Rate Of Adverse Drug Reactions Research Articles

Efficacy of an Adverse Drug Reaction Electronic Reporting System Integrated into a Hospital Information System

Adverse drug reaction (ADR) spontaneous reporting is the primary method of postmarketing drug surveillance; although it is an important part of postmarketing drug surveillance, it is underused. Before 2004, almost no ADRs were reported in our 400-bed hospital. As an electronic hospital information system was available in our hospital, we developed a tool (ADR-RS-IHIS) for ADR reporting integrated into the hospital information system to facilitate reporting through easy use, automatic input of certain information, increased accessibility, real-time review, and intervention. To analyze the efficacy of the ADR-RS-IHIS in increasing ADR reporting to the national drug surveillance system, propose and implement improvements to increase ADR reporting, and evaluate the impact of these improvements. Every ADR reported through the ADR-RS-IHIS was evaluated retrospectively. Two study phases for evaluating ADR-RS-IHIS efficacy were identified. Phase I took place April 2004-August 2006; in April 2006, an interim analysis was performed to propose improvements. Phase II took place September 2006-April 2007 for evaluation of the impact made by the proposed improvements. Efficacy in the phase I and improvement impact on phase II were measured as the number of ADRs reported to the national drug surveillance system. The rate of ADRs reported per month to the national system increased from 0 before 2004 to 0.91 in phase I and 1.62 in phase II (2.25 if delayed reporting was considered). Improvement measures included: allowing nurses to report ADRs in the same way as physicians and pharmacists, automatic form filling of certain information from the electronic hospital information system, easier ADR report analysis, and automatic notification to the allergy department regarding suspected allergies. An ADR reporting system integrated into the electronic hospital information system is effective for increasing the number of ADRs reported to the national drug surveillance system. Allowing nurses to report ADRs in a manner similar to that of physicians and pharmacists, as well as automatic entry of certain data into the form, contributes to the improvement of the system.

Antibiotic duration for treating uncomplicated, symptomatic lower urinary tract infections in elderly women

Urinary tract infections (UTI) are common in elderly patients. Authors of non systematic literature reviews often recommend longer treatment durations (7 to 14 days) for older women, but the evidence for such recommendations is unclear. To determine the optimal duration of antibiotic treatment for uncomplicated symptomatic lower UTI in elderly women. We contacted known investigators and pharmaceutical companies, screened reference lists of identified articles, reviews and books, and searched MEDLINE, EMBASE, CINAHL, Healthstar, Popline, Gerolit, Bioethics Line, The Cochrane Library, Dissertation Abstracts International and Index to Scientific & Technical Proceedings without language restriction. Date of most recent search: 7 May 2008. All randomised controlled trials (RCTs) comparing different treatment durations of oral antibiotics for uncomplicated symptomatic lower UTIs in elderly women were included. Whenever possible we obtained outcome data for older women included in studies with a broader age range. We excluded patients with fever, flank pain or complicating factors; studies with treatment durations longer than 14 days and prevention studies. The two authors independently assessed study quality and extracted data. Statistical analyses were performed using the random effects model and results expressed as risk ratio (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes with 95% confidence intervals (CI). Fifteen studies (1644 elderly women) were included. Three studies compared single dose with short-course treatment (3 to 6 days), six compared single dose with long-course treatment (7 to 14 days) and six compared short- with long-course treatment. Methodological quality of all studies was low except for a more recent geriatric study. There was a significant difference for persistent UTI between single dose and short-course treatment (RR 2.01, 95% CI 1.05 to 3.84) and single versus long-course treatment (RR 1.93, 1.01 to 3.70 95% CI), in the short-term (< 2 weeks post-treatment) but not at long-term follow-up or on clinical outcomes. Patients preferred single dose treatment (RR 0.73, 95% CI 0.60 to 0.88) to long-course treatments, but this was based on one study comparing different antibiotics. Short versus longer treatments showed no significant difference in efficacy. Rate of adverse drug reactions increased significantly with longer treatment durations in only one study. Short-course treatment (3 to 6 days) could be sufficient for treating uncomplicated UTIs in elderly women, although more studies on specific commonly prescribed antibiotics are needed.

Pharmacogenomics of Antiretrovirals

HIV infection is a serious but treatable disease, yet current treatment is limited by development of resistance and high rates of adverse drug reactions. Antiretroviral therapy is especially suitable for pharmacogenomic investigation as both drug exposure and treatment response can be reliably measured. Increasing knowledge about genes implicated in pharmacokinetics, mode of action, efficacy, and toxicity of drugs has already provided relevant results for clinical practice, for example: The strong association of the abacavir hypersensitivity reaction with HLA-B*5701 permits testing patients for the allele, and if present avoiding the drug and therefore preventing the reaction. Persons with the allele CYP2B6*6 present higher efavirenz "area under the curve" and have increased risk of neuropsychological toxicity. Additional gene variants are being discovered that influence the action of antiretroviral drugs. And, moreover, it is expected that larger-scale comprehensive genome approaches will profoundly improve the landscape of knowledge of HIV therapy in the future. The present article shows some recent patents related to the treatment of viral infections.

Adverse drug reactions induced by cardiovascular drugs in outpatients.

Considering increased use of cardiovascular drugs and limitations in pre-marketing trials for drug safety evaluation, post marketing evaluation of adverse drug reactions (ADRs) induced by this class of medicinal products seems necessary. To determine the rate and seriousness of adverse reactions induced by cardiovascular drugs in outpatients. To compare sex and different age groups in developing ADRs with cardiovascular agents. To assess the relationship between frequencies of ADRs and the number of drugs used. This cross-sectional study was done in cardiovascular clinic at a teaching hospital. All patients during an eight months period were evaluated for cardiovascular drugs induced ADRs. Patient and reaction factors were analyzed in detected ADRs. Patients with or without ADRs were compared in sex and age by using chi-square test. Assessing the relationship between frequencies of ADRs and the number of drugs used was done by using Pearson analysis. The total number of 518 patients was visited at the clinic. ADRs were detected in 105 (20.3%) patients. The most frequent ADRs were occurred in the age group of 51-60. The highest rate of ADRs was recorded to be induced by Diltiazem (23.5%) and the lowest rate with Atenolol (3%). Headache was the most frequent detected ADR (23%). Assessing the severity and preventability of ADRs revealed that 1.1% of ADRs were detected as severe and 1.9% as preventable reactions. Women significantly developed more ADRs in this study (chi square = 3.978, P<0.05). ADRs more frequently occurred with increasing age in this study (chi square = 15.871, P<0.05). With increasing the number of drugs used, the frequency of ADRs increased (Pearson=0.259, P<0.05). Monitoring ADRs in patients using cardiovascular drugs is a matter of importance since this class of medicines is usually used by elderly patients with critical conditions and underlying diseases.

Adverse Drug Reactions in the Post Coronary Care Unit Inpatients of a Teaching Hospital

The monitoring and reporting of adverse drug reactions (ADRs) in hospitals aims to identify and quantify the risks associated with the use of drugs. The present study was performed to characterize the rate and the pattern of ADRs, due to cardiovascular drugs and anticoagulants, in a tertiary care teaching hospital. For this purpose, all the patients treated with cardiovascular drugs and anticoagulants in the post coronary care unit (CCU) from September 2006 until January 2007 were actively monitored for ADRs. Data evalution was conducted for various parameters which included patient demographics, number of prescribed drugs, drug and reaction characteristics, and outcome of the reactions. Assessment was also done for causality, seriousness, and preventability. A total of 64 ADRs during the 4 months study period were evaluated. The overall rate of ADRs calculated from the patient population was 53%. No significant difference was seen in the overall rate of ADRs in males vs. females. The most commonly affected organ was gastro-intestinal system (14.06%). Nitroglycerin tablet (long-acting) and digoxin were the drugs most frequently reported (28.28%). In 20.31% of the reports, the patient had recovered from the reaction at the time of data collection. Upon causality assessment, the majority of the reports were rated as probable (64.06%). Serious and non-serious reactions accounted for 3.13% and 96.87% of the ADRs, respectively. In 9.37% of the reports, reaction was considered to be preventable. Our data revealed that ADRs in the post CCU occur rather frequently during hospitalization. Such studies enable us to obtain information on the rate and pattern of ADRs in the local population. These evaluations need to be followed by dissemination of the information to healthcare professionals to improve the quality of patient care and ensure safer use of drugs.

Adverse Drug Reactions (ADR) in the inPatients of Medicine Department of a Rural Tertiary Care Teaching Hospital and Influence of Pharmacovigilance in Reporting ADR

Objectives:(i) To find the incidence and study various aspects of Adverse Drug Reactions (ADR) in the inpatients of medicine department of Shree Krishna Hospital, a rural tertiary care teaching hospital. (ii) To test the impact of pharmacovigilance in reporting ADR.Material & Methods:A prospective study involving 600 patients admitted to the medical wards and TB & Chest diseases ward over a period of six months and a retrospective analysis of 600 case files for the corresponding period of the previous year were carried out to find the incidence rate of ADR, study various aspects of ADR like causality assessment, drugs frequently causing ADR etc. Suitably structured and pre-tested format was used for compiling the data.Results:In the prospective study, 18 of the 600 patients (3%) developed ADR. A significant number (77.78%) of patients developed ADR between the 3rd and 10th days of administering the drug/s. As the number of drugs increased, the incidence of ADR also increased. Majority of ADR (72.22%) occurred due to chemotherapeutic agents. 66.67% of ADR involved the gastrointestinal tract. None of the ADR was fatal. Sex of the patients did not influence the incidence rate of ADR. On the other hand, in the retrospective analysis, only ADR were reported in just 6 out of 600 patients (1%).Conclusion:The incidence rate of ADR is found to be much lower (3%) than the reported rate (10%-20%). Pharmacovigilance certainly contributes to picking up ADR.

Influence of Regulatory Measures on the Rate of Spontaneous Adverse Drug Reaction Reporting in Italy

The reporting of adverse drug reactions (ADRs) is the mainstay of post-marketing surveillance systems. Under-reporting and selective reporting are considered the main limitations of a spontaneous reporting-based pharmacovigilance system. However, excessive reporting induced by external events may also impair signal detection by increasing the noise level. The aim of this study was to examine the influence of regulatory measures and other external factors on the rate of ADR reporting in Italy, focusing on four situations occurring in the last 10 years: ACE inhibitor-induced cough; HMG-CoA reductase inhibitors ('statins') and rhabdomyolysis; nimesulide and hepatic toxicity; and cyclo-oxygenase (COX)-2 selective inhibitors ('coxibs') and increase in cardiovascular risk. The study was based on data from spontaneous reporting in six Italian regions collected from January 1995 to December 2005. We analysed a 10-year period as a reasonable time interval around the four situations of interest, highlighting the influence of regulatory measures on the rate of ADR reporting (number of reports per million inhabitants). Chi-squared tests were used to assess the statistical significance of any changes in ADR reporting. Drug sales data were also studied to examine possible changes in drug use. Sales data were expressed as daily defined dose per 1000 inhabitants per day. ACE inhibitors: a 5-fold increase in the reporting rate of ACE inhibitor-induced cough was observed in 1998 and 1999 following a restriction on reimbursement for angiotensin receptor blockers introduced in 1998 and removed at the end of 1999. Statins: after the withdrawal of cerivastatin in 2001, the ADR reporting rate increased more than 4-fold, with musculoskeletal ADRs representing about 60% of all the ADRs reported in that year, and progressively decreased in the following years. Nimesulide: an increase in hepatic ADR reporting was observed after withdrawal of the drug from the Finnish and Spanish markets in 2002. Coxibs: no important changes in the rate of cardiovascular events reporting in the period 2000-4 were observed. In 2005, after the withdrawal of rofecoxib in September 2004, both the ADR reporting rate and sales of the drug decreased drastically. Our data suggest that spontaneous ADR reporting can be influenced in different ways by external events. Our data emphasize the need for educational initiatives aimed at increasing the doctor's and patient's awareness of the usefulness and the limitations of spontaneous reporting in the pharmacovigilance system. Such initiatives should use appropriate risk communication strategies in order to avoid unnecessary alarm, which could cause unjustified interruption of therapies or misplaced confidence in new drugs.

How Safe is Intravenous N‐Acetylcysteine for the Treatment of Paracetamol Poisoning?

ObjectiveParacetamol poisoning remains one of the most common and potentially lethal ingestions. N‐acetylcysteine (NAC) has been proven to be a highly effective antidote. The aim of this study was to determine the rate of adverse drug reactions (ADR) to intravenous (IV) NAC. Our hypothesis was that IV NAC for the treatment of paracetamol toxicity has a low rate of adverse events.MethodsThis was an observational cohort study undertaken by explicit retrospective medical record review. It included patients who presented to the emergency department with paracetamol overdose over the ten‐year period from July 1995 to June 2004. The primary outcome measure was the occurrence of an ADR during NAC administration. Adverse drug reactions were classified as minor (including flushing, urticaria, pruritus, bronchospasm, tachycardia, and non‐ischaemic chest pain) and major (including hypotension, angio‐oedema and death). Data analysis was by descriptive statistics and chi‐square analysis using univariate analysis, Fisher's exact test and Mann‐Whitney U‐test. Inter‐rater agreement was checked for 9% of the sample.ResultsThere were 470 cases of paracetamol poisoning. Of these, 320 received IV NAC. Thirty‐six (11%, 95% CI 8–15%) of these patients developed ADRs. There were two major ADRs, one hypotension and one angio‐oedema (0.6%, 95% CI 0.02–2%). Two patients died during hospitalisation, but neither had an ADR to NAC. The most common ADRs were urticaria (20), flushing (15), bronchospasm (12), and pruritus (3). None of the variables analysed was a clinically significant predictor of increased ADR risk.ConclusionAdverse drug reactions after IV NAC infusion occur commonly, but most are minor. Treatment of paracetamol poisoning with IV NAC appears to be safe, however a large prospective study would be required to confirm this.

Advances in Pharmacogenomics of Antiretrovirals: An Update

Recent developments in the pharmacogenomics of antiretroviral drugs provide new prospects for predicting the efficacy of treatment and potential adverse effects. HIV/AIDS is a serious but treatable infectious disease, yet current treatment is limited by high rates of adverse drug reactions and development of resistance due to suboptimal drug concentrations in a significant proportion of patients. Antiretroviral therapy is especially suitable for pharmacogenomic investigation as both drug exposure and treatment response can be quantified and certain adverse effects can be assessed with validated measures. Additionally, there is increasing knowledge of the pharmacokinetics and dynamics of antiretroviral drugs, and some candidate genes implicated in the metabolism, transport and adverse effects have been identified. However, recent studies of the association of particular genes and their genetic variants with HIV management and adverse drug reactions have not provided unifying conclusions. This article reviews the most recently published work and summarizes the state of research in this area. Future directions for research and the application of this technology to the clinical practice of individualizing treatment for HIV management are discussed.

Safety and efficacy of intravenous N‐acetylcysteine for acetaminophen overdose: analysis of the Hunter Area Toxicology Service (HATS) database

ABSTRACTBackground: Acetaminophen (N‐acetyl-p‐aminophenyl; APAP) is the leading drug used in self-poisoning and frequently causes hepatotoxicity, including acute liver failure.Objective: To provide descriptive data on the safety and efficacy of intravenous N‐acetylcysteine (IV‐NAC) in the treatment of APAP toxicity, based on information in the Hunter Area Toxicology Service (HATS) database involving residents of the Greater Newcastle Area of New South Wales, Australia.Methods: This was a retrospective analysis of all APAP overdoses from January 1987 to January 2003. Data were collected prospectively according to a published protocol and included patient characteristics, exposures to APAP and other potential toxins, treatments, and outcomes. Primary safety/tolerability endpoints included the mortality rate and incidence of adverse drug reactions, while efficacy endpoints included alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels.Results: Of 1749 patients, 399 (22.8%) were treated with IV‐NAC. Of these, 37 (9.3%) had an adverse drug reaction to IV‐NAC, of which seven (1.8% of total) were anaphylactoid. There were five deaths in hospital (mortality rate = 0.3%), including two attributed to APAP (0.1%) and none to IV‐NAC. Of 64 patients who were treated with IV‐NAC within 8 hours after APAP ingestion and had available ALT/AST data, two (3.1%) developed hepatotoxicity (AST/ALT > 1000 IU/L) compared with 32 (25%) of 128 patients receiving IV‐NAC > 8 hours after APAP ingestion ( p = 0.0002). A total of 26 patients (15.6%) receiving IV‐NAC treatment within 8 hours after APAP ingestion had hospitalization stays > 48 hours compared with 70 (33.3%) receiving IV‐NAC > 8 hours after ingestion ( p < 0.0001).Conclusions: For patients with APAP overdose seen in the HATS database of New South Wales, Australia, in-hospital death was infrequent (< 1%) and hepatotoxicity was significantly less likely when IV‐NAC was administered within 8 hours after APAP ingestion compared with longer intervals ( p < 0.01). As a descriptive retrospective database analysis, this study could not exclude certain sources of bias, including temporal changes over the 16‐year course of data collection in the use of IV‐NAC and low ascertainment of mild, self-limiting reactions to IV‐NAC.

Postmarketing surveillance of the safety profile of infliximab in 5000 Japanese patients with rheumatoid arthritis

Objectives:A large-scale postmarketing surveillance (PMS) study was carried out to determine the safety profile of infliximab in Japanese patients with rheumatoid arthritis (RA).Methods:The PMS study was performed for all patients...

Patient choice promotes adherence in preventive treatment for latent tuberculosis

The aim of the present study was to compare the effect of patient choice on completion rates and adverse drug reactions for patients treated for latent tuberculosis infection (LTBI) using 3-month rifampicin and isoniazid treatment (3RH) or 6-month isoniazid treatment (6H). Data for all patients treated using 3RH or 6H for LTBI between 1998 and 2004 were analysed. In total, 675 patients attended for chemoprophylaxis. Of these, 314 received 3RH and 277 received 6H. From April 1, 2000, patients were offered a choice of regimen; 53.5% completed the regimen successfully, a further 10.3% potentially completed it successfully and 36.2% failed to complete treatment. Logistic regression analysis suggested that successful completion was more likely in patients who were younger (an association that was lost after removing all patients aged <16 yrs), were offered a choice of regimen and attended all clinic visits before commencing treatment. Treatment was discontinued due to adverse reactions in 16 (5.1%) patients who were prescribed 3RH and 16 (5.8%) who were prescribed 6H. Treatment failure was most likely during the first 4 weeks of treatment for both regimens. At 13 weeks of treatment, more patients taking 6H had stopped compared with those completing the 3RH regimen. Drug costs were greater using 6H compared with 3RH. In conclusion, offering a choice of regimen improves completion. Most patients chose the 3-month rifampicin and isoniazid treatment over the 6-month isoniazid treatment. Adverse drug reaction rates between the two regimens were similar.

Use and tolerability of newer antipsychotics and antidepressants: a chart review in a paediatric setting

To analyse the prescribing pattern and the safety profile of different atypical antipsychotics and selective serotonin reuptake inhibitors (SSRIs) during the years 2002-2003 in paediatric setting. Two Child Neurology and Psychiatry Divisions of Southern Italy (University of Messina and "Oasi Institute for Research on Mental Retardation and Brain Aging" of Troina). A retrospective chart review of all children and adolescents starting an incident treatment with atypical antipsychotics or SSRIs was performed. Within the first 3 months of therapy, any potential adverse drug reaction (ADR) was identified and the clinical outcome of psychotropic drug treatment was assessed. Rate of ADR in the first 3 months of therapy with atypical antipsychotics and SSRIs in children and adolescents. On a total of 97 patients' charts being reviewed, 73 (75%) concerned atypical antipsychotics and 24 (25%) SSRIs. Risperidone (N=45, 62%) was the most frequently prescribed antipsychotic drug, followed by olanzapine (24, 32%). Overall, 50 (68%) antipsychotic users reported a total of 108 ADRs during the first 3 months of therapy, leading to drug discontinuation in 23 patients (31%). Among 24 users of SSRI, 12 (50%) received paroxetine, 6 (25%) sertraline, 5 (21%) citalopram and 1 (4%) fluoxetine. Only paroxetine users (21%) reported at least one ADR, however, none of SSRI users withdrew drug treatment within first 3 months. ADRs occurred frequently during first 3 months of treatment with atypical antipsychotics and, to a lesser extent, with SSRIs in children and adolescents. Further investigations are urgently needed to better define the benefit/risk ratio of psychotropic medications in paediatric setting.

Genetic Nondiscrimination Legislation: A Critical Prerequisite for Pharmacogenomics Data Sharing

Russ B Altman1†, Neal Benowitz2, David Gurwitz3, Jeantine Lunshof4, Mary Relling5, Jatinder Lamba5, Eric Wieben6, Sean Mooney7, Kathleen Giacomini2, Scott Weiss8, Julie A Johnson9, Howard McLeod10, David Flockhart7, Richard Weinshilboum6, Alan R Shuldiner11, Dan Roden12, Ronald M Krauss13 & Mark Ratain14 †Author for correspondence 1Stanford University, Department of Genetics and Bioengineering, Clark S172, Stanford, CA 94305-5444, USA E-mail: Russ.Altman@ stanford.edu 2University of California, San Francisco 3Tel-Aviv University 4VU University Medical Center 5St Jude Children’s Research Hospital 6Mayo Clinic 7Indiana University School of Medicine 8Harvard Medical School 9University of Florida 10University of North Carolina 11University of Maryland 12Vanderbilt School of Medicine 13Children’s Hospital Oakland Research Institute 14University of Chicago On 31st January 2007, the US Senate Health, Education, Labor and Pensions Committee approved the Genetic Information Nondiscrimination Act (GINA) by a vote of 19:2. It was unanimously approved by the US Congress Committee on Education and Labor 2 weeks later. This legislation, aimed at preventing genetic discrimination in employment and insurance [1], will be imperative for protecting altruistic individuals who volunteer for genetic research [2]. There is an emerging consensus among researchers that genetic data must be accessible to individual research participants upon their request [3], while not putting them at risk with respect to their employment, insurance and additional personal aspects [4]. The GINA balances individual freedoms and privacy rights with societal needs for affordable and more effective healthcare and helps to pave the way for more personalized medicine [5]. Indeed, genetic information can be used to improve healthcare, in particular with regard to reducing the alarming rates of adverse drug reactions, which led to 6.7% of all US hospital admissions during 2004–2005 [6], consistent with earlier studies in the UK [7]. Increased use of individual genetic information about drug-metabolizing and drug-target gene alleles as part of healthcare treatment decisions may substantially reduce such morbidity [8]. However, building up the required knowledge depends on the analysis of large individual genotype/phenotype data sets from patient cohorts and requires open data sharing so that large, meaningful and less biased data sets are available to researchers [9]. Lack of open data sharing, in particular between the private and public sectors, hinders our ability to assemble large aggregated data sets [9]. A key obstacle for data sharing is concern about depositing data sets from individual study participants into public databases; some researchers fear they will be held responsible in cases where the data are re-identified (using computational data-mining techniques) and subsequently used (by employers or insurers) to discriminate against study participants. We therefore believe that legislation that offers protection to individuals or groups who share genetic information – against both re-identification and discrimination – is essential for efforts to move genomic medicine into practice. Legislation barring discrimination or stigmatization based on genetic information has been proposed for years, but enactment has become particularly urgent in view of rapidly falling genotyping costs [10], the scope of ongoing genome-wide association studies [11] and the increasing availability of comprehensive personal data in the public domain [4]. We therefore strongly support the current efforts to establish a solid legal framework as a primary means to protect individuals against misuse of their genetic information and as an essential tool for allowing open data sharing in pharmacogenomics.

Cotrimoxazole for prophylaxis or treatment of opportunistic infections of HIV/AIDS in patients with previous history of hypersensitivity to cotrimoxazole

Opportunistic infections continue to cause a significant amount of morbidity and mortality worldwide in patients infected with HIV. Trimethoprim-sulfamethoxazole (cotrimoxazole) is used in the treatment and prophylaxis of several opportunistic infections. In patients with HIV/AIDS, cotrimoxazole use can cause a higher rate of adverse drug reactions than in the general population. Given the cost-effectiveness of cotrimoxazole, the management of these adverse reactions has included continuing the drug (treating-through) and reintroducing the drug at a later date, either using dose-escalation (desensitization), or rechallenge at full dose. This systematic review is the first to examine the differences in patient outcomes between these strategies. To compare the rate of discontinuation of cotrimoxazole and adverse reactions among the three strategies of treating-through, desensitization, and rechallenge in patients living with HIV who previously had an adverse reaction to cotrimoxazole. We searched MEDLINE, EMBASE, LILACS, The Cochrane Library, Meeting Abstracts, AIDSTRIALS, ACTIS, Current Controlled Trials, The National Institutes of Health Clinical Trials Registry, and CenterWatch (search date May 2006). Randomised trials comparing treating-through, rechallenge, or desensitization of cotrimoxazole treatment or prophylaxis in adults (age 18 years or over) and/or children (age 17 years or under). Two reviewers independently assessed trial eligibility and quality, and extracted data. Where data were incomplete or unclear, a third reviewer resolved conflicts and/or trial authors were contacted for further details. Three trials that examined cotrimoxazole prophylaxis and involving 268 adults were included. Meta-analysis of these studies found a beneficial effect of using a desensitization protocol over a rechallenge protocol at six months of follow-up for preventing discontinuation of cotrimoxazole (number needed to treat (NNT) 7.14, 95% confidence interval (CI) 4.0-33.0), and for lower incidence of overall hypersensitivity (NNT 4.55, 95% CI 3.03-9.09). No severe hypersensitivity reactions occurred for either protocol in the three studies. In the small trials included in this review, when compared to cotrimoxazole rechallenge for prophylaxis of opportunistic infections, cotrimoxazole desensitization resulted in fewer treatment discontinuations and overall adverse reactions in HIV-infected patients with a previous history of mild or moderate hypersensitivity to cotrimoxazole. Paediatric data and trials in resource-poor settings are urgently required. Further randomised controlled trials are also needed for the treatment of opportunistic infections, treating-through, adjunctive medications, and different desensitization-dosing schedules.

Adverse drug reaction reporting by nurses in Sweden

To investigate whether nurses could be a useful tool for improving the reporting rate of adverse drug reactions (ADRs). Furthermore, we wanted to study how physicians working at the study departments would respond to nurses as reporters of ADRs and if the reporting from the nurses affected the reporting rate from the physicians. Three departments of internal medicine and one unit for orthopaedics were selected for the study. Nurses with special drug responsibilities were invited to participate. At the start of the study period, the nurses received an introduction with background, objective, method and other practical issues concerning the study. After this, an education programme about ADR reporting, definitions, and ADR classification according to mechanism and organ system was given. To study their knowledge about and attitude towards ADRs, a questionnaire was handed out to the nurses. A questionnaire was also handed out to all physicians at the participating departments in order to investigate their attitude towards nurses as reporters of ADRs. Fifty-four nurses participated in the study. During the study period, a total number of 23 reports with 39 ADRs were sent to the regional centres by the nurses. Seventeen (74%) of the reports were assessed as serious. Eight of the 39 ADRs were unlabelled and all reports were considered appropriate. The reporting rate from the physicians during the study period was similar to the previous year, indicating that the nurses contributed with additional reports. At the end of the study, the nurses thought that they had enough knowledge to report ADRs. Sixty-eight percent of the physicians did not object to nurses being included as reporters of suspected ADRs. Adverse drug reaction reporting by nurses could improve the overall safety of drugs.

Can Spontaneous Adverse Event Reporting Systems Really Be Used to Compare Rates of Adverse Events Between Drugs?

Can Spontaneous Adverse Event Reporting Systems Really Be Used to Compare Rates of Adverse Events Between Drugs?

Detection and incidence of drug-induced agranulocytosis in hospital: a prospective analysis from laboratory signals

Our objectives were to assess the detection and incidence of drug-induced agranulocytosis in two university hospitals using hematology laboratory data. A prospective study was undertaken at Toulouse University Hospital (France) and Navarra University Hospital (Spain) for 1 year (from 1 May 2004 to 30 April 2005). Using a computerized process and hematology laboratory data, all neutrophil counts with a value less than 500/mm(3) were registered, allowing identification of inpatients suffering from agranulocytosis during the period of the study. Medical records of all selected patients were then consulted. Cytostatic drugs were excluded from this study. During the period of the study, 225,659 neutrophil counts were performed in both hospitals, of which 2,835 (1.26%) had a neutrophil count less than 500/mm(3), corresponding to 739 patients. Seventeen patients were excluded because of lack of data, and 20 cases of infants younger than 3 months were excluded. Among the remaining patients (n = 702), 23 cases of drug-induced agranulocytosis (excluding cytostatic drugs) were suspected. All cases were classified as "serious" since they led to death in 2 cases, hospitalization or prolongation of hospitalization in 19 cases and threatening of vital prognosis in 2 cases. Withdrawal of suspected drugs was done in all cases with regression of neutropenia in 21 cases. According to hospitalization data, the annual incidence of drug-induced agranulocytosis was 1.62 (1.0-2.6) per 10,000 inpatients in Toulouse University hospital (based on 534 cases) and 3.24 (0.9-8.3) per 10,000 inpatients in Navarra University Hospital (based on 168 cases). The involved drugs were mainly antibacterial (30.4%), immunosuppressive (17.4%), antithyroid (13.0%), antiplatelet (8.7%) and nonsteroidal anti-inflammatory (8.7%) ones. Only seven cases from Toulouse University Hospital were spontaneously reported by physicians during the same period. Thus, the underreporting coefficient (U) was 2.71 (63.2%) in France. Our survey allowed us to identify the suspected drug-induced agranulocytosis through a prospective study in a large sample of inpatients using only laboratory data analysis. We also note an important underreporting rate of this serious adverse drug reaction (ADR) to the official French pharmacovigilance system. Laboratory data analysis could be used for identifying serious ADRs.

The Real-Life Safety and Efficacy of Vardenafil

To assess the safety, efficacy and patient acceptability of vardenafil treatment under real-life conditions in patients with erectile dysfunction (ED). The present publication shows the results of a subgroup analysis of a multinational post-marketing surveillance study, including 2824 Middle East patients with ED whose attending physician chose vardenafil as the most appropriate therapy. Patients were assessed at an initial visit for demographic and baseline characteristics. At one or two follow-up visits, covering a period of approximately 2 months or eight vardenafil intakes, patients were interviewed about overall treatment success (general improvement of erection, number of tablets taken until improvement, patient's satisfaction with overall efficacy and tolerability, comparison with last ED treatment). All adverse events were recorded and assessed for a possible relationship to treatment, and for severity. An overall improvement in erections was reported in 94.3% of patients. Most patients achieved treatment success after the first (67.0%) or second (83.6% cumulative) tablet. Diabetic patients had a similar improvement rate (92.2%) and 73.5% of patients who had undergone radical prostatectomy reported an overall improvement. The rate of adverse drug reactions (ADRs) was low (9.1% of patients). The most common ADRs were headache (5.8%), flushing (1.6%), nasal congestion (1.0%), dyspepsia (0.6%) and nausea (0.5%). In total, 88.9% of patients wanted to continue treatment with vardenafil. Vardenafil was effective, reliable and well tolerated in patients with ED treated under real-life conditions.

Repeat adverse drug reactions causing hospitalization in older Australians: a population‐based longitudinal study 1980–2003

To examine trends in the rate of repeat adverse drug reactions (ADRs) causing hospitalization in older Australians and to identify the most common ADRs and drugs most often implicated in repeat and first-time ADRs. Analysis of routinely collected hospital record administrative data, with International Classification of Diseases external cause codes for ADRs extracted from the Western Australia (WA) Hospital Morbidity Data System and WA Death Register, for people aged > or =60 years in 1980-2003. A total of 37 296 people aged > or =60 years with an ADR-related hospitalization were identified. Among them, 6853 (18.4%) patients had 10 212 repeat ADRs. Repeat ADRs consistently increased from 1980 and reached 30.3% of all ADRs by 2003. The mean time interval declined with each successive repeat ADR (810, 606 and 299 days for the first, second and higher ranked repeat episodes, respectively). The most common repeat ADRs were nausea/vomiting (8.0%), haemorrhage due to anticoagulants (5.5%), drug-induced osteoporosis (4.8%) and poisoning by cardiovascular agents (3.9%). The drugs most often involved in repeat ADRs were cardiovascular agents (15.6%), antineoplastic drugs (11.0%), corticoids (10.1%), anticoagulants (8.6%), antirheumatics/nonsteroidal anti-inflammatory drugs (5.1%) and opioids (4.9%). The trends of anticoagulants and antineoplastic drugs implicated in repeat ADRs were still rising at the end of the study. The specific drug classes involved in repeat ADRs differed in relative importance from first-time ADRs. Repeat ADR-related hospitalizations have consistently increased in elderly Australians from 1980 to 2003. Strategies to ensure the safer use of medicines, in particular anticoagulants, in this population are warranted.