RESUMEN
Achieving high follow-up rates after smoking cessation interventions (SCIs) is a general challenge. The aim of this study was to identify preferences among patients and therapists for improving follow-up rates and to assess smoking status at 6 months among patients lost to follow-up. From the Danish STOPbase for Tobacco and Nicotine, which collects data on SCI across health care, 20 representative patients lost to follow-up by routine procedures were identified together with 11 therapists. All participated in individual semi-structured phone interviews, which for patients also included 6-month smoking status. Deductive and inductive analyses were performed. Four themes emerged from the analyses with several subthemes, all regarding contacts. Both patients and therapists preferred to intensify the follow-up process by boosting it with additional attempts and using voice messages, e-mail and/or SMS, calling at specified times of the day and avoiding calls from unknown numbers. In addition, some patients mentioned that they were busy or were not carrying their mobile devices at the time of a call as a barrier. Some therapists mentioned that barriers could include an expectation of relapse, but also a poor mental state, the time of day and patient fear of public systems. Among the patients originally lost to follow-up, 35% (95% CI 16%-59%) experienced continuous smoking cessation for 6 months, and the overall national rate was 22% (21.6-23.3%). In conclusion, both patients and therapists preferred intensified follow-up. The 6-month smoking status for patients lost to follow-up seemed to be similar to that of the routinely followed-up patients. These findings will be examined experimentally in a larger study.
Asunto(s)
Cese del Hábito de Fumar , Humanos , Cese del Hábito de Fumar/psicología , Cese del Hábito de Fumar/métodos , Masculino , Femenino , Persona de Mediana Edad , Adulto , Dinamarca , Perdida de Seguimiento , Anciano , Estudios de Seguimiento , Prioridad del Paciente , Entrevistas como Asunto , Fumar/psicología , Fumar/epidemiologíaRESUMEN
BACKGROUND: Mental health plays a major role in children and adolescents with obesity. The aim of this study was (1) to compare mental health in children with obesity with the background population and (2) to investigate if mental health changed during one year in an obesity treatment program. METHODS: Data on self-reported mental health was collected in 107 children and adolescents (mean age 13.2 years) with obesity at first visit in an obesity treatment program and at one year follow-up (n = 47). Mental health was assessed by eight questions from the Danish Health Behaviour in School-aged Children (HBSC) questionnaire: (1) self-rated health (2) life satisfaction (3) feeling low (4) body-image (5) loneliness (6) self-esteem (7) self-efficacy and (8) social competence. Data was compared to a reference population based on HBSC data. BMI-SDS was based on Danish reference values. RESULTS: Children and adolescents with obesity had significantly higher odds of reporting negative body image and feeling low and lower odds of reporting high self-rated health and high self-esteem compared to a reference population. There was no difference between the groups regarding life-satisfaction, social competence, self-efficacy or feeling lonely. There were no significant changes in mental health from first visit to one-year follow-up. CONCLUSION: Our findings highlight the mental health difficulties in children and adolescents with obesity, and the importance of addressing these issues in obesity treatment. The results also indicate that children with obesity have psychosocial resources that should be exploited in treatment protocols.
Asunto(s)
Imagen Corporal , Índice de Masa Corporal , Salud Mental , Obesidad Infantil , Autoimagen , Autoeficacia , Humanos , Adolescente , Masculino , Femenino , Niño , Obesidad Infantil/psicología , Obesidad Infantil/terapia , Imagen Corporal/psicología , Dinamarca , Satisfacción Personal , Estudios de Seguimiento , Autoinforme , Habilidades Sociales , Soledad/psicologíaRESUMEN
BACKGROUND: The postoperative complication rate is 30-64% among patients undergoing muscle-invasive and recurrent high-risk non-muscle-invasive bladder cancer surgery. Preoperative risky alcohol use increases the risk. The aim was to evaluate the accuracy of markers for identifying preoperative risky alcohol. METHODS: Diagnostic test sub-study of a randomized controlled trial (STOP-OP trial), based on a cohort of 94 patients scheduled for major bladder cancer surgery. Identification of risky alcohol use using Timeline Follow Back interviews (TLFB) were compared to the AUDIT-C questionnaire and three biomarkers: carbohydrate-deficient transferrin in plasma (P-CDT), phosphatidyl-ethanol in blood (B-PEth), and ethyl glucuronide in urine (U-EtG). RESULTS: The correlation between TLFB and AUDIT-C was strong (ρ = 0.75), while it was moderate between TLFB and the biomarkers (ρ = 0.55-0.65). Overall, sensitivity ranged from 56 to 82% and specificity from 38 to 100%. B-PEth showed the lowest sensitivity at 56%, but the highest specificity of 100%. All tests had high positive predictive values (79-100%), but low negative predictive values (42-55%). CONCLUSIONS: Despite high positive predictive values, negative predictive values were weak compared to TLFB. For now, TLFB interviews seem preferable for preoperative identification of risky alcohol use.
RESUMEN
Financial incentives offered to those who quit smoking have been found effective, also in persons with low socioeconomic status (SES), but no previous study has investigated who benefits most: smokers with low or high SES. In this community-randomized trial ("Richer without smoking"), three Danish municipalities were randomized to reward persons who were abstinent when attending the municipal smoking cessation program (FIMs) and three municipalities were randomized to spend the same amount on smoking cessation campaigns recruiting smokers to the smoking cessation program (CAMs). The municipalities each received approximately USD 16,000. An intention-to-treat approach was used in analyses. In regression analyses adjusted for individual- and municipal-level differences, we found that smokers with high SES living in FIMs had significantly higher proportion of validated long-term successful quitters (OR (95% CI): 2.59 (1.6-4.2)) than high-SES smokers living in CAM. Smokers with low SES, however, did not experience the same benefit of financial incentives as smokers with high SES. Neither the FIMs nor the CAMs succeeded in attracting more smokers with low SES during the intervention year 2018 than the year before. Our study showed that smokers with low SES did not experience the same benefit of financial incentives as smokers with high SES.
Asunto(s)
Cese del Hábito de Fumar , Dinamarca , Humanos , Motivación , Fumadores , Fumar , Clase SocialRESUMEN
OBJECTIVES: To evaluate the efficacy of intensive smoking cessation interventions (ISCIs) directly compared with shorter interventions (SIs), measured as successful quitting. METHOD: Medline, Embase, the Cochrane Library and CINAHL were searched on 15 October 2021. Peer-reviewed randomised controlled trials (RCTs) of adult, daily smokers undergoing an ISCI were included. No setting, time or language restrictions were imposed. Risk of bias and quality of evidence was assessed using the Cochrane tool and Grading of Recommendations, Assessment, Development and Evaluation, respectively. Meta-analyses were conducted using a random-effects model. RESULTS: 17 550 unique articles were identified and 17 RCTs evaluating 9812 smokers were included. 14 studies were conducted in Europe or the USA. The quality of the evidence was assessed as low or moderate. Continuous abstinence was significantly higher in ISCIs in the long term (risk ratio 2.60, 95% CI 1.71-3.97). Direction and magnitude were similar in the short term; however, they were not statistically significant (risk ratio 2.49, 95% CI: 0.94-6.56). When measured as point prevalence, successful quitting was still statistically significant in favour of ISCIs, but lower (long term: 1.64, 1.08-2.47; short term: 1.68, 1.10-2.56). Sensitivity analysis confirmed the robustness of the results. CONCLUSION: ISCIs are highly effective compared to SIs. This important knowledge should be used to avoid additional morbidity and mortality caused by smoking.
Asunto(s)
Cese del Hábito de Fumar , Adulto , Europa (Continente) , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Fumar/epidemiología , Cese del Hábito de Fumar/métodos , Estados UnidosRESUMEN
In this Tutorial series, we aim to provide an accessible introduction to vibrational sum frequency generation (VSFG) spectroscopy, targeted toward people entering the VSFG world without a rigorous formal background in optical physics or nonlinear spectroscopy. In this article, we discuss in detail the processes of collecting and processing VSFG data, and user-friendly processing software (sfgtools) is provided for use by people new to the field. Some discussion of analyzing VSFG spectra is also given, specifically with a discussion of fitting homodyne VSFG spectra, and a discussion of what can be learned (both qualitatively and quantitatively) from VSFG spectra.
Asunto(s)
Vibración , Humanos , Análisis Espectral/métodos , Propiedades de SuperficieRESUMEN
The fascinating adhesion of gecko to virtually any material has been related to surface interactions of myriads of spatula at the tips of gecko feet. Surprisingly, the molecular details of the surface chemistry of gecko adhesion are still largely unknown. Lipids have been identified within gecko adhesive pads. However, the location of the lipids, the extent to which spatula are coated with lipids, and how the lipids are structured are still open questions. Lipids can modulate adhesion properties and surface hydrophobicity and may play an important role in adhesion. We have therefore studied the molecular structure of lipids at spatula surfaces using near-edge X-ray absorption fine structure imaging. We provide evidence that a nanometre-thin layer of lipids is present at the spatula surfaces of the tokay gecko (Gekko gecko) and that the lipids form ordered, densely packed layers. Such dense, thin lipid layers can effectively protect the spatula proteins from dehydration by forming a barrier against water evaporation. Lipids can also render surfaces hydrophobic and thereby support the gecko adhesive system by enhancement of hydrophobic-hydrophobic interactions with surfaces.
Asunto(s)
Lagartos , Sensilos , Adhesividad , Animales , Metabolismo de los Lípidos , Lípidos/química , Lagartos/metabolismo , Proteínas , Sensilos/metabolismoRESUMEN
(1) Background: Smoking cessation may be very difficult, even if smoking aggravates the prognosis of a disease, which has been shown to be the case for persons with rheumatoid arthritis (RA). In contrast, an association in patients with osteoarthritis (OA) is still disputed. The primary objective was to compare smokers diagnosed with RA and OA to controls, regarding smoking cessation rates after following the intensive 'Gold Standard programme' (GSP). Secondary objectives included the identification of significant prognostic factors for successful quitting. (2) Methods: In total, 24,652 patients were included in this prospective cohort study, after attending the national GSP for smoking cessation intervention 2006-2016, as registered in the Danish Smoking Cessation Database. Data were linked to the National Patient Register. Hereof, 227 patients (1%) were diagnosed with seropositive RA and 2899 (12%) with OA. Primary outcome was continuous abstinence six months after the planned quitting date. (3) Results: In total, 16,969 (69%) of the patients participated in the follow-up interviews. The adjusted odds ratios for successful quitting were similar to the control group for both RA (1.28, 95% CI: 0.90-1.80) and OA patients (0.92, 0.82-1.03). The outermost, strongest positive factor for successful quitting was compliance, defined as attending ≥75% of the meetings. To a lesser degree, attending an individual intervention was a positive predictor, while being heavy smokers, disadvantaged smokers, women, living with a smoker, and if GSP was recommended by health professionals were negative predictors. (4) Conclusions: The odds ratios for quitting were similar to controls for both RA and OR patients. Additional research is needed to determine effective actions towards increased attendance at the programmes.
Asunto(s)
Artritis Reumatoide , Osteoartritis , Cese del Hábito de Fumar , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/epidemiología , Dinamarca/epidemiología , Femenino , Humanos , Osteoartritis/epidemiología , Estudios ProspectivosRESUMEN
BACKGROUND AND PURPOSE: High alcohol intake is associated with increased risk of postoperative complications. Alcohol cessation intervention is recommended prior to elective surgery. We investigated short- and long-term effects of perioperative intensive alcohol intervention in relation to acute ankle fracture surgery. PATIENTS AND METHODS: 70 patients requiring ankle fracture surgery and consuming ≥ 21 drinks weekly (1 drink = 12 g ethanol) were randomized to a manual-based 6-week intensive standardized alcohol cessation program, the Gold Standard Program (GSP-A), or treatment as usual (TAU), on the day of operation. GSP-A included 5 personal meetings, patient education, and motivational and pharmacological support (alcohol withdrawal prophylaxis, B vitamins, and low-dose disulfiram). Complications requiring treatment were measured after 6 weeks and 1 year. Alcohol intake was validated by biomarkers. Quality of life (QoL) was measured by the SF-36. Hospital costs were obtained from the National Hospital Costs Register. RESULTS: Postoperatively, complete alcohol cessation was higher in the GSP-A than in the TAU group (18/35 vs. 5/35, number needed to treat = 3, p ≤ 0.001), but not lowrisk consumption in the long term (10/35 vs. 7/33, p = 0.5). Number of complications in the short and long term (12/35 vs. 14/33, 16/35 vs. 18/33), the SF-36 score, or hospital costs in the short and long term (6,294 vs. 8,024, 10,662 vs. 12,198), were similar between the groups. INTERPRETATION: Despite an effect on alcohol cessation and a positive tendency as regards the other outcomes, the postoperative complications, QoL, and costs were similar. Better perioperative strategies for acute surgical patients with high alcohol intake therefore need to be developed.
Asunto(s)
Alcoholismo , Fracturas de Tobillo , Síndrome de Abstinencia a Sustancias , Alcoholismo/complicaciones , Etanol , Humanos , Educación del Paciente como Asunto , Complicaciones Posoperatorias/prevención & control , Calidad de Vida , Síndrome de Abstinencia a Sustancias/prevención & controlRESUMEN
Geckos have the astonishing ability to climb on vertical surfaces due to the adhesive properties of fibrous setae at the tips of their toe pads. While the adhesion mechanism principle, based on van der Waals interactions of myriads of spatula located at the outermost end of the setal arrays, has been studied extensively, there are still open questions about the chemistry of gecko setae. The gecko adhesive system is based on keratin fibrils assembled to support the entire setal structure. At the same time, the structure and alignment of keratin molecules within the ultrafine spatula tissue, which can support the enormous mechanical strain, still remain unknown. We have studied the molecular structure of gecko spatula using near-edge X-ray absorption fine structure (NEXAFS) imaging. We indeed found that the setae consist of a ß-sheet structure aligned with the adhesion direction of the setae. Such alignment may provide mechanical stability to the setae and resistance to wear across different length scales.
Asunto(s)
Lagartos , Sensilos , Adhesividad , Adhesivos , Animales , Queratinas , Rayos XRESUMEN
Interfaces between bulk media are often where critical molecular processes occur that can dictate the chemistry of an entire macroscopic system. Optical spectroscopy such as IR or Raman spectroscopy is often challenging to apply to interfaces due to contributions from bulk phases that dominate the spectra, masking any detail about the interfacial layer. Vibrational sum frequency generation (VSFG) spectroscopy is a nonlinear spectroscopy that allows vibrational spectra of molecules at interfaces to be directly measured. This Tutorial series is aimed at people entering the VSFG world without a rigorous formal background in optical physics or nonlinear spectroscopy. In this article, we present the fundamental theory of VSFG spectroscopy, with a focus on qualitative, intuitive explanation of the relevant physical phenomena, with minimal mathematics, to enable a newcomer to VSFG spectroscopy to quickly become conversant in the language and fundamental physics of the technique.
Asunto(s)
Vibración , Agua , Humanos , Espectrometría Raman , Propiedades de Superficie , Agua/químicaRESUMEN
In this Tutorial series, we aim to provide an accessible introduction to vibrational sum frequency generation (VSFG) spectroscopy, targeted toward people entering the VSFG world without a rigorous formal background in optical physics or nonlinear spectroscopy. In this article, we describe in depth how a broadband VSFG spectrometer is designed and constructed, using the instrument in SurfLab, Aarhus University, as an illustrative case. Detailed information about specific instrumentation (together with reasons why things are the way they are) is given throughout. This information is often omitted in other descriptions of such instrumentation and so will be invaluable to people new to the field.
Asunto(s)
Vibración , Humanos , Análisis Espectral/métodos , Propiedades de SuperficieRESUMEN
INTRODUCTION: Tobacco is still one of the single most important risk factors among the lifestyle habits that cause morbidity and mortality in humans. Furthermore, tobacco has a heavy social gradient, as the consequences are even worse among disadvantaged and vulnerable groups. To reduce tobacco-related inequity in health, those most in need should be offered the most effective tobacco cessation intervention. The aim of this study is to facilitate and improve the evaluation of already implemented national tobacco cessation efforts, focusing on 10 disadvantaged and vulnerable groups of tobacco users. METHODS AND ANALYSIS: This is a prospective cohort study. Data will be collected by established tobacco cessation counsellors in Sweden. The study includes adult tobacco or e-cigarette users, including disadvantaged and vulnerable patients, receiving in-person interventions for tobacco or e-cigarette cessation (smoking, snus and/or e-cigarettes). Patient inclusion was initiated in April 2020. For data analyses patients will be sorted into vulnerable groups based on risk factors and compared with tobacco users without the risk factor in question.The primary outcome is continuous successful quitting after 6 months, measured by self-reporting. Secondary outcomes include abstinence at the end of the treatment programme, which could be from minutes over days to weeks, 14-day point prevalence after 6 months, and patient satisfaction with the intervention. Effectiveness of successful quitting will be examined by comparing vulnerable with non-vulnerable patients using a mixed-effect logistic regression model adjusting for potential prognostic factors and known confounders. ETHICS AND DISSEMINATION: The project will follow the guidelines from the Swedish Data Protection Authority and have been approved by the Swedish Ethical Review Authority before patient inclusion (Dnr: 2019-02221). Only patients providing written informed consent will be included. Both positive and negative results will be published in scientific peer-reviewed journals and presented at national and international conferences. Information will be provided through media available to the public, politicians, healthcare providers and planners as these are all important stakeholders. TRIAL REGISTRATION NUMBER: NCT04819152.
Asunto(s)
Sistemas Electrónicos de Liberación de Nicotina , Cese del Hábito de Fumar , Cese del Uso de Tabaco , Adulto , Humanos , Estudios Prospectivos , Suecia/epidemiología , NicotianaRESUMEN
The aim of this community-randomised smoking cessation (SC) trial was to investigate both recruitment and SC-rates in three municipalities offering financial incentives (FIM) to smokers who stop smoking when attending a municipal SC-program and compare these with three municipalities investing in a campaign (CAM) that should encourage smokers to use the SC-program. Furthermore, in a non-randomised matched control design we investigated whether there was a difference in recruitment and SC-rates in the three FIM and the three CAM, comparing each with three matched control municipalities (MCM). Each municipality received approx. $16,000. The FIM rewarded persons who were abstinent when attending the municipal SC-program. The CAM spent the money on a campaign recruiting smokers to the SC-program. Two of three FIM were only partly active in recruiting smokers in the intervention year 2018. An intention-to-treat (ITT) approach was used in analyses. Complete case analyses and multiple imputation were used to address loss to follow-up. No difference in recruitment was found between the CAM and the FIM (p = 0.954), in adjusted analyses. In ITT analyses, FIM achieved significantly higher odds of validated abstinence from smoking at one-year follow-up (OR (95%CI): 1.63(1.1-2.4)), but not of self-reported continuous abstinence after six months than CAM. Compared with no intervention, campaigns increased the recruitment of smokers to the SC-program while financial incentives increased six months abstinence rates. In a randomised trial, no difference was demonstrated in the effect of financial incentives and campaigns to recruit smokers to a SC-program and financial incentives seemed superior to help smokers staying smoke-free for a year. TRIAL REGISTRATION: ClinicalTrials.Gov ID: NCT03849092.
Asunto(s)
Cese del Hábito de Fumar , Dinamarca , Promoción de la Salud , Humanos , Motivación , FumadoresRESUMEN
Background: It is challenging to maintain effects of public health interventions. For residential health camps benefits often disappear as the child returns home. Furthermore, long-term effects are often not measured or reported. This paper presents the study protocol for an evaluation of an extended maintenance intervention offered to children who have completed a 10-week residential health camp at one of the five Danish Christmas Seal Houses (DCSH). The target group of DSCH is 7-14-year-olds with social, mental, and/or overweight issues and the overall aim of the camp is to increase life satisfaction and a healthy lifestyle. The primary aim of this study is to assess the effectiveness of the maintenance intervention on children's life satisfaction (primary outcome) and BMI Z-score (secondary outcome) 1 year after health camp. Methods: The extended maintenance intervention is developed by DCSH and delivered to each child and family individually by an intervention coordinator to help children maintain positive benefits of the health camp on life satisfaction and health behaviors after returning to their homes. Intervention activities target the child and the family. The effect will be tested in a quasi-experimental design: The intervention is offered to half of the children at one of the five DSCH (intervention group, N~144) while the other half and the children at the other four DSCH receive a standard maintenance intervention (control group, N~894). Children will complete questionnaires on life satisfaction measured by an adapted version of the Cantril ladder and height and weight prior to health camp, at the end of health camp, 3 months and 1 year after the end of health camp. To enable per protocol analysis and nuanced interpretation of effect estimates, we will monitor the implementation of the intervention by a process evaluation study among children, parents, and follow up coordinators using qualitative and quantitative methods. Discussion: We present a systematic approach to evaluating practice-based interventions in a research design. The study will provide new knowledge on the effectiveness of individualized maintenance interventions on long-term effects on life satisfaction and weight loss among children. Trial registration: Prospectively registered at Current Controlled Trials ISRCTN 13011465 https://www.isrctn.com/ISRCTN13011465.
Asunto(s)
Satisfacción Personal , Adolescente , Índice de Masa Corporal , Niño , Dinamarca , Humanos , PadresRESUMEN
INTRODUCTION: Parents can act as important agents of change and support for healthy childhood growth and development. Studies have found that parents may not be able to accurately perceive their child's weight status. The purpose of this study was to measure parental perceptions of their child's weight status and to identify predictors of potential parental misperceptions. METHODS: We used data from the World Health Organization (WHO) European Childhood Obesity Surveillance Initiative and 22 countries. Parents were asked to identify their perceptions of their children's weight status as "underweight," "normal weight," "a little overweight," or "extremely overweight." We categorized children's (6-9 years; n = 124,296) body mass index (BMI) as BMI-for-age Z-scores based on the 2007 WHO-recommended growth references. For each country included in the analysis and pooled estimates (country level), we calculated the distribution of children according to the WHO weight status classification, distribution by parental perception of child's weight status, percentages of accurate, overestimating, or underestimating perceptions, misclassification levels, and predictors of parental misperceptions using a multilevel logistic regression analysis that included only children with overweight (including obesity). Statistical analyses were performed using Stata version 15 1. RESULTS: Overall, 64.1% of parents categorized their child's weight status accurately relative to the WHO growth charts. However, parents were more likely to underestimate their child's weight if the child had overweight (82.3%) or obesity (93.8%). Parents were more likely to underestimate their child's weight if the child was male (adjusted OR [adjOR]: 1.41; 95% confidence intervals [CI]: 1.28-1.55); the parent had a lower educational level (adjOR: 1.41; 95% CI: 1.26-1.57); the father was asked rather than the mother (adjOR: 1.14; 95% CI: 0.98-1.33); and the family lived in a rural area (adjOR: 1.10; 95% CI: 0.99-1.24). Overall, parents' BMI was not strongly associated with the underestimation of children's weight status, but there was a stronger association in some countries. DISCUSSION/CONCLUSION: Our study supplements the current literature on factors that influence parental perceptions of their child's weight status. Public health interventions aimed at promoting healthy childhood growth and development should consider parents' knowledge and perceptions, as well as the sociocultural contexts in which children and families live.
Asunto(s)
Obesidad Infantil , Índice de Masa Corporal , Peso Corporal , Niño , Conocimientos, Actitudes y Práctica en Salud , Humanos , Masculino , Sobrepeso/epidemiología , Padres , Obesidad Infantil/diagnóstico , Obesidad Infantil/epidemiología , Encuestas y Cuestionarios , Organización Mundial de la SaludRESUMEN
Petroleum asphaltenes are surface-active compounds found in crude oils, and their interactions with surfaces and interfaces have huge implications for many facets of reservoir exploitation, including production, transportation, and oil-water separation. The asphaltene fraction in oil, found in the highest boiling-point range, is composed of many different molecules that vary in size, functionality, and polarity. Studies done on asphaltene fractions have suggested that they interact via polyaromatic and heteroaromatic ring structures and functional groups containing nitrogen, sulfur, and oxygen. However, isolating a single pure chemical structure of asphaltene in abundance is challenging and often not possible, which impairs the molecular-level study of asphaltenes of various architectures on surfaces. Thus, to further the molecular fundamental understanding, we chose to use functionalized model asphaltenes (AcChol-Th, AcChol-Ph, and 1,6-DiEtPy[Bu-Carb]) and model self-assembled monolayer (SAM) surfaces with precisely known chemical structures, whereby the hydrophobicity of the model surface is controlled. We applied solutions of asphaltenes to these SAM surfaces and then analyzed them with surface-sensitive techniques of near-edge X-ray absorption fine structure (NEXAFS) and X-ray photoelectron spectroscopy (XPS). We observe no adsorption of asphaltenes to the hydrophobic surface. On the hydrophilic surface, AcChol-Ph penetrates into the SAM with a preferential orientation parallel to the surface; AcChol-Th adsorbs in a similar manner, and 1,6-DiEtPy[Bu-Carb] binds the surface with a bent binding geometry. Overall, this study demonstrates the need for studying pure and fractionated asphaltenes at the molecular level, as even within a family of asphaltene congeners, very different surface interactions can occur.
RESUMEN
OBJECTIVE: To determine whether the IV infusion of adrenomedullin, a potent vasodilator belonging to calcitonin family of peptides, provokes attacks of migraine in patients. METHODS: Twenty patients with migraine without aura participated in a placebo-controlled and double-blind clinical study. In a randomized crossover design, the patients received an IV infusion of human adrenomedullin (19.9 pmol/kg/min) or placebo (saline) administrated via an automated IV pump (20 minutes). The patients participated in 2 study days with a washout period of minimum of 7 days. The primary outcome of the study was predefined as a difference in migraine incidence (0-12 hours), and the secondary outcomes were the area under curve (AUC0-12 hours) for the headache intensity score and AUC0-90 minutes for mean arterial blood pressure (MAP), flushing, and heart rate (HR). RESULTS: Eleven patients with migraine without aura (55%) fulfilled migraine attacks criteria after adrenomedullin infusion compared to only 3 patients who reported attack (15%) after placebo (p = 0.039). We found that patients reported in a period of 0 to 12 hours stronger headache intensity after adrenomedullin compared to placebo infusion (p = 0.035). AUC0-90 minutes value for HR and flushing (p < 0.05) was significant and for MAP (p = 0.502) remained unchanged. Common reported adverse events were facial flushing, heat sensation, and palpitation (p < 0.001). CONCLUSION: Our data implicate adrenomedullin in migraine pathogenesis. This suggests that adrenomedullin or its receptors are novel therapeutic targets for the treatment of migraine. However, we cannot discount the possibility that adrenomedullin may be acting through the canonical calcitonin gene-related peptide receptor. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT04111484.
Asunto(s)
Adrenomedulina/farmacología , Presión Arterial/efectos de los fármacos , Rubor/inducido químicamente , Cefalea/inducido químicamente , Frecuencia Cardíaca/efectos de los fármacos , Migraña sin Aura/inducido químicamente , Vasodilatadores/farmacología , Adulto , Estudios Cruzados , Método Doble Ciego , Femenino , Humanos , Infusiones Intravenosas , Masculino , Proyectos Piloto , Distribución Aleatoria , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
OBJECTIVE: Migraine is a prevalent and disabling neurological disease. Its genesis is poorly understood, and there remains unmet clinical need. We aimed to identify mechanisms and thus novel therapeutic targets for migraine using human models of migraine and translational models in animals, with emphasis on amylin, a close relative of calcitonin gene-related peptide (CGRP). METHODS: Thirty-six migraine without aura patients were enrolled in a randomized, double-blind, 2-way, crossover, positive-controlled clinical trial study to receive infusion of an amylin analogue pramlintide or human αCGRP on 2 different experimental days. Furthermore, translational studies in cells and mouse models, and rat, mouse and human tissue samples were conducted. RESULTS: Thirty patients (88%) developed headache after pramlintide infusion, compared to 33 (97%) after CGRP (p = 0.375). Fourteen patients (41%) developed migraine-like attacks after pramlintide infusion, compared to 19 patients (56%) after CGRP (p = 0.180). The pramlintide-induced migraine-like attacks had similar clinical characteristics to those induced by CGRP. There were differences between treatments in vascular parameters. Human receptor pharmacology studies showed that an amylin receptor likely mediates these pramlintide-provoked effects, rather than the canonical CGRP receptor. Supporting this, preclinical experiments investigating symptoms associated with migraine showed that amylin treatment, like CGRP, caused cutaneous hypersensitivity and light aversion in mice. INTERPRETATION: Our findings propose amylin receptor agonism as a novel contributor to migraine pathogenesis. Greater therapeutic gains could therefore be made for migraine patients through dual amylin and CGRP receptor antagonism, rather than selectively targeting the canonical CGRP receptor. ANN NEUROL 2021;89:1157-1171.