Mild Adverse Drug Reactions Research Articles

Retrospective analysis of non-laboratory-based adverse drug reactions induced by intravenous radiocontrast agents in a Joint Commission International-accredited academic medical center hospital in China.

The authors retrospectively analyzed the pattern and characteristics of non-laboratory-based adverse drug reactions (ADRs) induced by intravenous radiocontrast agents in a large-scale hospital in China during 2014–2015. There were 314 ADR cases among 118,208 patients receiving enhanced CT or MRI examinations. The frequency of moderate/severe ADRs defined by Chinese Society of Radiology (ie, severe vomiting, systematic urticaria, facial swelling, dyspnea, vasovagal reaction, laryngeal edema, seizure, trembling, convulsions, unconsciousness, shock, death, and other unexpected adverse reactions) was rare (0.0431%), whereas the mild ADRs were uncommon (0.2225%) and accounted for 83.76% of ADRs. Frequency of ADRs induced by iodinated contrast agents was related with examination site, sex, and type of patient settings (P<0.01) and was higher compared with gadolinium contrast agents (0.3676% vs 0.0504%, P<0.01). From 2014 to 2015, frequencies of total and moderate/severe ADRs induced by iodinated contrast agents decreased significantly (0.4410% vs 0.2947%, P<0.01; 0.0960% vs 0.0282%, P<0.01, respectively). Frequency of ADRs differed among different iodinated contrast and gadolinium contrast (P<0.05) agents. Iopromide’s ADR frequency in 2014 was significantly higher compared with iopamidol, ioversol, or iohexol (P<0.01). Frequency of moderate/severe ADRs induced by iodixanol was 4.1–5.4 times that of iohexol, iopromide, or iopamidol. Rash was the predominant ADR subtype (84.39%) and occurred more frequently with iodixanol compared with iohexol, iopamidol, or ioversol (P<0.01). Overall, 21.97% of ADR cases had allergy history or atopy traits, and these cases experienced ADRs earlier than the negative ones (17.19 min vs 85.34 min, P<0.01). The mean time to onset of ADRs was increased in patients receiving iodixanol compared with other iodinated contrast agents (323.77 min vs 42.36 min, P<0.01). Overall, 37.26% of ADRs occurred within 5 min and 84.08% of ADRs occurred within 30 min. Efficient quality improvement in decreasing ADRs induced by radiocontrast agents has been achieved by multidisciplinary collaboration.

Effect of prolonged-released oxycodone/naloxone in postoperative pain management after total knee replacement: a nonrandomized prospective trial

PurposeThe purpose of this study was to examine the effect of postoperative prolonged release oxycodone/naloxone (OXN) in comparison to other opioids (control group) on the early postoperative rehabilitation outcome after total knee replacement. MethodsIn a prospective, noninterventional, nonrandomized clinical trial, 80 patients were assigned to either the OXN group or a control group. Postoperative outcome and pain level at days 3, 6, 21, 35, and 6months were evaluated using the Bowel Function Index, Brief Pain Inventory Short Form questionnaire, the Hospital for Special Surgery score, modified Larson score, and the ability to attend physiotherapy. Medications were recorded and safety analysis was done. Both groups were compared using an analysis of covariance. ResultsThere were no significant differences between both groups regarding pain levels. OXN group patients reported better bowel function (median values of 0.0 for the OXN group and 20.0 for the control group). No effect of treatment group (P=.19) and no treatment-by-visit interaction on Hospital for Special Surgery final score (P=.67) could be detected, but Larson function score in the early postoperative phase was significantly better in the OXN group (P=.018). The proportion of OXN group patients who were able to attend without any restriction was 58.1%. The proportions of patients in the OXN group and control group who experienced mild or moderate adverse drug reactions were 23.3% and 37.8%, respectively. There were no serious adverse drug reactions. ConclusionIn conclusion, OXN provides an effective analgesia and offers several benefits such as higher ability to participate in physiotherapy and better functional results. Incidence and severity of constipation can be reduced by using prolonged-released OXN as compared with other opioids.

Relationship between clozapine dose, serum concentration, and clinical outcome in children and adolescents in clinical practice.

Information on dose- and concentration-related clinical effects of clozapine treatment in children and adolescents is scarce. This study aimed to examine the relationship between dose, serum concentration, and clinical outcome as well as the influencing factors thereof in paediatric patients treated with clozapine. Data from a routine Therapeutic Drug Monitoring (TDM) service between 2004 and 2014 were studied in 68 patients, aged 11-18years. Severity of illness, therapeutic effectiveness and adverse drug reactions (ADRs) were assessed by standardized means. A relationship between the daily dose (mean 319mg, 4.9mg/kg) and serum concentration (mean 387ng/ml) of clozapine was found with the variation in dose explaining 30% of the variability in clozapine serum concentrations. Also gender contributed to the variability, however, no influence of age or concomitant medications was detected. Furthermore, a significant association was found between clozapine serum concentration and the occurrence of ADRs. Patients without ADRs had a lower mean serum concentration than those with mild (261.4 vs 407.3ng/ml, P=0.018) and moderate ADRs (261.4 vs 416.3ng/ml, P=0.028). As clozapine was estimated to be effective in lower blood concentrations, guidance on a possibly lower therapeutic range of clozapine serum levels in paediatric patients is provided. With ADRs increasing under higher concentrations, TDM is strongly recommended in paediatric clozapine therapy for individualized dosing. Dose adjustment in females also might be reasonable according to gender-related differences in serum concentrations. However, regarding the limitations of this study results should be validated in larger studies with more standardized designs.

What influences persistence with medicines? A multinational discrete choice experiment of 2549 patients.

The aim was to examine patients' stated preferences to persist with medicines and to explore the influence of psychosocial and sociocognitive factors. Community-dwelling, hypertensive patients recruited from nine European countries were invited to complete a discrete choice experiment (DCE) with attributes for treatment benefits, mild yet common adverse drug reactions (ADRs), rare but potentially life-threatening ADRs and dosing frequency. Patients responded to the binary choice of which medicine would they be most likely to continue taking. Data were analyzed using a random effects logit model. Two thousand five hundred and forty-nine patients from Austria (n=321), Belgium (n=175), England (n=315), Germany (n=266), Greece (n=288), Hungary (n=322), the Netherlands (n=231), Poland (n=312) and Wales (n=319) completed the DCE. All attributes significantly influenced patients' stated preference to persist with medications (P < 0.05). Patients were willing to accept decreases in treatment benefits of 50.6 percentage points (95% CI 46.1, 57.9) for a very rare (as opposed to rare) risk of severe ADR, 28.3 percentage points (95% CI 25.2, 33.1) for a once daily instead of twice daily dosing and 0.74 percentage points (95% CI 0.67, 0.85) for a 1% point reduction in mild ADRs. Models accounting for psychosocial and sociocognitive characteristics were significantly different from the base case. Patients' intention to persist with treatment was associated with their willingness to trade potential benefits, harms and dosing frequency. Psychosocial and sociocognitive factors influenced the extent of trading. The utility model may have value in assessing patients' likelihood of persisting with medicines and to tailor treatment to maximize persistence.

Frequency, types, severity, preventability and costs of Adverse Drug Reactions at a tertiary care hospital

IntroductionHospital-based adverse drug reaction (ADR) monitoring and reporting studies are conducted to identify, quantify and minimize such risks associated with the use of drugs particularly on long-term basis. Kashmir province of Indian state of Jammu and Kashmir presents a huge market for medicines that runs into millions of rupees. Yet there was no provision to monitor these drugs for their adverse effects prior to this study in any of the leading hospitals of the province. As such the present study, which was first of its kind in the valley, was undertaken to assess the frequency, preventability, category, severity, causality, extension of hospital stay and costs of drug-related adverse effects in Kashmiri patients at a Srinagar-based tertiary care hospital. MethodsA prospective, observational, cohort study on 5482 patients was undertaken over a 270day period. Adult patients admitted in Internal Medicine in-patient department (IPD), presenting to the Internal Medicine out-patient department (OPD) and those visiting the Accident and Emergency Department of the study hospital were included in the study. Patients belonging to both the sexes were screened and monitored on a daily basis for the occurrence of any ADRs. Definition of ADR given by the World Health Organization (WHO) was used and causality of suspected ADRs was determined using Naranjo's algorithm whereas severity was assessed using modified Hartwig's scale and preventability was determined using Hallas methodology. Costs of ADRs and extension in hospital stay were calculated as per Lagnaou and Nicholas methodology respectively. ResultsADRs accounted for 6.23% of adult Kashmiri patients visiting the tertiary care hospital under study, either for referral or hospitalization, with the majority (81.57%) of these ADRs being preventable; 23.68% of patients had mild ADRs, 69.29% had ADRs of moderate severity, and 7.01% had severe ADRs. Four classes of drugs most frequently suspected in admissions due to ADRs were anti-infective agents (40.92%) including anti-tubercular drugs (13.15%), steroids (14.03%), anti-coagulants (8.77%), and NSAIDs (7.89%). Increasing age and female gender were identified as risk factors. The total cost to the hospital due to hospitalization of patients presenting with ADRs over the 9-month period in the internal medicine IPD was found to be USD 22469 at the time of this study. Discussion/conclusionThe present work is the maiden pharmacovigilance study conducted on Kashmiri patients, especially at a tertiary care teaching hospital that has provided baseline information about the prevalence of ADRs and their distribution among different age groups, genders, organ systems affected, and therapeutic classes of medicines. The data collected will be useful for long term and more extensive ADR monitoring on Kashmiri patients and will also be useful in framing policies toward the rational use of drugs. This study led to the establishment of a full-fledged pharmacovigilance centre and initiation of pharmaceutical care services in the study hospital.

IncobotulinumtoxinA use in aesthetic indications in daily practice: a European multicenter, noninterventional, retrospective study.

PurposeTo characterize utilization patterns and treatment satisfaction with incobotulinumtoxinA for aesthetic indications and assess adherence to the Summary of Product Characteristics.Patients and methodsData were collected retrospectively from physicians in Germany, France, and the UK regarding patients (n=638) treated with incobotulinumtoxinA for aesthetic indications. Data on indication, treatment interval, dose injected, physician and patient satisfaction, and adverse drug reactions were recorded according to routine daily practice.ResultsMost patients (76.0%) received incobotulinumtoxinA for glabellar frown lines (GFL) and were given doses of ≤20 U. The majority of treatment intervals were 5 months or longer. Overall, 64.1% of patients were treated for off-label indications, sometimes in combination with treatment for GFL. The most frequently treated off-label indications were horizontal forehead lines (38.6%) and/or crow’s feet (CF; 31.7%); for CF, >95% of injected doses were ≤24 U. In Germany, a smaller proportion of patients were given incobotulinumtoxinA treatment for CF (27.6%), compared with France (40.4%) and the UK (33.2%), although country-specific differences were less prominent when treatment cycle data for CF were examined. Treatment satisfaction among physicians and patients (overall, and for GFL specifically) was very high, with excellent tolerability and only one mild adverse drug reaction reported.ConclusionIn daily practice, incobotulinumtoxinA is mainly used for GFL; however, its use for CF and horizontal forehead lines (often in combination with GFL) is relatively common. Treatment satisfaction across aesthetic indications is high, and incobotulinumtoxinA is well tolerated, with time intervals of 5 months or longer between injections in the majority of cases. When considering factors such as dose and treatment interval, adherence to the Summary of Product Characteristics when treating GFL in daily practice is good. These results support previous reports that incobotulinumtoxinA is an effective treatment for GFL, with an excellent safety profile. Furthermore, incobotulinumtoxinA may display efficacy and tolerability in other indications.

A randomised, parallel-group comparison study of diquafosol ophthalmic solution in patients with dry eye in China and Singapore

AimsTo compare the efficacy and safety of 3% diquafosol ophthalmic solution with those of 0.1% sodium hyaluronate ophthalmic solution in patients with dry eye in China and Singapore.MethodsA total of...

Clinical observation of the adverse drug reactions caused by non-ionic iodinated contrast media: results from 109,255 cases who underwent enhanced CT examination in Chongqing, China.

To analyse the pattern and factors that influence the incidence of adverse drug reactions (ADRs) induced by non-ionic iodinated contrast media and to evaluate their safety profiles. Data from 109,255 cases who underwent enhanced CT examination from 1 January 2008 to 31 August 2013 were analysed. ADRs were classified according to the criteria issued by the American College of Radiology and the Chinese Society of Radiology. A total of 375 (0.34%) patients had ADRs, including 281 mild (0.26%); 80 moderate (0.07%); and 14 severe (0.01%) ADRs; no death was found. 302 (80.53%) of the ADRs occurred within 15 min after examination. Patients aged 40-49 years (204 cases, 0.43%; p < 0.01) or who underwent coronary CT angiography (93 cases, 0.61%; p < 0.01) were at a higher risk of ADRs. Female patients (180 cases, 0.40%; p < 0.01) or outpatients had significantly higher incidence rates of ADRs. The symptoms and signs of most of the ADRs were resolved spontaneously within 24 h after appropriate treatment without sequelae. The occurrence of ADRs is caused by the combined effects of multiple factors. The ADRs induced by non-ionic iodinated contrast media are mainly mild ones, while moderate or severe ADRs are relatively rare, suggesting that enhanced CT examination with non-ionic iodinated contrast media is highly safe, and severe adverse events will seldom occur under appropriate care. The study included 109,255 patients enrolled in various types of enhanced CT examinations, which could reflect ADR conditions and regulations in Chinese population accurately and reliably.

Perception of Nigerian medical students on adverse drug reaction reporting.

Spontaneous reporting (SPR) and intensive monitoring are the conventional systems used for detecting, recording, and reporting adverse drug reactions (ADRs). Using spontaneous reporting a lot of successes has been made as existing ADRs were identified and new ones prevented through this methods. The aim of this appraisal was to evaluate the knowledge, attitude, and the practice of medical students with regards to ADRs reporting and to see if differences exist between the level of study and genders. The questionnaire was adopted, modified, and validated from previous studies. It comprised of 25 questions. It was administered year-IV and V medical students of Bayero University Kano, Nigeria. The data collected were coded and analyzed using the Statistical Package for the Social Sciences (SPSS) version 20, currently known as IBM SPSS Statistics. The response rate was 74%. Among the 108 participants, 80% got the definition of ADRs correct; 63% of them knew the precise functions of pharmacovigilance (PV). In addition, 82% strongly agreed that ADR reporting is health care workers responsibility; 82% also said PV should be taught in detail. Meanwhile, 99% have noticed patient experiencing ADRs; 67% said even mild ADRs should be reported. The outcome of this study showed good knowledge and attitude with respect to ADRs and PV among the medical students surveyed. Unfortunately, the practice of medical students was found to be unsatisfactory. There is a need to upgrade the students teaching the curriculum with respect to ADRs monitoring.

Pattern of Adverse Drug Reactions in Children Attending the Department of Pediatrics in a Tertiary Care Center: A Prospective Observational Study.

AIMTo study the pattern of various adverse drug reactions (ADRs) occurring in children attending the Department of Pediatrics, SMGS Hospital, Jammu over 1 year.SUBJECTS AND METHODSThis was a prospective study, with study population of patients attending Department of Pediatrics over a period of 1 year. A structured format was used to enroll the participants. A pilot study was conducted to test the suitability of the format and feasibility of the study. The study was carried out to review various pattern of ADRs by using the Naranjo probability scale, and severity was assessed by using the Hartwig severity scale. ADRs were classified according to the classification used by the Adverse Drug Reaction Monitoring Center, Central Drugs Standard Control Organization, New Delhi, India.RESULTSIn the present study, 104 patients were found to have developed acute drug reactions. Among these, 83.6% were type B, 14.42% type A, and 1.92% were type U. Furthermore, 25.96% ADRs were due to anticonvulsants, followed by antibiotics (22.11%), antipyretics (11.53%), vaccination (8.65%), steroids (6.73%), decongestants (5.67%), snake antivenom and antiemetics (3.84%), and fluids, insulin, and antacids (1.92%). The patients’ dermatological system was involved in 67.30%, followed by the central nervous system (CNS) in 11.53% patients. Renal system was involved in 6.73% patients. Cardiac, musculoskeletal, metabolic, and other systems were involved in 4.80%, 3.84%, 2.88%, and 0.96%, respectively. According to the Hartwig severity scale of ADRs, 64.4% patients had moderate ADRs, 29.8% patients had severe ADRs, and 5.76% had mild ADRs. In the present study, 64.4% patients expressed moderate severity, whereas 29.8% expressed high severity and 5.76% expressed mild ADRs.CONCLUSIONADRs were seen in 71% of the patients between 1 and 5 years of age, 26% in the age group of 5–10 years, and 3% were more than 10 years old. Anticonvulsants (25.96%) and antibiotics (22.11%) were responsible for majority of ADRs. Rash (55.76%) was the most common presentation of ADR. Owing to the high number of ADRs, the present study points to the need for rigid adverse drug monitoring among pediatric patients to ensure the safety of drug therapy.

Effectiveness and safety of ferric carboxymaltose treatment in children and adolescents with inflammatory bowel disease and other gastrointestinal diseases.

BackgroundThe treatment of iron deficiency anemia in children with inflammatory bowel disease is a particular challenge and often insufficient. Absorption of orally given iron may be impaired by intestinal inflammation and treatment with oral iron may aggravate intestinal inflammation. This retrospective study is the first to describe the use of intravenous ferric carboxymaltose (FCM) in the pediatric setting.MethodsAll subjects who had received at least one dose of FCM intravenously in the observation period were included in this analysis with data collected for up to 3 months post last FCM dose.ResultsIn total, 72 children between 0 and 18 years with underlying gastrointestinal disorders had been treated for concomitant iron deficiency anemia. The majority of patients had Crohn’s disease (40.3%) or ulcerative colitis (30.5%). The total number of FCM administrations was 147, the mean number per patient was 2.0 and the mean cumulative dose 821 mg iron (median single dose: 500 mg; max. 1000 mg). Post administration of FCM, correction of iron deficiency anemia was observed with improved mean hemoglobin levels from 9.5 g/dL at baseline to 11.9 g/dL within 5–12 weeks. Decreases in white cell count, platelets and C-reactive protein were observed post FCM, potentially suggesting reduced inflammation with iron repletion. Three subjects reported mild adverse drug reactions related to FCM; two of these were considered to be potentially related to long duration of administration and to high volume of saline solution for dilution. As such, the method of administration was amended to have a maximum infusion time of 60 minutes and dilution with less than or equal to 100 mL saline solution.ConclusionsOverall FCM was well tolerated in this pediatric population and appeared to be effective in correcting iron deficiency anemia. We cannot exclude that the correction of iron deficiency anaemia is in some part due to the treatment of the underlying disease and not related to the iron supplementation only.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-230X-14-184) contains supplementary material, which is available to authorized users.

Hyperactivity, concentration difficulties and impulsiveness improve during seven weeks’ treatment with valerian root and lemon balm extracts in primary school children

BackgroundValerian root and lemon balm extracts have previously shown efficacy and excellent tolerability in children<12 years suffering from restlessness and insomnia. We now examined whether treatment with a fixed combination of both may also improve concentration, hyperactivity and impulsiveness. Methods169 primary school children suffering from hyperactivity and concentration difficulties but not meeting ADHD criteria were treated in an observational study by 27 office based pediatricians with a recommended daily dose of 640mg valerian root extract WS® 1014 and 320mg lemon balm extract WS® 1303 (Sandrin®), and evaluated by pediatricians and parents using standardized questionnaires at baseline, weeks 2 and 7. ResultsThe fraction of children having strong/very strong symptoms of poor ability to focus decreased from 75% to 14%, hyperactivity from 61% to 13%, and impulsiveness from 59% to 22%. Parent rated social behavior, sleep and symptom burden showed highly significant improvements. Only in two children mild transient adverse drug reactions were observed. ConclusionIn primary school children with restlessness, concentration difficulties and impulsiveness treatment with WS® 1014 and WS® 1303 (Sandrin®) provides a viable option in addition to counseling and education.

DD-012 Pharmacists and biosimilars: when “strong” actions means “strong” outcomes

BackgroundDespite new documents published from EMA and the Italian Drug Agency with the aim of clarifying the quality assurance, efficacy and safety of biosimilar drugs, the clinicians are still reluctant...

Consequences, measurement, and evaluation of the costs associated with adverse drug reactions among hospitalized patients in China

BackgroundAdverse drug reactions (ADRs) are a leading cause of morbidity in developed countries and represent a substantial burden on health-care resources. Many countries spent 15% to 20% of their hospital budgets to treat drug complications. However, few studies have measured the pharmacoeconomic effects of ADRs on hospitalized patients in China. The study estimates the costs of ADRs as identified from the spontaneous voluntary reports completed from healthcare professionals. To do so, we calculate these costs, determine the sum of Medicare payments and their proportion of total healthcare spending, and evaluate the incidence of ADRs, characteristics of hospitalized ADR patients, and outcomes of ADRs in China.MethodsThis retrospective survey studied patients who experienced ADRs during their hospitalization at a Chinese tertiary-care teaching hospital. The patients were divided into group A and group B according to general ADRs and serious ADRs in Provisions for Adverse Drug Reaction Monitoring and Reporting. The direct costs included treatment fees, inspection fees, laboratory fees, materials fees, bed charges, drug charges, nursing care, meals, and other expenses and the sunk-cost losses were calculated according to the hospital information system (HIS). Indirect costs of ADR treatment were calculated according to the human capital approach. The epidemiological characteristics of ADRs were evaluated.Results2739 were diagnosed with ADR during the study period, which translates to an ADR rate of 0.81%. The total socioeconomic loss from 2739 cases of ADR was estimated at ¥817401.69, consisting of direct costs of ¥603252.81 and indirect costs of ¥214148.88. On average, the costs per patient amounted to ¥196.10 in group A, ¥7032.29 in group B. The sum of medicare payment and proportion were ¥219061.13 (65.23%) and ¥105422.02 (39.42%) in group A and B. The ADR incidence in old-age patients was significantly higher than in other age groups (P < 0.0001). The most common drug class associated with ADRs represented antibiotics (957 patients, 34.94%).ConclusionsThe costs of especially severe ADRs could not be ignored, and in this hospital 0.13% of patients were diagnosed with ADRs associated with relatively higher direct costs than who suffered from mild ADRs, largely due to extended hospitalization.

AB0338 Evaluation of tocilizumab treatment continuation rate stratified by time of start of administration

BackgroundThe utility of treating rheumatoid arthritis (RA) with a biological agent is often evaluated by the treatment continuation rate combining safety and therapeutic effect. However, there are few reports from...

Chinese herb formulae for treatment of erectile dysfunction: a systematic review of randomised controlled clinical trials

To assess the beneficial and adverse effects of orally therapies of Chinese herb formulae (CHF) for erectile dysfunction (ED), four electronic databases were searched until 23 June 2012. Randomised clinical trials testing CHF or combined with Western medicine therapy (WMT) against placebo, another different CHF and WMT were included. Study selection, data extraction, assessing of bias risk and data analysis were conducted according to the Cochrane handbook. Twenty-one randomised controlled clinical trials (involving 2253 patients) were included, and the bias risks were not low. Funnel plots of comparing CHF to another CHF on the clinical comprehensive effectiveness were asymmetrical. The compositions of CHF used were greatly complex. The analyses showed that some CHF or combined with WMT had significant effects on cure rate, total clinical effective rates, IIEF-5 scores, erectile quality scores, erection angles of penis and recovery times of erection compared with the controls. Eight trials reported mild adverse drug reactions, mostly involving gastrointestinal symptoms. It was concluded that some therapies of CHF may be more effective than the controls for treatment of ED. However, because of the generally not low risks of bias, CHF are not recommended for ED. Further research that demonstrates their mechanisms of action and meaningful efficacies must be carried out by rigorously designed, randomised controlled trials.

Safety of benznidazole use in the treatment of chronic Chagas' disease

To assess the safety of benznidazole use in adult patients with chronic Chagas' disease. The Naranjo algorithm was applied to classify the causality of adverse drug reactions (ADRs). In total, 190 patients were treated with benznidazole over a period of 4-180 days (mean 58.90 ± 36.54 days) with a dose of 50-500 mg/day (221.33 ± 57.16 mg/day). Of the 190 patients treated, 93 had ADRs and 59 of these interrupted treatment. There was a higher incidence of ADRs among female and young adult patients. There was a higher incidence of ADRs during the first 30 days of treatment. Interruption of treatment was more frequent in women. Among the patients who interrupted treatment, 39 had mild ADRs, 19 had moderate ADRs and 1 had a severe ADR. There were no interruptions in treatment for 97 patients without ADRs. The survival curves indicated that the time until interruption of treatment in patients with moderate and severe ADRs was lower than in patients with mild or no ADRs. The most frequent disorders were in the skin (26.3%), gastrointestinal system (9.5%) and nervous system (5.3%). The Naranjo algorithm was a useful tool to reduce the underreporting of ADRs. Events were common, but were associated with low morbidity and were reversible upon discontinuation of drug treatment. Moreover, there were no fatal events; therefore, benznidazole treatment was considered safe.

Primary Prophylaxis for Pneumocystis jirovecii Pneumonia in Patients with Connective Tissue Diseases

The aim of our study was to examine the primary prophylactic effect of sulfamethoxazole/trimethoprim single strength (SMZ/TM SS) against Pneumocystis jirovecii pneumonia (PCP) in connective tissue disease (CTD) patients with immune dysfunction induced by the long-term use of prednisolone. Prevalence of adverse drug reactions (ADRs) to sulfonamide in these patients was the secondary outcome. This was a retrospective cohort study. Medical records of CTD patients who were treated with prednisolone ≥20 mg per day or equivalent doses of corticosteroid for more than 2 weeks and were followed for at least 12 weeks after receiving this dosage of corticosteroids at the Rheumatology clinic of Ramathibodi Hospital between October 2006 and September 2007 were reviewed. Information regarding clinical status, laboratory features, and clinical course of the enrolled subjects was recorded. There were 138 episodes of PCP risk in 132 CTD patients; 59 episodes received SMZ/TM SS, while 79 episodes did not. All 6 PCP cases developed in patients without prophylaxis with an overall incidence of 4.3%. The incidence of PCP between the 2 groups was significantly different (P = 0.038). Absolute risk reduction and relative risk reduction were 7.3% and 100%, respectively. All ADR developed in 5 systemic lupus erythematosus patients (8.5%): 4 had drug rashes and 1 had mild hepatitis. There was no correlation between the use of, or allergic reactions to, SMZ/TM and lupus flare. Sulfamethoxazole/trimethoprim single strength can be used effectively as a primary prophylaxis against PCP in high-risk CTD patients. Only mild ADR developed at this dosage. Further evaluations in larger groups of CTD patients are warranted.

A multicenter comparison of the safety of oral versus intravenous acetylcysteine for treatment of acetaminophen overdose

Oral and intravenous (IV) N-acetylcysteine (NAC) are used for the treatment of acetaminophen poisoning. The objective of this multicenter study was to compare the safety of these two routes of administration. Methods. We conducted a multicenter chart review of all patients treated with NAC for acetaminophen poisoning. The primary safety outcome was the percentage of patients with NAC-related adverse events. Results. A total of 503 subjects were included in the safety analysis (306 IV-only, 145 oral-only, and 52 both routes). There were no serious adverse events related to NAC for either route. Nausea and vomiting were the most common related adverse events and were more common with oral treatment (23 vs. 9%). Anaphylactoid reactions were more common with IV administration (6 vs. 2%). Conclusions. IV and oral NAC are generally mild adverse drug reactions.

Clinical evaluation of trimetazidine in patients with coronary heart disease and chronic heart failure

Objective To evaluate the clinical therapeutic effects and safety of trimetazidine(TMZ) in patients with coronary heart disease(CHD)and chronic heart failure(CHF). Methods 114 patients with CHD and CHF were randomly divided into treatment group 50 cases and the control group 64 cases. The control group was given conventional anti-heart failure therapy; The treatment group were given 20 mg trimetazidine (3 times per day) on the basis of conventional therapy of the control group. The course of treatment all were 6 months in 2Groups. Clinical efficacy, left ventricular end-diastolic diameter (LVEDD), left ventricular ejection fraction (LVEF) ,serum B-type natriuretic peptide(BNP) ,6 min walk test,and adverse drug reactions were observed before and 6 months after therapy. Results After treatment for 6 months, the total effective rate of the treatment group was significantly higher than that of the control group( P ＜ 0.05 ); The LVEDd, LVEF, 6-minute walking distance and the level of BNP in the treatment group improved significantly better than that of the control group ( P ＜ 0.05 ); the treatment group occurred few and mild adverse drug reactions. Conclusion Long-term use trimetazidine treating in patients with with CHD and CHF can improve cardiac function, safe and effective. Key words: Coronary heart disease; Chronic heart failure; Trimetazidine