Correlation between steady-state plasma concentration of antituberculous drugs and age, inclusion of rifampicin in the treatment regimen, adverse drug reactions and other clinical parameters

A regional hospital in Hong Kong examined the correlation between plasma concentrations of rifampicin, pyrazinamide, isoniazid and its metabolite hydrazine and age, inclusion of rifampicin in the treatment regimen, adverse drug reactions and other clinical parameters. One hundred eighty subjects with tuberculosis were admitted consecutively to the medical wards of the Prince of Wales Hospital over a one and a half year period. Elderly patients > 65 years were randomized into one of two treatments with and without rifampicin in addition to isoniazid, pyrazinamide and ethambutol; younger patients received all four drugs. Plasma antituberculous drug concentrations were determined using high performance liquid chromatography. Elderly patients taking rifampicin had a higher mean steady-state concentration of isoniazid, together with a higher incidence of adverse effects compared with those not taking rifampicin. No age related differences were observed for the other drugs. For the whole group, higher mean concentrations of hydrazine, rifampicin and pyrazinamide were associated with a higher incidence of adverse effects and the presence of coexisting diseases. It is concluded that in sick elderly patients with coexisting diseases, use of rifampicin in the antituberculous regimen should be accompanied by close monitoring for side effects, and that there may be an indication for use of lower dosages of antituberculous drugs in such patients.     

Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies

OBJECTIVE: To estimate the incidence of serious and fatal adverse drug reactions (ADR) in hospital patients. DATA SOURCES: Four electronic databases were searched from 1966 to 1996. STUDY SELECTION: Of 153, we selected 39 prospective studies from US hospitals. DATA EXTRACTION: Data extracted independently by 2 investigators were analyzed by a random-effects model. To obtain the overall incidence of ADRs in hospitalized patients, we combined the incidence of ADRs occurring while in the hospital plus the incidence of ADRs causing admission to hospital. We excluded errors in drug administration, noncompliance, overdose, drug abuse, therapeutic failures, and possible ADRs. Serious ADRs were defined as those that required hospitalization, were permanently disabling, or resulted in death. DATA SYNTHESIS: The overall incidence of serious ADRs was 6.7% (95% confidence interval [CI], 5.2%-8.2%) and of fatal ADRs was 0.32% (95% CI, 0.23%-0.41%) of hospitalized patients. We estimated that in 1994 overall 2216000 (1721000-2711000) hospitalized patients had serious ADRs and 106000 (76000-137000) had fatal ADRs, making these reactions between the fourth and sixth leading cause of death. CONCLUSIONS: The incidence of serious and fatal ADRs in US hospitals was found to be extremely high. While our results must be viewed with circumspection because of heterogeneity among studies and small biases in the samples, these data nevertheless suggest that ADRs represent an important clinical issue.     

Urolithiasis in children in West Algeria]

OBJECTIVE: To evaluate if the histamine H2 blockers (H2B) are adequately prescribed in hospitalized patients outside intensive care units. BACKGROUND: H2B are frequently prescribed. However their good tolerance and easy access have contributed to misuse them. METHODS: Six hundred and seventy eighth hospitalized patients from three different Mexican institutions were included in a prospective study, 100 patients from each hospital who were taking H2B were selected. We investigated the indication for prescribing them as well as the type, dose and adverse effects, international recommendations were taken into account to assess if the treatment was correctly prescribed. RESULTS: Two hundred twenty seven patients (76%) received H2B for prophylactic reasons, however a clear justification for their use was found in only 79 of the cases (35%). H2B were prescribed to treat peptic ulcer disease or upper gastrointestinal bleeding in 17 patients (6%). Two out of three patients received more than 10 doses of H2B, being ranitidine the most frequently prescribed. CONCLUSIONS: Although H2B have a low rate of adverse reactions, their use in hospitalized patients should be rigorously controlled. In fact, the majority of our patients did not need them. Thus, their routine use should be proscribed to avoid unnecessary costs.     

Compliance and adverse drug reactions: a prospective study with ethinylestradiol using continuous compliance monitoring

This study examined the relationship between adverse reactions and patient compliance with ethinylestradiol at 40 micrograms twice daily versus 20 micrograms four times daily. In a randomized study 61 female patients with primary infertility were prescribed the drug twice daily (n = 31) or four times daily (n = 30). Ethinylestradiol was administered for 7 days before the sperm cervical mucus penetration-test was performed for hormonal standardization of the cervical mucus quality. Drug compliance was measured by continuous monitoring using the Medication Event Monitoring System. Two parameters were evaluated: percentage of prescribed doses taken (administration compliance) and adherence to the prescribed dose schedule (regimen compliance, number of days with two or four dosing events recorded). Adverse drug reactions were assessed using a standardized questionnaire. Fourty-four women experienced side effects, of which 81% were rated by patients as being mild. Patient compliance was higher with the twice daily than with the four times daily regimen: 85% versus 65% prescribed doses taken (P < 0.05). There was no significant difference in compliance comparing patients with and without adverse reactions (82% versus 72%, respectively), but compliance was lower and more irregular with at least 3 versus one or two adverse reactions reported: 54% versus 84% in administration compliance and 31% versus 58% in regimen compliance (P < 0.05). Compliance was also lower in patients with nausea and vomiting than in those without these symptoms, 59% versus 91% and 34% versus 66% (P < 0.005), respectively, and lower with moderate or severe compared to mild side effects; 48% versus 85% and 25% versus 59% (P < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)     

Differences in perceived and presented adverse drug reactions in general practice

BACKGROUND: Postmarketing surveillance (PMS) studies are frequently based on data from general practitioners (GPs). Patients, however, do not always report to their GP suspected adverse drug reactions. SETTING: A postmarketing cohort study on adverse reactions to sumatriptan, performed with assistance of drug dispensing GPs in The Netherlands. METHODS: Questionnaires were sent to all drug-dispensing GPs in The Netherlands, as well as to their patients on sumatriptan. To avoid bias, no specific adverse reactions were mentioned in the questionnaires. RESULTS: Of the GPs, 589 (86%) responded; of the patients, 1202 (70%) responded. The most frequently reported suspected adverse reactions to sumatriptan reported by the GPs were dizziness (1.7%), nausea or vomiting (1.5%), drowsiness or sedation (1.4%), and chest pain (1.3%). The most frequently reported suspected adverse reactions by the patients were paraesthesia (11.7%), dizziness (8.1%), feeling of heaviness (8.0%), and chest pain (7.9%). Neither the GPs nor the patients reported serious adverse reactions. CONCLUSIONS: First, patients experience significantly more suspected adverse reactions than are registered by their GP. In view of this higher frequency of reporting of suspected adverse reactions, postmarketing studies with data from GPs only, may underestimate the cumulative incidence of adverse reactions. Second, we conclude that it is possible to obtain useful additional information about adverse drug reactions from patients by sending them questionnaires via their GP.     

Adverse events and cost savings three years after implementation of guidelines for outpatient contrast-agent use

The ability of guidelines limiting the use of low-osmolality contrast media (LOCM) to save money without jeopardizing patient care was studies. In February 1993 an academic medical center implemented guidelines to reduce the use of LOCM for outpatient computed tomography and excretory urography; the guidelines limited LOCM to patients at high risk of adverse reactions to contrast agents. Data on contrast media received and frequency of adverse events were compiled from billing sheets and incident reports for March 1993 through February 1996. The number of patients receiving LOCM over the three years was 1325, and the number receiving high-osmolality contrast media (HOCM) was 4435. Of the HOCM recipients, 165 (3.7%) had adverse reactions; 0.4% of these reactions were major, 3.1% were minor, and 0.2% were extravasations. Among LOCM-treated patients, 35 (2.7%) had adverse reactions; 0.5% were major, 1.7% were minor, and 0.5% were extravasations. The only significant difference in adverse effects between the groups was in the frequency of minor reactions. The costs of HOCM and LOCM over the three years were $54,660 and $152,523, respectively. Had 90% of the 5760 patients received LOCM, the total cost of contrast agents would have been $603,723; thus, the estimated drug cost saving was $396,540, or $132,180 annually. With costs of treating adverse events factored in, the net annual cost saving was $132,093. Guidelines limiting the use of LOCM to high-risk patients saved an academic medical center an estimated $132,093 annually in drug costs for specific outpatient imaging procedures, without adversely affecting patient care.     

Virological characterization and liver histology in HCV positive subjects with normal and elevated ALT levels

In a retrospective study of the pattern of drugs used in the initial treatment of hypertension, 300 case notes of hypertensive patients attending medical clinics at the Korle-Bu Teaching Hospital, Accra and whose treatment were initiated during the period 1973-1993, were reviewed. The mean age of patients was 55 years, mean pre-treatment systolic and diastolic pressures were 179.5 +/- 25. 5 and 108.5 +/- 14.2 mm Hg, respectively, with 85% of patients being female. The frequencies of individual drugs prescribed for the initial treatment of hypertension were: diuretics (90%), reserpine (46%), methyldopa (31%), and propranolol (30%). Single drug treatment was prescribed for 18%, two drugs for 60% and three or more (multiple drugs) for 22% of patients. The mean number of drugs per patient was 2.2 Patients prescribed multiple drugs had pre-treatment systolic and diastolic blood pressures which were significantly (p < 0.01) higher than those prescribed 2 drugs which were, in turn, higher (p < 0.001) than those prescribed single drugs. The results showed that during the period 1973-1993, diuretic based "stepped care" therapy was the main first line anti-hypertensive drug management regime. "Old" anti-hypertensive drugs were more commonly used than newer ones. The cost and availability drugs and the pretreatment blood pressure were probably the main determinants of the choice of the type and number of drugs prescribed.     

HIV seroprevalence rate and incidence of adverse skin reactions in adults with pulmonary tuberculosis receiving thiacetazone free anti-tuberculosis treatment in Yaounde, Cameroon

To determine the HIV seroprevalence in adult patients with pulmonary tuberculosis in Yaounde and to compare the incidence of adverse skin reactions in patients with and without HIV infection receiving thiacetazone-free antituberculosis treatment, we studied 235 consecutive patients aged 15 years or more admitted into the Chest Clinic of Hospital Jamot in Yaounde with a diagnosis of pulmonary tuberculosis from July 1 to December 31, 1994. HIV testing was done using two ELISAs and confirmed by Western blot. Each patient was monitored for adverse skin reactions to antituberculosis treatment during the two month initial phase of therapy in hospital. Of the 235 patients studied, 156 (66%) were males (mean age: 33 years) and 79 were females (mean age: 30.3 years). Overall, 16.6% (39 cases) of the 235 patients were HIV seropositive. The prevalence of HIV infection was significantly higher in women (24%) than in men (12.5%) (p = 0.02). Adverse skin reactions to antituberculosis treatment were observed in eleven (4.7%) of the 235 patients. The incidence of the reactions was significantly higher in HIV seropositive (23.1%) than in HIV seronegative patients (1.0%) (p < 10 - 7). Two HIV seropositive patients who developed Stevens-Johnson syndrome died. The drugs incriminated for adverse skin reactions in the nine patients who survived were pyrazinamide (four cases) and rifampicin (five cases).     

Adverse reactions to trimethoprim-sulfamethoxazole among children with human immunodeficiency virus infection

BACKGROUND: The clinical course of HIV infection is frequently different among infants and children from that in adults. In adults among the most common sources of morbidity related to therapy are adverse drug reactions, notably to trimethoprim-sulfamethoxazole. Although there are case reports of serious adverse reactions to trimethoprim-sulfamethoxazole among infants and children with HIV infection, the precise rate and clinical characteristics of these adverse reactions among HIV-infected children are unknown. METHODS: We reviewed the clinical records of all children referred to a regional HIV clinic in a 6-year period. Therapy and suspected adverse drug reactions to therapy were reviewed by one of the investigators not involved in patient care. Adverse drug reactions were identified and characterized according to previously established criteria. RESULTS: During this time 78 children were referred for assessment of possible HIV infection, 45 of whom were ultimately determined to have the infection. Twenty-five were treated with trimethoprim-sulfamethoxazole, 15 (60%) of whom tolerated therapy and 10 (40%) of whom had adverse reactions. The most common type of adverse reaction was erythema multiforme (70%), followed by neutropenia (20%) and Stevens-Johnson syndrome (10%). In two patients a serious adverse reaction to trimethoprim-sulfamethoxazole led to the diagnosis of HIV infection. CONCLUSIONS: The overall incidence and type of serious adverse reactions to trimethoprim-sulfamethoxazole among infants and children with HIV infection appear to be similar to those among adults.     

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.     

Rate of neuronal fallout in a transsynaptic cerebellar model

PURPOSE: A retrospective study was undertaken of the late adverse reactions following the injection of contrast media. The purpose was to determine whether there was a difference between non-ionic monomeric (iohexol) and non-ionic dimeric (iodixanol) contrast media in the reactions produced. MATERIAL AND METHODS: A total of 3,408 patients were sent a written questionnaire in which they were asked to confirm or deny any subjective discomfort or adverse event during a period of one hour to one week after a previous radiological examination with contrast medium. Patients who had undergone angiography (i.v. or i.a. injection) and CT (i.v. injection) were included. Objective signs of an allergy-like reaction were listed and the patients were asked to subjectively quantify any consequent discomfort. RESULTS: The compliance rate was 84%. Of the 3075 injections finally included in the study, 133 (4.3%) had resulted in contrast-medium-related adverse reactions of which 72 (2.3%) were immediate and 61 (2%) were late. Iohexol induced late reactions in 14/851 (1.7%) cases, and iodixanol in 24/1218 (2.0%) cases following i.v. injection and in 23/1006 (2.3%) cases following i.a. injection. The differences were not significant. There were no differences between the two contrast media in the subjective rating of discomfort except that the patients who had received iodixanol also had the highest individual-intensity score. No patient had been hospitalized owing to an adverse reaction and all reactions had been regarded as mild or moderate. CONCLUSION: The number of late adverse reactions was low. There was no difference in the frequency of the late adverse reactions following i.v. injection between iodixanol and iohexol. There was also no difference in the reactions between the i.a. and i.v. injections of iodixanol.     

Adverse effects associated with selective serotonin reuptake inhibitors and tricyclic antidepressants: a meta-analysis

BACKGROUND: The use of antidepressant medications and the resulting costs have increased dramatically in recent years, partly because of the introduction of selective serotonin reuptake inhibitors (SSRIs). An assessment of the clinical and economic aspects of SSRIs compared with the older tricyclic antidepressants (TCAs) was initiated to generate information for purchasers of these drugs as well as clinicians. One component of this study was an examination of the adverse effects associated with the use of these drugs. METHODS: Searches of bibliographic databases (for January 1980 through May 1996) and manual scanning of both peer-reviewed publications and other documents were used to identify double-blind, randomized controlled trials involving at least one SSRI and one TCA. For the study of adverse effects, only trials that had at least 20 patients in each trial arm and that reported rates of adverse effects in both arms were retained. In total 84 trials reporting on 18 adverse effects were available. Meta-analyses were undertaken to calculate pooled differences in rates of adverse effects. The question of whether the method of eliciting information from patients about adverse effects made a difference in the findings was also examined. Finally, differences in drop-out rates due to adverse effects were calculated. RESULTS: The crude rates of occurrence of adverse effects ranged from 4% (palpitations) to 26% (nausea) for SSRIs and from 4% (diarrhea) to 27% (dry mouth) for TCAs. The differences in the rates of adverse effects between the 2 types of drugs ranged from 14% more with SSRIs (for nausea) to 11% more with TCAs (for constipation). The results did not depend on the method of eliciting information from patients. There were no statistically significant differences between drug classes in terms of drop-outs due to adverse effects. INTERPRETATION: SSRIs and TCAs are both associated with adverse effects, although the key effects differ between the drug classes. Further explanation of the adverse effects and their relation to discontinuation of medication will require better studies involving prospective collection of quality-of-life data.     

Adjunctive therapy in epilepsy with new antiepileptic drugs: is it of any value?

A total of 97 patients were recruited into a prospective, follow-up study after they were prescribed an adjunctive antiepileptic drug. The patients were followed up over a 6-month period. The interview included questions on Quality of Life, side-effects, adverse events and seizure frequency and severity. We operationally defined patients 'satisfaction' as (i) still on new drug; (ii) experiencing no side-effects (iii) experiencing no adverse events and (iv) had a greater than 50% reduction in seizures. A total of 13 patients (17%) reported being 'satisfied' according to our operational definition.     

Bio-dissolution of spent nickel-cadmium batteries using Thiobacillus ferrooxidans

BACKGROUND: To evaluate the magnitude, nature and chronicity of the use of medications on the part of non-institutionalized elderly individuals as well as the complexity of their treatment routine. METHOD: Cross-section study through door-to-door survey of all individuals age 65 or above. Municipality of Villanueva de los Castillejos (Huelva). The surveyor asked the person to show him/her all of the medications he/she was using without overlooking any, recorded the brand name, dosage and frequency with which the medication in question was taken, and the approximate length of time, in months or in years, over which said medication had been taken. Measurement methods were included for the purpose of assessing the complexity of the treatment routine. RESULTS: Information was gathered from 362 subjects (83.8% of the actual population). Of all those surveyed, 83.1% was taking one or more medications daily, for an average (standard deviation) of 2.6 (2.0). Those used most were antihypertensive drugs (41.8%), peripheral vasodilators for circulation to the brain (21.3%), benzodiazepine derivatives (17.4%) and nonsteroid antiinflammatory drugs (14.1%). 91.3% and 46.1% of the subjects who were taking medication daily, had been taking one or more drugs for at least 1 and 5 years, respectively. The medication in question was taken on the average of one to two times a day. Approximately 20% of the population surveyed was taking medication solely when certain symptoms arose, and 7.3% of the drugs were prescribed regularly, but not daily. CONCLUSIONS: The quantity and chronicity of the consumption of medications is high, although comparable to that of other Spanish studies conducted employing similar means and methods. The routine prescribed seems simple for seniors.     

Hospital intensive monitoring of adverse reactions of ACE inhibitors

BACKGROUND AND AIMS: Angiotensin II converting enzyme (ACE) inhibitors represent one of the most important pharmacological instruments for the treatment of arterial hypertension and are currently also used for other cardiovascular indications. The actions of ACE-inhibitors mainly depends on blocking the ACE enzyme in the renin-angiotensin-aldosterone system. However, the ACE enzyme also has a kinase activity. The inhibition of this enzyme may also cause an accumulation of tissue mediators (bradykinin) responsible for a number of adverse reactions. METHODS: An intensive hospital monitoring programme of adverse reactions to drugs, known as MIO[symbol: see text]'96, was carried out by the Centre of Pharmacoepidemiology of the Faculty of Medicine and Surgery at the Second University of Naples during the period 25 March-18 April 1996. The main aims of the programme were to highlight the incidence of adverse reactions to the drugs monitored and the definition of the risk/benefit ratio taking account of the main physiological and pathophysiological variations of patients. This paper reports the results of the programme of adverse effects correlated to the use of ACE-inhibitors. A total of 175 records were compiled for 105 patients receiving antihypertensive treatment with a number of ACE-inhibitors (captopril, enalapril, lisinopril); a very high mean incidence of adverse events was documented (22%) without any severe undesirable effects. RESULTS: The following adverse events were documented (the cumulative incidence is given in brackets): dysgeusia (17%), flush (8%), headache (33%), exanthema (17%), diarrhoea (8%), vertigo (8%), xerostomia (8%). Coughing was not reported in any patient. CONCLUSIONS: Further periods of intensive monitoring will be required to obtain a greater quantity of data from the Intensive Monitoring of adverse events through the MIO[symbol: see text]'97 programme.