Evaluation of adherence to pharmacological treatments by undocumented migrants with chronic diseases: a 10-year retrospective cohort study.

OBJECTIVES: To investigate the time course of medication adherence and some of the factors involved in this process in undocumented migrants with chronic diseases. DESIGN: Retrospective cohort study. SETTING: A big non-governmental organisation in Milano, Italy, giving medical assistance to undocumented migrants. PARTICIPANTS: 1918 patients, 998 females and 920 males, with at least one chronic condition (diabetes, cardiovascular diseases (CVDs), mental health disorders) seen over a period of 10 years (2011-2020). Their mean age was 49.2±13 years. RESULTS: Adherence to medications decreased over 1 year in all patients. This was more evident during the first 2 months of treatment. Patients on only one medication were less adherent than those on more than one medication; at 6 months the percentage of patients with high adherence was 33% vs 57% (p<0.0001) for diabetes, 15% vs 46% (p<0.0001) for mental disorders and 35% vs 59% (p<0.0001) for CVDs. Patients with mental disorders had the lowest adherence: 25% at 6 months and 3% at 1 year. Mental disorders, when present as comorbidities, greatly reduced the probability of being highly adherent: risk ratio (RR) 0.72 (95% CI 0.57 to 0.91; p=0.006) at 3 months, RR 0.77, (95% CI 0.59 to 1.01; p=0.06) at 6 months, RR 0.35 (95% CI 0.13 to 0.94; p=0.04) at 1 year. This was especially evident for patients with CVDs, whose percentage of high adherents decreased to 30% (p=0.0008) at 6 months and to 3% (p=0.01) at 1 year. We also noted that highly adherent patients usually were those most frequently seen by a doctor. CONCLUSIONS: Interventions to increase medication adherence of undocumented migrants with chronic diseases are necessary, particularly in the first 2 months after beginning treatment. These should be aimed at people-centred care and include more outpatient consultations. Educational interventions should especially be taken into consideration for patients on monotherapy.

Cost-utility analysis of add-on vericiguat for the treatment of chronic heart failure with reduced ejection fraction in China.

OBJECTIVE: This study aimed to evaluate the cost-utility of the addition of vericiguat for treating chronic heart failure (CHF) in China from the healthcare payer's perspective. METHODS: A Markov model was built to estimate the cost and utility of treating CHF using vericiguat plus standard treatment (vericiguat group) vs. standard treatment alone (standard treatment group). The clinical parameters (mortality of cardiovascular and hospitalization rate of HF) were calculated according to the VICTORIA clinical trial. The HF cost and utility data were obtained from the literature published in China. One-way sensitivity analysis and probability sensitivity analysis were performed. RESULTS: According to the 13-year model, vericiguat was more expensive (155599.07 CNY vs. 259396.83 CNY) and more effective (4.41 QALYs vs. 4.54 QALYs). The incremental cost-utility ratio (ICUR) was 802389.27 CNY per QALY. One-way sensitivity analysis revealed that cardiovascular mortality in the two groups was the parameter that had the greatest impact on the results. The GDP per capita in 2022 in China was 85,700 CNY. The probability sensitivity analysis (PSA) showed that the probability of vericiguat being cost-effective was only 41.7% at the willingness-to-pay (WTP) threshold of 3 times GDP per capita (257,100 CNY). CONCLUSIONS: In China, the treatment of CHF with vericiguat is not cost-effective. The drug price could decrease to 145.8 CNY, which could be considered cost-effective.

Dietary Influence on Drug Efficacy: A Comprehensive Review of Ketogenic Diet-Pharmacotherapy Interactions.

It is widely acknowledged that the ketogenic diet (KD) has positive physiological effects as well as therapeutic benefits, particularly in the treatment of chronic diseases. Maintaining nutritional ketosis is of utmost importance in the KD, as it provides numerous health advantages such as an enhanced lipid profile, heightened insulin sensitivity, decreased blood glucose levels, and the modulation of diverse neurotransmitters. Nevertheless, the integration of the KD with pharmacotherapeutic regimens necessitates careful consideration. Due to changes in their absorption, distribution, metabolism, or elimination, the KD can impact the pharmacokinetics of various medications, including anti-diabetic, anti-epileptic, and cardiovascular drugs. Furthermore, the KD, which is characterised by the intake of meals rich in fats, has the potential to impact the pharmacokinetics of specific medications with high lipophilicity, hence enhancing their absorption and bioavailability. However, the pharmacodynamic aspects of the KD, in conjunction with various pharmaceutical interventions, can provide either advantageous or detrimental synergistic outcomes. Therefore, it is important to consider the pharmacokinetic and pharmacodynamic interactions that may arise between the KD and various drugs. This assessment is essential not only for ensuring patients' compliance with treatment but also for optimising the overall therapeutic outcome, particularly by mitigating adverse reactions. This highlights the significance and necessity of tailoring pharmacological and dietetic therapies in order to enhance the effectiveness and safety of this comprehensive approach to managing chronic diseases.

Integration of persistence in the 5P-medicine approach for age-related chronic diseases.

5P medicine is defined as Personalized, Predictive, Preventive, Participatory, and Population-based. 5P medicine may be improved by including a factor that could provide information about the therapeutic value of a particular drug treatment and measure its effectiveness in clinical practice. We propose that this factor may be treatment persistence, and that its addition to 5P medicine would allow to define a new improved 6P medicine. Persistence is the length of time between initiation and the last dose, which immediately precedes discontinuation, that is, a definitive suspension of the treatment. By including this sixth P, the persistence, we would be able to present the value of a treatment for each individual patient with its own characteristics, state of the disease, with more than one age-related diseases and patient journey. Persistence is a concept of the value of a treatment that includes the three main stakeholders of the pharmacotherapeutic process: Patient, Physician, and Pharmacist. Persistence is becoming a useful measure to evaluate the long-term effectiveness of therapies in real-world setting in chronic diseases. Drug treatments with longer persistence are more likely to provide better disease control and to be amenable to dose adjustment in order to optimize treatment cost in age-related chronic diseases. Long-term persistence could be a measure of a drug´s real-world performance and has been shown to aid in clinical decision-making.

Effect of pregabalin initiation on diuretic requirements in patients with chronic heart failure.

BACKGROUND: Literature on pregabalin use in patients with heart failure is largely limited to patient case reports and cohort studies. OBJECTIVE: This study aimed to evaluate the effect of pregabalin initiation on diuretic requirements in patients with heart failure. METHODS: A retrospective analysis of patients with heart failure who were started on pregabalin between January 1, 2014, and September 1, 2021, at the Veterans Affairs North Texas Health Care System was used. The primary objective was to determine the median change in loop diuretic dose, in furosemide dose equivalents, 6 months after pregabalin initiation. RESULTS: Of 58 patients analyzed, there was no statistically significant difference in the primary outcome (P = 0.162). The secondary outcomes were found to be nonstatistically significant, and there was no correlation between pregabalin dose and outcomes. CONCLUSION: This represents the largest analysis of diuretic dose requirements in patients with heart failure after initiation of pregabalin. Although there was no difference in the median change of diuretic dose prescribed, pregabalin should still be used with caution.

Patient activation and medication adherence in adults.

BACKGROUND: Patients' level of medication adherence provides conflicting results in its relationship to patient activation. Multiple factors may be contributing to these mixed results. OBJECTIVES: The primary purpose was to assess the association of patient activation to medication adherence in adults with chronic health conditions and low health literacy (HL). Secondary objectives were to determine whether age, education, gender, and race were associated with activation. METHODS: Participants completed self-report questionnaires regarding chronic disease self-management. Patient activation was measured using Hibbard's Patient Activation Measure (PAM). Self-report of medication adherence was determined using the Gonzalez-Lu adherence questionnaire. Block regressions first assessed the relation of demographic variables and education to adherence and then the added relation of patient activation in a second model. RESULTS: The analyses included 301 participants (mean age 58 years; 53% female; mean chronic conditions of 6.6). Some of the most common chronic conditions included hypertension (60%), arthritis (51%), depression (49%), and hyperlipidemia (43%). The relation of older age to greater medication adherence was significant (P < 0.05) in both models. The addition of PAM was significantly related to better adherence (P < 0.001) and also increased the R squared value from 0.04 to 0.09. This change resulted in a moderate effect size (d = 0.50). CONCLUSION: Evaluating patient activation at baseline may predict those more likely to be medication adherent in patients with low HL.

Uso de opioides en pacientes con enfermedad crónica avanzada en situación de últimos días / Use of opioids in patients with advanced chronic disease in the last days of life

Objetivo: Conocer el uso de opioides en el paciente con enfermedad crónica avanzada en los últimos días de vida. Métodos: Estudio retrospectivo, multicéntrico, descriptivo y analítico. Se recogieron datos de los servicios de Geriatría del Hospital Universitario La Paz, Medicina Interna del Complejo Hospitalario de Toledo, Unidad de Hospital a Domicilio del Hospital Marina Baixa de la Vila Joiosa y del Hospital Centro de Cuidados Laguna. Se incluyeron en el estudio los pacientes ingresados con enfermedad avanzada no oncológica fallecidos entre el 1 de marzo de 2019 y el 29 de febrero de 2020. Se estudiaron distintas variables: edad, sexo, enfermedad principal, motivo de ingreso, valoración por cuidados paliativos, uso previo de opioides, uso de opioides en situación de últimos días, opioide, dosis, vías de administración e indicación. Resultados: En el estudio se incluyeron 261 pacientes, 143 (55 %) mujeres y 118 (45 %) hombres, con una edad media de 84 años. La enfermedad principal más frecuente fue la demencia, seguido de insuficiencia cardiaca y patología respiratoria. El motivo de ingreso más frecuente fue deterioro debido a la enfermedad de base seguido de infección respiratoria y sepsis. En la situación de últimos días, la mayoría de los pacientes tenían pauta de opioide basal (94 % morfina) y de rescate (98 % morfina). La vía de administración más utilizada fue la subcutánea (98 %) y la indicación más frecuente fue la disnea (42 %). La mediana de dosis equivalente de morfina oral diaria por enfermedad principal y por motivo de ingreso fue de 30 mg/día. Conclusiones: El uso de opioides en las enfermedades crónicas avanzadas en situación de últimos días está ampliamente extendido. La morfina es el opioide más usado, independientemente de la enfermedad. La vía de administración más utilizada es la subcutánea. No encontramos diferencias entre pacientes con diferentes patologías. (AU)

Objective: To determine the use of opioids in patients with advanced chronic disease in the last days of life. Methods: A retrospective, multicenter, descriptive, analytical study. Data were collected from the Geriatrics Department of Hospital La Paz, Internal Medicine Department of Complejo Hospitalario de Toledo, Hospital at Home Unit of Hospital Marina Baixa in0 La Vila Joiosa, and Hospital Centro de Cuidados Laguna. The study included patients with advanced non-oncological disease who died between 1 March 2019 and 29 February 2020. Different variables were studied: age, sex, main disease, reason for admission, palliative care assessment, previous opioid use, opioid use in last days, opioid, dose, routes of administration, and indication. Results: The study included 261 patients, 143 (55 %) women and 118 (45 %) men, with a mean age of 84 years. The most frequent main disease was dementia, followed by heart failure and respiratory pathology. The most frequent reason for admission was deterioration due to the underlying disease followed by respiratory infection and sepsis. In the last-day situation, most patients had a baseline (94 % morphine) and rescue (98 % morphine) opioid regimen. The most common route of administration was subcutaneous (98 %) and the most common indication was dyspnea (42 %). The median daily oral morphine equivalent dose per main disease and reason for admission was 30 mg/day. Conclusions: The use of opioids in advanced chronic illness in the last days situation is widespread. Morphine is the most commonly used opioid regardless of disease. The most used route of administration is subcutaneous. We found no differences between patients with different pathologies. (AU)

Cuidados populares de las enfermedades crónicas entre indígenas Pijao durante la pandemia por Covid-19 / Folk care of chronic diseases among Pijao indigenous people during the Covid-19 pandemic

Justificación: la pandemia por Covid-19 ocasionó interrupción de los servicios dirigidos a atender las enfermedades crónicas provocando reajustes en el cuidado de los pacientes. Objetivo: Describir los cuidados populares empleados por los indígenas Pijao para el tratamiento y control de enfermedades crónicas, en contexto de pandemia, en Bogotá (Colombia). Metodología: Estudio cualitativo de tipo micro-etnográfico. Participaron 16 indígenas Pijao. Los datos, recolectados por medio de entrevistas y observación, fueron analizados temáticamente. Resultados: emergieron tres categorías, (1) del territorio de origen a la ciudad: cuidados populares para el tratamiento de las de enfermedades, (2) viviendo con la enfermedad: signos y síntomas de las de enfermedades, y (3) procura de otros recursos para el cuidado: autoatención y apoyo familiar. Conclusión: la trayectoria de cuidado de los Pijao con enfermedades crónicas fue permeada por la pandemia, convirtiendo los cuidados populares, caracterizados por un sincretismo de saberes, en parte fundamental de su rutina de cuidados. (AU)

Justification: The Covid-19 pandemic caused an interruption in the services aimed at attending to chronic diseases, resulting in readjustments in the care of patients. Objective: To describe the popular care used by the Pijao indigenous people for treating and controlling chronic diseases in the context of the pandemic in Bogotá (Colombia). Methodology: Qualitative micro-ethnographic study. Sixteen Pijao indigenous people participated. The data collected through interviews and observation were analyzed thematically. Results, three categories emerged: (1) from the territory of origin to the city: popular care for the treatment of illnesses, (2) living with the illness: signs and symptoms of illnesses, and (3) seeking other resources for care: self-attention and family support. Conclusion: the care trajectory of the Pijao with chronic diseases was permeated by the pandemic, turning popular care, characterized by a syncretism of knowledge, into a fundamental part of their care routine. (AU)

Atención farmacéutica al paciente ingresado en una unidad multidisciplinar de paciente crónico complejo / Pharmaceutical care for the patients admitted to a multidisciplinary complex chronic patient unit

Objetivo: evaluar la contribución del farmacéutico mediante el análisis de la prescripción potencialmente inapropiada y la conciliación del tratamiento domiciliario en la unidad de pacientes crónicos complejos de un hospital terciario. Métodos: estudio observacional, prospectivo y multidisciplinar de los pacientes de la unidad de pacientes crónicos complejos de un hospital durante febrero de 2019 - junio de 2020. El equipo multidisciplinar del crónico complejo elaboró un checklist con una selección de fármacos no recomendados basado en los criterios STOPP/START, Beers y PRISCUS y fármacos susceptibles de desprescripción según los criterios LESS-CHRON. El farmacéutico aplicaba el checklist diariamente en los pacientes que ingresaban en la unidad, además de realizar la conciliación del tratamiento domiciliario revisando el tratamiento prescrito con el detallado en la receta electrónica domiciliaria. Por eso, se recogieron las siguientes variables: edad, sexo y número de fármacos al ingreso como variables independientes, y variables dependientes: número de fármacos al alta, tipo de prescripción potencialmente inapropiada, motivos de conciliación, fármacos implicados y grado de aceptación de la recomendación por parte del médico prescriptor para evaluar la contribución farmacéutica. El análisis estadístico se realizó con IBM® SPSS® Statistics22. Resultados : se revisaron 621 pacientes con una mediana de edad de 84 años (56,4% mujeres), y se intervino en 218 (35,1%). La mediana del número de fármacos fue de 11 (2-26) al ingreso y de 10 (0-25) al alta. Se realizaron 373 intervenciones: 235 por conciliación de la medicación (78,3% aceptadas), 71 por medicamentos no recomendados (57,7% aceptadas), 42 por desprescripción (61,9% aceptadas) y 25 por otros motivos. ... (AU)

Objective: To assess the pharmacist’s contributions by analysing potentially inappropriate prescription and home treatment reconciliation in the complex chronic patient unit of a tertiary hospital.MethodObservational, prospective, multidisciplinary study of patients in the complex chronic patient unit of a hospital during February 2019 - June 2020. Multidisciplinary team of the complex chronic developed a checklist with a selection of non-recommended drugs based on STOPP/START, Beers and PRISCUS criteria, and drugs susceptible to deprescription according to LESS-CHRON criteria. The pharmacist applied the checklist daily in patients admitted to the unit, in addition to reconciling home treatment by reviewing the prescribed treatment with that detailed in the electronic home prescription. Therefore, the following variables were collected: age, sex and number of drugs on admission as independent variables, and dependent variables: number of drugs at discharge, type of potentially inappropriate prescription, reasons for reconciliation, drugs involved and degree of acceptance of the recommendation by the prescribing physician to assess the pharmaceutical contribution. The statistical analysis was performed with IBM® SPSS® Statistics22.Results: We reviewed 621 patients with a median age of 84 years (56.4% women), and intervention was performed in 218 (35.1%). The median number of drugs was 11 (2-26) at admission and 10 (0-25) at discharge 373 interventions were performed: 235 for medication reconciliation (78.3% accepted), 71 for non-recommended drugs (57.7% accepted), 42 for deprescription (61.9% accepted) and 25 for other reasons. Statistically significant differences were observed between the number of drugs at discharge and at admission in both intervention patients (n = 218) and complex chronic patients (n = 114) (p < 0.001 in both cases). ...(AU)

A aplicabilidade das pics na assistencia de enfermagem em pacientes com doença crônica: revisão integrativa / The applicability of pics in nursing care for patients with chronic disease: integrative review / La aplicabilidad de la pics en los cuidados de enfermería a pacientes con enfermedades crónicas: revisión integradora

A implementação das PICs no Brasil é uma realidade, dessa forma, compreende-se que o enfermeiro é o profissional que em tese deve possuir habilidades para aplicar as técnicas em pacientes. Com base nisso, o objetivo do trabalho foi descrever a atuação da enfermagem através de Planos de ações por intermédio das PICs em individuos com diminuição da qualidade de vida em razão do desenvolvimento de doenças crônicas degenerativas. Dessa forma, o presente artigo trata-se de uma revisão integrativa de literatura. Os resultados obtidos mostram que a aplicabilidade das PICs, está consolidada, sendo uma prática bastante utilizada na intervenção terapêutica de indivíduos portadores de doenças crônicas degenerativas, na qual as mais utilizadas são: plantas medicinais, reiki, homeopatia, acupuntura e auricuoterapia, entretanto, em relação a assistência de enfermagem, foi observado impasses em relação a capacitação profissional. Logo, concluímos que com base nas produções cientificas existentes a respeito das PICs, a prática infere em diversos benefícios ao indivíduo, estas que se convergem a promoção de maior qualidade de vida ao paciente com doenças crônicas, porém, a falta de capacitação profissional revela um impasse ainda persistente.

The implementation of PICs in Brazil is a reality, therefore, it is understood that the nurse is the professional who, in theory, must have the skills to apply the techniques to patients. Based on this, the objective of the study was to describe the role of nursing through Action Plans through PICs in individuals with reduced quality of life due to the development of chronic degenerative diseases. Thus, this article is an integrative literature review. The results obtained show that the applicability of PICs is consolidated, being a practice widely used in the therapeutic intervention of individuals with chronic degenerative diseases, in which the most used are: medicinal plants, reiki, homeopathy, acupuncture and auricutherapy, however, in regarding nursing care, impasses regarding professional training were observed. Therefore, we conclude that based on the existing scientific productions regarding PICs, the practice infers in several benefits to the individual, these that converge to the promotion of a better quality of life for the patient with chronic diseases, however, the lack of professional training reveals a stalemate still persistent.

La implementación de los PICs en Brasil es una realidad, por lo tanto, se entiende que la enfermera es el profesional que, en teoría, debe tener las habilidades para aplicar las técnicas a los pacientes. Con base en esto, el objetivo del estudio fue describir el papel de la enfermería a través de Planes de Acción por medio de PICs en individuos con calidad de vida reducida debido al desarrollo de enfermedades crónico degenerativas. Así, este artículo es una revisión bibliográfica integradora. Los resultados obtenidos muestran que la aplicabilidad de los PICs está consolidada, siendo una práctica ampliamente utilizada en la intervención terapéutica de individuos con enfermedades crónicas degenerativas, en la que las más utilizadas son: plantas medicinales, reiki, homeopatía, acupuntura y auricuterapia, sin embargo, en lo que respecta a los cuidados de enfermería, se observaron impasses en cuanto a la formación profesional. Por lo tanto, concluimos que con base en las producciones científicas existentes en relación a las PICs, la práctica infiere en varios beneficios al individuo, estos que convergen a la promoción de una mejor calidad de vida para el paciente con enfermedades crónicas, sin embargo, la falta de formación profesional revela un impasse aún persistente.

Programa de seguimiento farmacoterapéutico integral a pacientes crónicos y polimedicados. Programa Piloto en pacientes con Diabetes tipo 2. Resultados / Integral medication review with follow up program to chronic and poymedicated patients. Pilot Program in patients with type 2 Diabetes Mellitus

Introducción: La Farmacia comunitaria vasca tiene una larga tradición de colaboración con la Dirección de Farmacia del Departamento de Salud del Gobier-no Vasco. En mayo de 2017 se firmó un Convenio de colaboración entre el Departamento de Salud y los tres colegios de farmacéuticos vascos “para la puesta en marcha de un Programa piloto de Segui-miento Farmacoterapéutico Integral a pacientes crónicos polimedicados” en el que el farmacéutico comunitario realizaría seguimiento farmacotera-péutico a pacientes con Diabetes tipo2. Método: Se realizó el servicio de seguimiento farmacoterapéutico en farmacias de tres organi-zaciones sanitarias integradas de Alava, Bizkaia y Gipuzkoa. Participaron 18 farmacias con 7 pacien-tes cada una. Criterios de inclusión: paciente con diabetes tipo2 que tomaban 8 o más principios activos de forma continuada. Durante los 12 meses de estudio se analizaron tres puntos: inicio (V1), 6 meses (V2) y al finalizar el estudio (V3).Resultados: De los 127 pacientes inicialmente previstos finalizaron el estudio 87. No se obtuvie-ron diferencias significativas en el valor de HbA1c entre inicio y final. Por el contrario, el número de problemas de salud no controlados disminuyó en un 47% (p=0,001) sin que se modificase el número de medicamentos. Los PRM más frecuentes en V3 fueron el conocimiento insuficiente del medicamen-to (34%) y la falta de adherencia (19%). Mejoraron tanto el conocimiento y la adherencia (p<0,001) como la calidad de vida (p<0,05). Conclusiones: Aunque el programa no ha tenido impacto en el valor de la HbA1c, sí ha contribuido a controlar otros problemas de salud, así como la adherencia, el conocimiento sobre los medicamen-tos y la calidad de vida de los pacientes. (AU)

Introduction: Basque community pharmacy has a long tradition of collaborating with Basque health authorities. In May 2017, a collaboration agreement was signed between the Department of Health and the three Basque Pharmaceutical Associations "for the implementation of a Pilot Program for Medi-cation review with follow up service for chronic polymedicated patients". Method: The medication review with follow up service was carried out in pharmacies of three integrated health organizations in Alava, Bizkaia and Gipuzkoa. 18 pharmacies participated with 7 patients each. Inclusion criteria: patients with type 2 diabetes who were taking 8 or more medicines. During the 12 months of the study, three points were analyzed: baseline (V1), 6 months (V2) and at the end of the study (V3).Results: Of the 127 initially planned patients, 87 completed the study. No significant differences were obtained in the HbA1c value between baseline and the end. In contrast, the number of uncontro-lled health problems decreased by 47% (p=0.001) without changing the number of medications. The most frequent DRPs in V3 were insufficient knowle-dge of the medication (34%) and lack of adherence (19%). Both, knowledge and adherence (p<0.001) and quality of life (p<0.05) improved.Conclusions: Although the program has not had an impact on the value of HbA1c, it has contributed to controlling other health problems, as well as adher-ence, knowledge about medications and the quality of life of patients. (AU)

Adaptación familiar: del diagnóstico al tratamiento de la condición crónica del niño / Adaptação da família: do diagnóstico ao tratamento da condição crônica da criança / Adaptation experienced by families from diagnosis to treatment of the child's chronic condition

Objetivo: Conocer la adaptación de las familias desde el diagnóstico hasta el tratamiento de la enfermedad crónica del niño.Material y Método: Investigación cualitativa, proveniente de un estudio multicéntrico, los datos aquí presentados se refieren a la recolección realizada en la ciudad de Pelotas/RS, en el año de 2019. Participaron de la investigación quince familiares/cuidadores de niños con enfermedades crónicas ingresados en unidades pediátricas de hospitales. Se realizaron entrevistas semiestructuradas y la información fue analizada mediante análisis temático e interpretada por el marco teórico: La Teoría de Enfermería – modelo de adaptación de Roy. Resultados: De los participantes de la investigación, diez eran madres, tres padres y dos abuelas. Los familiares siguen una trayectoria en busca del diagnóstico del niño, enfrentando dificultades en esta experiencia, como el impacto del diagnóstico, los riesgos y repercusiones de la enfermedad, así como la falta de información y la comunicación ineficaz entre profesionales y familiares, además de las dificultades para pasar a la finalización del tratamiento. Consideraciones finales: Es necesario reflexionar críticamente sobre el acercamiento a las familias de niños con enfermedades crónicas, con el objetivo de identificar las situaciones de vulnerabilidad que enfrentan para que los profesionales puedan atenderlas, buscando una atención integral a partir de sus demandas. Además, es fundamental adoptar una comunicación eficaz, mejorando el proceso de trabajo para mejorar el diálogo y el entendimiento con las familias sobre el diagnóstico, los riesgos, el tratamiento y las repercusiones de la enfermedad crónicas del niño. (AU)

Objetivo: Conhecer a adaptação das famílias do diagnóstico ao tratamento da condição crônica da criança. Material e métodos: Pesquisa qualitativa, oriunda de estudo multicêntrico, os dados aqui apresentados referem-se a coleta feita na cidade de Pelotas/RS, no ano de 2019. Participaram da pesquisa 15 familiares/cuidadores de crianças com condições crônicas internadas em unidades de pediatria de hospitais do município. Foram realizadas entrevistas semiestruturadas e as informações foram analisadas por meio da análise temática e interpretadas pelo referencial teórico: A Teoria de enfermagem – O modelo de adaptação de Roy. Resultados: Dos participantes da pesquisa dez eram mães, três pais e duas avós. Os familiares realizam uma trajetória em busca do diagnóstico da criança, enfrentando dificuldades nessa vivência, tais como impacto diante do diagnóstico, riscos e repercussões da doença, assim como a falta de informações e comunicação ineficaz entre profissionais e familiares, além de dificuldade no deslocamento para realização do tratamento. Considerações finais: É necessário refletir criticamente sobre a abordagem às famílias das crianças com condições crônicas, visando a identificação das situações de vulnerabilidade enfrentadas por essas para que os profissionais possam atendê-las primando pela integralidade do cuidado com base em suas demandas. Ademais, é imprescindível adotar uma comunicação eficaz, aprimorando o processo de trabalho no sentido de melhorar o diálogo e o entendimento para com as famílias sobre o diagnóstico, os riscos, o tratamento e as repercussões advindas da doença crônica da criança. (AU)

Objective: To know the adaptation process experienced by families from diagnosis to treatment of the child’s chronic condition. Material and method: This was a multicenter, qualitative study. Data presented refer to the collection carried out in the municipality of Pelotas, state of Rio Grande do Sul, in 2019. Participants were fifteen family members/caregivers of children with chronic conditions admitted to pediatric units in hospitals. Semi-structured interviews were applied and the information was analyzed through thematic analysis and interpreted using the theoretical framework: The Nursing Theory – Roy’s adaptation model. Results: The group of participants was composed of ten mothers, three fathers and two grandmothers. Family members follow a trajectory in search of the child’s diagnosis, facing difficulties in this experience, such as the impact of the diagnosis, risks, and repercussions of the disease, as well as the lack of information and ineffective communication between professionals and family members, in addition to difficulties in moving to the treatment site. Final considerations: It is necessary to critically reflect on the approach to families of children with chronic conditions, aiming at identifying the situations of vulnerability faced so that professionals can serve them, striving for comprehensive care based on their demands. Furthermore, it is essential to adopt effective communication, improving the work process to stimulate dialogue and understanding with families about the diagnosis, risks, treatment, and consequences of the child’s chronic disease.

Adesão ao tratamento do diabetes mellitus em pacientes da atenção primária à saúde / Adherence to the treatment of diabetes mellitus in patients in primary health care / Adherencia al tratamiento de la diabetes mellitus en pacientes de atención primaria

O Diabetes Mellitus (DM) é uma doença crônica, que tem elevada prevalência na sociedade e representa um problema de saúde pública devido à natureza de suas complicações, acredita-se que a dificuldade na manutenção do tratamento, pode estar relacionada a deficiência ou falta de adesão. O estudo teve como objetivo relatar à adesão ao tratamento do Diabetes Mellitus na Atenção Primária a Saúde. Trata-se de um estudo descritivo, com abordagem qualitativa, realizado com 30 pacientes diabéticos de uma Unidade de Atenção Primária à Saúde de Guaiúba-CE, no período de agosto a outubro de 2021. A coleta de dados deu-se por entrevista semiestruturada utilizando questões norteadoras sobre adesão ao tratamento, adoção de práticas promotoras de saúde e posteriormente sujeita a análise de conteúdo. Observou-se que a adesão ao tratamento do diabetes envolve inúmeros desafios, relacionados principalmente ao usuário e sistemas de saúde/profissionais. Os maiores desafios encontrados foram em relação a supervalorização do tratamento medicamentoso frente a adoção de hábitos saudáveis e de ações promotoras de autocuidado. Nesse cenário, nota-se a importância de conhecer os fatores que influenciam na adesão ao tratamento com o intuito de se lançar estratégias para aperfeiçoar o planejamento de ações e intervenções a esses pacientes.

Diabetes Mellitus (DM) is a chronic disease that is highly prevalent in society and represents a public health problem due to the nature of its complications. The study aimed to report on the adherence to treatment of Diabetes Mellitus in Primary Health Care. This is a descriptive study, with a qualitative approach, conducted with 30 diabetic patients from a Primary Health Care Unit in Guaiúba-CE, in the period from August to October 2021. Data were collected through semi-structured interviews using guiding questions about adherence to treatment, adoption of health-promoting practices and later subjected to content analysis. It was observed that diabetes treatment adherence involves numerous challenges, mainly related to the user and health systems/professionals. The biggest challenges found were related to the overvaluation of drug treatment against the adoption of healthy habits and self-care promoting actions. In this scenario, it is important to know the factors that influence treatment adherence in order to develop strategies to improve the planning of actions and interventions for these patients.

La diabetes mellitus (DM) es una enfermedad crónica, que tiene una alta prevalencia en la sociedad y representa un problema de salud pública debido a la naturaleza de sus complicaciones, se cree que la dificultad para mantener el tratamiento puede estar relacionada con la deficiencia o falta de adherencia. El estudio tenía como objetivo informar sobre la adherencia al tratamiento de la Diabetes Mellitus en Atención Primaria. Se trata de un estudio descriptivo con enfoque cualitativo, realizado con 30 pacientes diabéticos de una Unidad de Atención Primaria de Salud de Guaiúba-CE, en el período de agosto a octubre de 2021. La recogida de datos se llevó a cabo mediante entrevistas semiestructuradas en las que se utilizaron preguntas orientativas sobre la adherencia al tratamiento y la adopción de prácticas de promoción de la salud, y posteriormente se sometieron a un análisis de contenido. Se ha observado que el acceso al tratamiento de la diabetes conlleva numerosos desafíos, relacionados principalmente con el usuario y los sistemas de salud/profesionales. Los mayores retos encontrados estaban relacionados con la sobrevaloración del tratamiento farmacológico frente a la adopción de hábitos saludables y acciones de promoción del autocuidado. En este escenario, se constata la importancia de conocer los factores que influyen en la adherencia al tratamiento para poner en marcha estrategias que mejoren la planificación de las acciones e intervenciones para estos pacientes.

Pertinence de l'exigence d'un essai préalable avec un immunosuppresseur dans les indications de paiement des médicaments biologiques: gastroentérologie et dermatologie / Relevance of the prerequisite of the use of an immunosuppressant drug for the coverage of biologic agents (gastroenterology and dermatology)

INTRODUCTION: Au cours des dernières années, les médicaments biologiques se sont ajoutés à l'arsenal thérapeutique des maladies inflammatoires chroniques. Afin d'assurer un usage responsable de ces agents coûteux, leur paiement est actuellement autorisé suivant l'essai préalable de certains traitements conventionnels, notamment des immunosuppresseurs, à moins d'intolérances ou de contre-indications. Toutefois, des associations médicales en gastroentérologie et en dermatologie font état d'un décalage entre les indications de paiement des médicaments biologiques et les meilleures pratiques cliniques. Actuellement, lorsque l'utilisation des médicaments biologiques sans l'essai préalable des immunosuppresseurs est requise, une assistance par un programme de soutien aux patients et aux patientes pourrait être offerte par les fabricants des médicaments biologiques, selon certaines conditions. Dans le traitement des maladies inflammatoires de l'intestin, l'utilisation précoce des médicaments biologiques par le biais de ces programmes de soutien semble être une pratique bien établie et largement répandue depuis plusieurs années. Avec l'entrée en vigueur en avril 2021 de l'article 80.2 de la Loi sur l'assurance médicaments, lequel interdit le paiement ou le remboursement d'un médicament ou d'une fourniture dont le paiement est couvert par le régime général d'assurance médicaments, des associations médicales ont partagé des préoccupations quant à l'accès des médicaments biologiques sans l'essai préalable des immunosuppresseurs au ministère de la Santé et des Services Sociaux (MSSS). Notons que les médicaments biologiques, qu'ils soient de référence ou biosimilaires, font actuellement partie des exceptions prévues au règlement. Afin d'évaluer la pertinence des préalables de traitement dans les indications de paiement des médicaments biologiques, le MSSS a demandé à l'Institut national d'excellence en santé et en services sociaux (INESSS) de mobiliser les savoirs quant à la place des immunosuppresseurs et des médicaments biologiques dans les domaines de la gastroentérologie et de la dermatologie. MÉTHODOLOGIE: Tout d'abord, les indications de paiement des médicaments biologiques inscrits sur les listes de médicaments du Québec (ou dont la décision du ministre est en attente) ont été comparées à celles des autres provinces canadiennes. Ensuite, une revue rapide de la littérature a été réalisée pour répertorier notamment les recommandations des guides de pratique clinique (GPC) concernant la place des médicaments biologiques et des immunosuppresseurs dans la prise en charge de la maladie de Crohn chez l'adulte et l'enfant, de la colite ulcéreuse chez l'adulte et du psoriasis en plaques chez l'adulte. Finalement, les savoirs expérientiels et contextuels ont été recueillis par l'intermédiaire d'une invitation à recevoir des commentaires sur le plan de travail de l'INESSS et d'une consultation d'experts comprenant des gastroentérologues et des dermatologues. RÉSULTATS: Les GPC retenus dans les travaux relatent le manque d'étude de bonne qualité évaluant le moment optimal pour l'introduction des médicaments biologiques dans le traitement. Néanmoins, selon les données disponibles et le degré de valorisation de plusieurs autres facteurs, y compris les risques de complications, la gravité de la maladie, la réponse aux traitements antérieurs et les coûts, les sociétés savantes ont émis des recommandations concernant diverses séquences de traitement avec les médicaments biologiques, autant avant que suivant un traitement par les immunosuppresseurs. Pour le traitement des maladies inflammatoires de l'intestin, la plupart des GPC sélectionnés présentent des recommandations au sujet de l'utilisation des médicaments biologiques suivant un traitement conventionnel, lequel inclut l'acide 5-aminosalicylique (5-ASA) et (ou) les corticostéroïdes et (ou) les immunosuppresseurs. Plusieurs GPC font toutefois également état d'un changement de paradigme vers l'utilisation des médicaments biologiques en première intention de traitement, particulièrement chez les personnes qui ont des facteurs de risque de mauvais pronostic, afin de prévenir les complications, l'hospitalisation et le recours à la chirurgie. Très peu d'essais ont comparé l'efficacité des médicaments biologiques par rapport à celle des immunosuppresseurs, et ceux répertoriés ne sont pas représentatifs de la pratique clinique actuelle avec les médicaments biologiques. Les immunosuppresseurs sont généralement recommandés pour le maintien de la rémission et pourraient constituer une option de traitement acceptable suivant l'atteinte d'une rémission par les corticostéroïdes, mais leur utilisation suscite des préoccupations liées à leur innocuité, notamment le risque de lymphome T hépatosplénique associé aux thiopurines, telles l'azathioprine et la mercaptopurine. Pour le traitement du psoriasis en plaques, les recommandations issues des GPC sélectionnés concernant la place des médicaments biologiques dans le traitement sont peu nombreuses. Néanmoins, tous les GPC retenus s'accordent pour recommander l'utilisation des médicaments biologiques suivant un traitement par les agents de rémission systémiques conventionnels, lesquels incluent les immunosuppresseurs (principalement la cyclosporine et le méthotrexate) et l'acitrétine. Un GPC suggère également l'introduction précoce des médicaments biologiques dans des situations particulières. L'efficacité différentielle entre les médicaments biologiques et les agents de rémission systémiques conventionnels relève principalement de comparaisons indirectes. Une méta-analyse en réseau réalisée par le groupe Cochrane rapporte que la plupart des médicaments biologiques serait plus efficace que les agents de rémission systémiques conventionnels pour atteindre une réduction d'au moins 90 % sur le Psoriasis Area and Severity Index (PASI90). Par ailleurs, des enjeux d'innocuité sont liés aux agents de rémission systémiques conventionnels : le traitement continu par la cyclosporine n'est pas recommandé en pratique au-delà d'un an en raison des risques de néphrotoxicité, l'acitrétine pouvant causer des effets muco-cutanés et le méthotrexate, entraîner une hépatotoxicité. PERSPECTIVE DES EXPERTS ET AUTRES PARTIES PRENANTES: Pour le traitement des maladies inflammatoires de l'intestin, malgré l'absence de données de bonne qualité entre les immunosuppresseurs et les médicaments biologiques, les experts consultés estiment, selon leur expérience clinique, que les médicaments biologiques présentent une efficacité supérieure et un profil d'innocuité favorable par rapport aux immunosuppresseurs. Dans ce contexte, ils considèrent que l'essai des immunosuppresseurs avant l'autorisation des médicaments biologiques expose les patients à des risques de toxicité, de progression de la maladie et de complications. Afin d'éviter ces risques aux personnes qui en font usage, les cliniciens rapportent que l'utilisation des médicaments biologiques sans l'essai préalable des immunosuppresseurs par l'intermédiaire des programmes de soutien aux patients financés par les fabricants est une pratique bien établie au Québec depuis plusieurs années. En dermatologie, les cliniciens rapportent que les préalables de traitement dans les indications de paiement des médicaments biologiques pour le traitement du psoriasis en plaques pourraient forcer le choix d'options thérapeutiques souvent inappropriées pour les patients. Ils mentionnent que seul le méthotrexate dispose d'une réelle place dans le traitement du psoriasis en plaques modéré à grave. Les cliniciens reconnaissent que les délais engendrés par l'essai préalable d'au moins deux agents de rémission systémiques conventionnels, tel que requis actuellement dans les indications de paiement des médicaments biologiques, n'influencent pas le pronostic vital des patients. Toutefois, ils jugent important d'adapter le traitement à la condition particulière des personnes qui en font usage afin de réduire les plaques de psoriasis tout en limitant la survenue d'effets indésirables. CONCLUSIONS: Le moment optimal pour l'introduction des médicaments biologiques par rapport aux immunosuppresseurs dans les domaines de la gastroentérologie et de la dermatologie n'a pas été évalué dans des études de bonne qualité. Ainsi, les présents travaux démontrent une inadéquation entre la pratique clinique actuelle en gastroentérologie et les données probantes de bonne qualité disponibles. À ce propos, l'expérience clinique acquise au cours des dernières années avec les médicaments biologiques dans le traitement des maladies inflammatoires de l'intestin a mené les gastroentérologues à préconiser leur utilisation sans l'essai préalable des immunosuppresseurs. Les cliniciens estiment que l'exigence d'un traitement antérieur par les immunosuppresseurs dans les indications de paiement des médicaments biologiques pour le traitement des maladies inflammatoires de l'intestin devrait être retirée, principalement puisque les immunosuppresseurs retarderaient la guérison et exposeraient les patients à des risques de toxicité et de complications non négligeables, selon eux. Bien que la situation soit quelque peu différente en dermatologie, les cliniciens consultés soutiennent également le retrait de cette exigence pour le psoriasis en plaques.

INTRODUCTION: Over the past few years, biologic agents have been included in the therapeutic arsenal for treating chronic inflammatory diseases. To ensure responsible use of these costly drugs, their payment is currently only authorized following the use of conventional treatments (notably immunosuppressants), except in the presence of intolerances or contraindications. However, medical associations in gastroenterology and dermatology report a disconnect between coverage information for biologic agents and best clinical practices. At present, when biologic agents must be used without any prior trials of immunosuppressants, patients can, under certain conditions, receive assistance from biologic drug manufacturers for access through a patient support program. In the treatment of inflammatory bowel diseases, the early use of biologic agents through such support programs appears to be an established and widespread practice for several years. With the coming into force of section 80.2 of the Act respecting prescription drug insurance in April 2021, which prohibits the payment or reimbursement of a medication or supply covered by the Public Prescription Drug Insurance Plan, medical associations shared their concerns regarding access to biologic agents without any prior trials of immunosuppressants with the Ministère de la Santé et des Services sociaux (department of health issues and social services) (MSSS). It bears noting that biologic agents, whether they are reference products or biosimilars, are included in the exceptions provided for under the regulation. To assess the relevance of the prerequisite of the use of an immunosuppressant for the coverage of biologic agents, the MSSS asked the Institut national d'excellence en santé et en services sociaux (INESSS) to draw on the existing knowledge regarding the role of immunosuppressants and biologic agents in gastroenterology and dermatology. METHODOLOGY: First, coverage information for biologic agents listed on Québec drug formulary (or for which the Minister's decision is pending) was compared with that in other Canadian provinces. Then, a rapid review of the literature was performed to identify CPG (Clinical practice guidelines) recommendations regarding the place of biologic agents and immunosuppressants in the treatment algorithm of Crohn's disease in adults and children, ulcerative colitis in adults and plaque psoriasis in adults. Lastly, experiencebased and contextual knowledge was gathered through an invitation to receive feedback on the INESSS' work plan and from a consultation panel including gastroenterologists and dermatologists. RESULTS: The CPGs selected report a lack of quality studies on the best timing for incorporating biologic agents into a treatment plan. However, according to available data and the importance of several other factors, including the risk of complications, the severity of the illness, the response to previous treatments and the associated costs, learned societies made recommendations regarding various sequences of treatment with biologic agents, both before and after a treatment with immunosuppressants. For the treatment of inflammatory bowel diseases, most of the CPGs selected comprise recommendations as to the use of biologic agents following a conventional treatment that includes 5-ASA (aminosalicylic acids) and/or corticosteroids and/or immunosuppressants. Numerous CPGs, however, report a paradigm shift towards the use of biologic drugs as the front-line treatment, especially for persons at risk of a poor prognosis, to prevent complications, hospitalization and the need for surgery. Very few clinical trials have compared the efficacy of biologic agents and immunosuppressants, and the ones reported are not representative of current clinical practices with biologic agents. Immunosuppressants are generally recommended to maintain complete remission and could prove an acceptable treatment option once remission is achieved with corticosteroids; however, concerns associated with their safety have been raised, notably regarding the risk of hepatosplenic T-cell lymphoma due to thiopurines, such as azathioprine and mercatopurine. There are few recommendations in the selected CPGs regarding the role of biologic drugs in the treatment of plaque psoriasis. However, all of the CPGs selected agree in recommending the use of biologic drugs following a treatment with conventional systemic agents, which include immunosuppressants (primarily cyclosporine and methotrexate) and acitretin. One CPG also suggests resorting to the early use of biologic agents in special situations. The differential efficacy of biologic drugs and conventional systemic agents was mainly established through indirect comparisons. A network meta-analysis performed by Cochrane reports that most biologic drugs would be more effective than conventional systemic agents at achieving a decrease of at least 90% on the Psoriasis Area and Severity Index (PASI90). In addition, conventional systemic agents have certain safety issues: ongoing treatment with cyclosporine is not recommended beyond one year given the risks of nephrotoxicity, acitretin can cause mucocutaneous effects and methotrexate can induce hepatotoxicity. OPINIONS OF EXPERTS AND OTHER STAKEHOLDERS: For the treatment of inflammatory bowel diseases, despite the lack of quality data on immunosuppressants and biologic agents, the experts consulted believe, based on their clinical experience, that biologic agents offer a superior efficacy and a more favourable safety profile compared to immunosuppressants. Given this, they also consider that requiring a trial with an immunosuppressant before allowing the use of a biologic agent exposes patients to risks, among them toxicity, disease progression and complications. To avoid such risks, clinicians report that the use of biologic agents without the prior use of immunosuppressants through manufacturer-funded patient support programs is a wellestablished practice in Québec since many years. Clinicians in the field of dermatology report that the inclusion of preliminary treatments for the coverage of biologic agents in plaque psoriasis could result in patients being inappropriately treated. They mention that among the systemic drugs listed as prerequisite (acitretin, cyclosporin and methotrexate), methotrexate is the preferred agent for treating moderate to severe plaque psoriasis. The clinicians acknowledge that the delays resulting from the trial of at least two traditional systemic agents, as currently required in the coverage information for biologic agents, is not life-threatening for patients. However, they do believe that the treatment should be tailored based on the specific condition of the persons who benefit from it, to reduce psoriatic plaques while limiting the occurrence of adverse effects. CONCLUSIONS: The optimal timing for the introduction of biologics agents versus immunosuppressants in the field of gastroenterology and dermatology has not been assessed in good quality studies. Current research illustrates a discrepancy between actual clinical practices in gastroenterology and the quality evidence-based data available. The clinical experience using biologic drugs to treat inflammatory bowel diseases acquired over the past few years has led gastroenterologists to favour their use without a preliminary treatment with immunosuppressants. Clinicians consider that requiring such a prior treatment with immunosuppressants in the payment indications of biologic drugs for inflammatory bowel diseases should be ceased, mainly because immunosuppressants delay healing and expose patients to risks that include toxicity and non-negligeable complications. And while the circumstances are somewhat different in the field of dermatology, the clinicians consulted also support the removal of this requirement from payment indications of biologic drugs in the case of plaque psoriasis. Given a lack of data, this work did not evaluate the economic impact of withdrawing the requirement regarding prior treatment with immunosuppressants from the coverage information for biologic agents. This would likely generate a significant increase in costs, but the amounts involved should be compared to the cost of complications and other avoidable consequences. It should also be noted that a large portion of these costs are currently borne by the manufacturers, through patient support programs.

Recent Advances of Microneedles and Their Application in Disease Treatment.

For decades, scientists have been doing a lot of research and exploration to find effective long-term analgesic and/or disease-modifying treatments. Microneedles (MNs) are a simple, effective, and painless transdermal drug delivery technology that has emerged in recent years, and exhibits great promise for realizing intelligent drug delivery. With the development of materials science and fabrication technology, the MN transdermal drug delivery technology has been applied and popularized in more and more fields, including chronic illnesses such as arthritis or diabetes, cancer, dermatocosmetology, family planning, and epidemic disease prevention, and has made fruitful achievements. This paper mainly reviews the latest research status of MNs and their fabrication methodology, and summarizes the application of MNs in the treatment of various diseases, as well as the potential to use nanotechnology to develop more intelligent MNs-based drug delivery systems.

Efficacy and safety of gefapixant, a P2X3 receptor antagonist, in refractory chronic cough and unexplained chronic cough (COUGH-1 and COUGH-2): results from two double-blind, randomised, parallel-group, placebo-controlled, phase 3 trials.

BACKGROUND: Gefapixant is an oral P2X3 receptor antagonist that has previously shown efficacy and safety in refractory chronic cough and unexplained chronic cough. We therefore aim to confirm the efficacy and safety of gefapixant in participants with refractory chronic cough and unexplained chronic cough. METHODS: COUGH-1 and COUGH-2 were both double-blind, randomised, parallel-group, placebo-controlled, phase 3 trials. COUGH-1 was done in 156 sites in 17 countries and COUGH-2 in 175 sites in 20 countries. We enrolled participants who were 18 years or older with a diagnosis of refractory chronic cough or unexplained chronic cough of 1 year duration or more. Participants were also required to have a cough severity visual analogue scale score of 40 mm or more at screening and baseline. Eligible participants were randomly allocated (1:1:1), using a computer-generated allocation schedule, to one of three treatment groups: placebo, gefapixant 15 mg twice per day, or gefapixant 45 mg twice per day. All study treatments were given orally. Participants were treated over a 12-week main study period in COUGH-1 and a 24-week main study period in COUGH-2; followed by extension periods for a total of up to 52 weeks of treatment in both trials. The primary outcome was placebo-adjusted mean change in 24-h cough frequency at 12 weeks in COUGH-1 and 24 weeks in COUGH-2. Both studies were registered with ClinicalTrials.gov, NCT03449134 (COUGH-1) and NCT03449147 (COUGH-2). FINDINGS: From March 14, 2018, (first participant screened) to July 26, 2019, (last participant screened) 732 patients were recruited in COUGH-1 and 1317 in COUGH-2. COUGH-1 randomly assigned and treated 730 participants (243 [33×3%] with placebo, 244 [33×4%] with gefapixant 15 mg twice per day, and 243 [33×3%] with gefapixant 45 mg twice per day); COUGH-2 randomly assigned and treated 1314 participants (435 [33×1%] with placebo, 440 [33×5%] with gefapixant 15 mg twice per day, and 439 [33×4%] with gefapixant 45 mg twice per day). Participants were mostly female (542 [74×2%] of 730 in COUGH-1 and 984 [74×9%] of 1314 in COUGH-2). The mean age was 59×0 years (SD 12×6) in COUGH-1 and 58×1 years (12×1) in COUGH-2, and the mean cough duration was 11·6 years (SD 9·5) in COUGH-1 and 11·2 years (9·8) in COUGH-2. Gefapixant 45 mg twice per day showed significant reductions in 24-h cough frequency compared with placebo at week 12 in COUGH-1 (18·5% [95% CI 32·9-0·9]; p=0·041) and at week 24 in COUGH-2 (14·6% [26·1-1·4]; p=0·031). Gefapixant 15 mg twice per day did not show a significant reduction in cough frequency versus placebo in both studies. The most common adverse events were related to taste disturbance: ageusia (36 [4·9%] of 730 in COUGH-1 and 86 [6·5%] of 1314 in COUGH-2), dysgeusia (118 [16·2%] in COUGH-1 and 277 [21·1%] in COUGH-2), hypergeusia (3 [0·4%] in COUGH-1 and 6 [0×5%] in COUGH-2), hypogeusia (19 [2·6%] in COUGH-1 and 80 [6·1%] in COUGH-2), and taste disorder (28 [3·8%] in COUGH-1 and 46 [3·5%] in COUGH-2). INTERPRETATION: Gefapixant 45 mg twice per day is the first treatment to show efficacy with an acceptable safety profile in phase 3 clinical trials for refractory chronic cough or unexplained chronic cough. FUNDING: Merck Sharp & Dohme.

Biguanide Pharmaceutical Formulations and the Applications of Bile Acid-Based Nano Delivery in Chronic Medical Conditions.

Biguanides, particularly the widely prescribed drug metformin, have been marketed for many decades and have well-established absorption profiles. They are commonly administered via the oral route and, despite variation in oral uptake, remain commonly prescribed for diabetes mellitus, typically type 2. Studies over the last decade have focused on the design and development of advanced oral delivery dosage forms using bio nano technologies and novel drug carrier systems. Such studies have demonstrated significantly enhanced delivery and safety of biguanides using nanocapsules. Enhanced delivery and safety have widened the potential applications of biguanides not only in diabetes but also in other disorders. Hence, this review aimed to explore biguanides' pharmacokinetics, pharmacodynamics, and pharmaceutical applications in diabetes, as well as in other disorders.

Albendazole reduces hepatic inflammation and endoplasmic reticulum-stress in a mouse model of chronic Echinococcus multilocularis infection.

BACKGROUND: Echinococcus multilocularis causes alveolar echinococcosis (AE), a rising zoonotic disease in the northern hemisphere. Treatment of this fatal disease is limited to chemotherapy using benzimidazoles and surgical intervention, with frequent disease recurrence in cases without radical surgery. Elucidating the molecular mechanisms underlying E. multilocularis infections and host-parasite interactions ultimately aids developing novel therapeutic options. This study explored an involvement of unfolded protein response (UPR) and endoplasmic reticulum-stress (ERS) during E. multilocularis infection in mice. METHODS: E. multilocularis- and mock-infected C57BL/6 mice were subdivided into vehicle, albendazole (ABZ) and anti-programmed death ligand 1 (αPD-L1) treated groups. To mimic a chronic infection, treatments of mice started six weeks post i.p. infection and continued for another eight weeks. Liver tissue was then collected to examine inflammatory cytokines and the expression of UPR- and ERS-related genes. RESULTS: E. multilocularis infection led to an upregulation of UPR- and ERS-related proteins in the liver, including ATF6, CHOP, GRP78, ERp72, H6PD and calreticulin, whilst PERK and its target eIF2α were not affected, and IRE1α and ATF4 were downregulated. ABZ treatment in E. multilocularis infected mice reversed, or at least tended to reverse, these protein expression changes to levels seen in mock-infected mice. Furthermore, ABZ treatment reversed the elevated levels of interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α and interferon (IFN)-γ in the liver of infected mice. Similar to ABZ, αPD-L1 immune-treatment tended to reverse the increased CHOP and decreased ATF4 and IRE1α expression levels. CONCLUSIONS AND SIGNIFICANCE: AE caused chronic inflammation, UPR activation and ERS in mice. The E. multilocularis-induced inflammation and consecutive ERS was ameliorated by ABZ and αPD-L1 treatment, indicating their effectiveness to inhibit parasite proliferation and downregulate its activity status. Neither ABZ nor αPD-L1 themselves affected UPR in control mice. Further research is needed to elucidate the link between inflammation, UPR and ERS, and if these pathways offer potential for improved therapies of patients with AE.