Higher Risk Of Adverse Drug Reactions Research Articles

Evaluation of major adverse events of clozapine based on accordance to an international titration guideline.

Clozapine is the only antipsychotic approved for treatment-resistant schizophrenia, but without appropriate monitoring, it can be associated with potentially fatal outcomes. An International Adult Clozapine Titration Guideline categorizes patients into normal or slow metabolizers. Categorization provides clozapine titration schedules and recommends regular c-reactive protein (CRP) and clozapine concentration monitoring to reduce the risk of adverse drug reactions (ADRs). The impact of the guideline on clozapine ADRs has not been evaluated. A retrospective chart review assessed clozapine titrations, laboratory monitoring, ADRs, and discontinuations for clozapine-naive adult inpatients at a single center from January 1, 2013, to June 1, 2022. Each patient's cumulative weekly clozapine dosage was compared with their guideline recommended dosage to create a percent accordance. Linear logistic regression evaluated the relationship between titration speed and the presence of an ADR, while descriptive statistics analyzed laboratory monitoring. Forty-three patients were included, with the majority being White males with schizophrenia. An inverse relationship existed between the last inpatient week clozapine dose percent accordance and the probability of an ADR. Nonobese patients were less likely than obese patients to experience an ADR (odds ratio = 0.17; 95% CI, 0.03-0.99). CRP and clozapine concentration monitoring was suboptimal. Based on our small retrospective review of primarily White males, more aggressive clozapine titrations did not increase ADRs. Future studies with more diverse samples are needed and should focus on specific ADRs, which may have increased occurrence with rapid titrations. Obese patients were at higher risk of ADRs, correlating with the guideline-recommended slower titrations for these patients.

Diabetes mellitus increases risk of adverse drug reactions and death in hospitalised older people: the SENATOR trial.

Adverse drug reactions (ADRs) are a major cause of morbidity and mortality, especially in older people. Older people with diabetes mellitus may be at especially high risk of ADRs but this risk has not been well studied. This study aimed to compare severity and type of ADRs in hospitalised, multimorbid older people with and without diabetes and secondly to assess the impact of ADRs on mortality, rehospitalisation and length of stay. Participants in the SENATOR (Software Engine for the Assessment and optimization of drug and non-drug Therapy in Older peRsons) trial were assessed for 12 common and 'other' prevalent and incident adverse drug reactions using a blinded end-point adjudication process. Descriptive analyses, logistic regression and mediation analyses were undertaken. Of 1537 people in the SENATOR trial, 540 (35.1%) had diabetes mellitus (mean age 77.4 ± 7.3years, 58.5% male). In the total population, 773 prevalent and 828 incident ADRs were reported. Both prevalent and incident symptomatic hypoglycaemia and incident acute kidney injury (AKI) were significantly more common in people with diabetes (p < 0.05). Patients with diabetes had higher all-cause mortality at 12weeks than those without (9.1% vs 6.3%, p = 0.04). Mediation analysis revealed that mortality was significantly higher (OR = 1.43, Sobel test p = 0.048) in people with diabetes and ADRs causing AKI. Older multimorbid people with diabetes presenting to hospital with acute illness have significantly more ADRs than those without, and a significantly higher mortality that is mediated by medication-associated AKI and poorer renal function.

CYP3A4*22 and CYP3A5*3 impact efficacy and safety of diazepam in patients with alcohol withdrawal syndrome

Background Diazepam is one of the most commonly prescribed pharmaceuticals for the treatment of alcohol withdrawal syndrome (AWS). However, diazepam sometimes is ineffective, and some patients experience dose-dependent adverse drug reactions (ADR). Previous studies have shown that diazepam metabolism involves the CYP3A4 and CYP3A5 isoenzymes, whose activity is highly variable between individuals, which may contribute to differences in clinical response. Purpose The study aimed to investigate the effects of the genetic polymorphisms CYP3A4*22 and CYP3A5*3 on the efficacy and safety of diazepam in patients with AWS. Materials and methods One hundred male AWS patients received 30 mg/day diazepam by intramuscular injections for 5 days. Genotyping for CYP3A4*22 (rs35599367) and CYP3A5*3 (rs776746) was performed by real-time polymerase chain reaction with allele-specific hybridization. The efficacy and safety assessments were performed using psychometric scales. Results Patients who carry CT and TT genotypes by polymorphic marker C > T intron 6 (rs35599367) of the CYP3A4 gene had a higher risk for ADR and demonstrated lower safety of diazepam therapy (p < 0.001; two-way ANOVA). Conclusion These results suggest that genotyping for common CYP3A variants might have the potential to guide benzodiazepine withdrawal treatment.

Adverse Drug Reactions in Pediatric Oncohematology: A Systematic Review.

Introduction: Adverse drug reactions (ADR) are an important cause of morbidity and mortality in pediatric patients. Due to the disease severity and chemotherapy safety profile, oncologic patients are at higher risk of ADR. However, there is little evidence on pharmacovigilance studies evaluating drug safety in this specific population. Methods: In order to assess the incidence and characteristics of ADR in pediatric patients with oncohematogical diseases and the methodology used in the studies, a systematic review was carried out using both free search and a combination of MeSH terms. Data extraction and critical appraisal were performed independently using a predefined form. Results: Fourteen studies were included, of which eight were prospective and half focused in inpatients. Sample size and study duration varied widely. Different methods of ADR identification were detected, used alone or combined. Causality and severity were assessed frequently, whereas preventability was lacking in most studies. ADR incidence varied between 14.4 and 67% in inpatients, and 19.6–68.1% in admissions, mainly in the form of hematological, gastrointestinal and skin toxicity. Between 11 and 16.4% ADR were considered severe, and preventability ranged from 0 to 74.5%. Conclusion: ADR in oncohematology pediatric patients are frequent. A high variability in study design and results has been found. The use of methodological standards and preventability assessment should be reinforced in order to allow results comparison between studies and centers, and to detected areas of improvement. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=96513, identifier CRD42018096513.

Association between benzodiazepine prescriptions and potential risk factors of adverse drug reactions among elderly and very elderly: findings from Friuli Venezia Giulia region, Italy

Background: benzodiazepines (BDZs) highly increase the risk of adverse drug reactions (ADRs), especially in the elderly with certain medical conditions. &#x0D; Methods: point-prevalence study in December 2017; 2,456 patients ≥65 years were included from 14 regional public and private hospitals, 24 long-term chronic care facilities (LTCCFs) and 20 nursing homes (NHs). Data regarded BDZ prescriptions and comorbidities, co-prescriptions, or concurrent diseases, which could increase the risk of ADRs in BDZ users. Univariate and multivariate logistic regression analyses were used to assess associations between ADRs in BDZ users vs. non-users, as well as within users. &#x0D; Results: 671 patients were prescribed BDZ, whose half were in NHs. Being prescribed 10 or more drugs was twice more common among BDZ users compared to non-users. BDZs were prescribed for long-term to 80% of patients in NHs, while proportions were halved in hospitals and LTCCFs. In the analyses within BDZ users, patients in NHs and LTCCFs were at higher risk of dementia and concurrent use of opioid analgesic and antipsychotics compared to hospitalized patients. &#x0D; Conclusions: the use of BDZs in older patients is common in FVG. A great extent of comorbidities and concurrent medications at higher risk of ADRs was found. Analyses in different healthcare settings can allow to drive evidence-based interventions in order to discourage the use of BDZs and monitor the raise of ADRs.

Adverse drug reactions to trimethoprim-sulfamethoxazole in systemic lupus erythematosus.

Trimethoprim-sulfamethoxazole (TMP-SMX), a prophylactic agent against pneumocystis pneumonia (PCP), can cause adverse drug reactions (ADRs), particularly in patients with systemic lupus erythematosus (SLE). However, the risk factors for ADRs remain unclear. Thus, we sought to examine the prevalence of TMP-SMX-related ADRs in patients with SLE and identify specific risk factors for ADR development in these patients. We retrospectively reviewed data from patients with connective tissue disease (CTD) who were administered TMP-SMX as a PCP prophylactic. The prevalence of ADRs was compared between patients with SLE and those with other CTDs. Univariate and multivariate analyses were conducted to identify risk factors for ADRs in patients with SLE. Of the 424 patients with CTD included in our study (SLE, n = 162; other CTDs, n = 262), 22 with SLE (13.6%) developed ADRs, and this rate was significantly higher than that observed in patients with non-SLE CTDs (n = 18 [6.9%], p = 0.033). In patients with SLE, univariate analyses revealed direct associations of ADRs with anti-Sm (p < 0.001), anti-RNP (p = 0.02), and anti-Ro/SS-A antibodies (p = 0.042). Multivariate analysis identified a significant association between anti-Sm antibody levels and the development of ADRs (adjusted odds ratio 5.27, 95% confidence interval 1.80-15.40, p = 0.002). Patients with SLE who are prophylactically administered TMP-SMX are at high risk of ADRs. Among these patients, those who display a positive anti-Sm antibody should be carefully monitored for ADRs.

Common causes and characteristics of adverse drug reactions in older adults: a retrospective study

BackgroundAging populations are often accompanied by comorbidity and polypharmacy, leading to increases in adverse drug reactions (ADRs). We sought to evaluate the causes and characteristics of ADRs in older Korean adults (≥65 years) in comparison to younger individuals (< 65 years).MethodsOf 37,523 cases reported at a Korean pharmacovigilance center from 2011 to 2018, we reviewed 18,842 ADRs of certain or probable causality on the basis of WHO-UMC criteria. We estimated the number of ADRs per 1000 patients exposed to the major culprit drugs, and incidence rate ratios were obtained to assess high- and low-risk medications in older adults.ResultsIn total, 4152 (22.0%) ADRs were reported for 3437 older adults (mean age, 74.6 years and 57.3% female). Tramadol (rate ratio, 1.32; 95% confidence interval [CI], 1.21–1.44; P < 0.001) and fentanyl (1.49, 1.16–1.92, P = 0.002) posed higher risks of ADRs in the older adults, whereas nonsteroidal anti-inflammatory drugs (NSAIDs) (0.35, 0.30–0.40, P < 0.001) and iodinated contrast media (ICM) (0.82, 0.76–0.89, P < 0.001) posed lower risks. Ratios of serious ADRs to NSAIDs (odds ratio, 2.16; 95% CI, 1.48–3.15; P < 0.001) and ICM (2.09, 1.36–3.21, P = 0.001) were higher in the older adults than in the younger patients. Analgesics primarily elicited cutaneous ADRs in the younger patients and gastrointestinal reactions in the older adults. ICM more commonly led to anaphylaxis in the older adults than the younger patients (3.0% vs. 1.6%, P = 0.019).ConclusionFor early detection of ADRs in older adults, better understanding of differences in the causes and characteristics thereof in comparison to the general population is needed.

Correlation of the Plasma Concentration of Eltrombopag With Efficacy in the Treatment of Refractory Aplastic Anemia: A Single-Centre Study in China.

Background and purpose: Eltrombopag (ELT) can be effective in the treatment of relapse/refractory aplastic anemia (AA) patients. Responses and adverse drug reactions (ADRs) differed greatly among individuals treated at the same dosage of ELT. Methods: Patients diagnosed with nonsevere aplastic anemia (NSAA) between January 2018 and January 2019 in Peking Union Medical Colleague Hospital who were refractory to immunosuppressive therapy were treated with ELT and followed up for at least 6 months. Plasma concentrations of ELT were detected by high-performance liquid chromatography-mass spectrometry after at least two months of ELT treatment and treatment at the same dosage for at least 2 weeks. The dose-concentration, concentration-response and concentration-ADR relationships were evaluated. Results: Among the 72 patients treated with ELT during the study period, 44 patients with complete data were enrolled. Six (13.6%) were males, and 38 were females (86.4%), with a median age of 54 years [interquartile range (IQR): 38.5–63]. At the time the ELT plasma concentration was detected, the median dosage of ELT was 75 (IQR 50–100) mg/d, the median time of total ELT exposure was 3 (IQR 2.0–6.0) months, and 37 (70.5%) patients had responded to ELT. The median concentration of ELT was 10.4 μg/ml (IQR 3.7–24.4 μg/ml). The concentration of ELT was positively correlated with the daily dose of ELT (r = 0.68, p < 0.001). Multivariate logistic regression analysis showed that the risk of inefficacy of ELT at a concentration between 11.2 and 15.2 μg/ml was 0.028-fold (95% CI: 0.001–0.864; p = 0.041) of that at a concentration between 3.2 and 7.2 μg/ml. The cutoff value for the concentration of ELT showing efficacy was 12.50 μg/ml according to the receiver operation characteristic curve. A higher risk of ADR was related to a longer total exposure to ELT (p = 0.012). Although the correlation was not significant, the odds ratio increased with the ELT concentration, suggesting that it was possible that an elevated risk of ADR was correlated with the ELT blood concentration. Conclusion: ELT is effective for the treatment of NSAA and has acceptable side effects. The plasma concentration of ELT was correlated with the dose and the effects of ELT.

Real-world efficacy and safety of two doses of cabazitaxel (20 or 25\u2009mg/m2) in patients with castration-resistant prostate cancer: results of a Japanese post-marketing surveillance study

BackgroundThe recommended starting dose of cabazitaxel for castration-resistant prostate cancer (CRPC) is 25 mg/m2 in Japan and Europe. Although lower doses are established alternatives based on randomized controlled trials, the safety and efficacy of 25 and 20 mg/m2 in real-world settings are not well established. Therefore, we investigated the safety and efficacy of cabazitaxel at the recommended starting dose or a lower dose (20 mg/m2) in real-world clinical practice.MethodsWe compared the safety and efficacy of cabazitaxel between patients who received cabazitaxel at starting doses of 25 and 20 mg/m2 (C25 and C20, respectively) in a Japanese post-marketing surveillance study of 662 patients with docetaxel-refractory CRPC. Safety was assessed in terms of adverse drug reactions (ADRs). Prostate-specific antigen (PSA) response rate, overall survival (OS), and time-to-treatment failure (TTF) were compared between the C25 and C20 groups in unmatched patients and after applying propensity score matching.ResultsThe C20 and C25 groups comprised 190 and 159 patients without matching and 112 patients per group after matching. In unmatched patients, any-grade (C25 vs C20: 89.3% vs 78.4%, Fisher’s p < 0.01) and grade ≥ 3 (81.1% vs 61.1%) ADRs were more frequent in the C25 group. Neutropenia (any grade: 61.6% vs 54.2%; grade ≥ 3: 55.3% vs 42.6%) and febrile neutropenia (grade ≥ 3: 30.2% vs 14.7%) were more frequent in the C25 group. In matched patients, the PSA response rate (reduction in PSA ≥30% from a baseline ≥5 ng/mL) was 26.4 and 32.0% in the C20 and C25 groups, respectively, median OS was 291 days (95% CI 230–not reached) versus not reached (hazard ratio 0.73, 95% CI 0.50–1.08), and TTF favored C25 (hazard ratio 0.75, 95% CI 0.57–0.99).ConclusionsClinicians should consider the patient’s risk of clinically significant ADRs and prophylactic granulocyte colony stimulating factor when selecting the starting dose of cabazitaxel for CRPC. Some patients at high risk of ADRs or unfit patients may benefit from a lower starting dose of 20 mg/m2, whereas fit patients may be candidates for a starting dose of 25 mg/m2.Trial registrationNot applicable.

Polypharmazie in der Anwendung von Psychopharmaka in der deutschen Kinder- und Jugendpsychiatrie – häufiger Regel als Ausnahme

Polypharmacy of psychotropic drugs in child and adolescent psychiatry in Germany - rather the rule than the exception Abstract. Background: Polypharmacy increases the risk of interactions and enhances the chance of adverse drug reactions (ADRs). Hence, child and adolescent psychiatrists generally try to avoid polypharmacy with psychotropic drugs. However, only little data regarding the frequency of polypharmacy in child and adolescent psychiatry are available. This study analyzes clinical data on polypharmacy and the possible association with a higher risk of ADRs in Germany, with a focus on antidepressants and antipsychotics. Methods: We investigated a total of 940 datasets from descriptive studies on therapeutic drug monitoring (TDM) of pediatric patients treated with different psychotropic drugs. Results: The frequency of polypharmacy ranged up to 45.6 % (escitalopram) and 72.1 % (olanzapine). In 17.4 % of the cases, polypharmacy consisted of four or more psycho-/neuropharmacological substances. No increased incidence of ADRs was reported with polypharmacy of antipsychotics compared to monotherapy. Polypharmacy with sertraline was associated with a higher number of ADRs. Discussion and Conclusion: There is a high prevalence of polypharmacy with psychotropic drugs in child and adolescent psychiatry in Germany. Conclusions concerning individual drugs should be drawn with care since the subsample sizes were relatively small. However, our results do provide an indication of the prevalence of polypharmacy, although the validity of the data is limited. There is an urgent need to analyze data from larger and more homogeneous groups under more controlled conditions.

Adverse Drug Reactions Across the Age Continuum: Epidemiology, Diagnostic Challenges, Prevention, and Treatments.

Adverse drug reactions (ADRs) are common and important complications of drug therapy for children. The risk for ADRs changes over childhood, as do the nature and types of ADRs. Importantly, the risk and nature of ADRs in children are markedly different from those of adults, and adult data cannot be relied on to guide safe drug therapy in children. There are groups of children, notably those with complex and chronic diseases, who are at substantial risk for ADRs. The evaluation of an undesired effect during therapy is ideally accomplished by an organized approach that is a skill that clinicians who care for children-especially those children at high risk for ADRs must have. Additionally, clinicians as well as drug regulatory agencies and industry need to be both vigilant and astute as well as aware that ADRs in children are often different in nature and frequency from those in adults. The increasing use of pharmacogenomics to guide drug dosing and the increasing number of biological agents will provide new sets of challenges to clinicians over the next decade.

Evaluation of Predisposing Factors Associated with Suspected Adverse Drug Reactions of Hospitalized Patients

: Objectives: To study the incidence and to evaluate the risk factors of suspected adverse drug reactions developed in the hospitalized patients of various departments and to assess the causality and severity of adverse drug reactions (ADRs). Methods: It was a retrospective-prospective study conducted in a tertiary care hospital for a period of two years two months, with a specific predefined criterion. A total of 254 subjects with ADRs were identified during the period of study for which 1:1 ratio of subjects with non-ADRs were taken. Subjects of all age groups and of either sex were enrolled. Risk factors included subjects’ age group, gender, polypharmacy, comorbidity, intercurrent diseases and concurrent interactive drugs. Statistical analysis used: Multiple logistic regression analysis was performed to find the association of risk factors with adverse drug reactions. Results: The incidence of suspected adverse drug reactions in hospitalized patients was13% (254/1952, 95%CI). Polypharmacy was the most significant predictor of adverse drug reactions (OR=55.952; 95%CI). Elderly population with multidrug therapy had developed the higher rate of ADRs. Cephalosporin’s 27.6%, fluoroquinolones 15.5%, penicillamines 12.1%, anti-hypertensive 8.7%, NSAIDs 8.3% were more frequently implicated. Risk factors for suspected ADRs were: age (more than 60 years) (OR=1.033: 95% CI), gender , comorbidity (OR=1.008; 95% CI), intercurrent diseases (OR=19.27; 95% CI). Conclusion: Polypharmacy, history of ADR, concurrent interactive drugs and inter current disease were the significant risk factors of adverse drug reactions. The elderly population was the vulnerable age group for ADRs. Multidrug therapy and comorbidity resulted in higher risk of ADRs in an older population. The Higher rate of suspected ADRs were probable and very less severe.Key words: Adverse drug reaction, Age, Comorbidity, Polypharmacy, Risk factor.

Clinical observation of the adverse drug reactions caused by non-ionic iodinated contrast media: results from 109,255 cases who underwent enhanced CT examination in Chongqing, China.

To analyse the pattern and factors that influence the incidence of adverse drug reactions (ADRs) induced by non-ionic iodinated contrast media and to evaluate their safety profiles. Data from 109,255 cases who underwent enhanced CT examination from 1 January 2008 to 31 August 2013 were analysed. ADRs were classified according to the criteria issued by the American College of Radiology and the Chinese Society of Radiology. A total of 375 (0.34%) patients had ADRs, including 281 mild (0.26%); 80 moderate (0.07%); and 14 severe (0.01%) ADRs; no death was found. 302 (80.53%) of the ADRs occurred within 15 min after examination. Patients aged 40-49 years (204 cases, 0.43%; p < 0.01) or who underwent coronary CT angiography (93 cases, 0.61%; p < 0.01) were at a higher risk of ADRs. Female patients (180 cases, 0.40%; p < 0.01) or outpatients had significantly higher incidence rates of ADRs. The symptoms and signs of most of the ADRs were resolved spontaneously within 24 h after appropriate treatment without sequelae. The occurrence of ADRs is caused by the combined effects of multiple factors. The ADRs induced by non-ionic iodinated contrast media are mainly mild ones, while moderate or severe ADRs are relatively rare, suggesting that enhanced CT examination with non-ionic iodinated contrast media is highly safe, and severe adverse events will seldom occur under appropriate care. The study included 109,255 patients enrolled in various types of enhanced CT examinations, which could reflect ADR conditions and regulations in Chinese population accurately and reliably.

Remedies Containing Asteraceae Extracts

The use of complementary therapies by patients has increased over the past 20 years, both in terms of self-medication and physician prescriptions. Among herbal medicines, those containing extracts of Asteraceae (Compositae), such as Echinacea spp., Arnica montana, Matricaria recutita and Calendula officinalis, are especially popular in the primary-care setting. However, there remains a gap between the growing acceptance of these remedies and the lack of data on their safety. The aim of this study was to analyse prescribing patterns and adverse drug reactions (ADRs) for Asteraceae-containing remedies in Germany. Primary-care physicians, all of whom were members of the German National Association of Anthroposophic Physicians were invited to participate in this prospective, multicentre, observational study. During the study period (September 2004 to September 2006), all prescriptions and suspected ADRs for both conventional and complementary therapies were documented using a web-based system. The study centre monitored all ADR reports and conducted a causality assessment according to Uppsala Monitoring Centre guidelines. Relative risks (RRs) and proportional reporting ratios (PRRs) were calculated. Thirty-eight physicians, 55% of whom were general practitioners and 45% were specialists, fulfilled the technical requirements and were included in the investigation. Because documenting all ADRs (i.e. serious and nonserious) was time consuming, only a subgroup consisting of seven physicians agreed to report nonserious in addition to serious ADRs. During the study period, a total of 50 115 patients were evaluated and 344 ADRs for conventional and complementary remedies were reported. Altogether, 18 830 patients (58.0% female, 60.3% children) received 42 378 Asteraceae-containing remedies. The most frequently prescribed Asteraceae was Matricaria recutita (23%), followed by Calendula officinalis (20%) and Arnica montana (20%). No serious ADRs for Asteraceae-containing remedies were reported. In the analysis of the subgroup of seven physicians who also documented nonserious ADRs, 11 nonserious ADRs for Asteraceae-containing remedies occurred in 6961 patients, resulting in an RR of 0.13 (95% CI 0.07, 0.23). The majority of reported ADRs for Asteraceae-containing remedies were classified as uncommon. A subgroup analysis comparing phytotherapeutic and homoeopathic preparations did not reveal any relevant differences. The PRR for Asteraceae-containing remedies with respect to all other prescriptions was 1.7 (95% CI 1.0, 2.0) for the system organ class 'skin and subcutaneous tissue disorders' (six ADRs) and 1.0 (95% CI 0.3, 3.6) for 'gastrointestinal disorders' (three ADRs). Neither result was significant according to the PRR criteria developed by Evans et al. This is the first study to provide a systematic overview of prescribing patterns and ADRs for Asteraceae-containing remedies in the German primary-care sector. Asteraceae-containing remedies were used frequently in this context, especially among children. Our results indicate that treatment with Asteraceae-containing remedies is not associated with a high risk of ADRs.

Colorectal adenomas: a prototype for the use of surrogate end points in the development of cancer prevention drugs.

Carcinogenesis is a multiyear, multistep, multipath disease of progressive genetic alterations and associated tissue damage. Chemoprevention is the use of drugs or other agents to inhibit, delay, or reverse this process. Despite the enormous population at risk of cancer who would benefit, drug

Adverse drug reaction risk factors in older outpatients

Background: Adverse drug reactions (ADRs) are common in older (age ≥65 years) outpatients (prevalence, 5%–35%), but there is no consensus on factors that put these patients at high risk for ADRs. Identifying a uniform set of risk factors would be helpful to develop risk models for ADRs for older outpatients and to implement targeted interventions for those patients at high risk for ADRs. Objective: The aim of this study was to identify potential risk factors for ADRs in older outpatients through a survey of geriatric experts and to determine their prevalence. Methods: A comprehensive literature search was conducted to find published articles on ADRs in older patients. Forty-four potential risk factors were identified through the literature search and 6 additional factors were suggested by the expert panel. Through a modified 2-round survey, based on the Delphi consensus method, of an expert panel of 5 physicians and 5 pharmacists, the probability that each of these 50 potential factors could contribute independently to placing an older outpatient at high risk for an ADR was rated on a 5-point Likert scale. After the survey responses were received, means and 95% Cls were calculated. Consensus was defined as a lower 95% confidence limit ≥4.0. Potential risk factors that reached consensus were then applied to a sample of older outpatients to determine their prevalence. Results: After 2 rounds, the expert panel reached consensus on 21 factors, including 12 medication-related factors and 9 patient characteristics. The most prevalent medication-related risk factors were opioid analgesics; warfarin; non-acetylsalicylic acid, non-cyclooxygenase-2 nonsteroidal anti-inflammatory drugs; anticholinergics; and benzodiazepines. The most prevalent patient characteristics included polypharmacy, multiple chronic medical problems, prior ADR, and dementia. Conclusions: An expert panel was able to reach a consensus on potential risk factors that increase the risk for ADRs in older outpatients. Many risk factors were common in a sample of older outpatients. Future research is needed to determine the predictive validity of these risk factors for ADRs in older outpatients.

Psychopathological syndromes in treatment with gyrase inhibitors

Psychopathological and neurological adverse drug reactions (ADR) have been repeatedly reported during treatment with gyrase inhibitors (fluorquinolones). Results of earlier studies indicated a high risk for ADR especially in the elderly with high dosage medication, psychiatric history and renal dysfunction. The pathophysiological mechanisms involved in the development of adverse CNS effects are not completely understood. GABA-ergic and monoaminergic mechanisms might play a major part. In a retrospective study conducted by the authors 4189 reports of consultant psychiatric examinations were analyzed. In 29 patients the suspicion of psychopathological ADR during treatment with ofloxacin or ciprofloxacin was documented. Psychopathological findings included delirious states, paranoid, depressive and manic syndromes, agitation, sleep disturbances, sopor and stupor. In elderly patients delirious and paranoid syndromes were predominant, whereas affective disturbances occurred more often in younger patients. In most cases multiple morbidity, liver or kidney diseases, simultaneous treatment with other antibiotics and immunosuppressants, former psychiatric disorders or psychosocial stress factors were present. The results of the study, methodological problems, aspects of risk analysis and implications for medical treatment are discussed.