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The malaria parasite Plasmodium falciparum replicates via schizogony: an unusual type of cell cycle involving asynchronous replication of multiple nuclei within the same cytoplasm. Here, we present the first comprehensive study of DNA replication origin specification and activation during Plasmodium schizogony. Potential replication origins were abundant, with ORC1-binding sites detected every â¼800 bp. In this extremely A/T-biased genome, the sites were biased towards areas of higher G/C content, and contained no specific sequence motif. Origin activation was then measured at single-molecule resolution using newly developed DNAscent technology: a powerful method of detecting replication fork movement via base analogues in DNA sequenced on the Oxford Nanopore platform. Unusually, origins were preferentially activated in areas of low transcriptional activity, and replication forks also moved fastest through lowly transcribed genes. This contrasts with the way that origin activation is organised in other systems, such as human cells, and suggests that P. falciparum has evolved its S-phase specifically to minimise conflicts between transcription and origin firing. This may be particularly important to maximise the efficiency and accuracy of schizogony, with its multiple rounds of DNA replication and its absence of canonical cell-cycle checkpoints.
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Malaria Falciparum , Parásitos , Animales , Humanos , Plasmodium falciparum/metabolismo , Parásitos/genética , Malaria Falciparum/parasitología , Replicación del ADN/genética , Ciclo Celular/genética , Origen de Réplica/genéticaRESUMEN
BACKGROUND: Biologic therapies have led to increasing numbers of patients with psoriasis who have clear or nearly clear skin. It is current practice to continue biologic therapy indefinitely in these patients, which contributes to a substantial long-term drug and healthcare burden. 'As needed' biologic therapy in psoriasis may address this; however, our understanding of patient and clinician perceptions of this strategy is limited. OBJECTIVES: The aim of this mixed-methods study was to gain insight into the perspectives of both patients and clinicians regarding the acceptability of an 'as needed' approach to biologic therapy in psoriasis, including potential barriers and enablers to implementation in routine care. METHODS: We first conducted UK-wide online scoping surveys of patients with psoriasis and dermatology clinicians to explore their views on 'as needed' biologic therapy. Using topic guides informed by these survey findings, we then carried out qualitative focus groups with patients and clinicians. Themes were identified using reflexive thematic analysis. RESULTS: Of 67 patients and 27 clinicians completing the scoping surveys, 67% (43 of 64 patients) and 78% (21 of 27 clinicians) supported the use of 'as needed' biologic therapy, respectively. Respondents highlighted advantages such as a reduction in healthcare burden and greater ownership of care. Challenges included logistics of 'as needed' drug provision and potential risks of disease flare and drug immunogenicity. Focus groups comprised 15 patients with psoriasis [9 female patients (60%), average disease duration 32 years (range 9-64)] and 9 dermatology clinicians [8 female clinicians (89%), average dermatology experience 20 years (range 8-33)]. Both patients and clinicians felt that an 'as needed' treatment approach will deliver a reduction in treatment burden and present an opportunity for patient-led ownership of care. Both groups highlighted the importance of ensuring ongoing access to medication and discussing the potential impact of psoriasis recurrence. Patient preferences were influenced by their lived experiences, particularly previous difficulties with medication delivery logistics and establishing disease control. Clinician perspectives were informed by personal experience of their patients adapting their own dosing schedules. Clinicians highlighted the importance of targeted patient selection for an 'as needed' approach, ongoing disease monitoring, and prompt reaccess to medications upon psoriasis recurrence. CONCLUSIONS: These data indicate that 'as needed' biologic therapy in psoriasis is acceptable for both patients and clinicians. Formal assessment of clinical effectiveness and cost-effectiveness is warranted to enable the real-world potential of this approach to be realized.
Psoriasis is a common skin disease that affects up to 2% of adults in the UK and causes red, scaly patches of skin. A new group of injectable medicines (called biologics) are extremely effective at controlling psoriasis. However, continuous use of these medicines can increase the risk of negative side-effects (such as infections). 'As needed' biologic therapy is when a person takes their biologic medication at the first sign of psoriasis recurrence (rather than continuously). This approach has potential to reduce the risks associated with taking biologics, while still maintaining good control of psoriasis symptoms. 'As needed' therapy has not been used in psoriasis yet, and so we wanted to know what people with psoriasis and healthcare professionals thought about this approach. We carried out national surveys of people with psoriasis and healthcare professionals to explore their views on 'as needed' biologic therapy. We also held group interviews to understand in more detail the positive aspects and potential issues with this approach. Overall, we found that an 'as needed' approach was viewed as acceptable by people with psoriasis and healthcare professionals. They thought this approach would reduce the negative impacts of treatment and allow patients to have more ownership of their care. Potential issues included the possibility of patients' psoriasis returning, as well as ensuring that they had access to medication quickly enough when needed. These findings indicate that 'as needed' biologic therapy in psoriasis is acceptable from both a patient and clinician perspective.
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Actitud del Personal de Salud , Psoriasis , Humanos , Psoriasis/tratamiento farmacológico , Femenino , Masculino , Adulto , Persona de Mediana Edad , Terapia Biológica/métodos , Aceptación de la Atención de Salud/estadística & datos numéricos , Productos Biológicos/uso terapéutico , Reino Unido , Grupos Focales , Dermatólogos/estadística & datos numéricos , AncianoRESUMEN
BACKGROUND: Sub-optimal medication adherence in pregnant women with chronic disease and pregnancy-related indications has the potential to adversely affect maternal and perinatal outcomes. Adherence to appropriate medications is advocated during and when planning pregnancy to reduce risk of adverse perinatal outcomes relating to chronic disease and pregnancy-related indications. We aimed to systematically identify effective interventions to promote medication adherence in women who are pregnant or planning to conceive and impact on perinatal, maternal disease-related and adherence outcomes. METHODS: Six bibliographic databases and two trial registries were searched from inception to 28th April 2022. We included quantitative studies evaluating medication adherence interventions in pregnant women and women planning pregnancy. Two reviewers selected studies and extracted data on study characteristics, outcomes, effectiveness, intervention description (TIDieR) and risk of bias (EPOC). Narrative synthesis was performed due to study population, intervention and outcome heterogeneity. RESULTS: Of 5614 citations, 13 were included. Five were RCTs, and eight non-randomised comparative studies. Participants had asthma (n = 2), HIV (n = 6), inflammatory bowel disease (IBD; n = 2), diabetes (n = 2) and risk of pre-eclampsia (n = 1). Interventions included education +/- counselling, financial incentives, text messaging, action plans, structured discussion and psychosocial support. One RCT found an effect of the tested intervention on self-reported antiretroviral adherence but not objective adherence. Clinical outcomes were not evaluated. Seven non-randomised comparative studies found an association between the tested intervention and at least one outcome of interest: four found an association between receiving the intervention and both improved clinical or perinatal outcomes and adherence in women with IBD, gestational diabetes mellitus (GDM), and asthma. One study in women with IBD reported an association between receiving the intervention and maternal outcomes but not for self-reported adherence. Two studies measured only adherence outcomes and reported an association between receiving the intervention and self-reported and/or objective adherence in women with HIV and risk of pre-eclampsia. All studies had high or unclear risk of bias. Intervention reporting was adequate for replication in two studies according to the TIDieR checklist. CONCLUSIONS: There is a need for high-quality RCTs reporting replicable interventions to evaluate medication adherence interventions in pregnant women and those planning pregnancy. These should assess both clinical and adherence outcomes.
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Asma , Infecciones por VIH , Enfermedades Inflamatorias del Intestino , Preeclampsia , Embarazo , Humanos , Femenino , Preeclampsia/tratamiento farmacológico , Preeclampsia/prevención & control , Asma/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Cumplimiento de la Medicación , Infecciones por VIH/tratamiento farmacológicoRESUMEN
INTRODUCTION: Pharmacists, as experts in medicines, are increasingly employed in general practices and undertake a range of responsibilities. Audit and feedback (A&F) interventions are effective in achieving behaviour change, including prescribing. The extent of pharmacist involvement in A&F interventions to influence prescribing is unknown. This review aimed to assess the effectiveness of A&F interventions involving pharmacists on prescribing in general practice compared with no A&F/usual care and to describe features of A&F interventions and pharmacist characteristics. METHODS: Electronic databases (MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, (Social) Science Citation Indexes, ISI Web of Science) were searched (2012, 2019, 2020). Cochrane systematic review methods were applied to trial identification, selection, and risk of bias. Results were summarized descriptively and heterogeneity was assessed. A random-effects meta-analysis was conducted where studies were sufficiently homogenous in design and outcome. RESULTS: Eleven cluster-randomized studies from 9 countries were included. Risk of bias across most domains was low. Interventions focussed on older patients, specific clinical area(s), or specific medications. Meta-analysis of 6 studies showed improved prescribing outcomes (pooled risk ratio: 0.78, 95% confidence interval: 0.64-0.94). Interventions including both verbal and written feedback or computerized decision support for prescribers were more effective. Pharmacists who received study-specific training, provided ongoing support to prescribers or reviewed prescribing for individual patients, contributed to more effective interventions. CONCLUSIONS: A&F interventions involving pharmacists can lead to small improvements in evidence-based prescribing in general practice settings. Future implementation of A&F within general practice should compare different ways of involving pharmacists to determine how to optimize effectiveness.PRISMA-compliant abstract included in Supplementary Material 1.
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Medicina General , Farmacéuticos , Humanos , Retroalimentación , Medicina Familiar y ComunitariaRESUMEN
BACKGROUND: Patients receiving placebo in clinical trials often report side-effects (nocebo effects), but contributing factors are still poorly understood. PURPOSE: Using a sham trial of the cognition-enhancing "smart pill" Modafinil we tested whether medication beliefs and other psychological factors predicted detection and attribution of symptoms as side-effects to placebo. METHODS: Healthy students (n = 201) completed measures assessing beliefs about medication, perceived sensitivity to medicines, negative affectivity, somatization, and body awareness; 66 were then randomized to receive Deceptive Placebo (told Modafinil-given placebo, 67 to Open Placebo (told placebo-given placebo, and 68 to No Placebo. Memory and attention tasks assessed cognitive enhancement. Nocebo effects were assessed by symptom checklist. RESULTS: More symptoms were reported in the Deceptive Placebo condition (M = 2.65; SD = 2.27) than Open Placebo (M = 1.92; SD = 2.24; Mann-Whitney U = 1,654, z = 2.30, p = .022) or No Placebo (M = 1.68; SD = 1.75, Mann-Whitney U = 1,640, z = 2.74, p = .006). Participants were more likely to attribute symptoms to Modafinil side-effects if they believed pharmaceuticals to be generally harmful (incidence rate ratio [IRR] = 1.70, p = .019), had higher perceived sensitivity to medicines (IRR = 1.68, p = .011), stronger concerns about Modafinil (IRR = 2.10, p < .001), and higher negative affectivity (IRR = 2.37, p < .001). CONCLUSIONS: Beliefs about medication are potentially modifiable predictors of the nocebo effect. These findings provide insight into side-effect reports to placebo and, potentially, active treatment.
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Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Cognición , Humanos , Modafinilo/efectos adversos , Efecto Nocebo , Preparaciones FarmacéuticasRESUMEN
AIMS: To investigate the risk of cardiovascular disease (CVD) events and all-cause mortality in patients with statin-related adverse drug reaction (ADR) consultation in primary care and examine whether different treatments following the ADR affect subsequent outcomes. METHODS: This was a retrospective cohort study of statin users between 2004 and 2019 using IQVIA Medical Research Data (formally known as the THIN database). Patients with statin-related ADR consultation were matched by propensity score (1:1) to statin users without ADR consultation based on demographics, comorbidities and concomitant medication. Cox proportional hazard regression was used to compare the risk of subsequent CVD event and all-cause mortality, stratified by history of CVD. In the secondary analysis among patients with statin-related ADR, treatment changes within a 1-year period following the ADR were examined and the outcomes were compared between different treatment groups. RESULTS: Among 1 564 687 statin users, 19 035 (1.22%) had a statin-related ADR consultation in primary care. The mean (standard deviation) follow-up time was 6.32 (3.74) years and 5.31 (3.83) years for CVD primary and secondary prevention cohorts, respectively. Statin-related ADR consultation was associated with subsequent CVD events in both cohorts (adjusted hazard ratio [HR] of 1.39 [95% CI 1.23, 1.57] and 1.34 [95% CI 1.25,1.42], respectively). In the secondary analysis among patients with statin-related ADR consultation, we found that (i) continued statin prescription or combination of any statin with additional lipid-lowering treatment (LLT) and (ii) other LLT only were associated with lower risks of CVD event (adjusted HR 0.71 [95% CI 0.64, 0.78] and 0.75 [95% CI 0.62, 0.92], respectively) and all-cause mortality (adjusted HR 0.46 [95% CI 0.42, 0.50] and 0.52 [95% CI, 0.43, 0.64], respectively), compared to discontinuation of all LLT. CONCLUSION: Statin-related ADR was associated with an increased risk of subsequent CVD event, indicating that these patients should be monitored more closely. Continued lipid-lowering medication is of importance to protect against CVD events and mortality.
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Enfermedades Cardiovasculares , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Enfermedades Cardiovasculares/inducido químicamente , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/epidemiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Lípidos , Atención Primaria de Salud , Derivación y Consulta , Estudios Retrospectivos , Reino Unido/epidemiologíaRESUMEN
OBJECTIVE: To develop and examine the reliability, and validity of a questionnaire measuring concordance for performing pressure-relief for pressure ulcer (PrU) prevention in people with Spinal Cord Injury (SCI). METHODS: Phase I included item development, content and face validity testing. In phase II, the questionnaire was evaluated for preliminary acceptability, reliability and validity among 48 wheelchair users with SCI. RESULTS: Thirty-seven items were initially explored. Item and factor analysis resulted in a final 26-item questionnaire with four factors reflecting concordance, perceived benefits, perceived negative consequences, and personal practical barriers to performing pressure-relief activities. The internal consistency reliability for four domains were very good (Cronbach's α = 0.75-.89). Pearson correlation coefficient on a test-retest of the same subjects yielded significant correlations in concordance (r2 = 0.91, p = .005), perceived benefit (r2 = 0.71, p < .04), perceived negative consequences (r2 = 0.98, p < .0001), personal barriers (r2 = 0.93, p= .002). Participants with higher levels of concordance reported a greater amount of pressure-relieving performed. Individuals viewing PrU as a threatening illness were associated with higher scores of concordance and tended to report a greater amount of pressure-relieving performance which provides evidence of criterion related validity. CONCLUSION: The new questionnaire demonstrated good preliminary reliability and validity in people with SCI. Further evaluation is necessary to confirm these findings using larger samples with follow-up data for predictive validity. Such a questionnaire could be used by clinicians to identify high risk of patients and to design individualised education programme for PrU prevention.
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Úlcera por Presión/prevención & control , Psicometría/normas , Traumatismos de la Médula Espinal/complicaciones , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Úlcera por Presión/etiología , Úlcera por Presión/psicología , Desarrollo de Programa/métodos , Psicometría/instrumentación , Psicometría/métodos , Reproducibilidad de los Resultados , Traumatismos de la Médula Espinal/psicología , Encuestas y CuestionariosRESUMEN
BACKGROUND: Women on opioid substitution treatment (WOST) are at heightened risk for the sexual transmission of sexually transmitted infections and blood-borne viruses. This study aimed to explore the opportunities to promote their sexual health in community pharmacies in UK. METHODS: Semi-structured interviews were conducted with 20 WOST and 14 community pharmacists (CPs). A focus group was run with three CPs. Participants were recruited in drug services and a service for sex workers (WOST), and in CP. Data collection took place between October 2016 and September 2017. Data were analyzed using Framework Analysis and directed Content Analysis. RESULTS: CPs could play a role in promoting sexual health among WOST. Sexual health screening, treatment and condom supply were suggested as potential ways of delivering pharmacy-based sexual health services. These services should be actively offered to WOST, delivered in a private space and free of cost. We identified several challenges to overcome in order to design and implement sexual health services for WOST in community pharmacies. CONCLUSIONS: This study highlights the potentially key role CPs can have promoting sexual health and addressing health inequities among WOST. Improvements in pharmacists' training are required in order to address stigma towards WOST, and promote trust and positive rapport. Structural changes are also needed to broaden the services available for this group of women and improve their access to healthcare.
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Farmacias , Analgésicos Opioides , Actitud del Personal de Salud , Femenino , Servicios de Salud , Humanos , Farmacéuticos , Rol Profesional , Investigación CualitativaRESUMEN
The aim of this analysis of historical data was to determine whether patients' pre-treatment beliefs about antiretroviral therapy (ART) predict the subsequent reporting of side effects. Data were collected as part of a prospective, 12-month follow-up study. Of 120 people starting ART, 76 completed follow-up assessments and were included in the analyses. Participants completed validated questionnaires assessing their beliefs about ART, beliefs about medicines in general, perceived sensitivity to adverse effects of medicines, depression and anxiety before initiating ART and after 1 and 6 months of treatment. Adherence was assessed at 1, 6 and 12 months. Pre-treatment concerns about ART were associated with significantly more side effects at 1 month (p < 0.05) and 6 months (p < 0.005). Side effects at 6 months predicted low adherence at 12 months (p < 0.005). These findings have implications for the development of interventions to support patients initiating ART by providing a mechanism to pre-empt and reduce side effects.
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Fármacos Anti-VIH/efectos adversos , Terapia Antirretroviral Altamente Activa/psicología , Ansiedad/psicología , Actitud Frente a la Salud , Depresión/psicología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/etiología , Infecciones por VIH/tratamiento farmacológico , Adulto , Terapia Antirretroviral Altamente Activa/efectos adversos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Cumplimiento de la Medicación/psicología , Cumplimiento de la Medicación/estadística & datos numéricos , Persona de Mediana Edad , Estudios Prospectivos , Encuestas y Cuestionarios , Reino UnidoRESUMEN
This meta-analysis investigated whether state anxiety and depression scores during assisted reproductive technology (ART) treatment and changes in state anxiety and depression scores between baseline and during ART treatment are associated with treatment outcome. PubMed, PsycInfo, Embase, ScienceDirect, Web of Science and Scopus were searched and meta-analytic data analysed using random effects models to estimate standardized mean differences. Eleven studies (2202 patients) were included. Women who achieved pregnancy had significantly lower depression scores during treatment than women who did not become pregnant (-0.302; 95% CI: -0.551 to -0.054, z = -2.387, P = 0.017; I2 = 77.142%, P = 0.001). State anxiety scores were also lower in women who became pregnant (-0.335; 95% CI: -0.582 to -0.087, z = -2.649, P = 0.008; I2 = 81.339%, P = 0.001). However, changes in state anxiety (d = -0.056; 95% CI: -0.195 to 0.082, z = -0.794; I2 = 0.00%) and depression scores (d = -0.106; 95% CI: -0.296 to 0.085, z = -1.088; I2 = 0.00%) from baseline to treatment were not associated with ART outcome. Clinics should aim to promote better psychosocial care to help patients manage the psychological and physical demands of ART treatment, giving realistic expectations.
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Ansiedad/psicología , Depresión/psicología , Infertilidad/terapia , Técnicas Reproductivas Asistidas/psicología , Estrés Psicológico/psicología , Adulto , Ansiedad/complicaciones , Depresión/complicaciones , Femenino , Humanos , Infertilidad/psicología , Embarazo , Resultado del Embarazo , Estrés Psicológico/complicaciones , Resultado del TratamientoRESUMEN
UNLABELLED: Drug-induced liver injury (DILI) is an important cause of acute liver failure, with limited therapeutic options. During DILI, oncotic necrosis with concomitant release and recognition of intracellular content amplifies liver inflammation and injury. Among these molecules, self-DNA has been widely shown to trigger inflammatory and autoimmune diseases; however, whether DNA released from damaged hepatocytes accumulates into necrotic liver and the impact of its recognition by the immune system remains elusive. Here we show that treatment with two different hepatotoxic compounds (acetaminophen and thioacetamide) caused DNA release into the hepatocyte cytoplasm, which occurred in parallel with cell death in vitro. Administration of these compounds in vivo caused massive DNA deposition within liver necrotic areas, together with an intravascular DNA coating. Using confocal intravital microscopy, we revealed that liver injury due to acetaminophen overdose led to a directional migration of neutrophils to DNA-rich areas, where they exhibit an active patrolling behavior. DNA removal by intravenous DNASE1 injection or ablation of Toll-like receptor 9 (TLR9)-mediated sensing significantly reduced systemic inflammation, liver neutrophil recruitment, and hepatotoxicity. Analysis of liver leukocytes by flow cytometry revealed that emigrated neutrophils up-regulated TLR9 expression during acetaminophen-mediated necrosis, and these cells sensed and reacted to extracellular DNA by activating the TLR9/NF-κB pathway. Likewise, adoptive transfer of wild-type neutrophils to TLR9(-/-) mice reversed the hepatoprotective phenotype otherwise observed in TLR9 absence. CONCLUSION: Hepatic DNA accumulation is a novel feature of DILI pathogenesis. Blockage of DNA recognition by the innate immune system may constitute a promising therapeutic venue.
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Enfermedad Hepática Inducida por Sustancias y Drogas/inmunología , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , ADN/metabolismo , Hepatocitos/efectos de los fármacos , Hígado/efectos de los fármacos , Acetaminofén/efectos adversos , Analgésicos no Narcóticos/efectos adversos , Animales , Hepatocitos/metabolismo , Hígado/metabolismo , Ratones Endogámicos C57BL , Activación Neutrófila , Neutrófilos/efectos de los fármacos , Neutrófilos/metabolismo , Receptor Toll-Like 9/metabolismoRESUMEN
This article focuses attention on monitoring and evaluation approaches that will help resource managers to manage for change and uncertainty in adaptive co-management (ACM). ACM is a learning-by-doing approach that aims to build flexible community-based natural resource governance systems through collaborative or otherwise participatory means. We describe the framework for monitoring and evaluation that we developed and applied in ten African countries, which includes fixed indicators and measures for co-management performance monitoring, a process evaluation element, a platform for repeat ecological surveillance, and a longitudinal household survey. We comment on the usefulness of this framework, and its applicability to a wide range of geographic contexts. We then present a four step model to assist managers in applying the framework to specific co-management problems. The model suggests a cascade approach to defining key evaluations questions at a systems, network, individual and synthesis level. We illustrate the application of our model and framework by means of a case study of a co-managed agroforestry program in western Kenya.
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Conservación de los Recursos Naturales/métodos , Monitoreo del Ambiente/métodos , Agricultura Forestal/métodos , África , Conducta Cooperativa , Humanos , Kenia , Modelos Teóricos , Evaluación de Programas y Proyectos de Salud , Características de la ResidenciaRESUMEN
OBJECTIVE: Nonadherence to antiepileptic drugs (AEDs) is a common cause of poor seizure control. This study examines whether reported adherence to AEDs is related to variables identified in the National Institute for Health and Clinical Excellence (NICE) Medicines Adherence Guidelines as being important to adherence: perceptual factors (AED necessity beliefs and concerns), practical factors (limitations in capability and resources), and perceptions of involvement in treatment decisions. METHODS: This was a cross-sectional study of people with epilepsy receiving AEDs. Participants completed an online survey hosted by the Epilepsy Society (n = 1,010), or as an audit during inpatient admission (n = 118). Validated questionnaires, adapted for epilepsy, assessed reported adherence to AEDs (Medication Adherence Report Scale [MARS]), perceptions of AEDs (Beliefs about Medicines Questionnaire [BMQ]), and patient perceptions of involvement in treatment decisions (Treatment Empowerment Scale [TES]). RESULTS: Low adherence was related to AED beliefs (doubts about necessity: t(577) = 3.90, p < 0.001; and concerns: t(995) = 3.45, p = 0.001), reported limitations in capability and resources (t(589) = 7.78, p < 0.001), and to perceptions of a lack of involvement in treatment decisions (t(623) = 4.48, p < 0.001). In multiple logistic regression analyses, these factors significantly (p < 0.001) increased variance in reported adherence, above that which could be explained by age and clinical variables (seizure frequency, type, epilepsy duration, number of AEDs prescribed). SIGNIFICANCE: Variables identified in the NICE Medicines Adherence Guidelines as potentially important factors for adherence were found to be related to adherence to AEDs. These factors are potentially modifiable. Interventions to support optimal adherence to AEDs should be tailored to address doubts about AED necessity and concerns about harm, and to overcome practical difficulties, while engaging patients in treatment decisions.
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Anticonvulsivantes/uso terapéutico , Epilepsia/tratamiento farmacológico , Epilepsia/psicología , Conocimientos, Actitudes y Práctica en Salud , Cumplimiento de la Medicación/psicología , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Anticonvulsivantes/sangre , Estudios Transversales , Femenino , Humanos , Masculino , Cumplimiento de la Medicación/estadística & datos numéricos , Persona de Mediana Edad , Poder Psicológico , Encuestas y Cuestionarios , Adulto JovenRESUMEN
BACKGROUND: Elephants are classified as critically endangered animals by the International Union for Conservation of Species (IUCN). Elephant endotheliotropic herpesvirus (EEHV) poses a large threat to breeding programs of captive Asian elephants by causing fatal haemorrhagic disease. EEHV infection is detected by PCR in samples from both clinically ill and asymptomatic elephants with an active infection, whereas latent carriers can be distinguished exclusively via serological assays. To date, identification of latent carriers has been challenging, since there are no serological assays capable of detecting seropositive elephants. RESULTS: Here we describe a novel ELISA that specifically detects EEHV antibodies circulating in Asian elephant plasma/serum. Approximately 80 % of PCR positive elephants display EEHV-specific antibodies. Monitoring three Asian elephant herds from European zoos revealed that the serostatus of elephants within a herd varied from non-detectable to high titers. The antibody titers showed typical herpes-like rise-and-fall patterns in time which occur in all seropositive animals in the herd more or less simultaneously. CONCLUSIONS: This study shows that the developed ELISA is suitable to detect antibodies specific to EEHV. It allows study of EEHV seroprevalence in Asian elephants. Results confirm that EEHV prevalence among Asian elephants (whether captive-born or wild-caught) is high.
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Anticuerpos Antivirales/sangre , Elefantes , Ensayo de Inmunoadsorción Enzimática/veterinaria , Infecciones por Herpesviridae/veterinaria , Herpesviridae/aislamiento & purificación , Inmunoglobulina G/aislamiento & purificación , Animales , Animales de Zoológico , Clonación Molecular , Ensayo de Inmunoadsorción Enzimática/métodos , Europa (Continente)/epidemiología , Femenino , Herpesviridae/inmunología , Infecciones por Herpesviridae/diagnóstico , Infecciones por Herpesviridae/virología , Masculino , Sensibilidad y Especificidad , Proteínas del Envoltorio Viral/genética , Proteínas del Envoltorio Viral/metabolismoRESUMEN
BACKGROUND: Rheumatoid arthritis (RA) is a common chronic inflammatory disease causing joint damage, disability, and reduced life expectancy. Highly effective drugs are now available for the treatment of RA. However, poor adherence to drug regimens remains a significant barrier to improving clinical outcomes in RA. Poor adherence has been shown to be linked to patients' beliefs about medicines with a potential impact on adherence. These beliefs are reported to be different between ethnic groups. The purpose of this study was to identify potential determinants of adherence to disease modifying anti-rheumatic drugs (DMARDs) including an assessment of the influence of beliefs about medicines and satisfaction with information provided about DMARDs and compare determinants of adherence between RA patients of White British and South Asian. METHODS: RA patients of either White British (n = 91) or South Asian (n = 89) origin were recruited from secondary care. Data were collected via questionnaires on patients': (1) self-reported adherence (Medication Adherence Report Scale-MARS); (2) beliefs about medicines (Beliefs about Medicines Questionnaire-BMQ); (3) illness perceptions (Illness Perceptions Questionnaire-IPQ) and (4) satisfaction with information about DMARDs (Satisfaction with Information about Medicines questionnaire-SIMS). In addition, clinical and demographic data were collected. RESULTS: The results revealed that socio-demographic factors only explained a small amount of variance in adherence whereas illness representations and treatment beliefs were more substantial in explaining non-adherence to DMARDs. Patients' self-reported adherence was higher in White British than South Asian patients (median 28 (interquartile range 26-30) vs median 26 (interquartile range 23-30) respectively; P = 0.013, Mann-Whitney test). Patients who reported lower adherence were more dissatisfied with the information they had received about their DMARDs (P < 0.001, Spearman correlation, SIMS action and usage subscale; P < 0.001, Spearman correlation, SIMS potential problems subscale) and had more negative beliefs about their DMARDs and were related to ethnicity with South Asian patients having more negative views about medicines. CONCLUSIONS: Socio-demographic factors were found to explain a small amount of variance in adherence. Illness representations and treatment beliefs were more important in explaining non-adherence to DMARDs. Clinicians managing South Asian patients with RA need to be aware that low adherence may be linked to negative beliefs about medicines and illness representations of RA.
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Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/etnología , Pueblo Asiatico/etnología , Cumplimiento de la Medicación , Población Blanca/etnología , Adulto , Anciano , Artritis Reumatoide/psicología , Pueblo Asiatico/psicología , Estudios Transversales , Inglaterra/etnología , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , Masculino , Cumplimiento de la Medicación/psicología , Persona de Mediana Edad , Encuestas y Cuestionarios , Población Blanca/psicologíaRESUMEN
The varied performance of Community Health Worker (CHW) programmes in different contexts has highlighted the need for implementation of research that focuses on programme delivery issues. This paper presents the results of process evaluations conducted on two different models of CHW programme delivery in adjacent rural communities in in Gem District of Western Kenya. One model was implemented by the Millennium Villages Project (MVP), and the other model was implemented in partnership with the Ministry of Health (MoH) as part of Kenya's National CHW programme.
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Agentes Comunitarios de Salud , Promoción de la Salud , Programas Nacionales de Salud , Organizaciones , Evaluación de Programas y Proyectos de Salud , Población Rural , Humanos , KeniaRESUMEN
Numerous obesity studies have coupled murine models with non-invasive methods to quantify body composition in longitudinal experiments, including X-ray computed tomography (CT) or quantitative nuclear magnetic resonance (QMR). Both microCT and QMR have been separately validated with invasive techniques of adipose tissue quantification, like post-mortem fat extraction and measurement. Here we report a head-to-head study of both protocols using oil phantoms and mouse populations to determine the parameters that best align CT data with that from QMR. First, an in vitro analysis of oil/water mixtures was used to calibrate and assess the overall accuracy of microCT vs. QMR data. Next, experiments were conducted with two cohorts of living mice (either homogenous or heterogeneous by sex, age and genetic backgrounds) to assess the microCT imaging technique for adipose tissue segmentation and quantification relative to QMR. Adipose mass values were obtained from microCT data with three different resolutions, after which the data were analyzed with different filter and segmentation settings. Strong linearity was noted between the adipose mass values obtained with microCT and QMR, with optimal parameters and scan conditions reported herein. Lean tissue (muscle, internal organs) was also segmented and quantified using the microCT method relative to the analogous QMR values. Overall, the rigorous calibration and validation of the microCT method for murine body composition, relative to QMR, ensures its validity for segmentation, quantification and visualization of both adipose and lean tissues.
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Composición Corporal , Imagen por Resonancia Magnética , Obesidad/diagnóstico , Tomografía Computarizada por Rayos X , Absorciometría de Fotón , Tejido Adiposo/metabolismo , Tejido Adiposo/patología , Animales , Humanos , Ratones , Obesidad/metabolismo , Obesidad/fisiopatologíaRESUMEN
OBJECTIVES: At the time of the survey, just over 2000 pharmacists were employed in UK general practice. Little is known about their influence on prescribing, and more specifically, the extent of their use of Audit and Feedback (A&F), an evidence-based method for behaviour change. This study aimed to explore pharmacists' current influence on prescribing in UK general practice. METHODS: A cross-sectional, online survey was open to general practice pharmacists in England, Northern Ireland, Scotland, and Wales between 9 September 2021 and 31 October 2021. The survey comprised 36 items, informed by the literature, including multiple choice and free-text questions about pharmacist responsibilities, involvement in prescribing audits (including use of A&F), use of prescribing guidelines, beliefs about influence on prescribing, and access to training and support. Descriptive statistics and frequencies were generated, and parametric analyses were conducted. KEY FINDINGS: In total, 155 responses were received from pharmacists in diverse practice locations, with a wide range of practice pharmacist experience. The majority (80%, n = 121) conducted prescribing audits, but only 21% (n = 32) reported undertaking A&F. Most respondents (90%, n = 140) used guidelines to inform their work, and 75% (n = 116) would welcome training on influencing prescribing. Pharmacists using A&F were more likely to believe in their ability to influence prescribing and to acknowledge this activity as part of their role. CONCLUSION: Despite substantial evidence of its effectiveness, A&F is under-used by practice pharmacists. An increased awareness and enablement of practice pharmacists in effective techniques might promote greater evidence-based prescribing in general practice.
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Medicina General , Farmacéuticos , Humanos , Estudios Transversales , Encuestas y Cuestionarios , Medicina Familiar y Comunitaria , Escocia , Actitud del Personal de SaludRESUMEN
OBJECTIVE: Medication-related beliefs, for example, beliefs that medicines are unnecessary or that side effects are likely, can influence medication behaviors and experiences, potentially impacting quality of life and mortality. At times, it may be useful to change medication-related beliefs, for example, to reduce patients' concerns about side effects when extensive evidence suggests side effects are rare. Currently we do not know the most effective methods to address medication beliefs. METHOD: Systematic review and meta-analysis of randomized controlled trials that measured medication-related beliefs in people prescribed medication for long-term condition(s). We extracted data on behavior change techniques (BCTs), belief measure, study and patient characteristics, risk of bias, and quality of description. RESULTS: We identified 56 trials randomizing 8,714 participants. In meta-analysis, interventions led to small-to-medium effects (n = 36, Hedges' g = .362, 95% confidence interval [CI] [.20, .52], p < .001) in increasing beliefs about medication need/benefit and reducing concerns about medication (n = 21, Hedges' g = -.435, 95% CI [-0.72, -0.15], p < .01). Effect sizes were higher for interventions that reported a significant effect on adherence. Problem solving, information about health consequences, and social support (unspecified) were the most prevalent BCTs. Fourteen BCTs were associated with significant effects on need/benefit beliefs and four BCTs were associated with significant effects on concern beliefs. CONCLUSION: It is possible to modify medication-related beliefs using a range of interventions and techniques. Future research should explore the best ways to operationalize these BCTs for specific health conditions to support medication beliefs and improve adherence. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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Terapia Conductista , Calidad de Vida , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Terapia Conductista/métodos , Cumplimiento de la MedicaciónRESUMEN
Background and Aims: Inflammatory Bowel Disease (IBD) affects many women of childbearing age. High levels of voluntary childlessness and high levels of pregnancy-related fears have been reported amongst these patients in several quantitative studies. We investigated the lived experiences of pregnant patients to better understand decision-making processes around family planning. Methods: Nine participants between 7 and 34 weeks pregnant (6 Crohn's Disease/3 Ulcerative Colitis), with an age range of 22-39 were recruited prospectively from three United Kingdom hospitals. Semi-structured interviews were conducted, and audio recorded. Interpretative phenomenological analysis was used to interpret the data. Results: Two main themes emerged: 1) IBD is perceived as a threat to family planning; and 2) healthcare professional advice, support, and reassurance was important. IBD was viewed as a potential threat to fertility and reproductive health. Consequently, women's lived experience of pregnancy is shaped by anxiety and pregnancy-related worries for mother and baby. Mothers actively sought out expert medical assurances to alleviate some of the perceived fears. Conclusion: Previous research has repeatedly found that women with IBD exhibit high levels of pregnancy-related worries and anxieties. Our findings find that high levels of anxiety are due to patients' perceptions that IBD is a threat to their reproductive health and their offspring. Women relied on a medicalized discourse to understand their IBD experiences during pregnancy and actively sought biomedical resources for assistance before and during pregnancy. Consultants should be aware that when dealing with pregnant patients, some women may experience anxiety and require extra support.