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Drug-induced vascular injury (DIVI) is a recurrent challenge in the development of novel pharmaceutical agents. In recent years, DIVI has been occasionally observed in nonhuman primates given RNA-targeting therapeutics such as antisense oligonucleotide therapies (ASOs) during chronic toxicity studies. While DIVI in laboratory animal species has been well characterized for vasoactive small molecules, and immune-mediated responses against large molecule biotherapeutics have been well described, there is little published information regarding DIVI induced by ASOs to date. Preclinical DIVI findings in monkeys have caused considerable delays in development of promising new ASO therapies, because of the uncertainty about whether DIVI in preclinical studies is predictive of effects in humans, and the lack of robust biomarkers of DIVI. This review of DIVI discusses clinical and microscopic features of vasculitis in monkeys, their pathogenic mechanisms, and points to consider for the toxicologist and pathologist when confronted with ASO-related DIVI. Relevant examples of regulatory feedback are included to provide insight into risk assessment of ASO therapies. [ABSTRACT FROM AUTHOR]

Drug-induced vascular injury (DIVI) is a recurrent challenge in the development of novel pharmaceutical agents. Although DIVI in laboratory animal species has been well characterized for vasoactive small molecules, there is little available information regarding DIVI associated with biotherapeutics such as peptides/proteins or antibodies. Because of the uncertainty about whether DIVI in preclinical studies is predictive of effects in humans and the lack of robust biomarkers of DIVI, preclinical DIVI findings can cause considerable delays in or even halt development of promising new drugs. This review discusses standard terminology, characteristics, and mechanisms of DIVI associated with biotherapeutics. Guidance and points to consider for the toxicologist and pathologist facing preclinical cases of biotherapeutic-related DIVI are outlined, and examples of regulatory feedback for each of the mechanistic types of DIVI are included to provide insight into risk assessment. [ABSTRACT FROM AUTHOR]

This article reviews the regulatory guidelines that provide for the inclusion of recovery groups in toxicology studies, presents the challenges in the design and interpretation of nonclinical recovery studies, and summarizes the best practices for the role of an anatomic pathologist regarding toxicology studies with recovery groups. Evaluating the potential recovery of histopathologic findings induced by a biopharmaceutical requires the active participation of one or more anatomic pathologists. Their expertise is critical in risk assessment regarding the potential for recovery as well as providing scientific guidance in the design and evaluation of studies with recovery groups. [ABSTRACT FROM PUBLISHER]

The purpose of this study is to provide an overview of patients' experiences using a precision medicine (PM) clinic that conducts pharmacogenomics-based (PGx) testing for adverse drug reactions. The study aimed to identify the features of the clinic valued most by patients and areas for improvement. A paper survey was used to collect data. Survey questions focused on patients' perceptions of the PM testing and the overall clinic experience. Sixty-seven patients completed the survey. Quantitative data were analyzed using SPSS and frequencies were reported. Open-ended responses were coded and organized thematically. Patients reported that the clinic services increased confidence in their medication usage. Feeling respected by staff, receiving education, and quick appointments were highly valued by patients. Suggested areas for improvement included better communication from the clinic to patients, expansion of clinic services, and education for other healthcare providers. The findings demonstrate that patient experience goes beyond the clinical care provided. Current and potential future providers of PM should invest the time and energy to configure their care delivery system to enhance the patient experience. [ABSTRACT FROM AUTHOR]

The article presents abstracts related to medical topics including transcatheter aortic valve implantation, the side effect of neostigmine, and the administration of remifentanil patient-controlled analgesia in labour.

The article presents a discussion paper on the impact of cytotoxic chemotherapy on patient's quality of life. It is cited that the aim of cytotoxic chemotherapy is to destroy the tumor before the drugs kill the patient. The inability of cytotoxic drugs to distinguish between normal and malignant cells puts the body at risk of some degree of toxicity. Patients who received the treatment reported greater incidence of treatment-related side effects than those receiving hormonal therapy.

The article presents abstracts on dentistry which include oral health, adverse drug interactions in dentistry and lysine decarboxylase in gingivitis.

The article focuses on therapeutic targets and scientific progress toward the development of appropriate animal models by utilizing novel strategies that will help in understanding the pathogenesis and pathophysiology of anorexigen-induced valvulopathy and pulmonary arterial hypertension (PAH). According to the author, various safety issues, such as valvulopathy with fenfluramine and PAH with aminorex, were initially not predicted by routine preclinical toxicology studies. The author also discusses the translatability challenges of drug effects from animals to humans.

Background: Post-intensive care syndrome (PICS) is defined as a new or worsening impairment in physical, cognitive, or mental health following critical illness. Intensive care unit recovery centers (ICU-RC) are one means to treat patients who have PICS. The purpose of this study is to describe the role of pharmacists in ICU-RCs. Research Question: What is the number and type of medication interventions made by a pharmacist at an ICU-RC at 12 different centers? Study Design and Methods: This prospective, observational study was conducted in 12 intensive care units (ICUs)/ICU-RCs between September 2019 and July 2021. A full medication review was conducted by a pharmacist on patients seen at the ICU-RC. Results: 507 patients were referred to the ICU-RC. Of these patients, 474 attended the ICU-RC and 472 had a full medication review performed by a pharmacist. Baseline demographic and hospital course data were obtained from the electronic health record and at the ICU-RC appointment. Pharmacy interventions were made in 397 (84%) patients. The median number of pharmacy interventions per patient was 2 (interquartile range [IQR] = 1,3). Medications were stopped and started in 124 (26%) and 91 (19%) patients, respectively. The number of patients that had a dose decreased and a dose increased was 51 (11%) and 43 (9%), respectively. There was no difference in the median total number of medications that the patient was prescribed at the start and end of the patient visit (10, IQR = 5, 15). Adverse drug event (ADE) preventive measures were implemented in 115 (24%) patients. ADE events were identified in 69 (15%) patients. Medication interactions were identified in 30 (6%) patients. Interpretation: A pharmacist plays an integral role in an ICU-RC resulting in the identification, prevention, and treatment of medication-related problems. This paper should serve as a call to action on the importance of the inclusion of a pharmacist in ICU-RC clinics. [ABSTRACT FROM AUTHOR]

This document is a response to a comment made by Dr. Yoshiro Noguchi regarding a paper titled "Drugs That Interact With Colchicine Via Inhibition of Cytochrome P450 3A4 and P-Glycoprotein: A Signal Detection Analysis Using a Database of Spontaneously Reported Adverse Events (FAERS)." The authors of the response address two main issues raised by Dr. Noguchi: the potential for false signals due to overwhelming reports in concomitant medications, and the statistical approach used. The authors clarify that their study aimed to understand the potential impact of known interactions rather than finding unknown interactions. They also explain their methodology, which involved analyzing situations with at least 5 reports mentioning the adverse event and both medications. The authors disagree with the claim that their methods are questionable and defend their approach as conservative and transparent. [Extracted from the article]

This paper critically examines the approach to studying and intervening in organizations that derives from the work of Melanie Klein. It proposes that Klein's emphasis on reparation, while clearly valuable for effecting change, can also induce undue guilt that stymies employee subjectivity and damages the organization. The term "reparation compulsion" is offered to capture this particular dynamic. Defined as the incessant drive to atone for guilt, reparation compulsion has both individual and collective correlates that together constitute a unique and hitherto unexplored organizational pathology. Two vignettes are used to demonstrate the limits of reparation in a work setting before turning to Menzies' classic case study of a nursing service, which is revisited in light of the pitfalls of guilt-driven labor. Together, these illustrations revise and expand upon Menzies' concept of social defense, placing reparation compulsion at the core of a newfound "depressive" social defense system that has direct repercussions for those working in the caring professions, and particularly those afflicted with "compassion fatigue." Specifically, the argument is made that compassion fatigue is not just an unfortunate side effect of caring, but constitutive of an organization in which repairing others requires a chronic disrepair of the self. The paper concludes with discussing the implications for the psychoanalytic study of organizations. [ABSTRACT FROM AUTHOR]

Background: The use of biomarkers varies from disease etiognosis and diagnosis to signal detection, risk prediction, and management. Biomarker use has expanded in recent years, however, there are limited reviews on the use of biomarkers in pharmacovigilance and specifically in the monitoring and management of adverse drug reactions (ADRs). Objective: The objective of this manuscript is to identify the multiple uses of biomarkers in pharmacovigilance irrespective of the therapeutic area. Design: This is a systematic review of the literature. Data Sources and Methods: Embase and MEDLINE database searches were conducted for literature published between 2010-March 19, 2021. Scientific articles that described the potential use of biomarkers in pharmacovigilance in sufficient detail were reviewed. Papers that did not fulfill the United States Food and Drug Administration (US FDA) definition of a biomarker were excluded, which is based on the International Conference on Harmonisation (ICH)−E16 guidance. Results: Twenty-seven articles were identified for evaluation. Most articles involved predictive biomarkers (41%), followed by safety biomarkers (38%), pharmacodynamic/response biomarkers (14%), and diagnostic biomarkers (7%). Some articles described biomarkers that applied to multiple categories. Conclusion: Various categories of biomarkers including safety, predictive, pharmacodynamic/response, and diagnostic biomarkers are being investigated for potential use in pharmacovigilance. The most frequent potential uses of biomarkers in pharmacovigilance in the literature were the prediction of the severity of an ADR, mortality, response, safety, and toxicity. The safety biomarkers identified were used to evaluate patient safety during dose escalation, identify patients who may benefit from further biomarker testing during treatment, and monitor ADRs. [ABSTRACT FROM AUTHOR]

Anaphylaxis is an uncommon but important cause of serious morbidity and even mortality in the perioperative period. The Australian and New Zealand College of Anaesthetists (ANZCA) with the Australian and New Zealand Anaesthetic Allergy Group (ANZAAG) have developed clinical management guidelines that include six crisis management cards. The content of the guidelines and cards is based on published literature and other international guidelines for the management of anaesthesia-related and non-anaesthesia-related anaphylaxis. The evidence is summarised in the associated background paper (Perioperative Anaphylaxis Management Guidelines [2016] www.anzca.edu.au/resources/endorsed-guidelines and www.anzaag.com/Mgmt%20Resources.aspx). These guidelines are intended to apply to anaphylaxis occurring only during the perioperative period. They are not intended to apply to anaphylaxis outside the setting of dedicated monitoring and management by an anaesthetist. In this paper guidelines will be presented along with a brief background to their development. [ABSTRACT FROM AUTHOR]

Objective: Drug interactions are a common cause of morbidity and mortality and may require prompt discontinuation of therapeutic regimens due to harmful side effects. Patients with acute coronary syndromes are likely to be prescribed multiple medications that are metabolized through the cytochrome P450 system, increasing the probability for drug interaction. Atorvastatin and simvastatin are both well known to interact with the oral P2Y12 agent ticagrelor. The purpose of this paper is to describe the interaction of ticagrelor with rosuvastatin leading to rhabdomyolysis, which is less clearly defined in the literature. Method: We report a case of a 74-year-old male who presented with bilateral lower extremity weakness and difficulty ambulating for one month after being prescribed ticagrelor for a drug eluting stent, in the setting of already being on rosuvastatin. His clinical picture and laboratory findings were consistent with a diagnosis of rhabdomyolysis. His medications were adjusted to a regimen of clopidogrel and alirocumab. One month later, he returned to his baseline status. Results: The mechanism of interaction between rosuvastatin and ticagrelor appears to be multifactorial. It may be caused by CYP450-mediated metabolism from a small amount of crossover between isoenzymes. Ticagrelor may also cause acute kidney injury, increasing the concentration of rosuvastatin. Other mechanisms of interaction include genetic differences in the organic anion transporter polypeptides and transportation through p-glycoprotein. Conclusion: Future pharmacokinetic studies are warranted to better understand the interaction. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to assess the safety profiles of two biosimilar medicines (rituximab and trastuzumab) in the treatment of cancer patients within a Portuguese oncology hospital. Methods: This hospital-based prospective observational study followed a cohort event monitoring approach focused on signalling suspected adverse drug reactions (ADRs). Patients undergoing treatment with rituximab biosimilar CT-P10 (Truxima®) or trastuzumab biosimilar CT-P6 (Herzuma®) were recruited over an 11-month and a 6-month period, respectively. Clinicians identified eligible patients and used paper-based forms to report all ADRs associated with biosimilar medicines. ADR case reports were assessed for seriousness, expectedness and causality in the Pharmacovigilance Unit of Coimbra. Results: Ninety-four patients received biosimilar medicines (rituximab, n = 35; trastuzumab, n = 59). Of those, 4 patients (11.4%) experienced 16 ADRs with rituximab and 1 patient (1.7%) experienced 5 ADRs with trastuzumab. All case reports contained serious and expected ADRs that were at least probably related with biosimilar medicines under study. Based on the MedDRA PT coding, the most reported ADR for rituximab CT-P10 was chest discomfort (n = 4; 19.1%), followed by odynophagia (n = 2; 9.5%). Trastuzumab CT-P6 was associated with back pain, headache, pain in extremity, tachypnoea and tremor (each, n = 1; 4.8%). Conclusion: The results of this study suggest that using biosimilar rituximab and biosimilar trastuzumab to treat cancer patients in the real-world clinical setting is associated with acceptable safety profiles. No new safety problems were identified. [ABSTRACT FROM AUTHOR]

The purpose of a non-inferiority trial is to assert the efficacy of an experimental treatment compared with a reference treatment by showing that the experimental treatment retains a substantial proportion of the efficacy of the reference treatment. Statistical methods have been developed to test multiple experimental treatments in three-arm non-inferiority trials. In this paper, we report the development of procedures that simultaneously test the non-inferiority and the superiority of experimental treatments after the assay sensitivity has been established. The advantage of the proposed test procedures is the additional ability to identify superior treatments while retaining an non-inferiority testing power comparable to that of existing testing procedures. Single-step and stepwise procedures are derived and then compared with each other to determine their relative testing power and testing error in a simulation study. Finally, the suggested procedures are illustrated with two clinical examples. [ABSTRACT FROM AUTHOR]

Background: Idiopathic pulmonary fibrosis (IPF) is the most common idiopathic interstitial pneumonia and has a median survival after diagnosis of 2–5 years. Pirfenidone is the first approved antifibrotic drug for the treatment of IPF. Here we report the functional progress, side effects and survival data of a population of patients with IPF, diagnosed at our centre and treated with pirfenidone. Methods: We enrolled 91 patients with IPF (71 males) treated with pirfenidone. Clinical, survival and functional details were collected retrospectively at start of therapy and after 12, 24, 36 and 48 months of treatment. Lung function tests at least 12 months before starting therapy were available for 40 patients and were entered in the database, as well as side effects. Results: During the observation period (922 ± 529 days), 27 patients died, 5 patients underwent lung transplant and 10 patients interrupted therapy due to adverse events or IPF progression. The median survival was 1606 days. There was a significant reduction in disease progression rate, as measured by trend of forced vital capacity, after 1 year of therapy with respect to before treatment (p = 0.0085). Forced vital capacity reduction rate was progressively higher in the subsequent years of treatment. Treatment-related side effects were reported in 25 patients and were predominantly mild. Overall, four patients discontinued therapy due to severe photosensitivity. Conclusions: Our findings confirm the efficacy of pirfenidone in reducing functional progression of IPF and its excellent safety profile in a real-life setting. This study, designed on a long-term follow up, contributes to the growing evidence on safety, tolerability and efficacy of pirfenidone in IPF. The reviews of this paper are available via the supplemental material section. [ABSTRACT FROM AUTHOR]

Aim: Implementation of a web-form based pharmacovigilance plan for the spontaneous notification of adverse events to the Comirnaty® COVID-19 vaccine during its administration to hospital healthcare professionals. Methods: An electronic pharmacovigilance form was developed containing 8 pre-defined event options, an open answer option for the description of other events and/or symptoms, and a question about the overall intensity of symptoms. The adverse events reports were standardized according to physiological and pathological condition. Results: A total of 4119 adverse events notifications were obtained with a 45% rate of electronic notification. The most clinically relevant events reported were:tachycardia (n = 19), dyspnea (n = 7), chest pain (n = 6), facial/labial edema (n = 6), lipothymia (n = 5), bronchospasm (n = 2), herpetic infection (n = 2), vasculitis (n = 2), arrhythmia (n = 1), difficult to control arterial hypertension (n = 1), gastritis (n = 1), and spontaneous abortion (n = 1). Regarding the intensity of symptoms (n = 2928), 70.0% were reported as mild, 25.8% as moderate, and 4.27% as severe, with higher intensity in the second dose compared to first dose. The highest frequency of severe events were reported in the groups from 40 to 59 years in both vaccination periods. During the vaccination process, no hospitalizations and no deaths were notified and/or recorded. Conclusion: In this real world study, comparing with Comirnaty clinical trials program, it was observed a higher frequency of adenomegaly and gastrointestinal disorders. Noteworthy, the notification of a case of miscarriage. The use of hospital pharmacy pharmacovigilance electronic forms, seemed to be relevant to notification adherence and to obtain a greater and faster knowledge of COVID-19 vaccine safety profile [ABSTRACT FROM AUTHOR]

Introduction: Elderly with cancer often have multimorbidity, which determines a higher risk of polypharmacy. This is related to negative clinical results such as adverse drug reaction and emergence service visits. Furthermore, polypharmacy increases the risk of using potentially inappropriate medications. Objective: To evaluate the use of potentially inappropriate medication in elderly with multiple myeloma and associated factors. Methods: The study was conducted with older adults with multiple myeloma treated at outpatient oncology and hematology services in a southeastern Brazilian capital. Potentially inappropriate medications were classified using the American Geriatric Society/Beers 2019 Criteria. Variables were described using frequency and proportions, performing multiple logistic regression to identify factors associated with the use of potentially inappropriate medications. Results: One hundred fifty-three older adults with multiple myeloma were included, with a median age of 70.9 years. The median number of medications was 8, and 63% of patients used polypharmacy. More than half (54%) of the patients used potentially inappropriate medications, and proton pump inhibitors (46%) and benzodiazepines (8%) were the most employed therapeutic classes. Older adults who used potentially inappropriate medications differed from those who did not use them in the following characteristics: income up to three minimum wages, higher schooling level, private service, multimorbidity, hypertension, cardiovascular disease, chronic kidney disease, depression, adverse event, and polypharmacy. Higher schooling levels and polypharmacy were independently associated with the use of potentially inappropriate medications in the multivariate analysis. Conclusion: Potentially inappropriate medication use was high in patients with multiple myeloma studied. The use of polypharmacy and higher schooling levels were independently and positively associated with the use of potentially inappropriate medications. [ABSTRACT FROM AUTHOR]

One important goal in pharmaco-epidemiology studies is to understand the causal relationship between drug exposures and their clinical outcomes, including adverse drug events. In order to achieve this goal, however, we need to resolve several challenges. Most of pharmaco-epidemiology data are observational and confounding is largely present due to many co-medications. The pharmaco-epidemiology study data set is often sampled from large medical record databases using a matched case-control design, and it may not be representative of the original patient population in the medical record databases. Data analysis method needs to handle a large sample size that cannot be handled using existing statistical analysis packages. In this paper, we tackle these challenges both methodologically and computationally. We propose a conditional causal log-odds ratio (OR) definition to characterize causal effects of drug exposures on a binary adverse drug event adjusting for individual level confounders. Using a case-control design, we present a propensity score estimation using only case samples and we provide sufficient conditions for the consistency of the estimation of the causal log-odds ratio using case-based propensity scores. Computationally, we implement a principle component analysis to reduce high-dimensional confounders. Extensive simulation studies are performed to demonstrate superior performance of our method to existing methods. Finally, we apply the proposed method to analyze drug-induced myopathy data sampled from a de-identified subset of medical record database (close to 5 million patient records), The Indiana Network for Patient Care. Our method identified 70 drug-induced myopathy (p < 0.05) out 72 drugs, which have myoathy side effects on their FDA drug labels. These 70 drugs include three statins who are known for their myopathy side effects. [ABSTRACT FROM AUTHOR]

Objective This study was conducted to investigate medication-related problems after implementation of clinical pharmacy services at a speciality oncology care setting. Methods It was a prospective interventional study conducted for a period of three years at a private academic oncology care setting. Paper-based medical records and medication orders were reviewed and patients and care givers were interviewed to understand the treatment plan. All the medication-related problems were identified by clinical pharmacists by performing drug therapy review. Patients were also followed up at ambulatory care and in-patient units to ensure appropriate administration of anti-cancer drugs by nurses. All the medication-related problems were discussed with the concerned clinicians and then were resolved with the interventions of clinical pharmacists. Clinical significance of these interventions were assessed and classified as "Major", "Moderate "and "Minor". Educational, clinical and system-based interventions were developed and implemented to minimize medication-related problems at the study site. Results A total of 1359 medication-related problems were identified from 2120 medication orders reviewed of 1362 patients followed during the study period. The most common medication-related problems were lack of suboptimal supportive care (17.95%), inappropriate administration of medications (14.56%), untreated indication (14.20%), wrong dosing calculations (12.21%), drug–drug interactions (11.62%) and sub-therapeutic dose (11.11%). Clinical pharmacy interventions were made to resolve all the medication-related problems. Clinical significance of majority (n = 504, 37.08%) of medication-related problems was "Moderate" followed by "Major" (n = 434, 31.93%) and "Minor" (n = 421, 30.97%). Conclusion The study has demonstrated the importance of clinical pharmacy services in improving quality and safe use of medicines in oncology practice. Positive feedback of clinicians on clinical pharmacy services was a reflection of acceptance of clinical pharmacy interventions by clinicians. [ABSTRACT FROM AUTHOR]

Objectives:: Switching between different antipsychotic therapies is a frequent occurrence in the management of patients with schizophrenia and other psychotic disorders. This paper provides a review of the principles of antipsychotic switching and discusses pharmacological principles underlying adverse events that occur while switching olanzapine to another antipsychotic medication. It offers suggestions for management of switch-associated adverse events in clinical settings.Conclusions:: Few publications explore olanzapine switch-related adverse events, the underlying pharmacological principles and appropriate switching strategies to minimise the risk of adverse events. There is still a need for further studies to verify existing knowledge and assist in the development of 'gold standard' guidelines that outline appropriate switching strategies and duration of the switching process to reduce and avoid adverse events. [ABSTRACT FROM AUTHOR]

Introduction: Nowadays, based on several epidemiological data, iatrogenic disease is an emerging public health problem, especially in industrialized countries. Adverse drugs reactions (ADRs) are extremely common and, therefore, clinically, socially, and economically worthy of attention. Spontaneous reporting system for suspected ADRs represents the cornerstone of the pharmacovigilance, because it allows rapid detection of potential alarm signals related to drugs use. However, spontaneous reporting system shows several limitations, which are mainly related to under-reporting. In this paper, we describe two particular case reports, which emphasize some reasons of under-reporting and other common criticisms of spontaneous reporting systems. Materials and Methods: We performed a computer-aided search of Medline, PubMed, Embase, Cochrane library databases, national and international databases of suspected ADRs reports in order to identify previous published case reports and spontaneous reports about the ADRs reviewed in this paper, and to examine the role of suspected drugs in the pathogenesis of the described adverse reactions. Results: First, we reported a case of tizanidine-induced hemorrhagic cystitis. In the second case report, we presented an episode of asthma exacerbation after taking bimatoprost. Through the review of these two cases, we highlighted some common criticisms of spontaneous reporting systems: under-reporting and false causality attribution. Discussion and Conclusion: Healthcare workers sometimes do not report ADRs because it is challenging to establish with certainty the causal relationship between drug and adverse reaction; however, according to a key principle of pharmacovigilance, it is always better to report even a suspicion to generate an alarm in the interest of protecting public health. [ABSTRACT FROM AUTHOR]

Aims After oral administration, naproxen generates several side-effects related to stomach malfunction. Undoubtedly, the enteric dosage forms with naproxen can be considered as safer. Moreover, since it has been evidenced that development and growth of colorectal cancer is related to the presence of cyclooxygenase, naproxen is investigated in terms of the tumor prevention. The aim of the present work was to formulate and evaluate the properties of novel naproxen-loaded macrobeads, made on the basis of low-acyl gellan gum and its blends with carrageenans, guar gum, cellulose sulfate, and dextran sulfates. Method Seven formulations were prepared by ionotropic gelation. The morphology of the dried beads was evaluated by scanning electron microscopy. The next step focused on Raman spectroscopy and thermal analysis of naproxen, polymers, and the beads. Next, the swelling behavior was examined in three acceptor fluids at pH = 1.2; 4.5, and 7.4. The beads were evaluated regarding naproxen content and encapsulation efficiency. The last stage of the work concerned the drug release studies. Results Addition of any other polysaccharide than gellan resulted in flattening of the beads upon drying. Differential scanning calorimetry confirmed the crystalline form of naproxen. Raman spectra showed that no apparent interactions occurred. In the acidic environment, all the beads revealed the tendency to absorb water. The beads swelled to the greatest extent at pH = 4.5. Naproxen was released from the beads at a varied rate. At pH = 7.4, the most prolonged release was observed for the beads containing carrageenans. Conclusions We have proved that blending of gellan with various polysaccharides can change the pH-dependent properties of the beads loaded with naproxen. We believe that the information enclosed in the paper will be of particular importance regarding the development and characteristics of novel oral dosage forms based on natural polymers. [ABSTRACT FROM AUTHOR]

Background: Drug-induced lupus erythematosus (DILE) is the development of lupus-like syndrome following a drug exposure. DILE has been reported less frequently among children than adults. Methods: In this study, we present four children with DILE and similar published cases through a systematic literature review. Results: We report four children (three girls and one boy) who developed DILE associated with the use of topiramate, doxycycline, etanercept, and ethosuximide. Three of them were positive for anti-histone antibodies. In all patients, the drug was discontinued and symptoms resolved completely. The literature review revealed 48 articles describing 61 children with DILE. In the evaluation of 65 patients (our 4 patients and 61 patients from the literature), the most frequently reported drugs associated with DILE were ethosuximide (n = 13) and minocycline (n = 12). Fever (n = 33), arthralgia (n = 31), rash (n = 30), and arthritis (n = 29) were the most common clinical manifestations. Antinuclear antibody (ANA) was positive in 93.5% of patients and anti-histone antibodies were detected in 72.2% of the patients. As for treatment, the responsible drug was discontinued in all patients, and corticosteroids were initiated in 53.3%. Improvement was achieved in 92.0% of patients. Conclusion: For children presenting with SLE features, proper drug history is crucial since DILE may be more frequent than anticipated. An association of the relevant drug with the symptoms, and resolution of symptoms on drug withdrawal provides evidence for the diagnosis of DILE. [ABSTRACT FROM AUTHOR]

Background: Purple glove syndrome (PGS) is a rare condition characterized by limb edema, discoloration, and pain associated with intravenous and oral phenytoin administration. The pathophysiology is poorly understood, and there is no established treatment. Simple cases have previously been managed with hyaluronidase subcutaneous injections, with more severe cases resulting in compartment syndrome, debridement, or even amputation. Methods/Results: In this case report, a 2-year-old boy with status epilepticus developed PGS after receiving intravenous phenytoin via a cannula on the dorsum of the right hand. The patient was successfully managed by locally infiltrating subcutaneous hyaluronidase diffusely to the affected area, titrating its dose to effect, rather than aiming to adhere to any specific dosing limitation. The child was reviewed daily by the Plastic Surgery team until being discharged, and focal lesions began to demarcate after 48 hours, with epidermal loss but no deeper trauma. The epidermis peeled within one month, with healthy underlying skin found underlying when followed up in clinic. Conclusions: This case illustrates that subcutaneous administration of hyaluronidase and titrating to effect provides an effective and safe treatment for treating distal cases of early PGS in children. [ABSTRACT FROM AUTHOR]

Background: Individual disease modifying therapies approved for multiple sclerosis (MS) have limited effectiveness and potentially serious side effects, especially when administered over long periods. Sequential combination therapy is a plausible alternative approach. Natalizumab is a monoclonal therapeutic antibody that reduces leukocyte access to the central nervous system that is associated with an increased risk of progressive multifocal leukoencephalopathy and disease reactivation after its discontinuation. Cladribine tablets act as a synthetic adenosine analog, disrupting DNA synthesis and repair, thereby reducing the number of lymphocytes. The generation of prospective, rigorous safety, and efficacy data in transitioning from natalizumab to cladribine is an unmet clinical need. Objectives: To test the feasibility of transitioning patients with relapsing forms of MS natalizumab to cladribine tablets. Design: Cladribine tablets after treatment with natalizumab (CLADRINA) is an open-label, single-arm, multicenter, collaborative phase IV, research study that will generate hypothesis regarding the safety, efficacy, and immunological impact of transition from natalizumab to cladribine tablets in patients with relapsing forms of MS. Methods and analysis: Participants will be recruited from three different sites. The primary endpoint is the absolute and percent change from baseline of lymphocytes and myeloid cell subsets, as well as blood neurofilament light levels. The secondary endpoint is the annualized relapse rate over the 12- and 24-month trial periods. Exploratory endpoints include the expanded disability status scale, and magnetic resonance imaging outcomes. Discussion: The CLADRINA trial will generate data regarding the safety, efficacy, and immunological impact of the transition from natalizumab to cladribine. As the pace of immunological knowledge of MS continues, insight into disease modifying therapy transition strategies is needed. [ABSTRACT FROM AUTHOR]

Objective: To review the evidence of uncommon but fatal adverse event of hyperammonemic encephalopathy by tyrosine kinase inhibitors (TKI) and the possible mechanisms underlying this condition and to describe the case of a patient that developed drug-induced hyperammonemic encephalopathy related to TKI. Data Sources: Literature search of different databases was performed for studies published from 1 January 1992 to 7 May 2023. The search terms utilized were hyperammonemic encephalopathy, TKI, apatinib, pazopanib, sunitinib, imatinib, sorafenib, regorafenib, trametinib, urea cycle regulation, sorafenib, carbamoyl-phosphate synthetase 1, ornithine transcarbamylase, argininosuccinate synthetase, argininosuccinate lyase, arginase 1, Mitogen activated protein kinases (MAPK) pathway and mTOR pathway, were used individually search or combined. Data Summary: Thirty-seven articles were included. The articles primarily focused in hyperammonemic encephalopathy case reports, management of hyperammonemic encephalopathy, urea cycle regulation, autophagy, mTOR and MAPK pathways, and TKI. Conclusion: Eighteen cases of hyperammonemic encephalopathy were reported in the literature from various multitargeted TKI. The mechanism of this event is not well-understood but some authors have hypothesized vascular causes since some of TKI are antiangiogenic, however our literature review shows a possible relationship between the urea cycle and the molecular inhibition exerted by TKI. More preclinical evidence is required to unveil the biochemical mechanisms responsible involved in this process and clinical studies are necessary to shed light on the prevalence, risk factors, management and prevention of this adverse event. It is important to monitor neurological symptoms and to measure ammonia levels when manifestations are detected. [ABSTRACT FROM AUTHOR]

Objective: The aim of this paper was to review whether the $50m spent by the US National Institute of Mental Health in doing the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) trials found any useful evidence to change the clinical management of schizophrenia by psychiatrists. Conclusion: The CATIE trials were conducted in the US on 1460 enrolled patients in an effort to track how the drugs used to treat schizophrenia actually work in clinical practice (rather than in 6-week clinical trials). In a complex 3- phase design, patients were randomized to various types of (mostly) atypical antipsychotic drugs. Some 69-74% of patients switched antipsychotics for one reason or another during the 18 months of treatment. Some of the results were expensive confirmations of known prior results; of the commonly prescribed drugs, clozapine was the most effective, and olanzapine and ziprasidone caused the most and fewest metabolic side effects, respectively. The most stunning finding was that psychiatrists tend to ignore life-threatening, treatable medical conditions in patients presenting for treatment with schizophrenia. Of patients entering the study, 45% had untreated diabetes, 89% had untreated hyperlipidemias and 62% had untreated hypertension. This study failed to reveal anything of significant importance in the psychopharmacological treatment of schizophrenia, but did expose a woeful standard in the medical management of schizophrenia offered by psychiatrists. Psychiatrists should learn to properly treat diabetes, hyperlipidemia and hypertension when detected. [ABSTRACT FROM AUTHOR]

In recent decades, numerous methods have been developed for data mining of large drug safety databases, such as Food and Drug Administration's (FDA's) Adverse Event Reporting System, where data matrices are formed by drugs such as columns and adverse events as rows. Often, a large number of cells in these data matrices have zero cell counts and some of them are "true zeros" indicating that the drug-adverse event pairs cannot occur, and these zero counts are distinguished from the other zero counts that are modeled zero counts and simply indicate that the drug-adverse event pairs have not occurred yet or have not been reported yet. In this paper, a zero-inflated Poisson model based likelihood ratio test method is proposed to identify drug-adverse event pairs that have disproportionately high reporting rates, which are also called signals. The maximum likelihood estimates of the model parameters of zero-inflated Poisson model based likelihood ratio test are obtained using the expectation and maximization algorithm. The zero-inflated Poisson model based likelihood ratio test is also modified to handle the stratified analyses for binary and categorical covariates (e.g. gender and age) in the data. The proposed zero-inflated Poisson model based likelihood ratio test method is shown to asymptotically control the type I error and false discovery rate, and its finite sample performance for signal detection is evaluated through a simulation study. The simulation results show that the zero-inflated Poisson model based likelihood ratio test method performs similar to Poisson model based likelihood ratio test method when the estimated percentage of true zeros in the database is small. Both the zero-inflated Poisson model based likelihood ratio test and likelihood ratio test methods are applied to six selected drugs, from the 2006 to 2011 Adverse Event Reporting System database, with varying percentages of observed zero-count cells. [ABSTRACT FROM AUTHOR]

Objectives: Prescribing antipsychotic medications to children and adolescents with severe mental and developmental disorders is common; however, there is a lack of consensus on appropriate metabolic monitoring for this population. This review systematically evaluates studies examining metabolic monitoring of children and adolescents prescribed antipsychotic medication to understand the clinical practice of metabolic monitoring and identify opportunities to improve the safety of antipsychotic prescribing in this population. Methods: A systematic search for original research on metabolic monitoring in children and adolescents prescribed antipsychotics was conducted in six databases (PubMed, EMBASE, PsycINFO, The Cochrane Library [Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, CENTRAL], Cochrane Methodology Register and Web of Science [Science and Social Science Citation Index]) from inception to February 2020 following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies were assessed for quality and findings summarised using narrative synthesis. Results: Fifteen papers were identified. Studies agreed on the need for metabolic monitoring; however, there was a gap between guideline-recommended practice and clinical practice. Variable rates of baseline and subsequent monitoring were reported for both physical and biochemical parameters, with particularly low rates for monitoring requiring venesection. Younger age was also associated with lower monitoring rates. Implementation of quality improvement activities (new guidelines, staff education and checklists) improved monitoring rates although the measurement of biochemical parameters still occurred in only a minority of children. Conclusion: Despite widespread awareness and concern regarding metabolic side-effects, monitoring occurred inconsistently and infrequently, particularly for biochemical parameters requiring venesection. Monitoring of anthropometric measures (weight, body mass index and waist circumference) with escalation to more laboratory testing where metabolic concerns are identified may improve monitoring. Minimising iatrogenic harm, through reduced antipsychotic prescription where possible, is a clinical priority in this population. [ABSTRACT FROM AUTHOR]

This paper represents the position of the Canadian Psychiatric Association on the ethical and scientific issues related to the use of placebos in the evaluation of new psychotropic drugs. The position taken by the Association is that new psychotropic medications must be shown to he effective and must he weighed against the best current interventions. Placebo controls may be appropriate under certain circumstances, even when an established intervention is effective. These include situations in which placebo response rates are high, variable, or close to response rates for effective therapies. Placebo controls are also appropriate when established interventions carry a high risk of side effects or are effective against only certain symptoms of the disorder. [ABSTRACT FROM AUTHOR]

The role of preoperative fasting is well established in current anaesthetic practice with different guidelines for clear fluids and food. However, chewing gum may not be categorised as either food or drink by some patients, and may not always be specified in instructions given to patients about preoperative fasting. The aim of this paper was to review anaesthesia incidents involving gum chewing reported to webAIRS to obtain information on the risks, if any, of gum chewing during the preoperative fasting period. There were nine incidents involving chewing gum reported between late 2009 and early 2015. There were no adverse outcomes from the nine incidents other than postponement of surgery in three cases and cancellation in one. In particular, there were no reports of aspiration or airway obstruction. Nevertheless, there were five cases in which the gum was not detected preoperatively and was found in the patient's mouth either intraoperatively or postoperatively. These cases of undetected gum occurred despite patient and staff compliance with their current preoperative checklists. While the risk of increased gastric secretions related to chewing gum preoperatively are not known, the potential for airway obstruction if the gum is not detected and removed preoperatively is very real. We recommend that patients should be specifically advised to avoid gum chewing once fasting from clear fluids is commenced, and that a specific question regarding the presence of chewing gum should be added to all preoperative checklists. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to determine the relationship between medication regimen complexity-intensive care unit (MRC-ICU) score at 24 hours and medication errors identified throughout the ICU. Methods: A single-center, observational study was conducted from August to October 2021. The primary outcome was the association between MRC-ICU at 24 hours and total medication errors identified. During the prospective component, ICU pharmacists recorded medication errors identified over an 8-week period. During the retrospective component, the electronic medical record was reviewed to collect patient demographics, outcomes, and MRC-ICU score at 24 hours. The primary outcome of the relationship of MRC-ICU at 24 hours to medication errors was assessed using Pearson correlation. Results: A total of 150 patients were included. There were 2 pharmacists who recorded 634 errors during the 8-week study period. No significant relationship between MRC-ICU and medication errors was observed (r 2 =.13, P =.11). Exploratory analyses of MRC-ICU relationship to major interventions and harm scores showed that MRC-ICU scores >10 had more major interventions (27 vs 14, P =.27) and higher harm scores (15 vs 7, P =.33), although these values were not statistically significant. Conclusion: Medication errors appear to occur independently of medication regimen complexity. Critical care pharmacists were responsible for mitigating a large number of medication errors. [ABSTRACT FROM AUTHOR]

Drug-induced liver injury (DILI) remains a major concern in drug development from a patient safety perspective because it is the leading cause of acute liver failure. One mechanism of DILI is altered bile acid homeostasis and involves several hepatic bile acid transporters. Functional impairment of some hepatic bile acid transporters by drugs, disease, or genetic mutations may lead to toxic accumulation of bile acids within hepatocytes and increase DILI susceptibility. This review focuses on the role of hepatic bile acid transporters in DILI. Model systems, primarily in vitro and modeling tools, such as DILIsym, used in assessing transporter-mediated DILI are discussed. Due to species differences in bile acid homeostasis and drug-transporter interactions, key aspects and challenges associated with the use of preclinical animal models for DILI assessment are emphasized. Learnings are highlighted from three case studies of hepatotoxic drugs: troglitazone, tolvaptan, and tyrosine kinase inhibitors (dasatinib, pazopanib, and sorafenib). The development of advanced in vitro models and novel biomarkers that can reliably predict DILI is critical and remains an important focus of ongoing investigations to minimize patient risk for liver-related adverse reactions associated with medication use. [ABSTRACT FROM AUTHOR]

Objectives: This paper describes the implementation of a state-wide clozapine management system to improve the quality of care for those with treatment-resistant schizophrenia. This intervention includes standardised forms, computer-based monitoring and alerting and nurse-led clinics for stable consumers.Methods: Methods used during system development included medical record and clinical information system audit, consensus review of available evidence and qualitative review of existing forms, systems and stakeholder opinion.Results: Nurse-led monitoring safely reduced medical outpatient appointments by 119 per week in metropolitan public clinics. In the 15 months following the implementation of all interventions, mortality associated with physical illness not related to malignancy was reduced from an average of 5 deaths per year to one.Conclusions: Differing interpretations of clozapine guidelines have contributed to confusion around monitoring. Standardised documentation has helped to increase understanding and improve protocol adherence. A regular training programme has increased basic knowledge of risks and protocols. Computer-based documentation and alerting systems have improved communication between hospital and community-based teams and prompted early intervention reducing the risk of adverse events. These factors have combined to help improve outcomes in clozapine management. Nurse-led clinics are a safe and efficient alternative for monitoring clozapine treatment. [ABSTRACT FROM AUTHOR]

Ketoprofen is a non-steroidal anti-inflammatory drug (NSAID), which acts by blocking cyclooxygenase (COX 1 and 2), an enzyme involved in the production of prostaglandins, messengers in the development of inflammation. All NSAIDs reduce signs of inflammation by blocking this enzyme and therefore prostaglandin production. In Calabria, 3.69% of adverse drug reactions (ADRs) reported in the National Network of Pharmacovigilance concerns the use of ketoprofen; only in one case in which the patient was under the age of 12 years, hospitalization was required for severe episode of pancreatitis. In Italy, Ketoprofen is the 6th drug for ADRs incidence (560 ADRs in the year 2012, of which, 31% are severe). Despite the high rate of spontaneous reporting, it must be considered that ketoprofen is one of the most used NSAIDs; therefore, as it happens for other commonly used drugs (eg, amoxicillin), the total number of ADRs should be related to the therapeutic use. However, it remains the problem of fragile patients (eg, children) and the safety of the drug in different ages. This paper presents a retrospective study on 2012 ADRs reviewing literature on the safety of ketoprofen in the elderly, children, and during pregnancy. [ABSTRACT FROM AUTHOR]

The article discusses the healthcare industry. Topics discussed include paper on ignoring adverse effects (AEs) by Golder and colleagues, statement of the U.S. Food and Drug Administration (FDA) and the pharmaceutical giants on problems emerged after prescriptions are dispensed and issues over execution of clinical trials.

4-Methylamphetamine (4-MA) was originally developed as an appetite suppressant, but development was halted due to side effects. It has recently resurfaced as a new psychoactive substance in Europe, and is mostly found together with amphetamine. Around 11.5% of tested Dutch speed samples were positive for 4-MA. In Belgium, 4-MA was also found in speed samples. In 2011 and 2012, several fatal incidents after amphetamine use were observed in Belgium, the United Kingdom and The Netherlands. In all victims, toxicological analysis confirmed the presence of 4-MA, in addition to amphetamine. The observed blood amphetamine levels were too low to be fatal. Contrary to amphetamine, which displays noradrenergic and dopaminergic activity, 4-MA also shows serotonergic activity, which may contribute to the observed toxicity. Other mechanisms of toxicity are put forward in this paper as well. To conclude, the observed toxicity is most likely the result of the combined dopaminergic activity of amphetamine and the serotonergic activity of 4-MA. In addition, the presence of 4-MA may have dampened the psychoactive effects of amphetamine by attenuation of the amphetamine-induced dopamine release, potentially inclining users to ingest higher doses of contaminated speed. Also, slower metabolism of 4-MA and its MAO-inhibiting properties can also contribute to the unusual high toxicity of 4-MA. [ABSTRACT FROM PUBLISHER]

Retinoblastoma is a relatively uncommon childhood tumor. If untreated, RB grows to fill the eye and destroys the ocular globe’s internal architecture. Metastatic spread usually begins after the first 6 months, and death occurs within a matter of years. When treated, overall survival rounds 97%, the alkylating drug melphalan being the most extensively used chemotherapeutic agent in localized treatment. In our hospital, pediatric oncologists asked the Pharmacy Department for assessment in order to implement a new chemotherapy protocol for the treatment of advanced intraocular elegible retinoblastoma cases using melphalan administered directly through the ophthalmic artery. In this paper, we describe the protocol implementation carried out by our collaborative interdisciplinary team as well as the clinical outcomes of five cases treated with ophthalmic intra-arterial melphalan therapy. Oncology pharmacists can contribute with their knowledge to the implementation process of new collaborative practice protocols recommending doses, predicting possible adverse effects and assessing about drug stability and elaboration, packaging and administration methods. [ABSTRACT FROM PUBLISHER]

Bupropion is an antidepressant that is effective in the treatment of major depressive disorders, smoking cessation, and sexual side effects of selective serotonin reuptake inhibitors. Acute dystonia is characterized by prolonged muscle contraction often represented by spasms of the head and neck muscles as well as occasional jaw clenching and temporomandibular joint syndrome. Although it is believed that dystonia is the result of an abnormality of the basal ganglia, its pathophysiology is still unclear. A few cases of dystonia resulting from bupropion have been reported in prior research papers. This case report discusses a patient who had a neck spasm painful enough to wake him up and dystonic distortion after taking only one dose of 75 mg bupropion. The patient was a young 34-year-old man with a diagnosis of obsessive-compulsive disorder treated with 60 mg fluoxetine. Bupropion was added to his medications because of sexual side effects caused by the fluoxetine. It seems that we must be careful to watch for dystonic symptoms when bupropion is mixed with other drugs that affect serotonin reuptake. Although dystonia is a rare side effect of bupropion, physicians should be aware of it and manage it if it occurs. [ABSTRACT FROM AUTHOR]

Objective: Aripiprazole long acting injection (ALAI) is now available, and this paper aims to assist clinicians in deciding when to use ALAI.Conclusion: Aripiprazole is a partial dopamine agonist with low sedation, relatively favourable metabolic profile and a tendency to lower, rather than raise, prolactin. Available for over a decade, aripiprazole has been increasingly recognised by many clinicians as a useful option in the treatment of psychoses. ALAI is a suspension of crystalline aripiprazole in water which takes 5-7 days to reach steady state after an initial intramuscular injection. Monthly injections achieve steady state in four months. Studies have demonstrated that ALAI is effective in aripiprazole-responsive patients. ALAI was generally well tolerated, but more prone to cause extrapyramidal side-effects than the oral form. ALAI has not been compared with other depots. Although the recommended starting dose is 400 mg, it is likely that there will be significant inter-individual dose variation. Dose optimisation in each patient will be necessary for best effectiveness and tolerability. ALAI is currently appropriate for aripiprazole-responsive patients who need a depot, but clinicians are likely to try ALAI in patients who have been on other depots, particularly in whom weight gain and hyperprolactinaemia have been problematic. [ABSTRACT FROM AUTHOR]

In this paper we use published information to analyze the economic value of Direct to Consumer Advertising (DTCA). The reviewed research finds that DTCA leads to increased demand for the advertised drug and that the effect of the drug tends to be class-wide rather than product specific. There is weak evidence that DTCA may increase compliance and improve clinical outcomes. However, there is little research on the effect of DTCA on inappropriate prescribing or on the characteristics of patients who respond to treatment. On net, if the advertised drugs are cost effective on average and the patients using the drugs in response to the advertisement are similar to other users, DTCA is likely cost effective. Overall, the literature to date is consistent with the idea that DTCA is beneficial, but further research is needed before definitive conclusions can be drawn. [ABSTRACT FROM AUTHOR]

There has recently been a renewal of human research with classical hallucinogens (psychedelics). This paper first briefly discusses the unique history of human hallucinogen research, and then reviews the risks of hallucinogen administration and safeguards for minimizing these risks. Although hallucinogens are relatively safe physiologically and are not considered drugs of dependence, their administration involves unique psychological risks. The most likely risk is overwhelming distress during drug action ('bad trip'), which could lead to potentially dangerous behaviour such as leaving the study site. Less common are prolonged psychoses triggered by hallucinogens. Safeguards against these risks include the exclusion of volunteers with personal or family history of psychotic disorders or other severe psychiatric disorders, establishing trust and rapport between session monitors and volunteer before the session, careful volunteer preparation, a safe physical session environment and interpersonal support from at least two study monitors during the session. Investigators should probe for the relatively rare hallucinogen persisting perception disorder in follow-up contact. Persisting adverse reactions are rare when research is conducted along these guidelines. Incautious research may jeopardize participant safety and future research. However, carefully conducted research may inform the treatment of psychiatric disorders, and may lead to advances in basic science. [ABSTRACT FROM AUTHOR]

Objective: The aim of this paper was to describe the association of clozapine with life-threatening constipation. Method: Case report. Results: A 53-year-old man presented to the emergency department with severe abdominal pain and bilious vomiting after being on clozapine for over a year for schizoaffective disorder. Surgery revealed severe faecal impaction in the large and small bowel. Clozapine was ceased. There were significant difficulties in the subsequent psychiatric management. Clozapine was gradually reintroduced with concurrent laxative administration, which resulted in another episode of severe constipation with faecal impaction. Conclusions: Clozapine can be associated with potentially life-threatening constipation. Psychiatrists, especially consultation liaison psychiatrists, physicians, surgeons and radiologists, should be aware of the seriousness of clozapine-induced constipation and its potentially fatal complications. [ABSTRACT FROM AUTHOR]

This paper reviews the evidence for the efficacy of anticonvulsants in the continuation and maintenance phases of treatment of bipolar disorder, when there has been an episode of mania (Bipolar-I disorder). The evidence to be considered is primarily that arising from randomized controlled trials. A literature search was performed to identify all randomized controlled trials of anticonvulsants used as maintenance treatment for bipolar-I disorder. Placebo-controlled studies were preferred, however there have been relatively few of these and clinical practice must therefore be guided by evidence carrying a lower level of conviction. Valproate monotherapy lacks a convincing evidence base. The view that valproate is more effective than lithium in rapid cycling has not been borne out. Lamotrigine is effective in preventing depression after an episode of mania. As monotherapy, lithium appears superior to carbamazepine in bipolar patients not previously treated with either drug. The combination of lithium and carbamazepine may be superior to either drug alone, in certain treatment-resistant patients, but is associated with increased side effects, Other anticonvulsants tack evidence supporting their use in bipolar disorder except in treating comorbid alcohol dependence, anxiety and bulimic symptoms. Valproate continues to be recommended by most current guidelines despite the tack of evidence. [ABSTRACT FROM AUTHOR]

The purpose of this paper is to explore the possibility that adverse reactions and drug interactions arising from the use of homeopathic and herbal medicines could lead to confusion when adverse reactions to conventional medicines are reported. An extensive literature review was conducted on the occurrence of adverse reactions and drug interactions following the use of homeopathic or herbal remedies, and the potential for these to confound adverse event reporting to conventional medicines considered. The survey demonstrates the potential for herbal remedies and homeopathic products, to produce adverse drug reactions or drug interactions, and shows the scope for potential for confusion with those arising from conventional medicines. There is a need for greater awareness that adverse reactions apparently due to a conventional medicine, might in reality be due to a herbal medicine or a drug interaction between a herbal medicine and a conventional drug, particularly when a health professional is unaware of the extent of a patient's self-medication with alternative therapies. [ABSTRACT FROM AUTHOR]

Awide spectrum of drugs can sometimes give rise to numerous adverse orofacial manifestations, particularly dry mouth, taste disturbances, oral mucosal ulceration, and/or gingival swelling. There are few relevant randomized double-blind controlled studies in this field, and therefore this paper reviews the data from case reports, small series, and non-peer-reviewed reports of adverse drug reactions affecting the orofacial region (available from a MEDLINE search to April, 2003). The more common and significant adverse orofacial consequences of drug therapy are discussed. [ABSTRACT FROM AUTHOR]

Considerable debate has arisen regarding many aspects of attention deficit/hyperactivity disorder (ADHD), including the existence, diagnosis and prevalence of the disorder, the use of medications in treating young children for the disorder, and the long-term side-effects of the medications. A fundamental catalyst in this debate involves the numerous and diverse social representations of ADHD: the differing ways of perceiving what ADHD is, whom it affects, and the most appropriate treatments. This paper presents a discussion of social representations theory and its previous applications to the study of mental illness, connecting this theory with research in media framing. Quantitative and qualitative content analyses of print media representations of ADHD over a ten-year period are presented. Using results from the media analysis, we examine different processes through which these representations might influence perceptions of individuals experiencing ADHD-related symptoms, particularly as these perceptions relate to mental health treatment decisions. [ABSTRACT FROM AUTHOR]