Theresa Anderson

Medication use and the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis.

Background Toxic epidermal necrolysis and Stevens–Johnson syndrome are rare, life-threatening, drug-induced cutaneous reactions. We conducted a case–control study to quantify the risks associated with the use of specific drugs. Methods Data were obtained through surveillance networks in France, Germany, Italy, and Portugal. Drug use before the onset of disease was compared in 245 people who were hospitalized because of toxic epidermal necrolysis or Stevens–Johnson syndrome and 1147 patients hospitalized for other reasons (controls). Crude relative risks were calculated and adjusted for confounding by multivariate methods when numbers were large enough. Results Among drugs usually used for short periods, the risks were increased for trimethoprim–sulfamethoxazole and other sulfonamide antibiotics (crude relative risk, 172; 95 percent confidence interval, 75 to 396), chlormezanone (crude relative risk, 62; 21 to 188), aminopenicillins (multivariate relative risk, 6.7; 2.5 to 18), quinolones (multivariate rel...

Prevalence and characteristics of opioid use in the US adult population.

&NA; This report describes the prevalence of opioid use in the US adult population, overall and in subgroups, the characteristics of opioid use, and concomitant medication use among opioid users. Data were obtained from the Slone Survey, a population‐based random‐digit dialing survey. One household member was randomly selected to answer a series of questions regarding all medications taken during the previous week. There were 19,150 subjects aged ⩾18 interviewed from 1998 to 2006. Opioids were used ‘regularly’ (⩾5 days per week for ⩾4 weeks) by 2.0%; an additional 2.9% used opioids less frequently. Regular opioid use increased with age, decreased with education level, and was more common in females and in non‐Hispanic whites. The prevalence of regular opioid use increased over time and was highest in the South Central region. Nearly one‐fifth of regular users had been taking opioids for ⩾5 years. Concomitant use of ⩾10 non‐opioid medications was reported by 21% of regular opioid users compared to 4.5% of subjects who did not use opioids. Regular opioid users were more likely to use stool softeners/laxatives (9% vs. 2%), proton pump inhibitors (25% vs. 8%), and antidepressants (35% vs. 10%). From this nationally‐representative telephone survey, we estimate that over 4.3 million US adults are taking opioids regularly in any given week. Information on the prevalence and characteristics of use is important as opioids are one of the most widely prescribed classes of drugs in the US.

Oxalobacter formigenes May Reduce the Risk of Calcium Oxalate Kidney Stones

Most kidney stones are composed primarily of calcium oxalate. Oxalobacter formigenes is a Gram-negative, anaerobic bacterium that metabolizes oxalate in the intestinal tract and is present in a large proportion of the normal adult population. It was hypothesized that the absence of O. formigenes could lead to increased colonic absorption of oxalate, and the subsequent increase in urinary oxalate could favor the development of stones. To test this hypothesis, a case-control study involving 247 adult patients with recurrent calcium oxalate stones and 259 age-, gender-, and region-matched control subjects was performed. The prevalence of O. formigenes, determined by stool culture, was 17% among case patients and 38% among control subjects; on the basis of multivariate analysis controlling demographic factors, dietary oxalate, and antibiotic use, the odds ratio for colonization was 0.3 (95% confidence interval 0.2 to 0.5). The inverse association was consistently present within strata of age, gender, race/ethnicity, region, and antibiotic use. Among the subset of participants who completed a 24-h urine collection, the risk for kidney stones was directly proportional to urinary oxalate, but when urinary factors were included in the multivariable model, the odds ratio for O. formigenes remained 0.3 (95% confidence interval 0.1 to 0.7). Surprisingly, median urinary oxalate excretion did not differ with the presence or absence of O. formigenes colonization. In conclusion, these results suggest that colonization with O. formigenes is associated with a 70% reduction in the risk for being a recurrent calcium oxalate stone former.

Drugs in the aetiology of agranulocytosis and aplastic anaemia

Abstract:  Agranulocytosis and aplastic anaemia are rare but serious conditions known to be caused by numerous drugs. Most of what is known or suspected about the aetiology is based on case reports, with only a few formal epidemiological studies that provide quantitative estimates of risk. Updated results have been obtained from a combined analysis of data from 3 case‐control studies that used similar methods: the International Agranulocytosis and Aplastic Anemia Study (IAAAS), conducted in Israel and Europe; a study conducted in the northeast US; and a study conducted in Thailand. Totals of 362 cases of agranulocytosis, 454 cases of aplastic anaemia and 6458 controls were included in the analyses. The IAAAS and Thai study were population‐based, providing estimates of the incidence of the 2 dyscrasias. The overall annual incidence of agranulocytosis in the ambulatory population was 3.4/106 in the IAAAS and 0.8/106 in Thailand; by contrast the incidence of aplastic anaemia was 2.0/106 in the IAAAS and 4.1/106 in Thailand. A total of 21 compounds were significantly associated with an increased risk of agranulocytosis in the IAAAS and US studies. Excess risks ranged from 0.06 to 13 cases/106 users/wk; the most strongly associated drugs were procainamide, anti‐thyroid drugs and sulphasalazine. An association with drugs that had previously been suspected was also seen in Thailand. The overall aetiologic fractions of agranulocytosis due to drug use were 62% in the IAAAS, 72% in the US and 70% in Thailand. Eleven drugs were significantly associated with an increased risk of aplastic anaemia, with excess risks ranging from 1.4 to 60 cases/106 users in a 5‐month period. The most strongly associated drugs were penicillamine, gold and carbamazepine. Aetiologic fractions were 27% in the IAAAS, 17% in the US and 2% in Thailand, which paralleled the prevalence of use of associated drugs in the 3 populations. The present results confirm that agranulocytosis is largely a drug‐induced disease, with similar proportions accounted for in 3 disparate geographic regions. By contrast, although many of the expected associations were observed for aplastic anaemia, most of the aetiology is not explained by drugs. For all associated drugs, the excess risks are sufficiently low that blood dyscrasias should not figure prominently in the balancing of risks and benefits.

Evaluation of case reports of aplastic anemia among patients treated with felbamate.

Summary: Purpose: Felbamate (FBM) is a new antiepileptic drug (AED) that is often effective in seizure disorders refractory to other treatments; its use has been greatly restricted after cases of aplastic anemia were reported. To elucidate the putative association between FBM and aplastic anemia, we made a detailed evaluation of the first 31 reports.

An Epidemiologic Study of Severe Anaphylactic and Anaphylactoid Reactions among Hospital Patients: Methods and Overall Risks

To quantify the risk of severe anaphylaxis due to drugs and other exposures in hospital patients, a study of incident cases has been in progress since 1992, with data collection in Hungary, Spain, India, and Sweden. All cases of anaphylaxis that develop after admission to participating hospitals are enrolled. To confirm the diagnosis, clinical information for potential cases is reviewed by two physicians without knowledge of exposures, according to an algorithm developed for the study. Confirmed cases are classified as definite, probable, or possible anaphylaxis. As of March 1995, 123 cases were enrolled in Budapest, Barcelona, and Bombay/Pune (the study began in January 1996 in Sweden): 99 were classified as definite or probable anaphylaxis, and 24 as possible. Two of the 123 cases were fatal (2%). Based on the definite and probable cases and a denominator of 481,752 individuals in the nine participating institutions for which the age and sex distribution was known, we estimated the overall risk of severe anaphylaxis to be 154 per million hospital admissions; when the possible cases were included, the risk was 196 per million. The risk was higher among women, and it varied, although not linearly, according to age. A major problem in the epidemiologic evaluation of anaphylaxis has been resolved in the present study with the development of a case definition that, contrary to usual clinical practice, is independent of exposure. The results thus far indicate that severe anaphylaxis occurs infrequently among hospitalized patients and is rarely fatal.

Relation of aplastic anaemia to use of chloramphenicol eye drops in two international case-control studies

Although the use of chloramphenicol eye drops is thought to cause aplastic anaemia,1 this side effect has not been studied critically. We examined the use of ocular chloramphenicol in two population based case-control studies conducted with the same methods. 2 3 The data from the international granulocytosis and aplastic anaemia study were collected over varying times from 1980 to 1986 in Israel and in Ulm and Berlin (Germany), Milan (Italy), Budapest (Hungary), Sofia (Bulgaria), and Stockholm and Uppsala (Sweden); the total base population was about 19 million.2 Data collection continued independently in Sweden until 1992. The Thai study was conducted from 1989 to 1994 in Bangkok and from 1990 to 1994 in Khonkaen and Songkla; the total population was about 21 million.3 In both studies patients with aplastic anaemia were identified by regular telephone contacts with all hospitals in the study …

Factors Related to Colonization with Oxalobacter formigenes in U.S. Adults

GOALS To elucidate the determinants of Oxalobacter formigenes colonization in humans. BACKGROUND O. formigenes is a gram-negative anaerobic bacterium that colonizes the colon of a substantial proportion of the normal population and metabolizes dietary and endogenous oxalate. The bacterium has been associated with a large reduction in the odds of recurrent calcium oxalate kidney stones. Subjects were 240 healthy individuals from Massachusetts and North Carolina. O. formigenes was detected by culture of fecal swabs. Information on factors of interest was obtained by telephone interviews and self-administered questionnaires. STUDY RESULTS The overall prevalence of O. formigenes was 38%. Use of specific antibiotics previously thought to affect the bacterium was significantly related to colonization, with prevalences of 17%, 27%, and 36%, for those who had used these drugs <1, 1-5, and >5 years ago, compared with 55% in nonusers. There were no significant associations with demographic factors, nutrient intake, or medical history, although the prevalence appeared to increase somewhat with increasing oxalate consumption. CONCLUSIONS Some antibiotics markedly affect colonization with O. formigenes. Although no other factor was identified as having a material influence on the prevalence of the bacterium, there is much to learn about how an individual acquires the organism and which factors affect persistence of colonization.

Regional patterns in the incidence of aplastic anemia in Thailand

The annual incidence of aplastic anemia has been determined in a rigorous and standardized epidemiologic study conducted in Thailand. A total of 374 cases were identified over a period of 3–6 years in three geographically defined and distinct regions of the country; Bangkok, Khonkaen in the northeast, and Songkla in the south. The incidence was 3.9 cases per million persons in Bangkok, 3.0 per million in Songkla, and 5.0 per million in Khonkaen. These rates are as high or higher than in any region of Europe or Israel as reported in the International Agranulocytosis and Aplastic Anemia Study, in which the methods and case definition were the same. Rates were stable over the course of the study. There were marked differences in incidence between northern and southern rural regions of Thailand, and among Bangkok suburbs. These differences, together with an unusual peak in the incidence among young people in Bangkok, suggest the possibility of occupational and environmental factors in the etiology of aplastic anemia. Am. J. Hematol. 61:164–168, 1999.

Non-contrast-enhanced computerized tomography and analgesic-related kidney disease: report of the national analgesic nephropathy study.

Previous studies suggested that the non-contrast-enhanced computerized tomography (CT) scan is a highly reliable tool for the diagnosis of analgesic-associated renal disease. However, this issue has not been addressed in the US population. A total of 221 incident patients with ESRD from different regions of the United States underwent a helical CT scan and detailed questioning about drug history. Specific renal anatomic criteria were developed to determine whether a constellation of CT findings (small indented calcified kidneys [SICK]) is linked to analgesic ingestion. For approximating use before the onset of renal disease, only analgesic ingestion at least 9 yr before starting dialysis was considered relevant. Fifteen patients met the criteria for SICK. This represented 7% of the enrolled patients and approximately 1% of the total ESRD population. There was a significant increase in the estimated risk among patients with a history of heavy aspirin ingestion (odds ratio [OR] 7.4 [95% confidence interval (CI) 1.2 to 43] for > or =1 kg lifetime; OR 8.8 [95% CI 1.2 to 66] for > or =0.3 kg/yr). Total analgesic ingestion of > or =0.3 kg/yr also was significantly associated with SICK (OR 8.2; 95% CI 1.5 to 45). These findings were accounted for largely by combination products that contained aspirin and phenacetin (used by three patients with SICK), which are no longer available. In addition, the CT finding of SICK was present only in a minority of heavy analgesic users, yielding a sensitivity of 5 to 26%. Findings of SICK are infrequent in the US ESRD population and do not occur among a sufficient proportion of heavy analgesic users to render the non-contrast-enhanced CT scan a sensitive tool to detect analgesic-associated kidney injury.