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A variety of terms, such as "antiepileptic," "anticonvulsant," and "antiseizure" have been historically applied to medications for the treatment of seizure disorders. Terminology is important because using terms that do not accurately reflect the action of specific treatments may result in a misunderstanding of their effects and inappropriate use. The present International League Against Epilepsy (ILAE) position paper used a Delphi approach to develop recommendations on English‐language terminology applicable to pharmacological agents currently approved for treating seizure disorders. There was consensus that these medications should be collectively named "antiseizure medications". This term accurately reflects their primarily symptomatic effect against seizures and reduces the possibility of health care practitioners, patients, or caregivers having undue expectations or an incorrect understanding of the real action of these medications. The term "antiseizure" to describe these agents does not exclude the possibility of beneficial effects on the course of the disease and comorbidities that result from the downstream effects of seizures, whenever these beneficial effects can be explained solely by the suppression of seizure activity. It is acknowledged that other treatments, mostly under development, can exert direct favorable actions on the underlying disease or its progression, by having "antiepileptogenic" or "disease‐modifying" effects. A more‐refined terminology to describe precisely these actions needs to be developed. [ABSTRACT FROM AUTHOR]

The need for providing rapid and, possibly, on-the-spot analytical results in the case of intoxication has prompted researchers to develop rapid, sensitive, and cost-effective methods and analytical devices suitable for use in nonspecialized laboratories and at the point of need (PON). In recent years, the technology of paper-based microfluidic analytical devices (μPADs) has undergone rapid development and now provides a feasible, low-cost alternative to traditional rapid tests for detecting harmful compounds. In fact, µPADs have been developed to detect toxic molecules (arsenic, cyanide, ethanol, and nitrite), drugs, and drugs of abuse (benzodiazepines, cathinones, cocaine, fentanyl, ketamine, MDMA, morphine, synthetic cannabinoids, tetrahydrocannabinol, and xylazine), and also psychoactive substances used for drug-facilitated crimes (flunitrazepam, gamma-hydroxybutyric acid (GHB), ketamine, metamizole, midazolam, and scopolamine). The present report critically evaluates the recent developments in paper-based devices, particularly in detection methods, and how these new analytical tools have been tested in forensic and clinical toxicology, also including future perspectives on their application, such as multisensing paper-based devices, microfluidic paper-based separation, and wearable paper-based sensors. [ABSTRACT FROM AUTHOR]

Two easy-to-use, rapid, and inexpensive colorimetric-based assays for the detection of active constituent in nasal decongestant phenylephrine hydrochloride (PHP), in solution and their respective pharmaceutical preparations were reported. The assay principle depends on the diazotized sulfadimidine (DSDM) coupling with PHP active pharmaceutical compound under alkaline conditions to produce a colored azo-dye product. A UV/VIS spectrophotometry method was utilized to monitor the color absorbance change at 460 nm, with a linear calibration graph in the concentration range of 1-20 mg L-1 and a limit of detection of 0.22 mg L-1 and limit of quantification of 0.72 mg L-1 . A comparison was done using a paper-based microfluidic analytical device (µPADs) and color intensity change was measured using a Samsung note 9 camera to capture digital images and Image J software to analyze the color intensity development. A linear trend was observed above approximately 10 mg L-1 . Thus, paper-based microfluidic analytical devices (µPADs) can be used as an alternative platform to conventional methods to perform a semi-quantitative PHP drug analysis. The proposed method was applied for the determination of PHP in commercial pharmaceutical preparations. [ABSTRACT FROM AUTHOR]

Older people are often affected by impaired organ and bodily functions resulting in multimorbidity and polypharmacy, turning them into the main user group of many medicines. Very often, medicines have not specifically been developed for older people, causing practical medication problems for them like limited availability of easy to swallow formulations, easy to open packaging and dosing instructions for enteral administration. In 2020, the European Medicines Agency (EMA) published a reflection paper 'Pharmaceutical development of medicines for use in the older population', which discusses how the emerging needs of an ageing European population can be addressed by medicines regulation. The paper intends to help industry to better consider the needs of older people during pharmaceutical/clinical medicines development by summarising data on the most relevant topics, providing early suggestions on how to move forward and prompting expert discussions and studies into knowledge gaps. Topics include patient acceptability, (dis)advantages of an administration route, formulation, dosage form, packaging, dosing device and user instruction. While the paper is directed at older people and the pharmaceutical industry, the reflections are also relevant to younger patients with similar disease‐related needs and of value to other stakeholders parties, e.g., healthcare professionals, academics, patients and caregivers, as the paper makes clear what can be expected from industry and where collaborative work is needed. This commentary provides an overview of the different steps in the development of the reflection paper, discusses points considered most controversial and/or subject to (multidisciplinary) expert discussions and indicates their value for real world clinical practice. [ABSTRACT FROM AUTHOR]

Objective: The Patient Information Leaflet (PIL) is an authoritative document that all people with epilepsy in the EU receive when prescribed antiseizure medication (ASM). We undertook the first independent, comprehensive assessment to determine how understandable they are. Regulators state that when patients are asked comprehension questions about them, ≥80% should answer correctly. Also, recommended is that PILs have a maximum reading requirement of US grade 8. Methods: Study 1: We obtained 140 current ASM PILs written in English. "Readability" was assessed using four tests, with and without adjustment for influence of familiar, polysyllabic words. A total of 179 online materials on epilepsy were also assessed. Study 2: Two PILs from Study 1 were randomly selected (Pregabalin Focus; Inovelon) and shown to 35 people from the UK epilepsy population. Their comprehension was assessed. Study 3: To understand whether the student population provides an accessible alternative population for future examination of ASM PILs, Study 3 was completed, using the same methods as Study 2, except that participants were 262 UK university students. Results: Study 1: No PIL had a reading level of grade 8. Median was grade 11. Adjusting for context, the PILs were still at grade 10.5. PILs for branded ASMs were most readable. PILs were no more readable than (unregulated) online materials. Study 2: Users struggled to comprehend the PILs' key messages. The eight questions asked about pregabalin were typically answered correctly by 54%. For Inovelon, it was 62%. Study 3: Most student participants comprehended the PILs' key messages. The questions about Inovelon were answered correctly by 90%; for pregabalin it was 86%. Significance: This is the first independent and comprehensive examination of ASM PILs. It found that PILs being used fail to meet recommendations and regulatory requirements and risk not being understandable to a substantial proportion of users. In finding that people from the epilepsy population differ markedly in comprehension of PILs compared to students, this study highlights the importance of completing user testing with the target population. [ABSTRACT FROM AUTHOR]

Increased global longevity requires a re‐evaluation of current structures in society to adapt to the consequential demographic shift. As (very) old people are prone to impaired human organ and body functions resulting in, for example, multimorbidity, polypharmacy, hospitalisation and problems in medication management, it is increasingly acknowledged that re‐evaluations should include the suitability of pharmaceutical patient care as one of the cornerstones of public health. Following the 2011 European Medicines Agency (EMA) Geriatric Strategy, in 2017 the EMA published the draft "Reflection paper on the pharmaceutical development of medicines for use in the older population". The draft paper was opened for public consultation and specific attention and feedback (either supportive or with a proposal for revision) was asked on three design aspects: tablet breaking, drug administration through enteral feeding tubes and medication management. Following publication, the draft paper was presented at two public conferences attended by participants from different disciplines. This manuscript is intended to draw the attention of different stakeholder parties to the urgent need to collaborate on the emerging issues arising from increasing longevity and multimorbidity, and especially those associated with pharmaceutical patient care and drug product design, including the need for collaborative research into existing or emerging knowledge gaps. The manuscript focuses on the three aforementioned aspects of pharmaceutical development (tablet breaking, drug administration through enteral feeding tubes and medication management) as these highly relate to medication safety and efficacy and constitute persistent and typical challenges for older people, caregivers and healthcare professionals in daily clinical practice. [ABSTRACT FROM AUTHOR]

Early industrialization and the development of cheap production processes for paper have led to an exponential accumulation of paper-based documents during the last two centuries. Archives and libraries harbor vast amounts of ancient and modern documents and have to undertake extensive endeavors to protect them from abiotic and biotic deterioration. While services for mechanical preservation such as ex post de-acidification of historic documents are already commercially available, the possibilities for long-term protection of paper-based documents against fungal attack (apart from temperature and humidity control) are very limited. Novel processes for mechanical enhancement of damaged cellulosic documents use Ionic Liquids (IL) as essential process components. With some of these ILs having azole-functionalities similar to well-known fungicides such as Clotrimazole, the possibility of antifungal activities of these ILs was proposed but has not yet been experimentally confirmed. We evaluated the potency of four ILs with potential application in paper restoration for suppression of fungal growth on five relevant paper-infesting molds. The results revealed a general antifungal activity of all ILs, which increased with the size of the non-polar group. Physiological experiments and ultimate elemental analysis allowed to determine the minimal inhibitory concentration of each IL as well as the residual IL concentration in process-treated paper. These results provide valuable guidelines for IL-applications in paper restoration processes with antifungal activity as an added benefit. With azoles remaining in the paper after the process, simultaneous repair and biotic protection in treated documents could be facilitated. [ABSTRACT FROM AUTHOR]

Purpose: To report distribution of codes associated with a rheumatoid arthritis (RA) diagnosis recorded in Clinical Practice Research Datalink (CPRD) Aurum compared to the previously validated CPRD GOLD database as a critical step toward making decisions about CPRD Aurum's suitability for medical research.Patients and Methods: We analyzed the distribution of codes for RA diagnoses, labs, and treatments in the new CPRD Aurum database, compared to the CPRD GOLD database by selecting relevant indicators of RA diagnosis, treatment, and clinical care. We included all patients in England in CPRD Aurum and CPRD GOLD with an incident diagnosis code for RA on or after 1 January 2005 and at least two years recorded data before first RA diagnosis.Results: We found 53,083 and 18,167 patients with a new diagnosis code for RA in CPRD Aurum and CPRD GOLD, respectively. In both databases approximately 67% were female with similar mean ages at first diagnosis. There were few differences in RA-related recording patterns between the two data sources. Before first RA diagnosis, CPRD Aurum patients had more RA-specific labs and other supporting clinical codes. After diagnosis, CPRD Aurum patients had more RA diagnoses coded and more often had 10+ general RA labs than patients in CPRD GOLD. More CPRD GOLD patients had 10+ prescriptions for conventional disease-modifying antirheumatic drugs (cDMARD) compared to CPRD Aurum. Otherwise, the distribution of drugs used to treat RA was similar between databases. The standardized incidence of RA was similar between databases.Conclusion: Overall, among patients with a diagnosis code for RA, recording of diagnoses, prescription drugs, and labs were similar between CPRD Aurum and CPRD GOLD. Slight differences were found for a few variables, but overall, we found consistency between the databases. In addition, standardized incidence of RA was similar between databases. [ABSTRACT FROM AUTHOR]

The benefit of using the adapters as opposed to patient self-reporting of medication use is objective monitoring of patient adherence to their assigned medication protocol. Keywords: dermatology; electronic monitoring; medication adherence; topical medication EN dermatology electronic monitoring medication adherence topical medication 371 373 3 03/25/22 20220301 NES 220301 INTRODUCTION Medication nonadherence is associated with increased disease severity and poor disease outcomes. [Extracted from the article]

Immunoassays and high-performance liquid chromatography (HPLC) coupled with mass spectrometry (MS) are both widely used methods for drug screening in toxicology. We investigated an alternative approach for rapid drug screening: paper spray MS (PS-MS). In paper spray, the biofluid sample is spotted onto a paper substrate. Upon application of a spray solvent and an electric potential, extraction and ionization occur directly from the paper without any need for additional sample preparation. We developed two paper spray high-resolution MS/MS targeted drug screening assays using a quadrupole-orbitrap mass spectrometer, one the positive ion mode and one in the negative ion mode. In the positive ion mode, over 130 drugs and drug metabolites were semiquantitatively screened at sub-toxic concentrations in a single 2.5 min analysis. Limits of detection and calibration performances for each target compound are reported. The PS-MS/MS assay was tested on authentic postmortem specimens, and its screening ability and semi-quantitative performance were evaluated against independent LC-MS-MS screening and confirmation assays with good agreement. The paper spray MS/MS showed good qualitative agreement with LC-MS-MS; the true positive rate of paper spray MS/MS was 92%, and the true negative rate was over 98%. The quantitative results between the two methods were also acceptable for a screening application; Passing-Bablok regression yielded a slope of 1.17 and a Pearson's correlation coefficient of 0.996. A separate PS-MS/MS negative ion screening method was also developed for a small panel of barbiturates and structural analogs, demonstrating its potential for acidic drug detection and screening. [ABSTRACT FROM AUTHOR]

Poor research reporting is a major contributing factor to low study reproducibility, financial and animal waste. The ARRIVE (Animal Research: Reporting of In Vivo Experiments) guidelines were developed to improve reporting quality and many journals support these guidelines. The influence of this support is unknown. We hypothesized that papers published in journals supporting the ARRIVE guidelines would show improved reporting compared with those in non-supporting journals. In a retrospective, observational cohort study, papers from 5 ARRIVE supporting (SUPP) and 2 non-supporting (nonSUPP) journals, published before (2009) and 5 years after (2015) the ARRIVE guidelines, were selected. Adherence to the ARRIVE checklist of 20 items was independently evaluated by two reviewers and items assessed as fully, partially or not reported. Mean percentages of items reported were compared between journal types and years with an unequal variance t-test. Individual items and sub-items were compared with a chi-square test. From an initial cohort of 956, 236 papers were included: 120 from 2009 (SUPP; n = 52, nonSUPP; n = 68), 116 from 2015 (SUPP; n = 61, nonSUPP; n = 55). The percentage of fully reported items was similar between journal types in 2009 (SUPP: 55.3 ± 11.5% [SD]; nonSUPP: 51.8 ± 9.0%; p = 0.07, 95% CI of mean difference -0.3–7.3%) and 2015 (SUPP: 60.5 ± 11.2%; nonSUPP; 60.2 ± 10.0%; p = 0.89, 95%CI -3.6–4.2%). The small increase in fully reported items between years was similar for both journal types (p = 0.09, 95% CI -0.5–4.3%). No paper fully reported 100% of items on the ARRIVE checklist and measures associated with bias were poorly reported. These results suggest that journal support for the ARRIVE guidelines has not resulted in a meaningful improvement in reporting quality, contributing to ongoing waste in animal research. [ABSTRACT FROM AUTHOR]

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Introduction: Noncommunicable diseases (NCDs) are associated with high and rising burden of morbidity and mortality in sub-Saharan Africa, including Nigeria. Diabetes mellitus (DM) is among the leading causes of NCD-related deaths worldwide and is a foremost public health problem in Nigeria. As part of National policy, Nigeria has committed to implement the World Health Organization (WHO) Package of Essential Non-communicable Disease interventions for primary care. Implementing the intervention requires the availability of essential elements, including guidelines, trained staff, health management information systems (HMIS), equipment, and medications, in primary healthcare centers (PHCs). This study assessed the availability of the DM component of the WHO package, and the readiness of the health workers in these PHCs to implement a DM screening, evaluation, and management program to inform future adoption and implementation. Methods: This cross-sectional formative assessment adapted the WHO Service Availability and Readiness Assessment (SARA) tool to survey 30 PHCs selected by multistage sampling for readiness to deliver DM diagnosis and care in Abuja, Nigeria, between August and October 2021. The SARA tool was adapted to focus on DM services and the availability and readiness indicator scores were calculated based on the proportion of PHCs with available DM care services, minimum staff requirement, diagnostic tests, equipment, medications, and national guidelines/protocols for DM care within the defined SARA domain. Results: All 30 PHCs reported the availability of at least two full-time staff (median [interquartile range] = 5 [4–9]), which were mostly community health extension workers (median [interquartile range]) = 3 [1–4]. At least one staff member was recently trained in DM care in 11 PHCs (36%). The study also reported high availability of paper-based HMIS (100%), and DM screening services using a glucometer (87%), but low availability of DM job aids (27%), treatment (23%), and national guidelines/protocols (0%). Conclusion: This formative assessment of PHCs' readiness to implement a DM screening, evaluation, and management program in Abuja demonstrated readiness to integrate DM care into PHCs regarding equipment, paper-based HMIS, and nonphysician health workers' availability. However, strategies are needed to promote DM health workforce training, provide DM management guidelines, and supply essential DM medications. [ABSTRACT FROM AUTHOR]

Dapagliflozin across the range of ejection fraction in patients with heart failure: a patient-level, pooled meta-analysis of DAPA-HF and DELIVER. Obesity and cardiovascular disease: the effect of bariatric surgery Although we know that bariatric surgery effectively targets CV risk factors, its effect on cardiovascular disease is not well-established. Interestingly, 15% of all patients were treated with an SGLT2 inhibitor and subgroup analyses suggest a benefit in both, patients with and without SGLT2 inhibitor treatment. [Extracted from the article]

Background: Patient safety is a central healthcare policy worldwide. Adverse drug events (ADE) are among the main threats to patient safety. Children are at a higher risk of ADE in each stage of medication management process. ADE rate is high in the administration stage, as the final stage of preventing medication errors in pediatrics and neonates. The most effective way to reduce ADE rate is using medication administration clinical decision support systems (MACDSSs). The present study reviewed the literature on MACDSS for neonates and pediatrics. It identified and classified the data elements that mapped onto the Fast Healthcare Interoperability Resources (FHIR) standard and the functionalities of these systems to guide future research. Methods: PubMed/ MEDLINE, Embase, CINAHL, and ProQuest databases were searched from 1995 to June 31, 2021. Studies that addressed developing or applying medication administration software for neonates and pediatrics were included. Two authors reviewed the titles, abstracts, and full texts. The quality of eligible studies was assessed based on the level of evidence. The extracted data elements were mapped onto the FHIR standard. Results: In the initial search, 4,856 papers were identified. After removing duplicates, 3,761 titles, and abstracts were screened. Finally, 56 full-text papers remained for evaluation. The full-text review of papers led to the retention of 10 papers which met the eligibility criteria. In addition, two papers from the reference lists were included. A total number of 12 papers were included for analysis. Six papers were categorized as high-level evidence. Only three papers evaluated their systems in a real environment. A variety of data elements and functionalities could be observed. Overall, 84 unique data elements were extracted from the included papers. The analysis of reported functionalities showed that 18 functionalities were implemented in these systems. Conclusion: Identifying the data elements and functionalities as a roadmap by developers can significantly improve MACDSS performance. Though many CDSSs have been developed for different medication processes in neonates and pediatrics, few have actually evaluated MACDSSs in reality. Therefore, further research is needed on the application and evaluation of MACDSSs in the real environment. Protocol Registration: (dx.doi.org/10.17504/protocols.io.bwbwpape). [ABSTRACT FROM AUTHOR]

Lastly, in those 80 years or older at the time of cancer diagnosis, CV mortality exceeded cancer mortality for all nine cancer types after follow-up ranging from 1.9 years (melanoma) to 10.6 years (lung cancer). In those aged 6079 years, CV mortality exceeded cancer mortality for seven cancer types after follow-up ranging from 5 years (bladder cancer) to 17 years (lung cancer). Another population-based study on 100 000 patients with 9 different types of cancer from England investigated the risk of CV death.[10] In patients who were diagnosed with cancer below the age of 60 years, cancer mortality generally exceeded CV mortality except for uterine cancer, for which CV and cancer mortality were similar by 11 years of follow-up. [Extracted from the article]

Drug detection in biofluids has always been great importance for clinical diagnosis. Many detection technologies such as chromatography-mass spectrometry, have been applied to the detection of drugs. However, these technologies required multi-step operations, including complicated and time-consuming pretreatment processes and operations of bulky detection instruments, significantly limiting development of drug detection in clinical diagnosis. Herein, a portable 3D-printed paper cartridge was fabricated for fast sample preconcentration and direct drugs quantitative detection in biofluids by a portable Raman spectrometer. This cartridge contained both paper tip with silver nanowires to preconcentrate samples and achieve surface-enhanced Raman Scattering (SERS) measurement, and 3D-printed cartridge to build enclosed environment for the improvement of detection, which cost only one dollar. The preconcentration ability of the cartridge was up to 18.13-fold fluorescence enhancement and compared to the non-preconcentration method, it achieved 9.93-fold improvement of SERS performance. The anticancer drug of epirubicin hydrochloride, cyclophosphamide and their mixtures were quantitatively detected in the bovine serum or artificial urine. The integrated detection procedure required only 1 h, including sample pretreatment and preconcentration, drying, SERS measurements, and quantification analysis. This 3D-printed paper cartridge constituted a portable detection platform that would be potentially a practical and point-of-care detection tool for drug preconcentration and quantification on the clinical diagnosis. [Display omitted] • 3D-printed paper cartridge was fabricated for fast sample preconcentration and direct drugs quantitative detection in biofluids by a portable Raman spectrometer. • The preconcentration ability of the cartridge was up to 18.13-fold fluorescence and 9.93-fold enhancement of SERS. • The anticancer drug of epirubicin hydrochloride, cyclophosphamide and their mixtures were quantitatively detected in the bovine serum or artificial urine. • The integrated detection procedure of 3D-printed paper cartridge required only 1 hour, including sample pretreatment and preconcentration, drying, SERS measurements, and quantification analysis. [ABSTRACT FROM AUTHOR]

Abstract: The purpose of the present work was to evaluate the possibility of converting recycled paper sludge (RPS), an industrial residue stream with strong environmental impact, into valuable products. The approach used was based on the enzymatic conversion of major sludge components (cellulose and xylan) and the simultaneous (simultaneous saccharification and fermentation—SSF) or sequential (separate hydrolysis and fermentation—SHF) fermentation of the resulting sugars to ethanol. In the enzymatic hydrolysis step using Celluclast® 1.5L supplemented with Novozym® 188, a degree of saccharification of 100% was achieved. In relation to ethanol production using the yeast Pichia stipitis CBS 5773, SHF and SSF process efficiencies were compared. A slightly higher conversion yield was attained on SHF, corresponding to an ethanol concentration of 19.6gL−1, but 179h were needed. The SSF process was completed after 48h of incubation allowing the production of 18.6gL−1 of ethanol from 178.6gL−1 of dried RPS, corresponding to an overall conversion yield of 51% of the available carbohydrates on the initial substrate. These results demonstrate that the biological conversion of sludge to ethanol is efficient even with no pre-treatment or substrate supplementation. [Copyright &y& Elsevier]

The Medicines and Healthcare products Regulatory Agency was established in April 2003 by the merger of the Medicines Control Agency (MCA) and the Medical Devices Agency (MDA). This paper describes the scientific and organizational basis for the merger and describes the various challenges facing this new Agency. [ABSTRACT FROM AUTHOR]

The clinical response to classical immunosuppressant drugs (cIMDs) is highly variable among individuals. We performed a systematic review of published evidence supporting the hypothesis that gut microorganisms may contribute to this variability by affecting cIMD pharmacokinetics, efficacy or tolerability. The evidence that these drugs affect the composition of intestinal microbiota was also reviewed. The PubMed and Scopus databases were searched using specific keywords without limits of species (human or animal) or time from publication. One thousand and fifty five published papers were retrieved in the initial database search. After screening, 50 papers were selected to be reviewed. Potential effects on cIMD pharmacokinetics, efficacy or tolerability were observed in 17/20 papers evaluating this issue, in particular with tacrolimus, cyclosporine, mycophenolic acid and corticosteroids, whereas evidence was missing for everolimus and sirolimus. Only one of the papers investigating the effect of cIMDs on the gut microbiota reported negative results while all the others showed significant changes in the relative abundance of specific intestinal bacteria. However, no unique pattern of microbiota modification was observed across the different studies. In conclusion, the available evidence supports the hypothesis that intestinal microbiota could contribute to the variability in the response to some cIMDs, whereas data are still missing for others. [ABSTRACT FROM AUTHOR]

A Case of Ictal Fear with Various Psychiatric Manifestations and Memory Disturbance in Interictal Stages.Purpose:Ictal emotion corresponds to“affective seizures,” according to the Proposal for Revised Clinical and Electroencephalographic Classification of Epileptic Seizures by the International League Against Epilepsy (ILAE; 1981), and is characterized by the appearance of affective disorders such as fear, depression, pleasure, and anger. In particular, the ictal emotion, in which fear is the most commonly noted emotion, is referred to as“ictal fear.” In the present study, we report a patient with temporal lobe epilepsy, who showed ictal fear associated with various psychiatric manifestations including memory disturbance in the interictal stage that promptly subsided with antiepileptic drug (AED) administration.Case Report:A 24-year-old woman had recurrent episodes fear and anxiety. Family risk factors consisted of major depression in the maternal grandmother, but no familial history of epilepsy. The patient had a history of mumps with fever of 38°C at age 6 years without febrile convulsion. The present illness began around April 1997, when the patient became aware of swelling of the left ear membrane and a tinnitus-like noise, with an occasional feeling of her entire body floating in air. On March 6, 2000, severe giddiness suddenly developed, and from April of that year, she had pronounced drowsiness and hypersomnia. From January 2001, her giddiness and feeling of dizziness became marked, and she was overcome by an unpleasant feeling from January 16 to 17. From January 18 to 19 and on February 7 and 8 she manifested emotional lability. She had a depressive mood on February 22 and reversed to an elated mood the following day. On March 6, she experienced sudden severe left ear pain, which was diagnosed as migraine at a department of neurosurgery in another hospital. In addition, from about this time, anxiety and vague feeling of panic developed. From around April, she experienced autonomic seizures lasting 20 s, characterized by abnormal sensations of gooseflesh and coldness extending from the left posterior neck to cheek. These seizures occurred at a frequency of 20 to 30 times a day. Furthermore, she showed increased anxiety, depressive mood, and palpitations with feeling of left chest constriction in the interictal period. On May 25 and 26, autonomic seizures consisted of sudden severe nausea, and from June were characterized by a feeling of gooseflesh and coldness extending from the upper to lower arms bilaterally. The duration of these seizures was 10–20 s, and the frequency was 10 times/day. From the same period, she had various psychiatric symptoms such as hypobulia, declining activity, and a sense of guilt in the interictal period. From around August, her unpleasant feeling gradually worsened, and her voice became low, and her actions became slow. Furthermore, hypochondriacal and depressive symptoms became more marked, and appetite decreased, with the appearance of insomnia and suicidal ideation. On August 28, generalized tonic–clonic seizures (GTCSs) occurred twice, and after the first GTCS, she had ictal fear lasting 60–120 s, which occurred at a frequency of 4 to 5 times per day. The experience of ictal fear was engendered by the patient imagining a scene in which she was enveloped in the dark by some fearful thing and pursued by something of an unknown nature. Subsequently, her parents witnessed her screaming during the ictal fear. On September 21, she was admitted to our hospital for detailed examinations and treatment.Both the ictal and interictal symptoms improved with increasing doses of carbamazepine (CBZ). Clinical examinations revealed no particular hematologic or biochemical abnormalities, and the neurologic examination was normal. Psychometric examination showed FIQ, 87[verbal IQ (VIQ) 94; performance IQ (PIQ), 82] on the WAIS-R, with procedural memory showing a learning effect in both mirror drawing and tower of Hanoi puzzle. Interictal EEGs showed generalized high-amplitude slow-burst 6- to 7-Hz train, which disappeared after CBZ administration. Fluid-attenuated inversion recovery (FLAIR) images of sagittal magnetic resonance imaging (MRI) revealed high signal intensity areas in bilateral amygdala and hippocampal regions.[99mTc]-HMPAO single-photon emission computed tomography (SPECT) images depicted hypoperfusion findings in the right medial temporal lobe.Discussion:This case had onset of epilepsy at age 20 years, and her symptoms were initially diagnosed as migraine and anxiety disorder. At the time of admission to our hospital, memory disturbance and various psychiatric symptoms such as a sensation of fear, anxiety, and depression were noted, so that the presence of anxiety disorder and dissociative disorder was suspected. However, based on the EEG and brain-imaging findings, a diagnosis of epilepsy was made. The notable features in this case are summarized as follows: (a) simple partial seizures consisting primarily of ictal emotions associated with the experience of fear; (b) interictal symptoms including various psychiatric manifestations such as manic–depressive and anxiety symptoms and memory disturbance; (c) abnormal MRI and SPECT images in the medial temporal lobes, possibly compatible with hippocampal sclerosis; and (d) rapid amelioration of the ictal and interictal symptoms with CBZ administration, accompanied by the disappearance of the generalized high-amplitude slow waves on the EEG.Conclusions:These findings suggest that ictal emotion is induced by localized focal seizures in the hippocampus and the adjacent limbic system including the amygdala. Moreover, the fact that CBZ administration ameliorated the interictal symptoms comprising various psychiatric manifestations and memory disturbances suggests that functional dysfunction associated with enhanced interictal discharges in the limbic system caused the interictal symptoms. Etiologic Analysis of Epilepsy in Children.Purpose:A population-based neuroepidemiologic survey of childhood epilepsy was conducted in the Okayama Prefecture on December 31, 1999, as the prevalence day. We analyzed the presumptive causes in this survey to clarify the causes of childhood epilepsy in the general population.Methods:The segment of the population younger than 13 years in the Okayama Prefecture on the prevalence day was 250,997. The lists of children with epilepsy were collected from the medical records of 84 hospitals and clinics in and around Okayama Prefecture, and 2,220 cases were identified; the prevalence rate was 8.8 per 1,000. In this study, EEGs were examined in 99.3% of the cases. The 2,220 cases, however, included 889 cases with single seizures or seizures induced by fever, because they were diagnosed as epilepsy by definite EEG abnormalities. Generally, cases of single seizures or seizures induced by fever are excluded from epileptic seizures in epidemiologic studies. When the 889 cases are excluded, the prevalence rate for the 1,331 cases decreased to 5.3 per 1,000. The former 2,220 cases and the latter 1,331 cases were designated as group A and group B, respectively. An etiologic analysis was carried out in the two groups.Results:Group A: (a) Presumptive causes were identified in 816 (37.8%) cases, and 1,341 (60.4%) cases had unknown etiology. The other 63 (2.8%) cases were excluded from the total because of a lack of etiologic information. (b) Predisposition to convulsions or epilepsy within second-degree relatives was found in 20.3%. (c) Prenatal causes consisted of genetic neurologic diseases in 1.4%, chromosomal aberrations or malformations in 2.0%, cerebral dysgenesis in 2.0%, intrauterine infection in 0.1%, and congenital hydrocephalus in 0.4%. (d) Perinatal causes consisted of premature birth with a low birthweight in 3.2% and neonatal asphyxia or abnormal delivery in 4.8%. (e) Postnatal causes consisted of encephalitis or meningitis in 2.7%, intracranial hemorrhage or vascular disorder in 0.9%, head trauma in 0.6%, and brain tumor in 0.2%. Group B: (a) Presumptive causes were identified in 562 (42.2%) cases, and 735 (55.2%) cases had unknown etiology. The other 34 (2.6%) cases were excluded from the total because of a lack of etiologic information. (b) Predisposition to convulsion or epilepsy within second-degree relatives was found in 18.9%. (c) Prenatal causes consisted of genetic neurologic diseases in 2.1%, chromosomal aberrations or malformations in 2.8%, cerebral dysgenesis in 2.6%, intrauterine infection in 0.2%, and congenital hydrocephalus in 0.6%. (d) Perinatal causes consisted of premature birth with a low birthweight in 3.9%, and neonatal asphyxia or abnormal delivery in 6.8%. (e) Postnatal causes consisted of encerder in 1.4%, head trauma in 0.8%, and brain tumor in 0.3%. (f) No significant differences in the prevalence of etiologic factors were noted between groups A and B.Conclusions:These findings indicate the etiologic distribution of childhood epilepsy in the general population. Comparison of Neuropsychological Findings Before Temporal Lobectomy Between Patients with Both Amygdalohippocampal Seizures and Psychotic Manifestations and Patients with Only Seizures.Purpose:The objectives of the study were to classify patients with amygdalohippocampal seizures into two groups according to the status of psychotic manifestations such as delusion and hallucination and to compare the neuropsychological findings.Subjects and Methods:We reviewed the neuropsychological findings of 28 patients (14 male, 14 female patients) who underwent temporal lobectomy and classified them into patients with psychotic manifestations such as hallucination and delusion (group P) and patients without them (group N). All patients underwent neuropsychological examinations including the Japanese Wechsler Adult Intelligence Scale–Revised (WAIS-R), Minnesota Multiphasic Personality Inventory (MMPI), Japanese Wechsler Memory Scale–Revised (WMS-R), verbal paired-associates learning test, story recall test, Benton's visual retention test, Rey-Osterrieth's complex figure test, Kana pick-out test, Japanese Raven's colored progressive matrices, and Japanese western aphasia battery.Results:The 28 patients who underwent anterior temporal lobectomy had a mean age at surgery of 36.0 years and mean age at seizure onset of 13.8 years. They were composed of 15 patients with right-sided temporal resection and 13 patients with left-sided temporal resection. According to psychotic manifestations, we classified them into the groups P and N. Group P group consisted of seven patients (25% of all patients) whose mean age at surgery was 39.6 years and mean age at seizure onset was 10.9 years. Group N consisted of 21 patients (75%) whose mean age at surgery was 34.8 years and mean age at seizure onset was 14.8 years. No statistically significant differences were found in the ages at surgery and seizure onset. The scores, determined by using Benton's visual retention test (fail), were higher (p<0.05) in group P than in group N. The scores determined by using the depression (D), psychopathic deviation (Pd), paranoia (Pa), psychasthenia (Pt), schizophrenia (Sc) scales of MMPI were higher (p<0.05) in group P than in group N. The scores of the WMS-R attention/concentration test, verbal paired-associates learning test, story recall test, and Benton's visual retention test (pass) (p<0.05) were higher in group N than in group P. The patient background of group P was as follows: Group P consisted of one male and six females; three of whom had febrile seizures. One patient had right-sided temporal resection, and six patients had left-sided temporal resection. The mean age of psychotic manifestation development was 33.4 years. The psychotic manifestations were characterized by visual hallucinations in three patients, and delusion of reference and persecution in seven patients. The average number of antiepileptic drugs (AEDs) used was 2.9, and the major AEDs were phenytoin, carbamazepine, zonisamide, and clonazepam. Four patients were married, two patients were unmarried, and one patient was divorced. The educational level was junior high school in two patients, high school in three patients, and technical college in two patients. The WAIS-R IQ was 81.9; verbal IQ was 82.6; and performance IQ was 84.6.Conclusions:Group P was distinguished from group N by the clinical scales such as the D (p<0.05), Pd (p<0.05), Pt (p<0.05), Pa (p<0.01), and Sc (p<0.01) scales of the MMPI. Thus the MMPI is a useful tool for determining patients with psychotic manifestations. The attention/concentration results in the WMS-R, verbal paired-associate learning test (hard), story recall test, and Benton's visual retention test findings revealed that patients with both amygdalohippocampal seizures and psychotic manifestations had more severe memory and attention impairments than did the patients with only seizures. Epilepsy: The Clinical Profile, Outcome, and Epilepsy-Related Psychosis.Purpose:This prospective study was conducted to evaluate the clinical profile and the prognostic factors in 1,000 epilepsy patients attending a tertiary care hospital from the year 1996 to 2001.Methods:The evaluation in all cases included clinical assessment, intelligence testing with the Stanford–Binet scale, metabolic workup, EEG, and computed tomography (CT) scan. Magnetic resonance imaging (MRI) and MR angiography (MRA) were done in selected patients. Patients were classified as per the International League Against Epilepsy (ILAE) classification and were followed up with the primary end point of a 1-year seizure-free period. Epilepsy-related psychosis was included as a study parameter in the final 3 years of the study period (500 patients). The psychoses were classified into postictal (immediately after seizures, distinct from the delirious, confusional state after seizures), interictal (with a lucid interval of normal mentation of≥24 h between seizure and psychosis), and chronic psychosis (of>3 months' duration, present all the time). Statistical analysis was done with aχ2 test wherever relevant.Results:The ages of the patients ranged from 7 months to 74 years, with a mean of 30± 8 years; 55% of them were male patients. Of the cases, 59% had localization-related epilepsy, whereas 41% had generalized epilepsy. Myoclonic epilepsy was seen in 5%, and absence seizures, in 3%. On analyzing the etiology of seizures, 66% were cryptogenic or idiopathic, 16% had neurocysticercosis, 8% had tuberculosis, 3% were postinfective, 3% had a vascular etiology, 2% had congenital abnormalities, and 2% were posttraumatic. Twelve (2.4%) patients were diagnosed as epilepsy-related psychosis, of whom eight were male patients. The majority (seven of 12) had complex partial seizures. Postictal psychosis was diagnosed in four patients; seven had acute interictal psychosis, and one patient had chronic psychosis. The interictal and chronic psychoses were schizophreniform, whereas the postictal psychoses were nonspecific. EEG showed a temporal lobe focus in all seven of the complex partial seizures with psychosis and an extratemporal focus in three patients. Two of the patients had normal EEGs. Neuroimaging abnormalities seen in 10 patients included gliosis (three), calcified granulomas (three), medial temporal sclerosis (two), and nonspecific findings (two). Two patients had normal imaging studies.Conclusions:No significant difference was seen in seizure control between the subgroups of patients with generalized and localization-related epilepsy. Our results are in agreement with the recent studies that suggest that the types and causes of seizures are not significantly related to the seizure control. The most predictive factors for good outcome were younger age (p<0.05) and good intellectual development (p<0.05). Earlier studies found 0.5–9% of patients with epilepsy to have epilepsy-related psychosis. Epilepsy-related psychosis was seen in 2.4% of our patients. This factor should be kept in mind by the caregivers of patients with epilepsy. Occupational Ability of Patients with Intractable Epilepsy.Purpose:To examine the occupational ability including interpersonal skills of patients with intractable epilepsy and to identify factors relevant for employment.Methods:Forty-eight patients (36 men, 12 women) with intractable epilepsy were studied. The mean age was 26.6 years (range, 18–49). Average IQ by Wechsler Adult Intelligence Scale–Revised was 61.4 (range, 38–95). Epilepsy diagnoses were symptomatic partial epilepsy, 41; symptomatic generalized epilepsy, six; and idiopathic generalized epilepsy, one. Seizure types were generalized tonic–clonic seizure, 13; complex partial seizure, 29; simple partial seizure, 11; and other seizures, 10. Twenty-one patients had more than one seizure per week. Nineteen patients had seizures with falling that might cause injury. We evaluated the occupational abilities of the patients through observation during occupational therapy and by vocational aptitude tests. At the same time, their employment status 6 to 18 months after leaving the hospital was surveyed. We then compared the abilities of employed patients (Employed) with those of unemployed patients (Unemployed). Fisher's exact test and Mann–WhitneyUtest were used for statistical analyses.Results:(a) Work habits, comprehension, practicality (quickness at work, workmanship), and interpersonal skills were evaluated as normal only in 40%, 6%, 10%, and 23%, respectively, of the patients through observation. The results of vocational aptitude test were generally low. Subsequent employment status was employed, 15; community workshop, five; day care, three; unemployed, 14, and others (including housewife, student), 11. (b) Intelligence scores (IQ; mean± S.D.) were 63.8± 11.1 in the Employed and 63.8± 16.7 in the Unemployed (NS). Comprehension and practicality were evaluated as normal in 13% of the Employed and none of the Unemployed (NS). Overall work habits were evaluated as normal in 67% of the Employed and 7% of the Unemployed (p<0.01). The subitem“asking therapists, greeting” was evaluated as sufficient in 80% of the Employed and 21% of the Unemployed (p<0.01). Interpersonal skills were evaluated as normal in 53% of the Employed and none of the Unemployed (p<0.01); 13% of the Employed and 79% of the Unemployed had a tendency to be isolated from others (p<0.01). As for vocational aptitude tests, the Employed performed better in tests of motor coordination, skilled finger movements, and sorting coins than the Unemployed (p<0.05). Concerning seizure control, none of the Employed and 29% of the Unemployed had seizures with falling during the daytime (NS).Conclusions:Good seizure control, preserved work habits, good interpersonal skills, and skilled motor coots with intractable epilepsy. [ABSTRACT FROM AUTHOR]

The aim of this study was to further evaluate and optimize the Transwell® system for assessing the dissolution behavior of orally inhaled drug products (OIDPs), using fluticasone propionate as a model drug. Sample preparation involved the collection of a relevant inhalable dose fraction through an anatomical mouth/throat model, resulting in a more uniform presentation of drug particles during the subsequent dissolution test. The method differed from previously published procedures by (1) using a 0.4 µm polycarbonate (PC) membrane, (2) stirring the receptor compartment, and (3) placing the drug-containing side of the filter paper face downwards, towards the PC membrane. A model developed in silico, paired with the results of in vitro studies, suggested that a dissolution medium providing a solubility of about 5 µg/mL would be a good starting point for the method's development, resulting in mean transfer times that were about 10 times longer than those of a solution. Furthermore, the model suggested that larger donor/receptor and sampling volumes (3, 3.3 and 2 mL, respectively) will significantly reduce the so-called "mass effect". The outcomes of this study shed further light on the impact of experimental conditions on the complex interplay of dissolution and diffusion within a volume-limited system, under non-sink conditions. [ABSTRACT FROM AUTHOR]