Adverse reactions to D-penicillamine after gold toxicity.

The incidence of adverse reactions to D-penicillamine in 155 patients with rheumatoid arthritis was analysed and compared with their history of adverse reactions to gold. Out of 125 patients who took only D-penicillamine, 45 developed side effects from the drug, whereas of 27 patients with a history of gold toxicity, 18 also reacted adversely to D-penicillamine. All patients who took D-penicillamine within six months after an adverse reaction to gold developed side effects from D-penicillamine. Fourteen patients developed similar adverse reactions to D-penicillamine and gold, and the interval between treatments in this group was significantly shorter (p less than 0.01) than in those who developed either differing adverse reactions to both drugs or no reaction to D-penicillamine after treatment with gold. An interval exceeding six months between treatment with gold and treatment with D-penicillamine in patients who have developed adverse reactions to gold apparently reduces the risk of adverse reactions to D-penicillamine.     

Penicillamine in Rheumatoid Disease: A Long-term Study

Eighty-five patients with rheumatoid disease were treated with penicillamine, and 69 completed more than one year''s treatment. The main reason for discontinuing penicillamine in the 16 patients who withdrew was adverse reaction. The number of adverse reactions, however, declined when patients were given lower maintenance doses of penicillamine. In those who tolerated the drug the results of treatment were good. To prevent side effects the drug should be introduced gradually and maintenance doses should be the lowest which produce a satisfactory response. Urine should be monitored for protein and blood for changes in platelet and white cell counts at frequent intervals throughout treatment.     

Patients as a direct source of information on adverse drug reactions.

To determine whether patients should participate directly in detecting adverse reactions to drugs their ability to provide written reports of symptoms experienced during treatment with amoxycillin or trimethoprim-sulphamethoxazole was investigated. When compared with telephone interviews forms on which patients reported events were reliable (the observed agreement with the same statements posed during telephone calls was 85%, kappa = 0.56) and valid (sensitivity = 54%, specificity = 94%). Patients were also supplied with forms that invited them to report adverse reactions, and their perceptions were compared with those of a panel of experts, who were informed of all clinical events that had been reported during the detailed telephone interviews. Patients were more conservative than the experts in attributing clinical events to drug treatment. The extent of agreement varied and was notably poor for skin and bowel complaints (kappa = 0.13 in each case). The performance of event report forms and reaction report forms as instruments of detection was compared in a hypothetical situation in which the experts'' views represented the "truth" about adverse reactions to a new drug. Event reporting had a higher sensitivity than reaction reporting (42% v 24%) but a lower specificity (58% v 98%). National centres monitoring adverse drug reactions should probably resist pressure to accept reports of reactions directly from the public, but a system based on large scale reporting of events might be valuable in aiding the early detection of symptomatic reactions to new drugs.     

Adverse reactions to drugs in general practice.

Of 817 patients in a general-practice survey of adverse reactions to drugs, 41% were thought to have "certainly" or "probably" had a reaction to the drug prescribed. Adverse effects on the gastrointestinal and central nervous systems were the most frequently reported, and 90% of reactions had occurred by the fourth day of treatment. More patients given drugs acting on the central nervous system and antihistamines reported reactions than those in other categories. A higher incidence of adverse drug effects is shown in this general-practice survey than in other, mainly hospital-based, surveys. Further intensive surveillance for adverse effects of drugs is recommended to provide additional information on the burden of drug-induced disease in the community.     

Recognizing and reporting adverse drug reactions.

Although physicians in practice are most likely to see patients with adverse drug reactions, they may fail to recognize an adverse effect or to attribute it to a drug effect and, when recognized, they may fail to report serious reactions to the US Food and Drug Administration (FDA). To recognize and attribute an adverse event to a drug effect, physicians should review the patient''s clinical course, looking at patient risk factors, the known adverse reactions to the suspected drug, and the likelihood of a causal relationship between the drug and the adverse event-based on the temporal relationship, response to stopping or restarting the drug, and whether other factors could explain the reaction. Once an adverse drug reaction has been identified, the patient should be informed and appropriate documentation made in the patient''s medical record. Serious known reactions and all reactions to newly released drugs or those not previously known to occur (even if the certainty is low) should be reported to the FDA.     

Changes in Risk of Immediate Adverse Reactions to Iodinated Contrast Media by Repeated Administrations in Patients with Hepatocellular Carcinoma

Background

To elucidate whether repeated exposures to iodinated contrast media increase the risk of adverse reaction.

Materials and Methods

We retrospectively reviewed 1,861 patients with hepatocellular carcinoma who visited authors’ institution, a tertiary referral center, between 2004 and 2008. We analyzed cumulative probability of adverse reactions and risk factors. We categorized all symptoms into hypersensitivity reactions, physiologic reactions, and other reactions, according to the American College of Radiology guidelines, and evaluated each category as an event. We estimated the association between hazard for adverse reactions and the number of cumulative exposures to contrast media. We also evaluated subsequent contrast media injections and adverse reactions.

Results

There were 23,684 contrast media injections in 1,729 patients. One hundred and thirty-two patients were excluded because they were given no contrast media during the study period. Adverse reactions occurred in 196 (0.83%) patients. The cumulative incidence at 10^th, 20^th, and 30^th examination was 7.9%, 15.2%, and 24.1%, respectively. Presence of renal impairment was found to be one of risk factors for adverse reactions. The estimated hazard of overall adverse reaction gradually decreased until around 10^th exposure and rose with subsequent exposures. The estimated hazard of hypersensitivity showed V-shaped change with cumulative number of exposures. The estimated hazard of physiologic reaction had a tendency toward decreasing and that of other reaction had a tendency toward increasing. Second adverse reaction was more severe than the initial in only one among 130 patients receiving subsequent injections.

Conclusion

Repeated exposures to iodinated contrast media increase the risk of adverse reaction.     

Intensive Hospital Monitoring of Adverse Reactions to Drugs

A total of 1,268 patients admitted to hospital wards were kept under surveillance by one observer throughout their stay in hospital. All drugs given to them and the occurrence of adverse reactions were recorded.Drug reactions were found in 10·2% of the 1,160 patients who received drug therapy. Most reactions were due to known pharmacological actions of the drugs. Though only four reactions were of life-threatening seriousness, 80% of the 129 reactions observed were of moderate severity. Digitalis preparations, bronchodilator drugs, and ampicillin had the highest reaction rates. It is suggested that larger surveys of adverse reactions in relation to drug usage would make a useful contribution to the problem.     

Factors associated with anti-tuberculosis medication adverse effects: a case-control study in Lima, Peru

Background

Long-term exposure to anti-tuberculosis medication increases risk of adverse drug reactions and toxicity. The objective of this investigation was to determine factors associated with anti-tuberculosis adverse drug reactions in Lima, Peru, with special emphasis on MDR-TB medication, HIV infection, diabetes, age and tobacco use.

Methodology and Results

A case-control study was performed using information from Peruvian TB Programme. A case was defined as having reported an anti-TB adverse drug reaction during 2005–2010 with appropriate notification on clinical records. Controls were defined as not having reported a side effect, receiving anti-TB therapy during the same time that the case had appeared. Crude, and age- and sex-adjusted models were calculated using odds ratios (OR) and 95% confidence intervals (95%CI). A multivariable model was created to look for independent factors associated with side effect from anti-TB therapy. A total of 720 patients (144 cases and 576 controls) were analyzed. In our multivariable model, age, especially those over 40 years (OR = 3.93; 95%CI: 1.65–9.35), overweight/obesity (OR = 2.13; 95%CI: 1.17–3.89), anemia (OR = 2.10; IC95%: 1.13–3.92), MDR-TB medication (OR = 11.1; 95%CI: 6.29–19.6), and smoking (OR = 2.00; 95%CI: 1.03–3.87) were independently associated with adverse drug reactions.

Conclusions

Old age, anemia, MDR-TB medication, overweight/obesity status, and smoking history are independent risk factors associated with anti-tuberculosis adverse drug reactions. Patients with these risk factors should be monitored during the anti-TB therapy. A comprehensive clinical history and additional medical exams, including hematocrit and HIV-ELISA, might be useful to identify these patients.     

耐多药肺结核患者的胸部CT征象分析及其治疗转归的影响因素探讨

摘要 目的：分析耐多药肺结核（MDR-PTB）患者的胸部计算机断层扫描（CT）征象,并探讨其治疗转归的影响因素。方法：选取2017年1月~2020年10月期间东莞市第六人民医院收治的MDR-PTB患者（n=138）作为观察组,另选取东莞市第六人民医院同期收治的非MDR-PTB患者110例作为对照组,对比两组的胸部CT征象。观察组患者接受标准化方案治疗,按照是否治疗成功将其分为成功组（n=78）和失败组（n=60）,根据病历资料获取患者的临床资料,采用单因素和多因素Logistic分析MDR-PTB患者治疗转归的影响因素。结果：病变分布范围中：观察组的2个肺叶及以下例数占比低于对照组,全部肺叶侵犯例数占比高于对照组（P<0.05）,两组3个肺叶例数占比组间对比无统计学差异（P>0.05）。病变形态中：两组的多发空洞、合并支扩、合并气胸、实变、多发播散结节、条索、合并毁损、胸膜增厚例数占比组间对比有统计学差异（P<0.05）。而两组胸腔积液、斑片例数占比组间对比无统计学差异（P>0.05）。单因素分析显示,MDR-PTB患者的治疗转归与存在药物不良反应、病变分布范围、既往使用二线抗结核药物史、治疗6个月后痰细菌学转阴、规律服药、初始痰涂片等级有关（P<0.05）。多因素Logistic回归分析显示,既往使用二线抗结核药物史、存在药物不良反应、初始痰涂片等级为++ ~++++是MDR-PTB患者治疗转归的危险因素,而规律服药、治疗6个月后痰细菌学转阴是其保护因素（P<0.05）。结论：MDR-PTB患者病变范围较广,肺叶受累数量多,且易出现肺实质损害。同时存在药物不良反应、规律服药、既往使用二线抗结核药物史、初始痰涂片等级、治疗6个月后痰细菌学转阴是MDR-PTB患者治疗转归的影响因素。     

How good are articles on adverse drug reactions?

A study was carried out of the quality and completeness of articles on adverse drug reactions: 5737 articles from 80 countries published between 1972 and 1979 were studied. Only 61% of the articles included information on the number of patients treated and the number with adverse drug reactions, yet these are essential for calculating the incidence of adverse reactions. In only 55% could the incidence of a particular adverse reaction be calculated. Great importance is placed on articles on adverse reactions, particularly those that report on many patients. Authors and editors should ensure that articles include the following information: drug regimens, numbers of patients treated, numbers of patients developing adverse reactions, and nature and incidence of adverse reactions.     

Protein cross-match test for the diagnosis and prevention of reactions after the transfusion of blood and cryoprecipitate.

The examination by means of counterimmunoelectrophoresis for protein incompatibility of the serum of 62 patients who developed an allergic or pyretic post-transfusion reaction revealed incompatibility in 23 cases (37.2%). It was due to the presence of antibodies in 8 recipients (34.8%) and in 15 blood donors (65.2%). The incidence was significantly higher than in a control group of transfused patients who did not develop a reaction. In this group protein incompatibility was found in only 14.7%, 80% of which was due to antibodies in the recipient. In 13 (56.5%) of the patients with reactions agglutinating, cytotoxic or complement fixing antibodies against cellular antigens or IgG were found in addition to protein incompatibility. In 10 cases (43.5%) protein incompatibility was the only explanation for the clinical symptoms. When, in the treatment of multiply transfused haemophiliacs who regularly developed adverse reactions, donors for the preparation of cryoprecipitate were selected by means of the described technique, the almost obligatory reactions were prevented.     

Dyspnoea,asthma, and bronchospasm in relation to treatment with angiotensin converting enzyme inhibitors.

OBJECTIVE--To evaluate the occurrence of asthma and dyspnoea precipitated or worsened by angiotensin converting enzyme inhibitors. DESIGN--Summary of reports of adverse respiratory reaction in relation to treatment with angiotensin converting enzyme inhibitors that were submitted to Swedish Adverse Drug Reactions Advisory Committee and to World Health Organisation''s international drug information system until 1992. Sales of angiotensin converting enzyme inhibitors in Sweden were also summarised. SUBJECTS--Patients receiving angiotensin converting enzyme inhibitors who reported adverse respiratory reactions. MAIN OUTCOME MEASURES--Clinical characteristics of adverse reactions of asthma, bronchospasm, and dyspnoea. RESULTS--In Sweden 424 adverse respiratory reactions were reported, of which most (374) were coughing. However, 36 patients had adverse drug reactions diagnosed as asthma, bronchospasm, or dyspnoea. In 33 of these cases the indication for treatment with angiotensin converting enzyme inhibitors was hypertension, in only three heart failure. The respiratory symptoms occurred in about half of the patients within the first two weeks of treatment, and about one third needed hospitalisation or drug treatment. Dyspnoea symptoms occurred in conjunction with other symptoms from the airways or skin in 23 out of the 36 cases. In the WHO database there were 318 reports of asthma or bronchospasm, 516 reports of dyspnoea, and 7260 reports of cough in relation to 11 different angiotensin converting enzyme inhibitors. CONCLUSION--Symptoms of airway obstruction in relation to treatment with angiotensin converting enzyme inhibitors seem to be a rare but potentially serious reaction generally occurring within the first few weeks of treatment.     

米卡芬净与伊曲康唑治疗多发性骨髓瘤并发侵袭性真菌病的疗效和成本分析

目的 比较米卡芬净与伊曲康唑在多发性骨髓瘤并发侵袭性真菌病（IFD）病例治疗中的疗效及成本.方法 采用回顾性分析方法,入选2010年1月～2012年11月我科发生侵袭性真菌病的37例多发性骨髓瘤患者的临床资料.对比分析米卡芬净治疗组与伊曲康唑治疗组两组患者的疗效、治疗时间、治疗成本及不良反应.结果 米卡芬净组17例,伊曲康唑组20例,米卡芬净组治疗有效率为76.46％ （13/17）,伊曲康唑组治疗有效率70％ （14/20）,差异无统计学意义（P=0.42 ＞0.05）.米卡芬净组2例发生消化道不适反应.伊曲康唑组3例发生消化道不适反应,2例低钾血症并消化道不适反应;3例患者出现药物性肾功能损害,l例停药后肾功能恢复,2例出现急性肾功能损害.米卡芬净组不良反应发生率为11.76％ （2/17）,伊曲康唑不良发生率为40％ （8/20）,两组差异有统计学意义（P＜0.05）.以治疗第14天总有效率作为疗效判断标准,米卡芬净组和伊曲康唑组成本疗效比分别为263.73和289.11.结论 米卡芬净与伊曲康唑对骨髓瘤合并IFD的治疗有效率差异无统计学意义,不良反应差异有统计学意义,前者成本效益比优于后者.     

Adverse Reactions to Daily and Intermittent Rifampicin Regimens for Pulmonary Tuberculosis in Hong Kong

This paper reports the nature, incidence, and severity of adverse reactions to regimens of rifampicin and ethambutol given once weekly, twice weekly, or daily and to a standard reserve regimen in a total of 330 Chinese failure patients who completed at least six months'' chemotherapy in a therapeutic comparison in Hong Kong.The adverse reactions which occurred on the regimens of intermittent rifampicin were termed cutaneous, abdominal, “flu”, and respiratory; in addition, purpura and abnormal liver function tests were encountered. There was an association of adverse reactions with the interval between doses and with the dose size of rifampicin, the highest incidence occurring with once-weekly rifampicin in high dosage. A procedure was developed for managing adverse reactions to intermittent rifampicin. Of 202 patients treated with intermittent rifampicin 60 developed adverse reactions, but in only 7 (3%) was it necessary to terminate the drug, though a further 10 (5%) were changed to daily rifampicin. On daily rifampicin, generalized hypersensitivity, cutaneous reactions, (one with purpura), and impaired liver function were encountered. Adverse reactions on the standard ethionamide, pyrazinamide, and cycloserine regimen were frequent and some were serious.     

Hypersensitivity to antineoplastic agents: mechanisms and treatment with rapid desensitization

Hypersensitivity reactions (HSRs) to chemotherapy drugs, such as taxanes and platins, and to monoclonal antibodies limit their therapeutic use due to the severity of some reactions and the fear of inducing a potentially lethal reaction in highly sensitized patients. Patients who experience hypersensitivity reactions face the prospect of abandoning first-line treatment and switching to a second-line, less effective therapy. Some of these reactions are mast cell-mediated hypersensitivity reactions, a subset of which occur through an immunoglobulin (IgE)-dependent mechanism, and are thus true allergies. Others involve mast cells without a demonstrable IgE mechanism. Whether basophils can participate in these reactions has not been demonstrated. Rapid drug desensitization (RDD) is a procedure that induces temporary tolerance to a drug, allowing a medication allergic patient to receive the optimal agent for his or her disease. Through RDD, patients with IgE and non-IgE HSRs can safely be administered important medications while minimizing or completely inhibiting adverse reactions. Due to the clinical expansion and success of RDD, the molecular mechanisms inducing the temporary tolerization have been investigated and are partially understood, allowing for safer and more effective protocols. This article reviews the current literature on molecular mechanisms of RDD with an emphasis in our recent contributions to this field as well as the indications, methods and outcomes of RDD for taxanes, platins, and monoclonal antibodies.     

Drug surveillance data in a Canadian hospital.

Comparison of results of a Canadian hospital-based drug surveillance program with data from centres in the United States and Israel showed no important difference in the rate of drug exposures or adverse reactions. Drugs for symptomatic relief were frequently used in the Canadian centre. Women received more drugs and had more adverse reactions than men. Life-threatening and potentially fatal reactions were caused by commonly used drugs; autopsy findings may detect previously unsuspected relations between drug events and mechanisms of death. Voluntary reporting and intensive monitoring are both important in the field of adverse drug reactions.     

A Clinical Trial of Cephaloridine

Cephaloridine, a cephalosporin derivative, was administered to 30 selected patients, including 19 with moderate to severe impairment of renal function. This antibiotic eradicated infections due to Staphylococcus pyogenes, and urinary tract infections due to a single member of the species Escherichia coli or Aerobacter aerogenes, which were sensitive to the drug on bacteriological testing. The drug failed in mixed urinary tract infections.No adverse effects were observed except for the development of superinfection in patients with urinary tract infections. No allergic reactions were noted in 10 patients who had reported previous reactions to penicillin.From these studies in patients with renal disease, approximations can be made concerning dose requirements in these special cases. Because of the apparent absence of dose-related toxic effects in humans, cephaloridine was particularly useful in the treatment of patients with renal disease and infections due to susceptible bacteria.