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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]

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]

A fast methodology for the assay of parabens in drug and cosmetic preparations has been presented. The procedure developed is based on paper spray tandem mass spectrometry and isotope dilution approach. For each investigated paraben, the corresponding labeled standard has been used in order to improve the accuracy and reproducibility of the analyses. The MS experiments have been performed under MRM conditions, monitoring the transitions [M‐H]− → m/z 92 and [M‐H]− → m/z 98, respectively, for each analyte and the corresponding labeled internal standard. The quantitative assay has been performed using a calibration curve built from 2 to 15 mg/L. The method accuracy, in all case near 100%, was evaluated using fortified samples at two concentration levels, which are representative of the lower and the higher portion of calibration curve. The good values of LOQ, LOD, and reproducibility confirm the consistency of the developed approach. [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]

Rationale Significant advances have been made in the preparation of different morphologies of magnesium oxide (MgO), but the relationship between MgO morphology and its interactions with therapeutic drugs is rarely studied. Herein, we investigated the interactions between different morphologies of MgO and therapeutic drugs using paper spray mass spectrometry. Methods Different morphologies of MgO including trapezoidal, needle-like, flower-like and nest-like structures were prepared through a facile precipitation method. The as-obtained MgO particles were then coated onto the surface of filter paper via vacuum filtration strategy. The coated papers with different morphologies of MgO were used as the substrates for paper spray mass spectrometry to explore the interactions between different MgO and therapeutic drugs. Results Through investigating the interactions between different morphologies of MgO coated papers and therapeutic drugs, it demonstrated that, in contrast to the trapezoidal, needle-like and nest-like MgO coated papers, different drugs in dried blood spots (DBS) were more favourably eluted off from the paper coated with flower-like MgO due to its weaker surface basicity. Also, the signal intensities of different drugs during paper spray were highly dependent on their elution behaviours. Conclusions Paper spray mass spectrometry (MS) provides an avenue to elaborate the surface properties of MgO with different structures. The surface basicity of MgO played a crucial role in determining the elution behaviours of therapeutic drugs in DBS, and a more favourable elution behaviour tended to result in a higher MS signal. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Pharmacogenomic (PGx) research on the absorption, distribution, metabolism, and excretion (ADME) properties of drugs has begun to have impact for both drug development and utilization. To provide a cross-industry perspective on the utility of ADME PGx, the Pharmaceutical Research and Manufacturers of America (PhRMA) conducted a survey of major pharmaceutical companies on their PGx practices and applications during 2003-2005. This white paper summarizes and interprets the results of the survey, highlights the contributions and applications of PGx by industrial scientists as reflected by original research publications, and discusses changes in drug labels that improve drug utilization by inclusion of PGx information. In addition, the paper includes a brief review on the clinically relevant genetic variants of drug-metabolizing enzymes and transporters most relevant to the pharmaceutical industry. [ABSTRACT FROM AUTHOR]

To cite this article: Church MK, Maurer M, Simons FER, Bindslev-Jensen C, van Cauwenberge P, Bousquet J, Holgate ST, Zuberbier T. Risk of first-generation H1-antihistamines: a GA2LEN position paper. Allergy 2010; 65: 459–466. Background: First-generation H1-antihistamines obtained without prescription are the most frequent form of self-medication for allergic diseases, coughs and colds and insomnia even though they have potentially dangerous unwanted effects which are not recognized by the general public. Aims: To increase consumer protection by bringing to the attention of regulatory authorities, physicians and the general public the potential dangers of the indiscriminate use first-generation H1-antihistamines purchased over-the counter in the absence of appropriate medical supervision. Methods: A GA2LEN (Global Allergy and Asthma European Network) task force assessed the unwanted side-effects and potential dangers of first-generation H1-antihistamines by reviewing the literature (Medline and Embase) and performing a media audit of US coverage from 1996 to 2008 of accidents and fatal adverse events in which these drugs were implicated. Results: First-generation H1-antihistamines, all of which are sedating, are generally regarded as safe by laypersons and healthcare professionals because of their long-standing use. However, they reduce rapid eye movement (REM)-sleep, impair learning and reduce work efficiency. They are implicated in civil aviation, motor vehicle and boating accidents, deaths as a result of accidental or intentional overdosing in infants and young children and suicide in teenagers and adults. Some exhibit cardiotoxicity in overdose. Conclusions: This review raises the issue of better consumer protection by recommending that older first-generation H1-antihistamines should no longer be available over-the-counter as prescription- free drugs for self-medication of allergic and other diseases now that newer second- generation nonsedating H1-antihistamines with superior risk/benefit ratios are widely available at competitive prices. [ABSTRACT FROM AUTHOR]

Allergic rhinitis (AR) is a common condition with quality of life and economic implications for those affected. Numerous studies have attempted to evaluate treatments for rhinitis, seeking clinically meaningful efficacy and safety results to enable evidence-based treatment decisions. Traditional studies of medications for AR are hampered by many confounding environmental factors as well as suboptimal medication compliance. They are also an unsuitable setting for determination of precise pharmacodynamic properties of medications, including onset and duration of action. Allergen challenge chambers (ACCs) were developed to provide predetermined, controlled allergen levels and to limit variables inherent in traditional studies. An ACC hosts a number of allergen-sensitive subjects who may receive either medication or placebo in a closed environment regulated for temperature, humidity and other variables. Subjects' allergic responses are monitored using subjective and objective assessments throughout the study, and the resultant information contributes significantly to the clinical profile of a medication. This consensus paper provides an in-depth review of the role of ACCs as a means to evaluate treatments in AR, and concludes that ACC trials fulfil an important supportive role in the assessment of anti-allergic medication. [ABSTRACT FROM AUTHOR]

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]

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]

Drug transporters are critically important for the absorption, distribution, metabolism, and excretion (ADME) of many drugs and endogenous compounds. Therefore, disruption of these pathways by inhibition, induction, genetic polymorphisms, or disease can have profound effects on overall physiology, drug pharmacokinetics, drug efficacy, and toxicity. This white paper provides a review of changes in transporter function associated with acute and chronic disease states, describes regulatory pathways affecting transporter expression, and identifies opportunities to advance the field. [ABSTRACT FROM AUTHOR]

Objective To evaluate an e-diary developed for measuring headaches, triggers, and medication consumption, in terms of reliability and validity, and variables such as ease of use and participant compliance. Background For many decades, behavioral treatment of headaches has been evaluated via participants completing paper diaries recording their headaches and associated phenomena. There is some limited evidence supporting the reliability and validity of paper diaries, and criticisms have been offered such as the large amount of effort involved for both participants and researchers. This study evaluates a new e-diary that will operate on virtually any device that can connect to the internet, and yields 5 of the recommended outcome measures. Methods One hundred and eighty-one participants (146 females, 35 males) were allocated to 2 groups, e-diaries vs paper diaries, via a disproportionate stratified allocation process. The e-diary group included 4 subgroups based on the technology available to the participant, and the paper diary group included 2 subgroups, one parallel to the e-dairies (short paper), and one representative of traditional paper diaries (long paper). The study commenced with individuals who had self-identified as headache and migraine sufferers attending a screening session that included headache diagnosis. Participants who met selection criteria then completed the Headache Disability Inventory and a measure of quality of life (SF-36) to assess the convergent validity of the diaries, and the Depression Anxiety Stress Scales to assess the discriminant validity of the diaries. They also completed a Measure of Acceptance Questionnaire. Participants then completed the headache diaries over the next 30 days. Finally, participants completed for a second time the questionnaires completed previously. Results The 5 outcome measures - headache frequency, peak intensity, average intensity, duration, and medication usage - were found to have strong test-retest reliability ( r, 0.68-0.79), for all 3 types of diary. These 5 measures for the e-diaries were shown to have good convergent validity via comparison with scores on the Headache Disability Inventory ( r, 0.46-0.55) and SF-36 ( r, −0.35 to −0.49), and divergent validity via comparison with scores on the Depression Anxiety and Stress Scale ( r, 0.10-0.25). The long-paper diaries had significantly higher missing data scores ( M = 15.20, SD = 14.84) and more errors in data completion ( M = 5.47, SD = 3.28) than the e-diaries and short-paper diaries ( P < .05). In addition, the long-paper diaries were evaluated by the participants as more burdensome and significantly less easy to use than the e-diaries and short-paper diaries. Conclusions The e-diaries evaluated in this research would prove a useful tool in clinical trials of behavioral treatment for headaches. [ABSTRACT FROM AUTHOR]

Objective: Although Ireland has one of the highest levels of well‐being in Europe, having a health condition has been found to have a direct negative impact. The aim of this study is to evaluate the current situation and the experiences of patients with epidermolysis bullosa (EB), a rare genetic skin disease, and their relatives living in Ireland, with a focus on burdens and helpful practices. Methods and Measures: In a mixed‐methods design, a series of standardised questionnaires were combined with open‐ended questions. Via an online survey, data from n = 59 EB patients and relatives of EB patients living in Ireland were collected. Results: EB affects both the patients and their relatives. Burdens were found in relation to the visibility of EB, the degree of severity, the current health status, reduced mobility, the financial impact of EB, the psychosocial impact and personal and social resources. The paper also analyses existing resources and highlights opportunities for support and needs of improvement. Conclusion: Quality of life with EB is influenced by somatic symptoms and the psychosocial burden. Individual helpful practices in dealing with this rare disease can be considered as mediators, but they need to be supported by structural and healthcare improvements. Patient or Public Contribution: The perspective of EB patients, their relatives and EB experts were taken into account in the development of the study design via two feedback loops with the EB patient organisations DEBRA Ireland and DEBRA Austria. The design was adapted accordingly. Additionally, by including open‐ended questions, patients and relatives could contribute their individual perspectives and add insights into their lives with EB that might not have been captured with the structured online survey alone. [ABSTRACT FROM AUTHOR]

Microsampling has revolutionized pharmaceutical drug development and clinical research by reducing sample volume requirements, allowing sample collection at home or nontraditional sites, minimizing animal and patient burden, and enabling more flexible study designs. This perspective paper discusses the transformative impact of microsampling and patient‐centric sampling (PCS) techniques, emphasizing their advantages in drug development and clinical trials. We highlight the integration of liquid chromatography‐mass spectrometry (LC–MS) strategies for analyzing PCS samples, focusing on our research experience and a review of current literatures. The paper reviews commercially available PCS devices, their regulatory status, and their application in clinical trials, underscoring the benefits of PCS in expanding patient enrollment diversity and improving study designs. We also address the operational challenges of implementing PCS, including the need for bridging studies to ensure data comparability between traditional and microsampling methods, and the analytical challenges posed by PCS samples. The paper proposes future directions for PCS, including the development of global regulatory standards, technological advancements to enhance user experience, the increased concern of sustainability and patient data privacy, and the integration of PCS with other technologies for improved performance in drug development and clinical studies. By advancing microsampling and PCS techniques, we aim to foster patient‐centric approaches in pharmaceutical sciences, ultimately enhancing patient care and treatment efficacy. [ABSTRACT FROM AUTHOR]

A Case of Myoclonic Absence Epilepsy with Rightward Head Turning.Case Report:A 4-year-old girl born after full-term, uneventful gestation had myoclonic absence epilepsy with rightward head turning. Her motor and mental development was normal. Her grandfather had an episode of generalized seizure without fever at age 1 year. She had a febrile convulsion at age 10 months. At age 13 months, she had a generalized tonic–clonic seizure (GTCS) without fever. Between ages 13 and 17 months, she had five episodes of GTCSs, but did not receive anticonvulsants because of normal interictal EEG during sleep. She had no seizure during the subsequent 12 months despite no medication. At age 2 years 5 months, GTCSs recurred, and she had three episodes of falling attacks. Sleep EEG showed a normal background with a few spikes in the right frontal area. Treatment with carbamazepine was started. After treatment, she had no convulsive seizures except two episodes of loss of consciousness for a few seconds. Interictal EEG during sleep at age 3 years 3 months showed diffuse irregular polyspike-and-wave discharges. At age 3 years 8 months, she had myoclonic jerking. The myoclonic jerking lasted for 1–2 s and increased in frequency and duration after 2 months. The seizures were characterized by rhythmic myoclonic jerks of shoulders and arms and turning of the eye/head to the right. The seizure duration was 7–8 s. The seizures had abrupt onset and cessation. Ictal EEG showed bilateral, symmetrical, and synchronous 3-Hz spike-and-wave discharges. Brain magnetic resonance imaging (MRI) was normal. Her developmental quotient was 97. The seizures were controlled with high-dose valproic acid and ethosuximide. Interictal EEG at age 4 years 1 month was normal.Discussion:Myoclonic absence epilepsy (MAE) was first described by Tassinari et al. as a rare epileptic syndrome. According to their report, the prognosis for MAE was less favorable than that for pyknolepsy, often with mental deterioration, and possible evolution to other types of epilepsy. They also reported head and body deviation in some patients. The present case had myoclonic absence with rightward head turning and benign outcome, including normal development. Gastaut reported that versive or circling epilepsy with bilateral 3-cps spike–waves represented a benign form of primary generalized epilepsy. Aguglia et al. reported the occurrence of versive or circling seizures in idiopathic generalized epilepsies. The present case demonstrated that unilateral or clearly asymmetrical manifestations may be observed in generalized epilepsy. The Features of Localization-Related Epilepsy in Periventricular Leukomalacia.Purpose:Periventricular leukomalacia (PVL) is an important cause of chronic neurologic disability, such as spastic diplegia, delayed cognitive development, and epilepsy, in children born prematurely. Several reports have described the relationship between West syndrome and PVL, but the other types of epilepsy are not well documented. The aims of the present study were to determine whether the severity or outcome of epilepsy can be predicted from the degree of PVL.Methods:Seven epilepsy patients (two boys and five girls) born at 22–39 weeks of gestation and weighing 416–3,425 g were studied. Mean age at onset of epilepsy was 3 years 5 months (ranging from 1 year 5 months to 5 years 2 months). In all cases, the epileptic seizure was complex partial seizure[CPS;+secondarily generalized tonic–clonic convulsion (GTC)]. A diagnosis of PVL was made with magnetic resonance imaging (MRI) during late infancy, based on ventriculomegaly with an irregular margin accompanied by a periventricular abnormal high-intensity area on T2-weighted imaging. The subjects were divided into two groups according to the severity of PVL, based on MRI findings. Mild PVL (three cases) was defined as localized volume loss of periventricular white matter from around the trigonal zone to the occipital horns, and severe PVL (four cases) was diffuse volume loss extending to the frontal horns.Results:The three subjects in the mild-PVL group were term infants, and the other four were preterm infants. The onset age of CPSs was not significantly different between the two groups and was later than that for West syndrome previously reported. Interictal electroencephalogram (EEG) revealed spike discharges in occipital or parietal lesions in all seven cases. In the severe-PVL group, several spike discharges also were found in other lesions. On MRI findings, all cases had ventriculomegaly on both sides, and two of four cases with severe PVL had right-predominant ventriculomegaly, accompanied by uregyria in the right temporoparietal lesion on MRI.Conclusions:Regardless of the presence or absence of abnormal MRI findings of the cerebral cortex, all epilepsy cases with PVL had epileptic discharges in the occipital area on EEG. The severity of EEG and epileptic seizures may depend on the degree of PVL. Electroclinical Manifestations in a Patient with Vitamin B6 Dependency.Purpose:To identify the electroclinical manifestations in a patient with vitamin B6 dependency.Case Report:An 18-month-old female infant was first seen with hyperirritability and seizures. She was born at 39 gestational weeks. Her birth weight was 3,044 g, and Apgar scores were 9 at 1 min. No family history of epilepsy existed. She showed hyperirritability immediately after birth. During the neonatal period, hemorrhagic shock developed because of melena and intraventricular hemorrhage. At age 1 month, she was referred to us because of hyperirritability and intractable seizures. An interictal EEG revealed sporadic focal spikes. Simultaneous video-EEG monitoring demonstrated erratic myoclonia, serial spasms, partial seizures, or a combination of these seizures. A poorly organized slow high-voltage background with superimposed paroxysmal features was accompanied by erratic myoclonia. An ictal EEG showed a bilateral spiky high-voltage wave followed by voltage attenuation coinciding with the clinical spasms. An ictal EEG corresponding to a partial seizure had multiple foci. The seizures were resistant to antiepileptic drugs, including phenobarbital, carbamazepine, phenytoin, and lidocaine. At age 3 months, the seizures were controlled with vitamin B6. The diagnosis of vitamin B6 dependency was confirmed at age 12 months; seizures recurred 55 h after the discontinuation of vitamin B6 and again dramatically responded to intravenous vitamin B6.Conclusions:We report an infant with vitamin B6 dependency, who had a variety of seizures including erratic myoclonia, serial spasms, and partial seizures. Automatisms With Preserved Responses Without Verbal Responses in Temporal Lobe Epilepsy.Purpose:Automatisms with preserved responses (APRs) are observed in temporal lobe epilepsy (TLE) and have been regarded as a lateralizing sign of nondominant hemispheric origin. We report two patients with left TLE with APR without verbal responses, who had language dominance in the left and bilateral hemispheres respectively.Case Report:Case 1: A 19-year-old woman had intractable seizures consisting of lip smacking and right-hand fumbling. APRs were observed during seizures, but she could not show verbal responses. Magnetic resonance imaging (MRI) demonstrated left mesial temporal sclerosis. Video-EEG monitoring, positron emission tomography (PET), and single-photon emission computed tomography (SPECT) also suggested left mesial temporal lobe epilepsy. On Wada testing, her language dominance was bilateral. Functional MRI suggested that her sensory language area might be located in the right hemisphere and motor language area in the left hemisphere. Case 2: A 20-year-old woman had intractable seizures consisting of lip smacking and bilateral hand automatism. APRs were observed during attacks, but she could not answer in words. Left mesial temporal lobe epilepsy was documented with hippocampal sclerosis on MRI. Video-EEG monitoring, PET, and SPECT findings also suggested that the seizure originated in left temporal lobe. Her language dominance was in the left hemisphere, demonstrated by Wada testing and functional MRI.Conclusions:Our patients suggest that APRs without verbal response may occur in seizures originating in dominant or partially dominant temporal lobe. A Case with Absence Seizures of Frontal Lobe Origin: Simultaneous Video-EEG Findings.Absence seizures may be defined as a paroxysmal loss of consciousness of sudden onset and sudden end, which is associated with bursts of bilaterally synchronous 3-Hz spike-and-wave discharges recorded on the EEG. Usually, it is thought to be associated with a diffuse process affecting the brain, but absence seizures also are seen in some patients with localization-related epilepsy and accompanied by bursts of almost generalized 3-Hz spike-and-waves. We describe a 9-year-old boy first seen with absence seizures of frontal lobe origin, as recorded by a simultaneous video-EEG system.Case Presentation:At age 9 years, the patient experienced onset of absence seizures consisting of sudden arrest of speech and gesture, myoclonus of unilateral or bilateral angles of the mouth, alternation of consciousness, occasional simple automatisms, and brisk recovery of consciousness. Absence seizures occurred several times a day. He also experienced complex partial seizures 1 to 3 times a month with deviation of the head and eyes toward the left, elevation of left upper limbs, loss of consciousness, salivation, and tonic convulsion of left upper and lower limbs. Interictal EEG showed sporadic right frontal dominant high-voltage slow waves or spike-and-waves. There was no abnormal finding on brain magnetic resonance imaging. Interictal single-photon emission computed tomography indicated hypoperfusion of the dorsal and medial cortex of the right middle frontal lobe. Interictal positron emission tomography also indicated hypometabolic areas in the dorsal and medial cortex of the right frontal lobe, as well as in the right temporal and parietal cortex. Ictal EEG of a complex partial seizure could not be detected because of the low frequency of seizures. Simultaneous video-EEG recordings of 10 absence seizures revealed left frontal-dominant, diffuse high-voltage 3- to 3.5-Hz spike-and-wave complexes lasting several seconds. Partial seizures never preceded the absence seizures. Transverse bipolar montage recordings revealed that the first spike component of the spike-and-wave complexes of absence seizures always showed phase reversal on the right anterior temporal electrode. Subsequent components, however, showed phase reversal on the left anterior temporal electrode and continued at the end of seizures. EEG findings and neuroimaging studies suggested that the epileptogenic focus of absence seizures with myoclonus of the angles of mouth in this patient might have originated at the dorsal cortex of the right middle frontal lobe and immediately spread to the medial cortex of the frontal lobe. Both absence and complex partial seizures were well controlled with a combination of phenytoin and high-dose sodium valproate.Discussion:Pavone et al. reported the relation of absence seizures and the frontal lobe and concluded that the frontal maximum of the 3-Hz spike-and-wave pattern indicates frontal lobe involvement during absence seizures, including both prefrontal and frontomotor portions, and the prefrontal cortex is likely to account for the motor component of absence seizures such as myoclonic twitching. They also reported that this concept can be applied not only to the absence seizures occurring in generalized epilepsy but also to the rare cases with a primary frontal epileptogenic focus leading to absence seizures, as is in the present case. [ABSTRACT FROM AUTHOR]

The article cites a paper on the use of antidepressants by adults, written by Joanna Moncrieff and Irving Kirsch, published in the "British Medical Journal." According to the authors of the paper, prescribing of antidepressants has increased 253 percent over the last ten years. They suggest that review data from the U.S. National Institute for Health and Clinical Excellence indicate that SSRIs show no clinically meaningful advantage over placebo, consistent with some recent metaanalyses. Furthermore, they assert that claims that antidepressants are more effective for treating severe conditions lack supporting evidence.

Medication abortion with pills (mifepristone and misoprostol) challenges the spatiality of abortion provision because it creates the possibility for safe, self‐managed abortion outside of clinical infrastructure. This possibility has been contested by pro‐ and anti‐abortion actors for as long as medication abortion has been in existence. In this paper, I offer a legal geography account of medication abortion technology that examines how medication abortion has been regulated in the United States. Conceptually, the paper uses a legal geography methodology to probe the social spatialities that abortion laws construct. Empirically, the paper analyses trends in legislation to restrict medication abortion and two significant court challenges where abortion providers brought suit against medication abortion restrictions. Drawing on legislation and litigation over mifepristone, I demonstrate that restrictions on it function by anchoring mifepristone inside the clinical spaces and regulatory frameworks established for surgical abortion. In this way, mifepristone regulations circumscribe its availability in order to prevent the creation of alternative models for abortion provision that could re‐arrange its geography and expand abortion access. Medication abortion pills challenge the spatiality of abortion provision because they create the possibility for safe, self‐managed abortion outside of clinical infrastructures. This paper offers a legal geography account of medication abortion technology that examines how medication abortion has been regulated in the United States. The paper analyses trends in legislation to restrict medication abortion and two significant court challenges where abortion providers brought suit against medication abortion restrictions. [ABSTRACT FROM AUTHOR]

Building on macroeconomic research on technology searches in response to diminishing technological opportunities, we develop an industry-level search theoretic model of productivity, knowledge sources, and innovation. We argue that increasing the use of science in technology development increases the novelty of ideas in the innovation search distribution and thus increases the likelihood of finding productivity improvements. We also propose that this relationship will hold outside the traditional science-based industries (pharmaceuticals, chemicals), and that there is no similar relationship between productivity and non-science patents. Random effect analyses of 32 US manufacturing industries during 1985–1997 support these hypotheses. [ABSTRACT FROM AUTHOR]

Aims The publication of the Journal of Inebriety (1876–1914) chronicled the rise and fall of the first era of organized addiction medicine in the United States. Methods Findings from historical research, a content analysis of the Journal's 35 volumes and 141 issues and images from the Journal illustrate visually the medical treatment of addiction in the United States in the late 19th and early 20th centuries. Results Under the editorial direction of Dr T. D. Crothers, the Journal of Inebriety published papers and reviews focused primarily on the medical treatment of alcohol and opiate addiction within a growing international network of inebriate homes and asylums. Conclusions The history of the Journal of Inebriety mirrors efforts in America to forge a legitimized field of addiction medicine amid conflicting conceptualizations of the nature of severe alcohol and other drug problems. [ABSTRACT FROM AUTHOR]

In recent years sexualised drug use, usually referred to as chemsex, has become the object of intense media health‐related panic and increasing academic scrutiny. Critical social scientists have challenged pathologising perspectives, analysing the socio‐cultural and political economy dimensions of chemsex. Against the silence of geographers in this emerging field, the paper develops a geographical relational analysis of chemsex, focusing on the experiences of gay men living with HIV in two Italian cities (Bologna; Milan) and Italian gay men living with HIV in three English cities (Leicester; London; Manchester). Demonstrating the constitutive role of place in the practice of chemsex, the paper frames place relationally, that is, as the encounter between here and there, the material and the virtual, imagined geographies and lived spaces. To emphasise the central role of place and geographical knowledge to understand chemsex, the paper builds on 'weak theory', as it conceives things as open, entangled, connected and in flux, while focusing on ordinary practices and heterogeneity in more‐than‐human worlds. Showing how chemsex represents an embodied, relational geographical encounter among different human and non‐human actors, places (both physical and digital), imaginations and desires, the paper highlights the role of sexual practices in the relational construction of place‐making, therefore calling for an increased engagement with sex itself within the field of geographies of sexualities. The paper introduces a relational geographical perspective to the analysis of chemsex. Demonstrating the constitutive role of place in the practice of chemsex, the paper frames place relationally, i.e. as the encounter between here and there, the material and the virtual, imagined geographies and lived spaces. The paper calls for an increased engagement with the materiality of sex within the field of geographies of sexualities. [ABSTRACT FROM AUTHOR]

This paper explores the relationship between the illicit opium economy and processes of agrarian change in south‐western Shan State, Myanmar. This is a region where opium production has risen significantly since the 1990s despite the declining territorial control of insurgent groups long blamed for the country's illegal drug economy and alongside the deepening integration of the region's agriculture sector into national and global markets. This paper reveals how illicit opium cultivation has offered distressed smallholders a way to mitigate the worsening livelihood insecurities that have accompanied the commercialization of smallholder agriculture. Yet at the same time, opium cultivation has locked farmers into a set of highly unequal social relations that has enabled militias, businesspeople with ties to local (armed) authorities, moneylenders, and agricultural brokers to accumulate capital through their control over rural markets and credit systems while leaving poppy cultivators with little more than the means to reproduce their livelihoods. This paper thus shows how opium cultivation has enabled farmers to respond to worsening precarity by sustaining smallholder farming despite the worsening "reproduction squeeze" facing many households, although the opium economy has simultaneously played an instrumental role in reinforcing and deepening agrarian class relations. [ABSTRACT FROM AUTHOR]

Aims: Sewage treatment effluent with pharmaceutical residues is discharged into surface waters, raising societal concerns. The aim of this paper is to describe the Dutch chain approach on medicinal residues in water that has been implemented by the Dutch government. We show how stakeholders from both the health and water sectors have got actively involved. Within this chain approach, source measures as well as end‐of‐pipe measures are identified and, where feasible and effective, implemented. Methods: Descriptive paper on the Dutch chain approach. Results: Getting the water and health care sectors to talk with each other instead of about each other was the key accomplishment. Comprehension of each other's viewpoints, terminology, policy goals and span of control, was pivotal in setting shared goals, creating perspective about possible measures and actually taking (joint) action. Together, stakeholders agreed to act within their own possibilities, without pointing at others, and to focus on pragmatic measures. In this article, we provide examples of measures taken, pilot projects performed, and of measures that were not implemented. Besides this, we discuss the most important barriers encountered during this process and how they were overcome. Conclusion: The issue of pharmaceuticals in the environment is a wicked problem, which makes it necessary to work together with many stakeholders on possible solutions, avoiding paralysis by complexity. Most importantly, stakeholders need to invest in mutual understanding, keep an open communication, and feel invited to bring in solutions for their part of the chain. [ABSTRACT FROM AUTHOR]

There is a lack of consensus on the safety of the coadministration of drugs and red blood cells (RBCs). A systematic review was undertaken to establish the evidence base for this question and assess how the evidence may be translated into present clinical day practice. Comprehensive searches of MEDLINE, EMBASE, CINAHL, the Cochrane Library and hand searching of transfusion journals, guidelines and websites identified 12 relevant papers: 11 in-vitro experiments and 1 case report. Data on incidences of haemolysis and agglutination following coadministration were extracted and analysed. Overall findings suggest that iron chelators (two papers), antimicrobials (three papers) and lower doses of opioids (three papers) are safe to coadminister with RBCs. Haemolysis was observed with higher doses of opioids (three papers). Transposition of these findings to clinical practice is limited because of the lack of clinical applicability of in-vitro experiments and diversity in how, and what, clinical outcome measures were used. Further evidence from true clinical settings would be required to inform clinical practice on the efficacy and safety of the coadministration of drugs and RBCs. [ABSTRACT FROM AUTHOR]

Sirolimus is a mammalian target of rapamycin inhibitor (mTORI) with anti‐proliferative, antiangiogenic and immunosuppressive properties. While approved in Australia as an anti‐rejection medication for renal transplant patients, there is mounting evidence regarding the utility of oral and topical sirolimus in treating a plethora of dermatological conditions or conditions with cutaneous manifestations. Our aim was to present an overview of the evidence for current usage and breadth of the application of sirolimus in dermatology. We carried out a systematic review of all the literature published up to 31 August 2019 on oral and topical sirolimus with respect to dermatological conditions or conditions otherwise relevant to dermatology. While 3368 papers were initially produced in our search, 238 papers met our inclusion criteria and were examined in our review. The conditions examined were categorised into genodermatoses (9 conditions), infection (1 condition), inflammatory/autoimmune (10 conditions), neoplasm (3 conditions) and vascular (17 conditions). We extracted data on first author, publication year, journal, characteristics of the study and study patients, condition, drug modalities, drug efficacy, side effects, blood level of mTORI, co‐interventions and follow‐up. While there is level 1 evidence for the efficacy of sirolimus in conditions such as tuberous sclerosis complex (TSC) and GVHD prophylaxis, for many other conditions, the evidence is limited to level 4 evidence. Regarding oral systemic therapy, dosing regimens varied with the most common for children 0.8mg/m2 twice daily and for adults 1 mg twice daily. Doses were often adjusted to reach a typical trough level of between 5 and 15 ng/mL, though targets often varied. In the overall majority of cases, side effects were minimal or tolerable, including mucositis, cytopenias, lipid abnormalities and nausea/vomiting, and only a few cases had to stop due to adverse effects. Regarding topical therapy, concentration of formulations varied from 0.1% to 1% and were compounded into creams, ointments or gels and administered typically once or twice per day. The most common side effect was skin irritation. There were a number of limitations to our study. In particular, many of the published studies were case reports or case series with no comparator arm, leading to susceptibility of bias in conclusions drawn, in particular a high likelihood of publication bias. Given the heterogeneity amongst studies, comparisons or aggregation of results was difficult. There continues to be growing use of oral and topical sirolimus in dermatological conditions. It provides new therapeutic options to patients where previous therapies have either failed or are limited due to toxicity. However, further studies are warranted. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editor discusses various topics within the issue, including adherence to medicine of people with human immunodeficiency virus (HIV), the antiretroviral treatment access to older South Africans with HIV, and parenting of gay men with HIV.

The role of membrane transporters on pharmacokinetics (PKs), drug–drug interactions (DDIs), pharmacodynamics (PDs), and toxicity of drugs has been broadly recognized. However, our knowledge of modulation of transporter expression and/or function in the diseased patient population or specific populations, such as pediatrics or pregnancy, is still emerging. This white paper highlights recent advances in studying the changes in transporter expression and activity in various diseases (i.e., renal and hepatic impairment and cancer) and some specific populations (i.e., pediatrics and pregnancy) with the focus on clinical implications. Proposed alterations in transporter abundance and/or activity in diseased and specific populations are based on (i) quantitative transporter proteomic data and relative abundance in specific populations vs. healthy adults, (ii) clinical PKs, and emerging transporter biomarker and/or pharmacogenomic data, and (iii) physiologically‐based pharmacokinetic modeling and simulation. The potential for altered PK, PD, and toxicity in these populations needs to be considered for drugs and their active metabolites in which transporter‐mediated uptake/efflux is a major contributor to their absorption, distribution, and elimination pathways and/or associated DDI risk. In addition to best practices, this white paper discusses current challenges and knowledge gaps to study and quantitatively predict the effects of modulation in transporter activity in these populations, together with the perspectives from the International Transporter Consortium (ITC) on future directions. [ABSTRACT FROM AUTHOR]

The progress the Internet has experienced in recent years has brought about huge changes and social transformation in all aspects of our lives. One such aspect greatly impacted has been our health, where we can talk about the existence of an ‘Internet of Medical Things’. Amid this digital drift, we have seen the development of pharmaceutical drugs that provide information to patients and their attending healthcare teams concerning medication, doses ingested, and time of ingestion. These are digital pills or digital medication. In this context, the purpose of my paper is to analyze the ethical and legal impact of digital medication, further analyzing the implications concerning the right of service users to make decisions over their own health in Spain. [ABSTRACT FROM AUTHOR]

The national quality framework (NQF) has been implemented to improve the safety and quality of alcohol and other drug (AOD) treatment and provide a nationally consistent approach to treatment quality in Australia. At the same time, concerns have been raised that, in the absence of appropriate regulatory structures to support the NQF, the quality and safety of AOD treatment services cannot be guaranteed in Australia. An effective enforcement strategy is critical to the ability of the NQF to provide a nationally consistent approach to the delivery of AOD treatment in Australia. The monitoring and enforcement strategy proposed by the NQF encompasses two different mechanisms. For specialist AOD treatment providers in receipt of government funding, monitoring and enforcement of the NQF will occur via contractual arrangements. For providers not in receipt of government funding, monitoring and enforcement will be managed by regulatory mechanisms as decided by each jurisdiction. This proposed enforcement strategy raises the question of whether contractual arrangements are the most effective mechanism for monitoring and enforcing the NQF in publicly funded specialist AOD treatment providers. This paper considers whether a licensing regime may address the shortcomings that arise from the proposed strategy. It argues that the pluralistic approach to the monitoring and enforcement of the NQF will result in substantive differences in how the NQF is enforced both within individual jurisdictions and on a broader national level. A licensing regime, therefore, would be a more appropriate monitoring and enforcement strategy. [ABSTRACT FROM AUTHOR]

Background: Medication errors are a leading cause of harm to patients in hospital that can be decreased by electronic medication management systems. Aims: This study determined the effects of electronic prescribing using the Enterprise Patient Administration System (EPAS) on prescribing errors and adverse drug reaction (ADR) documentation in South Australian public hospitals. Methods: A prospective structured medication chart audit was conducted before (in 2012) and after the implementation (in Dec 2014) of EPAS, comparing the paper‐based National Inpatient Medication Chart (NIMC) with prescribing. All inpatients were eligible for inclusion in the study. Prescribing order errors were determined by the percentage of medication orders that had unclear, illegal or unsafe prescriptions. The quality of ADR documentation was assessed by the percentage of patients with correct documentation. Results: The total number of prescribing errors before and after the implementation of EPAS was 67.7 and 2.8 per 100 orders, respectively. The frequency of prescribing order errors due to unclear, illegal and unsafe prescriptions decreased to almost zero with EPAS. Prescriptions classified as unsafe due to incorrect dose, route of administration or dosing frequency decreased from 5.8% to 0.03% of medication orders before versus after EPAS implementation (p < 0.0001). Completed ADR documentation was similar between the paper‐based NIMC and EPAS, but the percentage of patients with ADR alerts who required them was 100% in EPAS compared with 27% on the NIMC (p < 0.0001). Conclusions: E‐prescribing using EPAS significantly decreased prescribing errors and increased ADR alerts. Continued implementation of electronic medication management systems is an important approach to improve medication safety. [ABSTRACT FROM AUTHOR]

Abstract: Background and Aims: Dr Leslie E. Keeley was perhaps the world's most famous addiction cure doctor at the turn of the 20th century, but mainstream medicine dismissed him as a quack because he dispensed a secret cure. This paper aims to describe Keeley's now largely forgotten story and to draw attention to the role of contextual issues in the acceptance or rejection of any theory of addiction, particularly the neuroscientific theories of the early 21st century. Methods: This study is a qualitative assessment and contextualization of historical documents. Its main sources are archival and are, for the most part, unknown to historians. The paper also offers intellectual and historical context that is drawn from leading historical and sociological analyses. Results: Keeley's addiction cure was dismissed as quackery because it failed to meet the changing standards of late 19th‐century professional medicine. This begs us to consider contextual issues in any assertion of the viability of addiction therapeutics, in the present as well the past. Conclusions: Keeley's near erasure from the historical record was a consequence of a broader, late 19th‐century medical power struggle that took precedence over the testimony of tens of thousands of satisfied patients who claimed that Keeley's cure worked. Context matters in the assessment of the viability of theories of addiction from the past, but also from the present. Historians and social scientists are well placed to make those assessments. [ABSTRACT FROM AUTHOR]

A list of forthcoming papers is presented including "Assessing the Impact of Educational Intervention in Hypertensive Patients" by Tai Mooi Ho, "A Nurse Led Intervention Improves Detection and Management of AKI in Malawi" by Christopher Kirwan and "Medication Adherence After Renal Transplantation - A Review of the Literature" by Anne Rebafka.

The article invites contributions in all fields of experimental pharmacology including studies on normal human subjects to be published in "British Journal of Pharmacology". The work should have a direct bearing on drugs and their actions. Papers describing the discovery and characteristics of new chemically defined compounds are welcomed.

Lists articles about the pharmacological modulation of skin neuromediators. Proteinase-activated receptors; Inflammation-coagulation network; Role of cell-surface proteolysis in terminating neuropeptide signaling.

The means by which patients acquire their medications differ between countries, and a knowledge of this is essential when conducting and interpreting pharmacoepidemiological studies. The aim of this paper is to provide an overview of how patients obtain medicines in Denmark, to relate these to nationwide registries available for research and to discuss the implications for research. Health services are predominantly tax‐funded in Denmark, with dentistry and some medicine bought at community pharmacies being exceptions, involving partial reimbursement of charges. The paper gives an overview of prescription medicines acquired from community pharmacies (including magistral preparations), over‐the‐counter medicines, vaccinations and in‐hospital medicine including so‐called "free medicine" (in Danish: "vederlagsfri medicin"). "Free medicine" is medicines for a defined list of diseases and indications that is provided free of charge to patients in outpatient clinics. The paper also describes the content of the various Danish data sources about medicine use, summarizes their strengths and limitations, and exemplifies the ways of evaluating their completeness. An example is provided of the regional variation in the means by which medicines are acquired. [ABSTRACT FROM AUTHOR]

Upscaling of medication adherence interventions to routine care is still challenging. This realist theory‐inspired review aimed to assess which intervention aspects are potentially important for the scalability of effective cardiovascular disease (CVD) medication adherence interventions and how they are reported in effectiveness studies. A total of 4097 articles from four databases were screened of which ultimately 31 studies were included. Relevant information on scalability was extracted using a theoretic framework based on the scalability assessment tool used in the QUALIDEC study for the following domains: (i) innovation, (ii) implementers and patients, (iii) adopting organizations and health system, and (iv) socio‐political context. Extracted articles were analysed for themes and chains of inference, which were grouped based on commonality and source of evidence to form new hypotheses. Six different domains relevant for scalability of adherence interventions were identified: (1) Complexity of the intervention; (2) training; (3) customization of the intervention; (4) drivers of the intervention; (5) technical interventions; and (6) stakeholder involvement. These six domains might be useful for the development of more scalable interventions by bridging the gap between research and practice. Data relevant for scalability is not well reported on in effectiveness trials for CVD medication adherence interventions and only limited data on scalability has been published in additional papers. We believe the adoption and reach of effective CVD medication adherence interventions will improve with increased awareness for the necessity of scalability in all phases of intervention development. [ABSTRACT FROM AUTHOR]

The most intuitive question for market access for medicinal products is the benefit/risk (B/R) balance. The B/R assessment can conceptually be divided into subquestions related to establishing efficacy and safety. There are additional layers to the B/R ratio for medical products, including questions related to dose selection, clinical and nonclinical pharmacology, and drug quality. Explicitly stating the actual questions and how they contribute to the overall B/R provides a structure that fosters better informed cross‐domain discussions. There is currently no systematic approach in the regulatory setting to assess and establish the acceptability of alternative methods and data sources. In most cases, the medicinal product sponsors tend to prioritize traditional data types and methods, which are well accepted by regulators for inclusion in regulatory submissions. This, in addition to the absence of rigor in the use and validation of new data types and methods, and the limited training of assessors in related fields can lead to increased regulatory skepticism toward new data types and methods. A data‐knowledge backbone is needed to mitigate the uncertainty in efficacy and safety characterization. This white paper discusses the value of explicitly redefining and restructuring the regulatory scientific decision making around the scientific question to be addressed. The ecosystem proposed is based on three pillars: (i) a repository connecting questions, data, and methods; (ii) the development and validation of high‐quality standards for data and methods; and (iii) credibility assessment. The ecosystem is applied to four use cases for illustration. The need for training and regulatory guidance is also discussed. [ABSTRACT FROM AUTHOR]

Background and Aims: Long‐acting injectable buprenorphine (LAIB) is a new treatment for opioid use disorder that is generating positive outcomes. Negative effects are typically mild and transient, but can occasionally be serious, resulting in treatment discontinuation/non‐adherence. This paper aims to analyse patients' accounts of how they felt during the first 72 h after initiating LAIB. Methods: Semi‐structured interviews were conducted (June 2021–March 2022) with 26 people (18 males and 8 females) who had started LAIB within the previous 72 h. Participants were recruited from treatment services in England and Wales and were interviewed by telephone using a topic guide. Interviews were audio‐recorded, transcribed and coded. The concepts of embodiment and embodied cognition framed the analyses. Data on participants' substance use, initiation onto LAIB and feelings were tabulated. Next, participants' accounts of how they felt were analysed following the stages of Iterative Categorization. Results: Participants reported complex combinations of changing negative and positive feelings. Bodily experiences included withdrawal symptoms, poor sleep, injection‐site pain/soreness, lethargy and heightened senses inducing nausea ('distressed bodies'), but also enhanced somatic wellbeing, improved sleep, better skin, increased appetite, reduced constipation and heightened senses inducing pleasure ('returning body functions'). Cognitive responses included anxiety, uncertainties and low mood/depression ('the mind in crisis') and improved mood, greater positivity and reduced craving ('feeling psychologically better'). Whereas most negative effects reported are widely recognized, the early benefits of treatment described are less well‐documented and may be an overlooked distinctive feature of LAIB. Conclusions: During the first 72 h after initiating long‐acting injectable buprenorphine, new patients report experiencing a range of interconnected positive and negative short‐term effects. Providing new patients with information about the range and nature of these effects can prepare them for what to expect and help them manage feelings and reduce anxiety. In turn, this may increase medication adherence. [ABSTRACT FROM AUTHOR]

Any drug can potentially induce a hypersensitivity reaction. If after the allergological work‐up the drug hypersensitivity reaction is confirmed, in most cases, the simple avoidance of the culprit drug and a suggestion of an unrelated alternative is enough. However, there are circumstances where the choice to stop the treatment affects the survival, the safety and/or the quality of life of the patient and the global outcome of the disease in question. When this occurs, drug desensitization can be the answer and should not be viewed as an extravagance, nor the pediatric age should be considered a contraindication. Drug desensitization in children can be safely and successfully performed, having a positive impact on the survival and overall prognosis. In general, the indications for DDS are the same in adults as in children. However, in this age group there are specificities that this paper aimed to describe, reviewing the mechanisms behind drug hypersensitivity and rapid drug desensitization, types of protocols, indications, and contraindications, as well as several technical aspects that are specific to the pediatric age. [ABSTRACT FROM AUTHOR]

Background: As people age, they are more likely to develop multiple long‐term conditions that require complicated medicine regimens. Safely self‐managing multiple medicines at home is challenging and how older people can be better supported to do so has not been fully explored. Aim: This study aimed to identify interventions to improve medicine self‐management for older people living at home and the aspects of medicine self‐management that they address. Design: A rapid review was undertaken of publications up to April 2022. Eight databases were searched. Inclusion criteria were as follows: interventions aimed at people 65 years of age or older and their informal carers, living at home. Interventions needed to include at least one component of medicine self‐management. Study protocols, conference papers, literature reviews and articles not in the English language were not included. The results from the review were reported through narrative synthesis, underpinned by the Resilient Healthcare theory. Results: Database searches returned 14,353 results. One hundred and sixty‐seven articles were individually appraised (full‐text screening) and 33 were included in the review. The majority of interventions identified were educational. In most cases, they aimed to improve older people's adherence and increase their knowledge of medicines. Only very few interventions addressed potential issues with medicine supply. Only a minority of interventions specifically targeted older people with either polypharmacy, multimorbidities or frailty. Conclusion: To date, the emphasis in supporting older people to manage their medicines has been on the ability to adhere to medicine regimens. Most interventions identify and target deficiencies within the patient, rather than preparing patients for problems inherent in the medicine management system. Medicine self‐management requires a much wider range of skills than taking medicines as prescribed. Interventions supporting older people to anticipate and respond to problems with their medicines may reduce the risk of harm associated with polypharmacy and may contribute to increased resilience in the system. Patient or Public Contribution: A patient with lived experience of medicine self‐management in older age contributed towards shaping the research question as well as the inclusion and exclusion criteria for this review. She is also the coauthor of this article. A patient advisory group oversaw the study. [ABSTRACT FROM AUTHOR]

Background: People with intellectual disabilities are known to have increased medical needs and are prescribed more medication than the general population. Understanding the reality of incorporating medication into their lives would help healthcare professionals provide care in more meaningful and personalised ways. Aim: A narrative review of the current literature relating to people with intellectual disabilities and their experience of medication/pharmaceutical care. Method: Electronic databases were searched for articles relating to intellectual disabilities and medication administration or pharmaceutical care. Other relevant papers identified from included article reference lists were also identified. A narrative literature was undertaken due to the heterogeneity of the identified papers. Results: A total of 29 studies from the literature searches were included alongside other relevant papers. Conclusions: The published literature noted some aspects of the medication‐related experiences of people with intellectual disabilities. However, a greater understanding of medication‐related experiences is still required. [ABSTRACT FROM AUTHOR]

The present study is an attempt to evaluate the in vitro anti‐inflammatory and in silico anticancer potentials of the plant Cassia auriculata (CA). The aerial parts of CA were subjected to solvent extraction, and the extracts were fractionised by gas chromatography and mass spectrometry analysis for its phytochemical content. The antiinflammatory activity of the extracts were confirmed by the IC50 value of 125.02 µg/ml for red blood cell membrane stabilisation and 195.7 µg/ml for inhibition of protein denaturation activity. The interaction of bioactive compounds of CA ethanol extract with target protein was predicted through molecular docking studies, serine/threonine–protein kinase B (AKT1), responsible for development and progression of lung cancer using AutoDock tools. Extensive studies have been carried out on a range of kinase inhibitors targeting Akt, but obtaining promising results is a challenge yet due to its toxicity and resistance issues. Yohimbine, undecanoic acid 10‐methyl‐ethyl ester and chrysin significantly bind to the target protein with least binding energy. Hence, the present paper establishes the anti‐inflammatory and anticancer capacities of CA ethanol extract as an alternative to the existing therapeutic approach to inflammation and cancer through a systematic in vitro and in silico approaches supplementing the findings. [ABSTRACT FROM AUTHOR]

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Although the digital revolution has transformed many areas of human endeavor, pharmaceutical drug development has been relatively slow to embrace the emerging technologies to enhance efficiency and optimize value in clinical trials. The topic has garnered even greater attention in the face of the coronavirus disease 2019 (COVID‐19) outbreak, which has caused unprecedented disruption in the conduct of clinical trials and presented considerable challenges and opportunities for clinical trialists and data analysts. In this paper, we highlight the potential opportunity with virtual or digital clinical trials as viable options to enhance efficiency in drug development and, more importantly, in offering diverse patients easier and attractive means to participate in clinical trials. Special reference is made to the implication of artificial intelligence and machine‐learning tools in trial execution and data acquisition, processing, and analysis in a virtual trial setting. Issues of patient safety, measurement validity, and data integrity are reviewed, and considerations are put forth with reference to the mitigation of underlying regulatory and operational barriers. [ABSTRACT FROM AUTHOR]

Aims: To review and synthesise the contemporary qualitative evidence, relating to the individual, healthcare professional and system‐level barriers and facilitators to injectable therapies in people with type 2 diabetes, and evaluate (using an intersectional approach to explore the diverse perspectives of different identities) whether views have changed with treatment and guideline advancements. Methods: A meta‐ethnography approach used. Eight databases searched from the years 2006 (GLP‐1 analogues introduced) to February 2021. Study selection (using a pre‐defined inclusion criteria), quality appraisal and data extraction, conducted independently by two reviewers. Results: Screened 7143 abstracts, assessed 93 full‐text papers for eligibility and included 42 studies—using data from 818 individuals with type 2 diabetes and 160 healthcare professionals. Studies covered a diverse range of views from healthcare professionals and individuals, including those relating to older adults and people from ethnic migrant backgrounds, and 10 studies rated moderate to strong research value. Key themes abstracted: barriers (physical/psychological/social) and facilitators (motivation/capability/opportunity). Conclusions: The first synthesis of contemporary qualitative data to adopt an intersectionality approach and explore diverse views relating to barriers and facilitators that influence engagement with injectable treatments for type 2 diabetes. A model is presented to help patients, health practitioners and policy makers identify barriers and facilitators and understand the complex interplay of physical, psychological and social factors involved when prescribing injectable therapies. Despite advances in injectable treatments and guidelines, findings highlight the many barriers that still exist and show how strongly held culturally‐specific health beliefs of people from diverse socio‐economic and ethnic backgrounds can become substantial obstacles to treatment. [ABSTRACT FROM AUTHOR]

Aim: To determine the efficacy of fenfluramine on seizure frequency in patients with Sunflower syndrome. Secondary endpoints were changes in electroencephalogram (EEG) characteristics, cognitive functioning, executive functioning, and quality of life. Method: In this open‐label study, patients underwent a 4‐week baseline period, followed by 3 months of treatment. An oral solution of fenfluramine was administered twice daily for 3 months. The dose was titrated up to a maximum dose of 0.7mg/kg/day or 26mg/day. Cardiac safety was monitored by transthoracic echocardiogram and electrocardiogram. EEGs, abbreviated neuropsychological testing, and questionnaires were administered before starting the study medication and again at the end of the treatment period. Results: Ten patients (eight females, two males; mean age 13y 4mo [SD 4y 11mo], range 7–24y) were enrolled in the study. Nine of the 10 patients completed the core study, eight of whom met the primary endpoint. There were no observations of cardiac valvulopathy or pulmonary hypertension during the study. Interpretation: Treatment with low‐dose fenfluramine resulted in a clinically significant reduction in seizure frequency, including hand‐waving episodes. Fenfluramine may be an effective treatment option for patients with Sunflower syndrome. What this paper addsNine patients with Sunflower syndrome were treated with fenfluramine.Eight patients were responders, displaying a ≥30% reduction in seizure activity.Six patients experienced a ≥70% reduction in hand‐waving episodes.Improvements on electroencephalogram were observed after treatment with fenfluramine.None of the patients developed evidence of cardiac valvulopathy or pulmonary hypertension. What this paper adds: Nine patients with Sunflower syndrome were treated with fenfluramine.Eight patients were responders, displaying a ≥30% reduction in seizure activity.Six patients experienced a ≥70% reduction in hand‐waving episodes.Improvements on electroencephalogram were observed after treatment with fenfluramine.None of the patients developed evidence of cardiac valvulopathy or pulmonary hypertension. [ABSTRACT FROM AUTHOR]

The public health sector, considered to be vital, especially in this pandemic crisis of COVID‐19, requires automation and control of drug distribution in pharmacies commonly called: "Dispensing." In this paper, we address the medication assignment problem for automated dispensing cabinets (ADCs). First, we use a network of conflicting timed event graphs (CTEGs), a class of timed Petri nets with shared resources, to model pharmaceutical cabinets. Second, we develop a new method for controlling CTEGs under mutual exclusion constraints (MECs) to solve the problem of drug assignment, using a control approach based on Min‐Plus algebra. Finally, a case study of assigning drugs is given to illustrate the proposed methodology and show the efficiency of the developed control laws. [ABSTRACT FROM AUTHOR]

Aims: To systematically review the literature investigating the links between stigma and the management of type 1 diabetes. Methods: A systematic literature review was conducted in accordance with PRISMA guidelines. Both quantitative and qualitative data were considered. Included papers were subject to quality assessment using the Mixed Methods Appraisal Tool (MMAT), and a narrative synthesis of results was reported. Results: Nineteen articles met the inclusion criteria and were included in the final analysis. Amongst these, one study used mixed methods, nine were qualitative, and nine were quantitative. All studies found a negative relationship between stigma and type 1 diabetes management. Qualitative studies provided a further understanding of the effects observed in the quantitative studies and found that stigma can affect self‐care activities, disclosure of diabetes, and the uptake of diabetes technology. Systemic causes of stigma and intersectional stigma were also observed. Conclusions: This review highlights that people with type 1 diabetes are negatively affected by stigma, irrespective of their age, gender, culture, or use of diabetes technology. Quantitative studies were limited, in that all studies were cross‐sectional, and there was a lack of standardisation across outcome measures. There is a need for interventions to target stigma on both an individual and a systemic level, particularly where people experience multiple intersecting stigmas. [ABSTRACT FROM AUTHOR]