpretation Our finding that VPA, at a dose used in epilepsy, does not show a beneficial effect on survival or disease progression in patients with ALS has implications for future trials with histone deacetylase inhibitors in ALS and other neurodegenerative diseases. The use of a sequential trial design allowed inclusion of only half the number of patients required for a classic trial design and prevented patients from unnecessarily continuing potentially harmful study medication. Ann Neurol 2009;66:227,234 [source] Enamel matrix derivative (Emdogain®) for periodontal tissue regeneration in intrabony defectsAUSTRALIAN DENTAL JOURNAL, Issue 1 2010M Esposito Background:, Periodontitis is a chronic infective disease of the gums caused by bacteria present in dental plaque. This condition induces the breakdown of the tooth supporting apparatus until teeth are lost. Surgery may be indicated to arrest disease progression and regenerate lost tissues. Several surgical techniques have been developed to regenerate periodontal tissues including guided tissue regeneration (GTR), bone grafting (BG) and the use of enamel matrix derivative (EMD). EMD is an extract of enamel matrix and contains amelogenins of various molecular weights. Amelogenins are involved in the formation of enamel and periodontal attachment formation during tooth development. Objectives:, To test whether EMD is effective, and to compare EMD versus GTR, and various BG procedures for the treatment of intrabony defects. Search strategy:, We searched the Cochrane Oral Health Group Trials Register, CENTRAL, MEDLINE and EMBASE. Several journals were handsearched. No language restrictions were applied. Authors of randomized controlled trials (RCTs) identified, personal contacts and the manufacturer were contacted to identify unpublished trials. Most recent search: February 2009. Selection criteria:, RCTs on patients affected by periodontitis having intrabony defects of at least 3 mm treated with EMD compared with open flap debridement, GTR and various BG procedures with at least 1 year follow-up. The outcome measures considered were: tooth loss, changes in probing attachment levels (PAL), pocket depths (PPD), gingival recessions (REC), bone levels from the bottom of the defects on intraoral radiographs, aesthetics and adverse events. The following time-points were to be evaluated: 1, 5 and 10 years. Data collection and analysis:, Screening of eligible studies, assessment of the methodological quality of the trials and data extraction were conducted in duplicate and independently by two authors. Results were expressed as random-effects models using mean differences for continuous outcomes and risk ratios (RR) for dichotomous outcomes with 95% confidence intervals (CI). It was decided not to investigate heterogeneity, but a sensitivity analysis for the risk of bias of the trials was performed. Main results:, Thirteen trials were included out of 35 potentially eligible trials. No included trial presented data after 5 years of follow-up, therefore all data refer to the 1-year time point. A meta-analysis including nine trials showed that EMD treated sites displayed statistically significant PAL improvements (mean difference 1.1 mm, 95% CI 0.61 to 1.55) and PPD reduction (0.9 mm, 95% CI 0.44 to 1.31) when compared to placebo or control treated sites, though a high degree of heterogeneity was found. Significantly more sites had <2 mm PAL gain in the control group, with RR 0.53 (95% CI 0.34 to 0.82). Approximately nine patients needed to be treated (NNT) to have one patient gaining 2 mm or more PAL over the control group, based on a prevalence in the control group of 25%. No differences in tooth loss or aesthetic appearance as judged by the patients were observed. When evaluating only trials at a low risk of bias in a sensitivity analysis (four trials), the effect size for PAL was 0.62 mm (95% CI 0.28 to 0.96), which was less than 1.1 mm for the overall result. Comparing EMD with GTR (five trials), GTR showed statistically significant more postoperative complications (three trials, RR 0.12, 95% CI 0.02 to 0.85) and more REC (0.4 mm 95% CI 0.15 to 0.66). The only trial comparing EMD with a bioactive ceramic filler found statistically significant more REC (-1.60 mm, 95% CI ,2.74 to ,0.46) at the EMG treated sites. Authors' conclusions:, One year after its application, EMD significantly improved PAL levels (1.1 mm) and PPD reduction (0.9 mm) when compared to a placebo or control, however, the high degree of heterogeneity observed among trials suggests that results have to be interpreted with great caution. In addition, a sensitivity analysis indicated that the overall treatment effect might be overestimated. The actual clinical advantages of using EMD are unknown. With the exception of significantly more postoperative complications in the GTR group, there was no evidence of clinically important differences between GTR and EMD. Bone substitutes may be associated with less REC than EMD. Plain language summary:, Enamel matrix derivative (Emdogain®) for periodontal tissue regeneration in intrabony defects. Emdogain might have some advantages over other methods of regenerating the tissue supporting teeth lost by gum disease, such as less postoperative complications, but has not been shown to save more compromised teeth or that patients noticed any aesthetic improvement 1 year after its application. Bacteria in plaque can cause gum disease (periodontitis) that breaks down tissue supporting teeth. Surgical cleaning tries to stop the disease to save loose teeth. Bone grafting, guided tissue regeneration and enamel matrix derivatives (such as Emdogain) aim to regenerate support tissues. Emdogain contains proteins (derived from developing pig teeth) believed to regenerate tooth attachment. The review found that adjunctive application of Emdogain regenerates about 1 mm more tissue than surgical cleaning alone, although it is unclear to which extent such improvement is noticeable since patients did not find any difference in the aesthetic results. Emdogain showed similar clinical results to guided tissue regeneration, but is simpler to use and determines less complications. Bone substitutes may induce less gum retraction than Emdogain. No serious adverse reactions to Emdogain were reported in trials. [source] Infliximab in the surgical management of complex fistulating anal Crohn's diseaseCOLORECTAL DISEASE, Issue 2 2005C. Talbot Abstract Objectives To assess prospectively the efficacy and safety of treatment of perianal Crohn's disease by means of a combination of surgical management and a standardized protocol for the intravenous infusion of infliximab. Methods A consecutive series of patients who presented with complex perianal Crohn's fistulae between November 1999 and March 2003 were included in the study. Perianal sepsis was eradicated with drainage of collections and insertion of setons. Infliximab was infused at 5 mg/kg at 0, 2, and 6 weeks. Setons were removed after the second infliximab infusion. Endpoints were defined as either complete, partial or no response as noted at subsequent outpatient follow up. Adverse reactions were recorded. Results Twenty-one patients had a median of three fistulae per patient (range 1,9). All patients tolerated the initial protocol, receiving a median of five infusions of infliximab (range 3,19); median follow up 20 months (range 12,52). Eleven patients (53%) were continued on maintenance therapy with 12 weekly infusions of infliximab for either a perceived clinical need for treatment or after a relapse of their symptoms. Ten (47%) patients experienced a complete response to treatment and the remaining 11 (53%) experienced a partial response. No patient failed to respond to treatment. Four adverse reactions were noted (2 mild allergies, 1 rash and 1 patient experienced joint pains). All adverse reactions settled with cessation of the drug infusion. Conclusions The combination of seton drainage and infusion of infliximab completely healed the perineum of 47% patients with complex fistulating perianal Crohn's disease. Partial response was seen in the remainder of patients. No serious adverse reactions reported. [source] | ||||||||||