Phase 2 study of cemiplimab in patients with metastatic cutaneous squamous cell carcinoma: Primary analysis of fixed-dosing, long-term outcome of weight-based dosing

BACKGROUND: Cemiplimab, a high-affinity, potent human immunoglobulin G4 monoclonal antibody to programmed cell death-1 demonstrated antitumor activity in a Phase 1 advanced cutaneous squamous cell carcinoma (CSCC) expansion cohort (NCT02383212) and the pivotal Phase 2 study (NCT02760498). Here we report the primary analysis of fixed dose cemiplimab 350 mg intravenously every 3 weeks (Q3W) (Group 3) and provide a longer-term update after the primary analysis of weight-based cemiplimab 3 mg/kg intravenously every 2 weeks (Q2W) (Group 1) among metastatic CSCC (mCSCC) patients in the pivotal study (NCT02760498). METHODS: The primary objective for each group was objective response rate (ORR) per independent central review (ICR). Secondary endpoints included ORR by investigator review (INV), duration of response (DOR) per ICR and INV, and safety and tolerability. RESULTS: For Group 3 (n=56) and Group 1 (n=59), median follow-up was 8.1 (range, 0.6 to 14.1) and 16.5 (range, 1.1 to 26.6) months, respectively. ORR per ICR was 41.1% (95% CI, 28.1% to 55.0%) in Group 3, 49.2% (95% CI, 35.9% to 62.5%) in Group 1, and 45.2% (95% CI, 35.9% to 54.8%) in both groups combined. Per ICR, Kaplan-Meier estimate for DOR at 8 months was 95.0% (95% CI, 69.5% to 99. 3%) in responding patients in Group 3, and at 12 months was 88.9% (95% CI, 69.3% to 96.3%) in responding patients in Group 1. Per INV, ORR was 51.8% (95% CI, 38.0% to 65.3%) in Group 3, 49.2% (95% CI, 35.9% to 62.5%) in Group 1, and 50.4% (95% CI, 41.0% to 59.9%) in both groups combined. Overall, the most common adverse events regardless of attribution were fatigue (27.0%) and diarrhea (23.5%). CONCLUSION: In patients with mCSCC, cemiplimab 350 mg intravenously Q3W produced substantial antitumor activity with durable response and an acceptable safety profile. Follow-up data of cemiplimab 3 mg/kg intravenously Q2W demonstrate ongoing durability of responses. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov, NCT02760498. Registered May 3, 2016, https://clinicaltrials.gov/ct2/show/NCT02760498

A meta-analysis on the prophylactic use of macrolide antibiotics for the prevention of disease exacerbations in patients with Chronic Obstructive Pulmonary Disease

SummaryIntroductionMacrolides are of unique interest in preventing COPD exacerbations because they possess a variety of antibacterial, antiviral and anti-inflammatory properties. Recent research has generated renewed interest in prophylactic macrolides to reduce the risk of COPD exacerbations. Little is known about how well these recent findings fit within the context of previous research on this subject. The purpose of this article is to evaluate, via exploratory meta-analysis, whether the overall consensus favors prophylactic macrolides for prevention of COPD exacerbations.MethodsEMBASE, Cochrane and Medline databases were searched for all relevant randomized controlled trials (RCTs). Six RCTs were identified. The primary endpoint was incidence of COPD exacerbations. Secondary endpoints including mortality, hospitalization rates, adverse events and likelihood of having at least one COPD exacerbation were also examined.ResultsThere was a 37% relative risk reduction (RR = 0.63, 95% CI: 0.45–0.87, p value = 0.005) in COPD exacerbations among patients taking macrolides compared to placebo. Furthermore, there was a 21% reduced risk of hospitalization (RR = 0.79, 95% CI: 0.69–0.90, p-value = 0.01) and 68% reduced risk of having at least one COPD exacerbation (RR = 0.34, 95% CI 0.21–0.54, p-value = 0.001) among patients taking macrolides versus placebo. There was also a trend toward decreased mortality and increased adverse events among patients taking macrolides but these were not statistically significant.ConclusionsProphylactic macrolides are an effective approach for reducing incident COPD exacerbations. There were several limitations to this study including a lack of consistent adverse event reporting and some degree of clinical and statistical heterogeneity between studies

Treatment patterns and outcomes following disease progression on anti-PD-1 therapies for advanced melanoma

Background: Anti-PD-1-based therapies prolong survival in advanced melanoma, but disease progression is common. This study evaluated treatment patterns and overall survival (OS) after anti-PD-1 progression. Methods: Retrospective data from patients with advanced melanoma and progression on anti-PD-1 treatment between 2014 and 2019 were taken from Flatiron Health, which reflects largely community practice. Treatment patterns and OS were analyzed for BRAF mutant (mt) and wild-type (wt) subgroups; OS was also examined across all patients. Results: Progression following anti-PD-1 was recorded for 679 patients. Median OS ranged from 5.0 to 11.3 months. Of 275 BRAFmt and 374 BRAFwt patients, 113 (41.1%) and 228 (61.0%) received no subsequent therapy, respectively. However, 48.4% of BRAFmt and 57.8% of BRAFwt patients continued anti-PD-1 treatment beyond progression. Conclusion: This real-world study underscores the need for effective treatments for advanced melanoma post-progression on anti-PD-1 therapy

Adherencia al tratamiento farmacológico y no farmacológico en pacientes con hipertensión arterial

La hipertensión Arterial fue durante mucho tiempo manejada con tratamiento farmacológico y no farmacológico reduciendo complicaciones y mortandad subyacente de esta enfermedad; sin embargo, alrededor 45% de las personas con hipertensión arterial desconocen los mecanismos de control de los signos y síntomas de esta patología. El anterior aspecto, intensifica la presencia de factores asociados a la no adherencia al tratamiento farmacológico, como el descuido del esquema terapéutico por el paciente, que es considerado el responsable del mal control de su enfermedad. Se puede llegar a observar y realizar el seguimiento continuo la adherencia farmacológica y no farmacológica de las personas que asisten al programa crónico. Es necesario poder identificar los factores que se asocian a la no adherencia del tratamiento farmacológico y no farmacológico y llegar a establecer estrategias que reduzcan y se mitiguen lo efectos de dicho factor .Para ello, se realizó un estudio descriptivo de corte trasversal, con pacientes que asisten al programa de hipertensos de una institución de salud, la cual fueron captadas los participantes por sexo fueron 123 hombre y 151 mujeres por parte de los factores que se pudieron identificar con mayor prevalencia son el consumo alcohol, tabaco ,alimento con aumento de azúcar y sal ,los factores asociados a momento de consumir el medicamento como la dosis correcta , horas adecuadas o si se toma su tratamiento indicado por su médico tratante.The arterial hypertension was managed for a long time with pharmacological and non-pharmacological treatment, reducing complications and underlying mortality of this disease; however, around 45% of people with high blood pressure are unaware of the control mechanisms for the signs and symptoms of this pathology. The above aspect intensifies the presence of factors associated with non-adherence to pharmacological treatment, such as neglect of the therapeutic scheme by the patient, who is considered responsible for poor control of their disease. The pharmacological and non-pharmacological adherence of the people who attend the chronic program can be observed and continuously monitored. It is necessary to be able to identify the factors that are associated with non-adherence to pharmacological and non-pharmacological treatment and to establish strategies that reduce and mitigate the effects of said factor. To do this, a descriptive cross-sectional study was carried out with patients who attend the hypertensive program of a health institution, which were captured participants by sex were 123 men and 151 women by the factors that could be identified with the highest prevalence are alcohol consumption, tobacco, food with increased sugar and salt , the factors associated with the time of consuming the medication such as the correct dose, appropriate hours or if you take your treatment indicated by your treating physician.Resumen. --1. Justificación. --- 2.Marco Referencial. -- 2.1 Marco Teórico. -- 2.1.1 Fisio Patogenia De La Hipertensión. -- 2.1.2 Tratamiento Y Manejo De La Enfermedad. -- 2.1.3 Factores Que Interviene Adherencia Al Tratamiento. -- 2.2 Marco Conceptual. -- 2.3Marco Legal. -- 2.4 Marco Epidemiológico. -- 3. Objetivos. -- 3.1 Objetivo General. -- 3.2Objetivos Específicos. -- 4. Metodología. -- 4.1 Tipo Y Diseño Del Estudio. -- 4.2 Universo De Estudio. -- 4.3 Población De Estudio. -- 4.4 Criterios De Inclusión Y Exclusión. -- 4.4.1 Criterios De Inclusión. -- 4.4.2 Criterios De Exclusión. -- 4.6 Aspectos Éticos. -- 5. Análisis De Resultados. -- 6.1 Perfil Sociodemográfico. -- 6.2 Factores Asociados A La No Adherencia Del Tratamiento Farmacológico. -- 6.3 Factores Asociados A La No Adherencia Del Tratamiento No Farmacológico. -- 7. Conclusión. -- 8. Discusión Bibliografía. -- Anexos

Intervenciones de enfermería en salud familiar en familias con ancianos con Alzheimer: revisión integrativa

Objective: To identify the scientific evidence of nursing interventions in family health in families with older adults with Alzheimer's. Method: Integrative review in PUBMED, Scopus, Web of Science, Virtual Health Library (VHL), Springer Links and ScienceDirect databases, using the health sciences descriptors (DECS): Family Health, Aged, Alzheimer, Family Nursing and Controlled Before-After Studies; the Boolean operator AND was used to join the descriptors. Results: Five articles were found that addressed nursing interventions focused on the primary caregiver and nursing interventions focused on the family. Main results: Five articles were found within which nursing interventions focused on the main caregiver and nursing interventions focused on the family are addressed. Overall conclusion: Family health interventions may be directed toward the primary caregiver or the entire family and will likewise have some indirect effect on the elderly person with Alzheimer's disease.Objetivo: Identificar la evidencia científica de las intervenciones de enfermería en salud familiar en familias con adultos mayores con Alzheimer. Método: Revisión de tipo integrativa en las bases de datos de PubMed, Scopus, Web of Science, biblioteca virtual en salud (BVS), SpringerLinks y ScienceDirect utilizando los descriptores de ciencias de la salud (DECS): Salud familiar (Family Health); Anciano (Aged); Alzheimer (Alzheimer), Enfermería familiar (Family Nursing) y estudios controlados antes y después (Controlled Before-After Studies); se utilizó el operador booleano AND para unir los descriptores. Resultados principales: Se encontraron 5 artículos dentro de los cuales se abordan Intervenciones de enfermería enfocadas al cuidador principal e intervenciones de enfermería enfocadas a la familia. Conclusión principal: Las intervenciones en salud familiar pueden ir orientadas hacia el cuidador primario o toda la familia e igualmente tendrá algún tipo de efecto indirecto sobre el anciano con Alzheimer

The Algal Polysaccharide Ulvan and Carotenoid Astaxanthin Both Positively Modulate Gut Microbiota in Mice

The intestinal microbial community (microbiota) is dynamic and variable amongst individuals and plays an essential part in gut health and homeostasis. Dietary components can modulate the structure of the gut microbiota. In recent years, substantial efforts have been made to find novel dietary components with positive effects on the gut microbial community structure. Natural algal polysaccharides and carotenoids have been reported to possess various functions of biological relevance and their impact on the gut microbiota is currently a topic of interest. This study, therefore, reports the effect of the sulfated polysaccharide ulvan and the carotenoid astaxanthin extracted and purified from the aquacultured marine green macroalgae Ulva ohnoi and freshwater green microalgae Haematococcus pluvialis, respectively, on the temporal development of the murine gut microbiota. Significant changes with the increase in the bacterial classes Bacteroidia, Bacilli, Clostridia, and Verrucomicrobia were observed after feeding the mice with ulvan and astaxanthin. Duration of the treatments had a more substantial effect on the bacterial community structure than the type of treatment. Our findings highlight the potential of ulvan and astaxanthin to mediate aspects of host-microbe symbiosis in the gut, and if incorporated into the diet, these could assist positively in improving disease conditions associated with gut health

A phase II trial of an alternative schedule of palbociclib and embedded serum TK1 analysis

Palbociclib 3-weeks-on/1-week-off, combined with hormonal therapy, is approved for hormone receptor positive (HR+)/HER2-negative (HER2-) advanced/metastatic breast cancer (MBC). Neutropenia is the most frequent adverse event (AE). We aim to determine whether an alternative 5-days-on/2-days-off weekly schedule reduces grade 3 and above neutropenia (G3 + ANC) incidence. In this single-arm phase II trial, patients with HR+/HER2- MBC received palbociclib 125 mg, 5-days-on/2-days-off, plus letrozole or fulvestrant per physician, on a 28-day cycle (C), as their first- or second-line treatment. The primary endpoint was G3 + ANC in the first 29 days (C1). Secondary endpoints included AEs, efficacy, and serum thymidine kinase 1 (sTK1) activity. At data-cutoff, fifty-four patients received a median of 13 cycles (range 2.6-43.5). The rate of G3 + ANC was 21.3% (95% CI: 11.2-36.1%) without G4 in C1, and 40.7% (95% CI: 27.9-54.9%), including 38.9% G3 and 1.8% G4, in all cycles. The clinical benefit rate was 80.4% (95% CI: 66.5-89.7%). The median progression-free survival (mPFS) (95% CI) was 19.75 (12.11-34.89), 33.5 (17.25-not reached [NR]), and 11.96 (10.43-NR) months, in the overall, endocrine sensitive or resistant population, respectively. High sTK1 at baseline, C1 day 15 (C1D15), and C2D1 were independently prognostic for shorter PFS (p = 9.91 × 1