Drug-induced Illness Research Articles

Hydrogel-based fluorescence assay kit for simultaneous determination of ceftazidime and avibactam

Monitoring the concentration of antibiotics rapidly and cost-effectively is crucial for accurate clinical medication and timely identification of drug-induced illnesses. Here, we constructed a novel fluorescent assay kit to monitor Zavicefta, an effective antibiotic composed of avibactam (AVI) and ceftazidime (CFZ) to treat carbapenem-resistant gram-negative bacteria infections. AVI can emit fluorescence, but CFZ cannot. To enable simultaneous measurement of both in one kit, we designed molecularly imprinted polymer (MIP) modified quantum dots (QDs) for CFZ determination. MIPs have received significant attention as an artificial antibody due to their exceptional specificity for various targets, particularly drugs with small molecular weight. Under the excitation wavelength of 350 nm, the detection process involves a decrease in QDs’ fluorescence signal at 600 nm owing to the “gate effect” between MIP and CFZ and the internal filtration effect between CFZ and QDs. Simultaneously, a fluorescence emission characteristic peak at 420 nm for AVI emerges. In addition, to simplify the operation procedure and improve determination throughput, the detection agents were incorporated into a hydrogel and placed in a 96-well plate, enabling concurrent quantification of AVI and CFZ within the respective range of 80–1000 μM and 1–1000 μM. The developed assay kit successfully determined AVI and CFZ in human serums and therapeutic drug monitoring in a live rabbit model. Recoveries of AVI and CFZ were 92.7–114%, with relative standard deviations below 6.0%. Moreover, a smartphone was employed to read the fluorescence signals, which was beneficial for cost reduction and out-of-lab analysis. This study will deliver a pragmatic resolution to developing high-throughput assay kits for drug determination.Graphical

Recovering Histories: Life and Labor after Heroin in Reform-Era China

Recovering Histories: Life and Labor after Heroin in Reform-Era China

Ten cases of drug reaction with eosinophilia and systemic symptoms (DRESS) treated with pulsed intravenous methylprednisolone

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare, life-threatening, drug-induced illness characterised by a widespread polymorphic eruption, fever and multivisceral involvement. There is little published on the management of DRESS. Prompt recognition and withdrawal of the causative drug is essential, along with supportive treatment. However, the condition commonly progresses despite these measures. Oral corticosteroids are usually given but the response can be suboptimal and result in a prolonged exposure to systemic glucocorticoid. We conducted a prospective single-centre study to determine the efficacy of pulsed intravenous methylprednisolone followed by a short reducing course of oral prednisolone in ten patients with confirmed DRESS. Rash and fever responded rapidly to methylprednisolone in all patients. Compared to pre-treatment assessments, there was a significant reduction in eosinophil count at day 14 and AST level at day 90 post-treatment. One patient developed acute hepatic failure, necessitating a liver transplant, and died 4 months later. In the immediate post-treatment phase, 1 patient developed type 1 diabetes and 1 patient developed a corticosteroid-induced psychosis. Long-term follow-up on 8/10 revealed all patients to be well, although one patient had persistent pruritus. An aggressive corticosteroid regimen in the management of DRESS is associated with good clinical outcome and acceptable tolerance.

Conversation with Bruce Ritson

In this occasional series we record the views and personal experience of people who have especially contributed to the evolution of ideas in the journal's field of interest. Dr Bruce Ritson was formerly Consultant Psychiatrist at the Royal Edinburgh Hospital and Senior Lecturer at Edinburgh University. He currently chairs the medical campaign group, Scottish Health Action on Alcohol Problems (SHAAP), which is hosted by the Royal College of Physicians of Edinburgh. He has had a long and fruitful research career.

The Role of Litigation in Defining Drug Risks

IN THE PAST DECADE, SEVERAL WIDELY USED PRESCRIPTION medications have been observed to cause lifethreatening adverse effects, and some have been removed from the market. When an approved medication is found to be unsafe, the courts are sometimes called on to determine fault and allocate remedies for injured parties. But in modern prescription drug cases, litigation has taken on additional significance. There are often important gaps in the ascertainment and reporting of adverse effects associated with prescription drugs, and the balance of information presented to physicians about the risks and benefits of medications may understate the former and inflate the latter. However, once it approves a drug, the US Food and Drug Administration (FDA) has limited authority to mandate further collection of data to better define adverse effects or to ensure compliance with suggested alterations in marketing practices. In this environment, litigation brought by government agencies and individual patients can help uncover previously unavailable data on adverse effects, questionable practices by manufacturers, and flaws in drug regulatory systems. Litigation can exert its effect through the discovery process, in which each side shares previously unavailable information relating to the issue in dispute, as well as by motivating proper disclosure initially by presenting the possibility of substantial damages in cases of misconduct. However, some have argued that such litigation adds to the risk and cost of medication development and is a poor way to influence patient care decisions or health policy. Given this controversy, we sought to explore the role of litigation in uncovering new information concerning drug-induced illness and the impact of litigation on drug policy. We evaluated several products recently subject to involvement of the legal system: rofecoxib (Vioxx), cerivastatin (Baycol), dexfenfluramine (Redux), paroxetine (Paxil), troglitazone (Rezulin), cisapride (Propulsid), valdecoxib (Bextra), and olanzapine (Zyprexa) (TABLE). Litigation strategies reviewed included individual and class-action lawsuits against pharmaceutical manufacturers and government investigations of pharmaceutical manufacturers for potentially illegal business practices or financial market manipulation. We sought to define the intersections among the civil justice system, the regulatory apparatus, and the science of pharmacoepidemiology, including the effects of those interactions on drug safety research, clinical knowledge, and regulatory policy.

Admissions caused by adverse drug events to internal medicine and emergency departments in hospitals: a longitudinal population-based study.

To estimate incidence rates of drug-related hospitalizations (DRHs) in a longitudinal population-based study with prospective event assessment. Cohort study and time-trend analysis. All departments of internal medicine and emergency departments in the urban regions of Jena and Rostock, Germany, serving about 520,000 residents. All patients admitted between October 1997 and March 2000. Patients with severe cutaneous reactions were excluded. Incidence of DRH was defined by symptoms or diagnoses at admission that were very likely, likely, or possibly caused by prescription medications, according to a standardized assessment. The incidence of DRH was 9.4 admissions per 10,000 treated patients [95% confidence interval (CI) 9.0-9.9]. Rates were highest for antithrombotics with 26.9 admissions per 10,000 treated patients (95% CI 23.6, 30.1). Most frequent events were gastroduodenal lesions and bleeding (45%). Digitalis preparations showed a linearly increasing trend from 2/10,000 to 14/10,000 during ten quarters ( P<0.0001), which was exclusively attributable to digitoxin, the major source of digitalis in the study area (93%). The incidence of DRH increased with age (4/10,000 to 20/10,000). The mean length of stays in patients with DRH was 13+/-10.6 days. Cumulative direct costs for hospitalization were Euro 4 million in the two urban study areas. The annual direct costs for Germany were estimated to be Euro 400 million. DRHs are a considerable public health and economic burden. A longitudinal design can observe changes in population-based incidence over time. This approach can be used for public-health planning or to evaluate outcomes of quality management programs designed to reduce drug-induced illness.

Worst Pills, Best Pills: A Consumer's Guide to Avoiding Drug-Induced Death or Illness

Worst Pills, Best Pills: A Consumer's Guide to Avoiding Drug-Induced Death or Illness

Description of a mixed ethnic, elderly population. III. Special diets, food preferences, and medicinal intakes.

The objective was to assess the use of physician-prescribed special diets, food preferences, and daily and occasional drug use by elderly participants in a Title III-C Nutrition Program. Data were collected by nonrandom interviews of congregate and meals-on-wheels clients. Chi-square was used to assess whether food and drug behaviors were related to six population variables: ethnicity, age, gender, congregate versus meals-on-wheels clients, proportion of noon meal usually eaten, and whether clients lived alone or with others. Special diets and daily and occasional medications showed no significant differences with regard to the six variables. Broccoli was the food disliked most frequently. Suggestions that certain foods be served more frequently were greater among white than black clients (p < .001) and among home delivery than among congregate clients (p < .005). Persons who regularly ate half or less of the noon meal made more suggestions for cooking foods differently (p < .005) and had longer lists of favorite foods (p < .001) than those who usually ate most of or all of the meal. Persons who lived alone had more suggestions for cooking foods differently (p < .005) and serving certain items more often (p < .05) than those who lived with other persons. Favorite foods, changes in cooking methods, and frequency of offering certain foods were not related significantly to age or to gender. Certain suggested changes in food choices and preparation can be implemented within Title III guidelines and may improve food intakes. While medicinal intakes were similar to those reported previously for the elderly cohort, there is reason for concern with regard to drug-induced illness.

How to spot illicit drug abuse in your patients

PREVIEWAlthough the incidence of drug abuse may be stabilizing in some areas of the United States, many of your patients may present with telltale signs of a drug-induced condition. What are the clinical clues that suggest use of various types of drugs? How can you differentiate between drug-induced conditions and psychiatric illness? The authors of this article answer these questions and review the clinical pharmacology of the most common classes of illicit drugs. They also provide a handy list of contemporary street names and adverse effects of the five main types of drugs of abuse.

Polypharmacy: Drug-Induced Illness in the Elderly

Polypharmacy: Drug-Induced Illness in the Elderly

Drug‐related problems as a cause of hospital admissions in Hong Kong

AbstractThe importance of drug‐related problems as a cause of hospital admissions in Hong Kong was studied in 925 patients admitted to two general medical wards at the Prince of Wales Hospital between November 1992 and February 1993. Drug‐related problems were judged to be the main reason for hospital admissions in 88 patients (9.5 per cent). These were adverse drug reactions (n = 57), drug poisoning (n = 22) and treatment failure consequent to noncompliance or inappropriate reduction in dosage (n = 9). The most important adverse drug reactions were gastrointestinal hemorrhage (36.8 per cent) and hypoglycemia (24.6 per cent), and the three drug classes that were most commonly involved were non‐steroidal anti‐inflammatory drugs (NSAIDs) (aspirin 12.3 per cent, non‐aspirin 28.1 per cent), sulphonylureas (19.3 per cent) and diuretics (12.3 per cent). Drug‐related problems are an important cause of hospital admissions, and much of the drug‐induced illnesses in Hong Kong could be preventable if particular attention was given to NSAID and sulphonylurea therapy. Patients should also be educated about the importance of good drug compliance.

ADVERSE DRUG EFFECTS

It has been emphasized repeatedly that drugs seldom exert their beneficial effects without also causing adverse side effects. The frequency of clinically important adverse effects is difficult to estimate, but the potential for drug-drug and drug-disease interactions and drug-induced illness is high and lends credence to the statement that there are no safe biologically active agents.

CLINICAL IMPLICATIONS OF DRUGS TAKEN BY OUR PATIENTS

An awareness of the various medications commonly prescribed for patients to self-administer will assist clinicians to anticipate the most commonly encountered medical diagnoses; will give clues to a patient's physical and emotional ability to undergo and respond to dental care; will alert clinicians to potential drug-drug and drug-disease interactions, and to the presence of drug-induced illness; and provide invaluable information that will help the clinician identify high-risk patients who may experience a life-threatening medical emergency while in the dental office.

End Organ Toxicities of Adverse Drug Reactions

Many commonly prescribed medications are capable of causing organ specific adverse effects that can involve every organ system of the body. This situation presents the clinician with a diagnostic problem, since the drug-induced illness often mimics the clinical - disease. Clinicians must be alert to the possibility that drugs can cause or exacerbate any disease. In order to assess effectively the possibility of an illness being a result of an adverse drug reaction, it is necessary to recognize the manifestations of that drug's adverse effects and indict the drug on the basis of its use and the subsequent development of illness. This article reviews the organ-specific toxicities of drugs known to affect the liver, kidney, blood and bone marrow, and ear.

Drug-induced illness in the elderly.

The elderly are predisposed to adverse drug reactions because of age-related physiologic changes, interaction of one drug with another, and interaction between a drug and a coexisting medical condition. Recognition of such adverse reactions is essential, because many are reversible and many are even preventable. Assessment of clinical disorders in the elderly should include evaluation of drugs as a causal or aggravating factor. Careful choice and dosage of drugs in the elderly will minimize the likelihood of drug-induced illness.

Drug-induced illness as a cause for admission to a community hospital.

To assess the rate of occurrence of drug-induced illness as a cause for admission to the general medicine service of a community hospital, charts were reviewed retrospectively of all patients admitted to the service over two randomly selected one-month periods. Statistical analysis was performed on patients over and under the age of 65, and on iatrogenic and noniatrogenic admissions. Twenty-three of 244 patients (9.4%) were admitted with drug-induced illness. Patients with drug-induced illness had 5.7 medications as compared to 3.2 medications per patient admitted for other reasons (P less than .05). A single drug was responsible for 61% of all drug-induced illness admissions. Aspirin and other nonsteroidal anti-inflammatory agents were most often implicated. Eighteen of 155 elderly patients (11.7%) were admitted with drug-induced illness. These patients were on an average of 6.3 medications as compared with 3.8 medications per elderly patient admitted for other causes (P less than .005). Polypharmacy and a preponderantly elderly population may explain the substantial number of admissions caused by adverse drug reactions. Further research to assess the role of patient age and the number and type of medications involved in the event of drug-induced illness requires standardization of definition and diagnostic criteria.

Rational Pharmacotherapy for the Elderly

Aging is accompanied by normal physiologic changes. Paralleling these changes, disease further contributes to a decline in optimal organ-system function. Many of these changes produce significant alterations in pharmacodynamics and pharmacokinetics that are relevant to safe and effective pharmacotherapy in the elderly. As aging is accompanied by disease, chronic disease states lead to polypharmacy and drug-drug interactions. Drug therapy may cause further decline in organ-system functions, precipitate or exacerbate preexisting disease, and produce drug-induced illness. Consequently, pharamcotherapy in the elderly should only be instituted following comprehensive dentomedical assessment. Use as few drugs as possible. Prescribe the lowest therapeutic dose. Assess the patient's response frequently for compliance, drug effects, and toxicity. Discontinue unnecessary medications.

Antisecretory drugs. Safe and effective?

Surveillance of takers of the antisecretory drug cimetidine has failed to reveal any disturbing trends. This pattern is reassuring but the difficulties of detecting drug-induced disease mimicking ordinary community complaints deserve emphasis. Experience since the surveillance study began has not revealed any disturbing trends. Observed mortality rates have fallen to match population expectation, both for ordinary disease and for cancer. The pattern is generally reassuring and suggests that significant drug-induced disease is not being missed. Nevertheless the ability of this or any other surveillance study to detect drug-induced illness mimicking ordinary disease is likely to be low.

Aging and the Kidney

Numerous anatomic and physiologic alterations occur in the kidney with aging. These changes affect the ability of elderly patient(s) to maintain homeostasis and alter response to medications, stress, illness, or changes in diet, mobility, or environment. Drug-induced illness and drug interactions are major problems in the elderly. Bone disease and fractures are associated with negative calcium balance and decreased production of 1,25-dihydroxycholecalciferol seen with aging. The geriatric patient is not immune to the primary glomerular diseases that occur in younger patients, although the relative incidence of pathologic diagnoses may differ. The high incidence of membranous glomerulonephritis in the elderly, and the well-known association between malignancy and membranous nephropathy strongly favor aggressive evaluation of the nephrotic syndrome in the geriatric age group. Attention must be given to consideration of appropriate end-stage renal disease treatment alternatives for the geriatric population, which now comprises the fastest-growing segment of the end-stage renal disease population.

The role of drug-induced illness in admissions to an intensive care unit.

All patients admitted during a 33-month period to a multidisciplinary intensive care unit were prospectively studied in order to determine the incidence and severity of drug-induced illness leading to the admission. The role of underlying diseases was assessed and the avoidability of drug-induced illness considered. Out of 1651 patients, 97 (5.88%) were admitted because of drug-induced illness; 74 of these had serious underlying diseases. 13 (13.4%) of the 97 patients died, but underlying diseases accounted for 4 of the 13 fatalities. In nearly half of the cases, the drug-induced illness appeared potentially avoidable.