Prospective observational study of adverse drug reactions to diclofenac in children

AIM

The aim of this study was to investigate the type of common (occurring in >1% of patients) adverse reactions caused by diclofenac when given to children for acute pain.

METHODS

A prospective observational study was undertaken on paediatric surgical patents aged ≤12 years at Great Ormond Street and University College London Hospitals. All adverse events were recorded, and causality assessment used to judge the likelihood of them being due to diclofenac. Prospective recruitment meant not all patients were prescribed diclofenac, allowing an analysis of utilization. Causality of all serious adverse events was reviewed by an expert panel.

RESULTS

Children prescribed diclofenac were significantly older, and stayed in hospital for shorter periods than those who were not. Diclofenac was not avoided in asthmatic patients. Data on 380 children showed they suffer similar types of nonserious adverse reactions to adults. The incidence (95% confidence interval) of rash was 0.8% (0.016, 2.3); minor central nervous system disturbance 0.5% (0.06, 1.9); rectal irritation with suppositories 0.3% (0.009, 1.9); and diarrhoea 0.3% (0.007, 1.5). No serious adverse event was judged to be caused by diclofenac, meaning the incidence of serious adverse reactions to diclofenac in children is <0.8%.

CONCLUSION

Children given diclofenac for acute pain appeared to suffer similar types of adverse reactions to adults; the incidence of serious adverse reaction is <0.8%.     

Prevalence and characteristics of adverse drug reactions at admission to hospital: a prospective observational study

AimsAdverse drug reactions (ADRs) contribute to poorer patient outcomes and additional burden to the healthcare system. However, data on the true burden, relevant types and drugs causing ADRs are lacking. The aim of this study was to determine the prevalence of ADR‐related hospitalization in the general adult population in Singapore and to investigate their characteristics.MethodsWe prospectively recruited 1000 adult patients with unplanned admission to a large tertiary‐care hospital. Two independent reviewers evaluated all suspected ADRs for causality, type, severity and avoidability. The prevalence of ADR‐related hospitalization was calculated based on ‘definite’ and ‘probable’ ADRs. Logistic regression was used to evaluate predictors for having an ADR at admission.ResultsThe prevalence of all ADRs at admission was 12.4% (95% CI: 10.5–14.6%) and ADRs causing admission was 8.1% (95% CI: 6.5–10.0%). The most common ADRs were gastrointestinal‐related. The most common drug category causing ADRs were cardiovascular drugs. Patients with ADRs had a longer length of stay than those who did not (median 4 vs. 3 days, P = 1.70 × 10⁻³). About 30% of ADRs at admission were caused by at least one drug with a clinical annotation in the Pharmacogenomics KnowledgeBase (PharmGKB), suggesting that some of these ADRs may have been predicted by pharmacogenetic testing.ConclusionsWe have quantified the burden and characteristics of clinically impactful ADRs in the Singaporean general adult population. Our results will provide vital information for efforts in reducing ADRs through targeted vigilance, patient education and pharmacogenomics in Singapore.     

A prospective study of adverse drug reactions to anti tuberculous drugs

A study of adverse drug reactions to anti tuberculosis therapy in the medical outpatients showed that the overall incidence of adverse reactions was 26 per cent. Side-effects to isoniazid and rifampicin were mainly hepatitis, nausea, vomiting. Ethambutol caused reversible optic neuritis in 7.9 per cent cases. Most adverse drug reactions occurred during the first 3 months of treatment.     

Mortality from adverse drug reactions in adult medical inpatients at four hospitals in South Africa: a cross-sectional survey

Aims

Fatal adverse drug reactions (ADRs) are important causes of death, but data from resource-limited settings are scarce. We determined the proportion of deaths in South African medical inpatients attributable to ADRs, and their preventability, stratified by human immunodeficiency virus (HIV) status.

Methods

We reviewed the folders of all patients who died over a 30 day period in the medical wards of four hospitals. We identified ADR-related deaths (deaths where an ADR was ‘possible’, ‘probable’ or ‘certain’ using WHO-UMC criteria and where the ADR contributed to death). We determined preventability according to previously published criteria.

Results

ADRs contributed to the death of 2.9% of medical admissions and 56 of 357 deaths (16%) were ADR-related. Tenofovir, rifampicin and co-trimoxazole were the most commonly implicated drugs. 43% of ADRs were considered preventable. The following factors were independently associated with ADR-related death: HIV-infected patients on antiretroviral therapy (adjusted odds ratio (aOR) 4.4, 95% confidence interval (CI) 1.6, 12), exposure to more than seven drugs (aOR 2.5, 95% CI 1.3, 4.8) and increasing comorbidity score (aOR 1.3, 95% CI 1.1, 1.7).

Conclusions

In our setting, where HIV and tuberculosis are highly prevalent, fatal in-hospital ADRs were more common than reported in high income settings. Most deaths were attributed to drugs used in managing HIV and tuberculosis. A large proportion of the ADRs were preventable, highlighting the need to strengthen systems for health care worker training and support.     

A prospective study of adverse drug reactions as a cause of admission to a paediatric hospital

1 A total of 512 consecutive paediatric hospital admissions of children 2 years old or less were evaluated to assess the extent and pattern of admission caused by suspected adverse drug reactions (ADRs). The proportion of suspected ADRs related to hospital admissions was 4.3%.
2 The organ-systems most commonly implicated were the central nervous system (40.5%), digestive system (16.7%), and skin and appendages (14.3%). Together, they accounted for 71.5% of admissions attributed to ADRs. The most common clinical manifestations inducing admission were convulsions (4 cases), dizziness (4), vomiting (3), and tremor, fever, itching and apnoea (2 cases each).
3 The four classes of drugs most frequently suspected in admissions due to ADRs were respiratory drugs (35%), anti-infective agents (25%), drugs active on the central nervous system (15%) and drugs used in dermatology (10%). The most common drugs related to ADRs were a combination of chlorpheniramine, diphenhydramine, phenylephrine, guaiphenesin and salicylic acid (4 cases), followed by fenoterol, adrenaline, paracetamol, DTP vaccine and antipolio vaccine (2 cases each).
4 There were no significant differences between children older and younger than 1 year (odds ratio 0.89; 95% CI 0.37–2.17) or between the sexes as regards hospital admittance due to suspected ADRs (odds ratio 1.94; 95% CI 0.72–5.42).
5 The results of this kind of study may be influenced by patterns of drug utilization. Nevertheless, the lack of specific studies of drug effects in young children makes it desirable to carry out pharmacoepidemiological studies in this age group.     

A prospective study of adverse drug reactions in hospitalized children

AIMS: There are few publications of adverse drug reactions (ADRs) among paediatric patients, though ADR incidence is usually stated to be higher during the first year of life and in male patients. We have carried out a prospective study to assess the extent, pattern and profile risk for ADRs in hospitalized patients between 1 and 24 months of age. METHODS: An intensive events monitoring scheme was used. A total of 512 successive admissions to two medical paediatric wards (47 beds) were analysed. The hospital records were screened daily during two periods (summer, 105 days and winter, 99 days), and adverse clinical events observed were recorded. RESULTS: A total of 282 events were detected; of these, 112 were considered to be manifestations of ADRs. The cumulative incidence was 16.6%, no differences being observed between periods. Although there were no differences between patients under and over 12 months of age, risk was found to be significantly higher among girls compared with boys (RR=1.66, 95% CI 1.03-2.52). The gastro-intestinal system was most frequently affected. The therapeutic group most commonly implicated was anti-infective drugs and vaccines (41.5%). The ADRs were mild or moderate in over 90% of cases. A consistent relationship was noted between the number of drugs administered and the incidence of ADRs. CONCLUSIONS: Hospitalized patients exhibited an ADR risk profile that included female sex and the number of drugs administered. No particular age predisposition was observed. The most commonly prescribed drugs are those most often implicated in ADRs in paediatric patients.     

Risk of falls after withdrawal of fall-risk-increasing drugs: a prospective cohort study

AIMS: Falling in older persons is a frequent and serious clinical problem. Several drugs have been associated with increased fall risk. The objective of this study was to identify differences in the incidence of falls after withdrawal (discontinuation or dose reduction) of fall-risk-increasing drugs as a single intervention in older fallers. METHODS: In a prospective cohort study of geriatric outpatients, we included 139 patients presenting with one or more falls during the previous year. Fall-risk-increasing drugs were withdrawn, if possible. The incidence of falls was assessed within 2 months of follow-up after a set 1 month period of drug withdrawal. Multivariate adjustment for potential confounders was performed with a Cox proportional hazards model. RESULTS: In 67 patients, we were able to discontinue a fall-risk-increasing drug, and in eight patients to reduce its dose. The total number of fall incidents during follow-up was significantly lower in these 75 patients, than in those who continued treatment (mean number of falls: 0.3 vs. 3.6; P value 0.025). The hazard ratio of a fall during follow-up was 0.48 (95% confidence interval (CI) 0.23, 0.99) for overall drug withdrawal, 0.35 (95% CI 0.15, 0.82) for cardiovascular drug withdrawal and 0.56 (95% CI 0.23, 1.38) for psychotropic drug withdrawal, after adjustment for age, gender, use of fall-risk-increasing drugs, baseline falls frequency, comorbidity, Mini-Mental State Examination score, and reason for referral. CONCLUSIONS: Withdrawal of fall-risk-increasing drugs appears to be effective as a single intervention for falls prevention in a geriatric outpatient setting. The effect was greatest for withdrawal of cardiovascular drugs.     

Frequency of adverse drug reactions in children: a prospective study

AIMS: To assess the frequency of adverse drug reactions (ADRs) in children in France. METHODS: In a prospective study over a period of 1 week, we evaluated the incidence of ADRs (1) as a cause of admission to a regional children's hospital; (2) occurring during hospitalization in a regional children's hospital; and (3) as a cause of consultation with private paediatricians. RESULTS: Four out of 260 children were admitted to the regional children's hospital for ADRs (1.53% [0.42, 3.89]) and six developed ADRs during hospitalization (2.64% [0.97, 5.66]), 4/428 attended the Accident and Emergency Department for ADRs (0.93% [0.25, 2.37]) and 8/1192 consulted a private paediatrician for ADRs (0.67% [0.29, 1.31]). CONCLUSIONS: Our results are in agreement with the incidence of ADRs in children found in others countries.     

1例胸痛患者使用碘造影剂后出现严重药物不良反应的案例分析

目的分析碘造影剂引发过敏反应与不适,为临床防治提供参考。方法患者因胸闷胸痛十余天使用碘造影剂进行冠状动脉造影后出现呼吸不畅,颜面部水肿等严重过敏反应,分析该表现与用药的相关性。结果该临床表现很可能为碘造影剂引发严重药物不良反应。结论碘造影剂过敏症状在临床中虽然少见,但在临床用药中应注意个体差异。早期预防和正确处理是减少严重药物不良反应的关键。     

Tolerability and safety of the intravenous immunoglobulin Octagam: a 10-year prospective observational study

PURPOSE: Following the approval of Octagam in 1995, an open prospective observational cohort study has been initiated to observe the tolerability of the intravenous immunoglobulin Octagam. This study aimed to evaluate the long-term safety profile of Octagam in daily use in the treatment of various primary (PID) and secondary (SID) immunodeficiencies and autoimmune diseases (AID). METHODS: Within a time period of 10 years, data were collected in 310 study sites. The treating physicians documented patient characteristics, treatment parameters and the occurrence of an adverse drug reaction (ADR) by using detailed case record forms (CRF). RESULTS: A total of 6357 patients of all ages received 92 958 infusions of Octagam. ADR occurred in 4.2% of the patients and in 0.35% of all infusions. Most of them (94.8%) were classified as nonserious, the majority (90.2%) were of mild or moderate intensity. The ADR frequency differed slightly between the indication groups, for example in PID patients ADR occurred in 8.3% of patients and 0.5% of infusions, in SID patients in 5.0% of patients and 0.62% of infusions. Rigors were reported most frequently, followed by fever, headache, nausea and flush. The ADR symptoms differed between the indication groups, rigors were predominantly described in SID patients, headache in PID and AID patients including idiopathic thrombocytopenic purpura (ITP). A relation between the ADR frequency and elevated infusion rates or high dosages was not detected. CONCLUSIONS: This unique 10-year observational study demonstrates that Octagam is well tolerated in routine clinical use with an overall ADR frequency of 0.35%.     

The changing pattern of adherence to antiretroviral therapy assessed at two time points, 12 months apart,in a cohort of HIV-infected children

Objective: In a previous multicentre study including 129 HIV-infected children, non-adherence to antiretroviral therapy was detected in 16% of patients and was mainly related to psychosocial rather than clinical or demographic features. The aim of this study was to explore the evolving pattern of adherence and its determinants in the same population of children. Methods: An observational, cross-sectional multicentre study was done through a structured interview to the caregivers of HIV-infected children. Adherence was quantitatively evaluated through a 4-day recall adherence instrument. Results: One hundred and twelve children were included. Nineteen (17%) omitted more than 5% of doses in the preceding 4 days and were considered non-adherent. Of these, 10 had been found non-adherent and nine adherent in the previous study. In parallel, nine of the originally non-adherent children had become adherent. Adherence rates were higher in children receiving therapy from foster parents than in children receiving therapy from biological parents. Dose number significantly correlated with adherence. Conclusions: Adherence to antiretroviral therapy is a dynamic phenomenon that changes with time. The evolving pattern shows a fairly constant distribution of adherence because a similar number of patients gain and lose adherence. Psychosocial rather than clinical features are major determinants of adherence.     

老年肺结核患者抗结核病药的不良反应分析

目的分析老年肺结核病患者抗结核病药的药品不良反应(ADR)发生情况,为临床合理用药提供参考。方法采用《药品不良反应文献源数据库》,检索60 a以上肺结核患者使用抗结核病药的ADR病例报告。以WHO-ART术语进行分类分析。结果73例病例(男56例,女17例),年龄(66.35±6.80)a,其中死亡6例。引起ADR的抗结核病药中,以利福平最多,占37%,其次是乙胺丁醇(19%)、异烟肼(13%)、吡嗪酰胺(9%)、链霉素(9%)、对氨基水杨酸钠(5%)。抗结核病药的ADR主要有皮肤及其附件损害(24%)、全身性损害(14%)、泌尿系统损害(9%)、血液系统损害(8%)、视觉损害(8%)、中枢及外周神经系统损害(8%)。结论利福平、乙胺丁醇、异烟肼、吡嗪酰胺、链霉素、对氨基水杨酸钠是引起老年肺结核患者ADR的主要药物。抗结核病药ADR主要表现有皮肤及其附件损害、全身性损害、泌尿系统损害、血液系统损害、视觉损害、中枢及外周神经系统损害。     

Variation of benzbromarone elimination in man — a population study

Summary The plasma benzbromarone concentration-time profile in a healthy subject who retained the compound much longer than other individuals is described. The data suggested that determination of the 24 h plasma concentration of the parent drug after a single oral dose of 100 mg benzbromarone would be an appropriate procedure to determine the elimination phenotype. Based on this procedure, 148 of 153 healthy individuals (97%) in a population study were found to eliminate benzbromarone rapidly. In one subject the 24 h benzbromarone plasma concentration was very similar to the that observed in the individual who had been more fully characterized. Four participants gave intermediate results. The data are compatible with a bimodal or trimodal distribution of different benzbromarone elimination phenotypes.     

Adherence to national guidelines for initiation of antiretroviral regimens in HIV patients: a Danish nationwide study

AIM

To determine the adherence to the national guidelines for start of highly active antiretroviral treatment (HAART) in HIV infected patients.

METHODS

We used a Danish nationwide cohort of HIV infected patients to calculate the fraction of patients who in the period 1997–2006 started HAART according to the guidelines from The Danish Society of Infectious Diseases. We used Kaplan-Meier tables to estimate time from fulfilling the criteria for start of HAART to initiation of the treatment. Cox regression and logistic regression was used to identify risk factors for delayed initiation of treatment and chance of being included in clinical trials.

RESULTS

The study included 3223 patients, 74% of whom initiated HAART in the study period. Ninety-four% fulfilled the criteria for start of HAART, with minor differences over calendar periods. Ninety-four% initiated a recommended regimen or were included in a clinical trial. Intravenous drug use predicted initiation of a non-recommended regimen and delay in start of HAART, while non-Caucasians were less likely to be included in clinical trials.

CONCLUSIONS

In a Western world setting, the adherence to national guidelines for start of HAART can be high. We suggest that simplicity of the guidelines, centralization of treatment and involvement of local clinicians in the development of guidelines are of major importance for high adherence to treatment guidelines.     

2010年5月—2012年5月北京市隆福医院抗生素不良反应的分析

目的 探讨北京市隆福医院2010年5月-2012年5月抗生素的使用及不良反应发生情况,为临床合理使用抗生素提供理论依据.方法 调查分析北京市隆福医院2010年5月-2012年5月病历635份,分析抗生素使用情况,总结抗生素使用过程中的不良反应及其临床危害.结果 抗生素使用率为46.61％ (296/635);预防性抗生素使用率为22.99％(146/635);联用抗生素病历89份,抗生素联用率为30.07％ (89/296).抗生素不良反应发生率为9.46％ (28/296),包括过敏反应、毒性反应、特异质反应和二重感染等.结论 熟练掌握抗生素的作用途径和可引起的不良反应,积极应对不良反应,有利于提高抗生素的合理使用水平,提高临床疗效,做到安全、合理用药.     

Adverse drug reaction profile of oseltamivir in Indian population: A prospective observational study

Objectives:

To analyze the pattern of adverse drug reactions (ADRs) of oseltamivir and its comparison with available data.

Materials and Methods:

Suspected or confirmed cases of H1N1 influenza A on therapeutic regimen and close contacts of cases H1N1 influenza A on prophylactic regimen of oseltamivir were included. Data were collected by personal interview after obtaining written informed consent. Causality, severity, and preventability assessments were done by using Naranjo''s scale, modified Hartwig and Siegel''s scale, and modified Schumock and Thornton Scale, respectively. Data were expressed in proportions. Frequency of ADRs in therapeutic and prophylactic groups were compared with phase III trial of oseltamivir by using Chi-square test.

Results:

Total 294 patients were interviewed. In prophylactic group, 107 of 257 (41.63%) and in therapeutic, group 23 of 37 (62.16%) developed ADRs. ADRs reported in therapeutic group was significantly (P = 0.029) higher as compared with prophylactic group. Frequently observed ADRs in both the groups were gastritis, nausea, vomiting, diarrhea weakness, sedation, loneliness, sadness, headache, and abdominal pain. Naranjo''s algorithm showed all ADRs in probable category in prophylactic group, 27.78% probable and 72.22% possible reactions in therapeutic group. Severity assessment showed 76% mild and 24% moderate reactions in therapeutic group, 89% mild and 11% moderate reactions in prophylactic group. Severity of ADRs was significantly higher in therapeutic group. Most of ADRs were in nonpreventable category, except gastritis, nausea and vomiting were in definitely preventable category.

Conclusion:

Oseltamivir is well tolerated in Indian population. Gastrointestinal side effects are most common and preventable.     

国内42年文献源抗糖尿病药物的不良反应分析

目的 :探讨我国抗糖尿病药物不良反应(ADR)发生的一般规律及有关特点 ,为临床用药提供资料。方法 :对个人呈报的ADR报告 ,参照国家卫生部ADR监测中心指定的原则列入分析文献源 ,ADR按世界卫生组织 (WHO)国际药品监测合作中心的药物ADR分类方法分类 ,我们收集了国内 4 2a文献源抗糖尿病药物的ADR资料 ,并进行文献计量学分析。结果 :抗糖尿病药物ADR的发生男性、女性数量相当 ;从年龄结构来看 ,ADR发生集中于 4 5～ 74a年龄段。抗糖尿病药物的ADR是以代谢和营养障碍、神经系统损害、精神紊乱、胃肠系统损害为主 ,其中除胃肠系统损害主要由阿卡波糖引起外 ,其余以磺酰脲类抗糖尿病药物占绝大多数 ;抗糖尿病药物的ADR绝大多数预后良好 ,但亦有相当数量的ADR留有后遗症甚至死亡 ,其中以格列本脲和苯乙双胍引起的ADR预后较差。结论 :抗糖尿病药物ADR涉及系统广泛 ,有些后果严重 ,应引起临床的重视