Types Of Adverse Effects Research Articles

Abstract 4725: Phenotypic single-cell analysis of nuclear stress responses in drug-treated prostate cancer cells

Abstract Chemotherapy with anti-cancer drugs aims to stop the growth of cancer cells either by killing them or by stopping them from dividing. The different specificities in inducing cellular damage responses are incompletely understood currently and may underlie the preferential effectiveness of anti-cancer drugs against different types of cancer cells. Better understanding and tools to measure drug-induced phenotypes in vitro may aid in assessing cellular heterogeneity of responses, determining potential effectiveness, estimating amount and types of adverse effects, and predicting likelihood of surviving populations for residual disease. To measure the types and extent of nuclear stress responses to cancer drugs, we studied nuclear organelle, namely nucleolar and Cajal body, phenotypes to drug-induced stress in prostate cancer cells. We utilized organelle-specific markers NPM, Fibrillarin, Coilin, and SMN1 in immunofluorescence staining to determine suitable markers for nuclear organelle stress. We used three different prostate cancer cells lines representing different biological types of advanced prostate cancer (AR positive, AR negative, and expressing AR transcript variant). Based on initial assessments, NPM and coilin immunostaining were selected for automated phenotypic analysis screening for drug effects. Using AI-assisted nuclear segmentation and feature-based single-cell phenotypic analysis, we demonstrated quantitative effects on nuclear morphology, nucleoli, and Cajal bodies with drug treatments. A proof-of-principle study with platinum-based chemotherapeutic agents in clinical use demonstrated heterologous responses to the platinum drugs that are associated with prostate cancer cell types with different AR status. Further, we have defined the corresponding quantitative responses for androgen deprivation therapy (ADT) drugs enzalutamide and bicalutamide in AR-positive prostate cancer cells. Our findings evidence variability of prostate cancer cells’ response to chemotherapy and have implications in future therapy regimen considerations. Furthermore, we have developed a fluorescence light microscopy-based method to assess nuclear stress response phenotypes in prostate cancer cells that can be used for high throughput drug screening. Citation Format: Enkhzaya Batnasan, Minttu Kärkkäinen, Sonja Koivukoski, Pekka Ruusuvuori, Leena Latonen. Phenotypic single-cell analysis of nuclear stress responses in drug-treated prostate cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4725.

Effects of delayed appointments in fixed orthodontic patients due to lockdown during the COVID-19 pandemic

ObjectivesTo determine the frequency of orthodontic emergencies and their impact on the treatment progress caused by delayed appointments due to the lockdown during the COVID-19 pandemic. Materials and methodsTwo hundred thirty-eight patients undergoing fixed orthodontic treatment participated in this cross-sectional study. A pre-structured questionnaire was divided into six parts (Part A-C comprised of orthodontic emergencies and Part D-F comprised of various adverse effects and impacts on treatment progress). Two specialist orthodontists performed clinical examinations to complete the questionnaire. The final data were expressed as frequency and percentage. ResultsMaximum number of patients reported four months after lockdown. Nearly half of the patients reported debonding of at least one of the brackets. Loosening of molar bands and debonding of second molar tubes were observed in 12.6% and 18.9% of patients, respectively. Ligation method failures were reported in 41.2% of the patients. Patients fitted with transpalatal arch/lingual arch skeletal anchorage showed a failure rate of 26.1% and 10%, respectively. Almost 29% of the patient complained of discomfort due to distal wire impingement. Undesired tooth movements were seen in almost 25% of patients. Alignment, space closure, and settling of occlusion were affected in 47.6%, 17.4%, and 35.7% of patients, respectively. ConclusionsThis study helps to determine various types of adverse effects that can occur due to delayed appointments. The study's outcomes suggest that clinicians should be prepared to deal with future pandemics or other causes that might lead to delayed appointments.

Predicting drug adverse effects using a new Gastro-Intestinal Pacemaker Activity Drug Database (GIPADD)

Electrical data could be a new source of big-data for training artificial intelligence (AI) for drug discovery. A Gastro-Intestinal Pacemaker Activity Drug Database (GIPADD) was built using a standardized methodology to test drug effects on electrical gastrointestinal (GI) pacemaker activity. The current report used data obtained from 89 drugs with 4867 datasets to evaluate the potential use of the GIPADD for predicting drug adverse effects (AEs) using a machine-learning (ML) approach and to explore correlations between AEs and GI pacemaker activity. Twenty-four “electrical” features (EFs) were extracted using an automated analytical pipeline from the electrical signals recorded before and after acute drug treatment at three concentrations (or more) on four-types of GI tissues (stomach, duodenum, ileum and colon). Extracted features were normalized and merged with an online side-effect resource (SIDER) database. Sixty-six common AEs were selected. Different algorithms of classification ML models, including Naïve Bayes, discriminant analysis, classification tree, k-nearest neighbors, support vector machine and an ensemble model were tested. Separated tissue models were also tested. Averaging experimental repeats and dose adjustment were performed to refine the prediction results. Random datasets were created for model validation. After model validation, nine AEs classification ML model were constructed with accuracy ranging from 67 to 80%. EF can be further grouped into ‘excitatory’ and ‘inhibitory’ types of AEs. This is the first time drugs are being clustered based on EF. Drugs acting on similar receptors share similar EF profile, indicating potential use of the database to predict drug targets too. GIPADD is a growing database, where prediction accuracy is expected to improve. The current approach provides novel insights on how EF may be used as new source of big-data in health and disease.

Analysis of anticholinergic adverse effects using two large databases: The US Food and Drug Administration Adverse Event Reporting System database and the Japanese Adverse Drug Event Report database.

IntroductionAnticholinergic adverse effects (AEs) are a problem for elderly people. This study aimed to answer the following questions. First, is an analysis of anticholinergic AEs using spontaneous adverse drug event databases possible? Second, what is the main drug suspected of inducing anticholinergic AEs in the databases? Third, do database differences yield different results?MethodsWe used two databases: the US Food and Drug Administration Adverse Event Reporting System database (FAERS) and the Japanese Adverse Drug Event Report database (JADER) recorded from 2004 to 2020. We defined three types of anticholinergic AEs: central nervous system (CNS) AEs, peripheral nervous system (PNS) AEs, and a combination of these AEs. We counted the number of cases and evaluated the ratio of drug–anticholinergic AE pairs between FAERS and JADER. We computed reporting odds ratios (RORs) and assessed the drugs using Beers Criteria®.ResultsConstipation was the most reported AE in FAERS. The ratio of drug–anticholinergic AE pairs was statistically significantly larger in FAERS than JADER. Overactive bladder agents were suspected drugs common to both databases. Other drugs differed between the two databases. CNS AEs were associated with antidementia drugs in FAERS and opioids in JADER. In the assessment using Beers Criteria®, signals were detected for almost all drugs. Between the two databases, a significantly higher positive correlation was observed for PNS AEs (correlation coefficient 0.85, P = 0.0001). The ROR was significantly greater in JADER.ConclusionsThere are many methods to investigate AEs. This study shows that the analysis of anticholinergic AEs using spontaneous adverse drug event databases is possible. From this analysis, various suspected drugs were detected. In particular, FAERS had many cases. The differences in the results between the two databases may reflect differences in the reporting countries. Further study of the relationship between drugs and CNS AEs should be conducted.

СТАТЬИ УГОЛОВНОГО ЗАКОНОДАТЕЛЬСТВА РОССИЙСКОЙ ФЕДЕРАЦИИ В ОТНОШЕНИИ НЕБЛАГОПРИЯТНЫХ ПОСЛЕДСТВИЙ ДЛЯ ЗДОРОВЬЯ И ЖИЗНИ ЧЕЛОВЕКА

The article is devoted to the analysis of the current criminal legislation of the Russian Federation in relation to crimes that provide for liability for causing harm to human health, in order to improve expert and legal tools for determining adverse consequences for human health and life. Research material: the Criminal Code of the Russian Federation and its comments. Research methods: selection and fixation of information, grouping of data, comparison, analysis and generalization of the identified patterns. As a result of the conducted research, a complete list of articles providing for liability for causing serious (51 in total), moderate (30) and minor harm to health (27) was determined. There are articles in which the severity of the harm to health is not specified (10) or the vague term "significant harm" is used (1). A number of articles (26) have been identified, in which the term "harm to health" is used instead of the term "violence", which is specified in the Decisions of the Plenum of the Supreme Court of the Russian Federation or comments to the Criminal Code of the Russian Federation as "harm to health". It is concluded that the concept of harm to health formed in the criminal legislation is broader than the one established in forensic medicine. In the current legislation, there is an abundance and heterogeneity of terms used to describe independent types of adverse effects on human health and life. Unification of the concept of harm caused to human health is required. An original definition of this concept is proposed.

Lethal and Sublethal Effects of Pyriproxyfen on Apis and Non-Apis Bees.

Pyriproxyfen is a juvenile hormone mimic used extensively worldwide to fight pests in agriculture and horticulture. It also has numerous applications as larvicide in vector control. The molecule disrupts metamorphosis and adult emergence in the target insects. The same types of adverse effects are expected on non-target insects. In this context, the objective of this study was to evaluate the existing information on the toxicity of pyriproxyfen on the honey bee (Apis mellifera) and non-Apis bees (bumble bees, solitary bees, and stingless bees). The goal was also to identify the gaps necessary to fill. Thus, whereas the acute and sublethal toxicity of pyriproxyfen against A. mellifera is well-documented, the information is almost lacking for the non-Apis bees. The direct and indirect routes of exposure of the non-Apis bees to pyriproxyfen also need to be identified and quantified. More generally, the impacts of pyriproxyfen on the reproductive success of the different bee species have to be evaluated as well as the potential adverse effects of its metabolites.

Safety of Single-Dose Oral Cefixime, Intramuscular Ceftriaxone, or Intramuscular Gentamicin for the Treatment of Gonorrhea: A Systematic Review and Meta-analysis.

To compare the incidence and types of adverse effects between 3 recommended treatment options for gonorrhea and to compare the incidence of injection site pain between single-dose intramuscular ceftriaxone and gentamicin. A keyword search of MEDLINE (1966 to September 2020), EMBASE (1947 to September 2020), and International Pharmaceutical Abstracts (1970 to September 2020) was conducted. The electronic search was supplemented with manual screening of references. Comparator studies reporting adverse effect outcomes of treatment with cefixime, ceftriaxone, or gentamicin for gonorrhea in humans were included. Data extracted included study year, authors, aim, setting, population, dosing protocols, and outcome results. A total of 298 articles were identified, of which 6 met inclusion criteria. Two randomized controlled trials compared ceftriaxone and gentamicin. Four randomized controlled trials compared cefixime and ceftriaxone. No differences were noted for the occurrence of at least 1 adverse effect between gentamicin and ceftriaxone (odds ratio [OR] = 0.81; 95% CI = 0.56-1.18) or between cefixime and ceftriaxone (OR = 1.11; 95% CI = 0.21-5.93). Injection site pain (ceftriaxone and gentamicin) and other adverse effects (all drugs) were common but occurred at similar rates between groups. Results of this review show a lack of signal for safety concerns with gentamicin-based regimens for the treatment of gonorrhea. Future research should investigate patient acceptability, especially for intramuscular injections. The use of single-dose cefixime, ceftriaxone, and gentamicin-based regimens for treatment of gonorrhea appears to be safe and acceptable for use in practice.

Contralateral Fracture-Dislocation of the Shoulder Due to Electric Shock

Electrical injuries are relatively common and can produce various types of adverse effects on organs, but injuries to the musculoskeletal system are less frequent. Bone injuries can involve both long and flat bones and they encompass several types: osteonecrosis, dislocation, and fracture. Cases of shoulder dislocation with fracture have been reported in the literature; the mechanism is linked to the tetanizing effect from the alternating current flow through the shoulder without a fall or a violent trauma. Posterior dislocation is the most common shoulder injury. We report the case of an anterior fracture-dislocation of the shoulder contralateral to the entry point and we emphasize that any pain or functional impotence in the context of electric shock, even when it’s distant from the entry point, should trigger suspicion of bone injury.

Denosumab treatment for giant-cell tumor of bone: a systematic review of the literature.

Denosumab is a human monoclonal antibody (mAb) that specifically inhibits tumor-associated bone lysis through the RANKL pathway and has been used as neoadjuvant therapy for giant-cell tumor of bone (GCTB) in surgical as well as non-surgical cases. The purpose of this systematic review of the literature, therefore, is to investigate: (1) demographic characteristics of patients affected by GCTBs treated with denosumab and the clinical impact, as well as, possible complications associated with its use (2) oncological outcomes in terms of local recurrence rate (LRR) and development of lung metastasis, and (3) characteristics of its treatment effect in terms of clinical, radiological, and histological response. A systematic review of the literature was conducted using PubMed, EMBASE, and COCHRANE search including the following terms and Boolean operators: "Denosumab" AND "primary bone tumor", "denosumab" AND "giant cell tumor", "denosumab" AND "treatment", and finally, "denosumab" AND "giant cell tumor" AND "treatment" since 2000. After applying inclusion and exclusion criteria, a total of 19 articles were included. The quality of the included studies was assessed using STROBE for the assessment of observational studies. A total of 1095 patients were included across all 19 studies. Across all the studies included, there were 615 females and 480 males. The mean patient age was 33.7 ± 8.3years when starting the denosumab treatment. The pooled weighted local recurrence rate was 9% (95% CI 6-12%) and the pooled weighted metastases rate was 3% (95% CI 1-7%). The most common adverse event was fatigue and muscular pain. Radiologic response was estimated to occur in 66-100% of the patients. A significant reduction in pain under denosumab treatment was reported in seven studies and additional improvement in function and mobility was reported by several authors. Only two studies reported musculoskeletal tumor society (MSTS) scores which were better after denosumab treatment. The use of denosumab as an adjuvant treatment of GCTB has shown a positive but variable histological response with consistent radiological changes and several types of adverse effects. There is a positive clinical response in terms of pain relief with decrease on the morbidity of surgical procedures to be performed. Finally, oncological outcomes are disparate with neither effect on metastatic disease nor local recurrence rates. IV.

Comparing the efficacy and safety of IL-17 inhibitors for treatment of moderate-to-severe psoriasis: a randomized double blind pilot study with a review of literature.

Psoriasis is a chronic skin disease in which interleukin-17A (IL-17A) has been found to play an important role. Commercially available anti-IL-17 drugs include brodalumab, ixekizumab (IXE), and secukinumab (SEC). To compare the safety and efficacy of IXE and SEC in patients with moderate-to-severe plaque psoriasis. The patients were randomized to the IXE or SEC group. Effectiveness was estimated by Physician's Global Assessment (PGA), Psoriasis Area and Severity Index (PASI), and Dermatology Life Quality Index (DLQI). Safety was assessed by documentation of adverse effects (AEs), routine laboratory values, and injection-site and allergic reactions. There were 155 patients in the IXE group and 158 in the SEC group. At week 12, PASI 75 was 76.77% (IXE) vs. 67.09% (SEC); PASI 90 42.58% (IXE) vs. 32.28% (SEC); PGA score of 0 or 1 at week 40 (79.52% vs. 74.4%) and at week 52 (61.83% vs. 58.12%) (p < 0.001). Also, DLQI score improvement was more pronounced in the IXE group. The rates and types of AEs were similar in both groups. Although both groups demonstrated a robust clinical response, a significant improvement in patient quality of life, and a satisfactory safety profile, the IXE group scored a notch higher.

Using the Symmetry Analysis Design to Screen for Adverse Effects of Non-vitamin K Antagonist Oral Anticoagulants.

Knowledge on adverse effects (AEs) related to non-vitamin K antagonist oral anticoagulants (NOACs) in real-world populations is sparse. Our objective was to identify signals of potential AEs in patients with atrial fibrillation (AF) initiating NOAC treatment using a hypothesis-free screening approach. Using the nationwide Danish registries, we identified patients with AF initiating dabigatran, rivaroxaban, or apixaban between 2011 and 2015 (n=50,627). Applying a symmetry analysis design, we screened for AEs of NOAC, as reflected by new drug treatments, incident diagnoses, or procedures. For signals with the lowest number needed for one additional patient to be harmed (NNTH), we evaluated whether they likely represented genuine AEs or other types of associations. Signals assessed as potential AEs were grouped into five categories for analysis of effect modification according to patient and drug characteristics. Of the identified signals, 61 were classified as potential AEs. Most signals could be categorized as the following types of AEs: bleedings, non-bleeding gastrointestinal symptoms, mental disease, urinary tract disorders, and musculoskeletal symptoms. Older age and first-ever use of anticoagulants was associated with strengthening of all "NOAC-adverse effect" associations. Conversely, use of low-dose NOAC and apixaban led to attenuation of most associations. Through a symmetry analysis-based hypothesis-free screening of large-scale healthcare databases, we were able to confirm well-established AEs of NOAC therapy in clinical practice as well as potential AEs that deserve further investigation.

Research Brief: Self-Reports of a Constellation of Persistent Antiandrogenic, Estrogenic, Physical, and Psychological Effects of Finasteride Usage Among Men.

Our research objective is to understand more, through subjective, self-reports on discussion boards/forums, persons’ experiences associated with the use of drugs that alter androgen metabolism, such as finasteride. Finasteride is an orally active, specific inhibitor of 5α-reductase, which is localized to many androgen-dependent tissues. Finasteride inhibits the conversion of testosterone (T) to dihydrotestosterone (DHT), and is commonly used to treat benign prostatic hypertrophy (BPH) and male pattern baldness (MPB), both disorders associated with elevated DHT levels and 5α-reductase activity in the prostate and hair follicles, respectively. It is now acknowledged that long-term use and discontinuation of finasteride has adverse effects (AEs); however, these claims have not been well documented. In this study, discussion board posts (forums) were analyzed as self-reports of what finasteride users indicate is problematic for them. Reports were categorized by the age of subjects as well as the types of AEs described: antiandrogenic, estrogenic, central, and nonspecific/severe. A total of 244 cases were recorded and analyzed on the discussion forum on propeciahelp.com. Among these, 74 (32%) cases reported antiandrogenic affects, 43 (19%) reported estrogenic effects, 70 (30%) reported central effects, 11 (5%) reported nonspecific/severe AEs, and 31 (14%) reported AEs in all categories. The categorization of AEs may prompt further investigation into the pathophysiology of post-finasteride syndrome (PFS). Also, subjective reports may engender greater understanding of the perceived lasting AEs of finasteride.

Antimicrobial activity of some plant extracts against bacterial pathogens isolated from faeces of red deer (Cervus elaphus).

Antibacterial activity is the most widely studied aspect of plant extracts. Antibiotics extensively produced and consumed in large quantities, have proved to be problematic due to various types of adverse effects. The development of bacterial resistance to currently available antibiotics has necessitated the search for new antibacterial agents. One of the alternative strategies for fighting antibiotic- resistant bacteria is the use of natural antimicrobial substances such as plant extracts. We tested the antimicrobial activity of nine extracts from different plants against pathogenic bacteria isolated from the faeces of red deer (Cervus elaphus). Selected bacteria commonly contaminated the natural environment and constitute a source of infection in other animals and humans. Extracts obtained from the following plants were tested: Hypericum perforatum L., Chamomilla recutita L., Achillea millefolium L., Salvia officinalis L., Thymus vulgaris L., Pinus sylvestris L., Mentha x piperita L., Valeriana officinalis L. and Foeniculum vulgare Mill. The highest degree of antibacterial properties was observed for Mentha x piperita L., narrower spectrum of activity possessed Hypericum perforatum L. Extracts of Achillea millefolium L. had the lowest spectrum of antibacterial activity. Our study confirms that many plant extracts shows in vitro antibacterial activity.

Statins and the cholesterol mortality paradox.

Large-scale randomised controlled trials, carried out in the context of secondary cardiovascular prevention, have shown that statins are superior to placebo: these drugs were shown to decrease cardiovascular events and total mortality. A further set of clinical trials compared high intensity to low/standard intensity LDL cholesterol lowering in the same setting (using either statins or a statin/ezetimibe association). In this case, a decrease in LDL cholesterol and a concomitant significant reduction in cardiovascular events were seen with intensive therapy, however with no change in total mortality. This phenomenon we may term the LDL cholesterol mortality paradox. It could be due either to the prevention (by high-intensity therapy) of episodes not severe enough to lead to the death of patients, or to high-intensity therapy leading to the death of some patients at the same time as preventing the death of others, with a null aggregate effect. Several types of adverse effects have been seen with statin therapy, such as a possible increased incidence of Diabetes mellitus and of myopathy. The decision to start high-intensity LDL cholesterol lowering (rather than low- or moderate-intensity statin treatment) should be evaluated on a case-by-case basis, taking into consideration the overall aspects of each patient, including the patient's preferences. High-intensity LDL cholesterol lowering, up to the present moment, has failed to produce a change in overall prognosis (total mortality), and should not therefore be mandatory in secondary cardiovascular prevention. It remains to be seen if a similar LDL cholesterol mortality paradox occurs with new drugs targeting plasma lipids.

Most systematic reviews of adverse effects did not include unpublished data

ObjectivesWe sought to identify the proportion of systematic reviews of adverse effects which search for unpublished data and the success rates of identifying unpublished data for inclusion in a systematic review. Study Design and SettingTwo reviewers independently screened all records published in 2014 in the Database of Abstracts of Reviews of Effects (DARE) for systematic reviews where the primary aim was to evaluate an adverse effect or effects. Data were extracted on the types of adverse effects and interventions evaluated, sources searched, how many unpublished studies were included, and source or type of unpublished data included. ResultsFrom 9,129 DARE abstracts, 348 met our inclusion criteria. Most of these reviews evaluated a drug intervention (237/348, 68%) with specified adverse effects (250/348, 72%). Over a third (136/348, 39%) of all the reviews searched, a specific source for unpublished data, such as conference abstracts or trial registries, and nearly half of these reviews (65/136, 48%) included unpublished data. An additional 13 reviews included unpublished data despite not searching specific sources for unpublished studies. Overall, 22% (78/348) of reviews included unpublished data/studies. ConclusionMost reviews of adverse effects do not search specifically for unpublished data but, of those that do, nearly half are successful.

Assessing and Reporting the Adverse Effects of Antipsychotic Medication: A Systematic Review of Clinical Studies, and Prospective, Retrospective, and Cross-Sectional Research.

Adverse effects (AEs) of antipsychotic medication have important implications for patients and prescribers in terms of well-being, treatment adherence, and quality of life. This review summarizes strategies for collecting and reporting AE data across a representative literature sample to ascertain their rigor and comprehensiveness. A PsycINFO search, following preferred reporting items for systematic reviews and meta-analyses statement guidelines, was conducted in English-language journals (1980 to July 2014) using the following search string: (antipsychotic* or neuroleptic*) and (subjective effect or subjective experience or subjective response or subjective mental alterations or subjective tolerability OR subjective well-being or patient perspective or self-rated effects or adverse effects or side effects). Of 7825 articles, 384 were retained that reported quantified results for AEs of typical or atypical antipsychotics among transdiagnostic adult, adolescent, and child populations. Information extracted included: types of AEs reported, how AEs were assessed, assessment duration, assessment of the global impact of antipsychotic consumption on subjective patient wellbeing, and conflict of interest due to industry sponsorship. Neurological, metabolic, and sedation-related cognitive effects were reported more systematically than affective, anticholinergic, autonomic, cutaneous, hormonal, miscellaneous, and nonsedative cognitive effects. The global impact of AEs on patient well-being was poorly assessed. Cross-sectional and prospective research designs yielded more comprehensive data about AE severity and prevalence than clinical or observational retrospective studies. The detection and classification of AEs can be improved through the use of standardized assessment instruments and consideration of the global impact on subjective patient wellbeing. Observational research can supplement information from clinical trials to improve the ecological validity of AE data.

Effect of thyroid hormone status and concomitant medication on statin induced adverse effects in hyperlipidemic patients.

Statins are effective treatment for the prevention of cardiovascular diseases and used extensively worldwide. However, adverse effects induced by statins are the major barrier of maximalizing cardiovascular risk reduction. Hypothyroidism and administration of drugs metabolized on the same cytochrome P450 (CYPP450) pathways where statin biotransformation occurs represent a significant risk factor for statin induced adverse effects including myopathy. Simvastatin, atorvastatin and lovastatin are metabolized by CYP3A4, fluvastatin by CYP2C9, while rosuvastatin by CYP2C9 and 2C19. We investigated the levels of the free thyroid hormones and CYP metabolism of concomitant medication in 101 hyperlipidemic patients (age 61.3 +/- 9.9 ys) with statin induced adverse effects including myopathy (56 cases; 55.4%), hepatopathy (39 cases; 38.6%) and gastrointestinal adverse effects (24 cases; 23.8%). Abnormal thyroid hormone levels were found in 5 patients (4.95%); clinical hypothyroidism in 2 and hyperthyroidism in 3 cases. 11 patients had a positive history for hypothyroidism (10.9%). Myopathy occured in one patient with hypothyroidism and two patients with hyperthyroidism. There were no significant differences in the TSH, fT4 and fT3 levels between patients with statin induced myopathy and patients with other types of adverse effects. 78 patients (77.2%) were administered drugs metabolized by CYP isoforms also used by statins (3A4: 66 cases (65.3%); 2C9: 67 cases (66.3%); 2C19: 54 cases (53.5%)). Patients with myopathy took significantly more drugs metabolized by CYP3A4 compared to patients with other types of adverse effects (p < 0.05). More myopathy cases were found in patients on simvastatin treatment (52% vs. 38%, ns.), while significantly less patients with myopathy were on fluvastatin treatment (13% vs. 33%, p < 0.05) compared to patients with other types of statin induced adverse effects. Both abnormal thyroid hormone status and administration of drugs metabolized by CYP3A4, 2C9 and 2C19 are common in our patients with statin induced adverse effects. Normalizing the thyroid hormone status and optimizing of the concomitant medication may reduce the risk of statin induced adverse effects.

Adverse events in patients in a Brazilian intensive care according to the readmission

Security policies for the patient are of interest to any health professional. The rates of adverse events in hospitals reach values ranging between 3.7 and 16.6%, being the highest range (40 to 70%) considered preventable or avoidable [1]. The objective of this study is to assess the prevalence and types of adverse effects in intensive care patients according to readmission.

Tolerabilities of Artemisinin-Based Combination Drugs among Patients with Uncomplicated Malaria in a Tertiary Institution Benin City, Nigeria

Background: The policy governing the treatment of malaria in Nigeria was changed in 2005 instituting the Artemisinin-Based Combination Therapies [ACTs] as first-line Drugs instead of Chloroquine due to rapidly developing resistance of Plasmodium falciparum. Methodology: The tolerability to [ACTs] was assessed in patients using a structured questionnaire and Visual analogue scale. These instruments were distributed systematically among the patients that presented with uncomplicated malaria after obtaining consent from the University of Benin Teaching Hospital, Benin City, Nigeria. Results: Among the five hundred and twenty patients that participated in the tolerability assessment of four different types of ACTs, male and female ratio was 1.3:1, Mean age 32.06 ± 2.3 years [Mean ± SD]. Artemether-Lumefantrine was the most frequently utilized and most tolerable. Two hundred and five [52.69%] respondents reported with forty-one different types of adverse effects of nine major systemic classes. Body weakness was the most frequent adverse effects reported in 112[54.63%] respondents. Adverse effects were significantly dependent on the type of ACTs used p<0.05; these were found to be most common with Artesunate-Mefloquine. Eleven patients were hospitalized due to very severe Body weakness and Dizziness. These severities were found common with Artesunate-Amodiaquine and Artesunate- Mefloqunie respectively. Despite the adverse effects, four hundred and seventy-six respondents (91.53%) were willing to repeat ACTs another time they have malaria. There were significant differences in symptomatic response on Days 0, 1, 2, 3, 7, 14 and 28 (p<0.05). 93% respondents felt extremely sick on Day 0, 68% had persistent fever on the third day of treatment and 71% had improved response after day 7. Conclusion: Anecdotal reports showed that ACTs have a modest tolerability, they are therefore recommended for patients that have uncomplicated malaria.

Integrative Chemical–Biological Read-Across Approach for Chemical Hazard Classification

Traditional read-across approaches typically rely on the chemical similarity principle to predict chemical toxicity; however, the accuracy of such predictions is often inadequate due to the underlying complex mechanisms of toxicity. Here, we report on the development of a hazard classification and visualization method that draws upon both chemical structural similarity and comparisons of biological responses to chemicals measured in multiple short-term assays ("biological" similarity). The Chemical-Biological Read-Across (CBRA) approach infers each compound's toxicity from both chemical and biological analogues whose similarities are determined by the Tanimoto coefficient. Classification accuracy of CBRA was compared to that of classical RA and other methods using chemical descriptors alone or in combination with biological data. Different types of adverse effects (hepatotoxicity, hepatocarcinogenicity, mutagenicity, and acute lethality) were classified using several biological data types (gene expression profiling and cytotoxicity screening). CBRA-based hazard classification exhibited consistently high external classification accuracy and applicability to diverse chemicals. Transparency of the CBRA approach is aided by the use of radial plots that show the relative contribution of analogous chemical and biological neighbors. Identification of both chemical and biological features that give rise to the high accuracy of CBRA-based toxicity prediction facilitates mechanistic interpretation of the models.