Curcuma latifolia Roscoe extract reverses inflammatory pain in mice and offers a favorable CNS safety profile.

ETHNOPHARMACOLOGICAL RELEVANCE: Curcuma latifolia Roscoe, a plant in the Curcuma genus, has been used as a food additive and folk medicine in Thailand to treat pelvic pain and improve premenstrual syndrome. Although it has been used for centuries, no scientific studies have proved its potential effects on inflammatory pain and central nervous system (CNS) safety profiles. AIM OF THE STUDY: This study aimed to evaluate the potential effects of the ethanolic extract of C. latifolia rhizome on inflammatory pain in mice, together with its CNS safety profiles. MATERIALS AND METHODS: First, network pharmacology was employed to identify the role of bioactive constituents in C. latifolia on inflammatory pain. In addition, in vitro pharmacology was also evaluated to confirm the anti-inflammatory activity of C. latifolia extract at cellular levels in activated macrophages and microglia. Furthermore, the efficacy of the plant extract in attenuating formalin-induced pain-like behaviors in mice was evaluated. Mice were orally administered the extract (125, 250, 500 mg/kg) followed by the measurement of formalin-induced pain-like behaviors. The LABORAS automated behavioral analysis and rotarod test were used to assess potential CNS side effects of C. latifolia extract (500 mg/kg) in mice. RESULTS: The results demonstrated that major bioactive constituents present in C. latifolia have the ability to regulate multiple targets, biological processes and pathways associated with inflammatory pain as assessed by network pharmacology. C. latifolia modulated peripheral and central immune cells via reducing proinflammatory mediators (NO, TNF-α, and IL-6). C. latifolia extract improved formalin-induced pain-like behaviors in a dose-dependent manner during phase II of the formalin test. The efficacy of the plant extract at doses of 250 and 500 mg/kg was comparable to that of the positive control (indomethacin 10 mg/kg). Furthermore, the highest therapeutic dose of the extract did not affect motor coordination, exploratory behaviors, general behaviors, and overall well-being of mice, indicating no development of potential CNS adverse effects after administration of the extract. CONCLUSION: These findings provide novel perspectives on using C. latifolia extract for pain management, considering its therapeutic efficacy and CNS safety.

Essential oil from leaves of Croton blanchetianus Baill does not present acute oral toxicity, has antigenotoxic action and reduces neurogenic and inflammatory nociception in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Croton blanchetianus Baill., popularly known as "marmeleiro preto", is an endemic plant from Brazil, being found mainly in the Northeast region. In traditional medicine, the use of medicines based on the leaves of this plant has been reported for the treatment of inflammatory processes, pain, urethral pain, gastrointestinal disorders, rheumatism and headache. AIM OF THE STUDY: The present work describes the chemical characterization, as well as toxicological evaluation and antinociceptive activity of an essential oil of C. blanchetianus leaves (EOCb). MATERIALS AND METHODS: The chemical constituents of the oil were identified by gas chromatography coupled to mass spectrometry (GC-MS). In vitro hemolytic activity was tested using mouse blood. Acute toxicity in mice was assessed by the oral or intraperitoneal administration of a single dose of 2000 mg/kg b.w. EOCb (1000 and 2000 mg/kg) was also evaluated for genotoxicity and antigenotoxicity in vivo using the micronucleus test. The antinociceptive activity of EOCb (25, 50 and 100 mg/kg) was evaluated through the abdominal writhing, formalin and tail flick tests. RESULTS: The chemical characterization indicated as major components α-pinene (21.23%), ß-phelandrene (13.92%), terpinolene (13.01%) and germacrene D (10.89%). EOCb did not cause hemolysis and was also neither toxic nor genotoxic, while protected the animals' bone marrow cells from damage caused by cyclophosphamide in oral treatment. However, all animals died after 15 min of intraperitoneal treatment. There was a reduction in the number of abdominal contortions (69.43-89.41%) as well as in licks in the first (38.77-84.47%) and second (59.75-90.74%) phases of the formalin test. In the latter case, the effects were reduced by naloxone and glibenclamide, indicating action via the opioid system and blockage of K+ channels. The latency time in the tail flick test also increased significantly. CONCLUSION: In conclusion, ingestion of EOCb proved to be safe when administered orally; however, it was lethal intraperitoneally. Additionally, EOCb protected mouse blood cell DNA against the action of cyclophosphamide and showed an antinociceptive effect via the opioid system and dependent on K+ channels.

Pingchong Jiangni recipe through nerve growth factor/transient receptor potential vanilloid 1 signaling pathway to relieve pain in endometriosis model rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Pingchong Jiangni recipe (PJR) is often used in the treatment of endometriosis (EM). This formula has been clinically validated by the State Administration of Traditional Chinese Medicine Key Specialties Collaborative Group for its therapeutic efficacy. Recently, our research team also confirmed that PJR has a shrinking effect on ovarian chocolate cysts. Additionally, PJR was also found to have a shrinking effect on EM lesions; however, the mechanism by which this effect occurs remains unclear. AIM OF THE STUDY: To explore the mechanisms by which PJR relieves pain in patients with EM. MATERIALS AND METHODS: A rat model of EM was established by autologous transplantation. PJR (3.78 g/kg, 7.56 g/kg, and 15.12 g/kg) was orally administered for 21 days. The rat grimace scale (RGS) score and paw withdrawal threshold (PWT) were measured at a fixed time during the experiment. Hematoxylin and eosin staining was performed to observe histopathological changes in EM rats after administration, enzyme-linked immunosorbent assay to evaluate the plasma expression of tumor necrosis factor-α (TNF-α) and nerve growth factor (NGF), and immunohistochemistry and western blotting to identify differences in the expression of pain-related factors in EM rats. RESULTS: The medium-dose group of PJR (7.56 g/kg) had the best effect on relieving pain in EM rats by reducing RGS, increasing PWT, reducing the ectopic endometrium, improving the cellular structure of the lesion, and reducing TNF-α and NGF levels. However, PJR significantly decreased the expression of transient receptor potential vanilloid 1 (TRPV1), phosphorylated TRPV1 (p-TRPV1), protein kinase C (PKC), and NGF. CONCLUSION: The mechanism by which PJR relieves EM pain may be through the downregulation of NGF, PKC, and TRPV1 expression.

Cefalea atribuida a ictus isquémico. Actualización semiológica y diagnóstica / Headache attributed to ischaemic stroke. An update on its semiology and diagnosis

Introducción: La cefalea es un síntoma frecuente tras el ictus isquémico agudo. Su identificación y diagnóstico constituyen un reto por el perfil de paciente y los criterios diagnósticos actuales de esta entidad. Los objetivos del estudio fueron determinar la prevalencia de cefalea atribuida a ictus isquémico y su forma persistente, y analizar las variables clinicodemográficas y el grado de cumplimiento de los criterios de la Clasificación Internacional de Cefaleas (ICHD-III). Pacientes y métodos: Es un estudio observacional analítico de cohortes prospectivo de pacientes ingresados con ictus isquémico agudo en la unidad de ictus de un hospital de tercer nivel en un período de 12 meses. Resultados: Se incluyó a 244 pacientes con ictus isquémico agudo (el 59,8%, varones; edad media: 71 ± 12,8 años). El 23,2% presentó cefalea en el momento del ingreso o bien en las primeras 72 horas y el 12,5% de ellos presentó cefalea persistente atribuida a ictus isquémico. El 62,5% cumplió los criterios diagnósticos de acuerdo con la ICHD-III. Conclusión: La cefalea tras el ictus isquémico es un síntoma frecuente. Su aparición se asoció al sexo femenino, al ictus de territorio vertebrobasilar y a puntuaciones bajas en la National Institutes of Health Stroke Scale. Sería recomendable revisar los criterios diagnósticos actuales.(AU)

Introduction: Headache is a common symptom in acute ischemic stroke which is often overlooked and undertreated because of focus in neurologic function, communication difficulties in stroke patients and the current diagnostic criteria of this type of headache. The present study aimed to determine the prevalence of Acute and Persistent Headache Attributed to Ischemic Stroke and to analyze the fulfillment of the criteria of the International Classification of Headaches (ICHD-IID). Patients and methods: Prospective observational analytical cohort study. The study population consisted of patients with acute ischemic stroke admitted to the Stroke Unit of a tertiary care hospital over a period of 12 months. Results: Two hundred and forty-four patients with acute ischemic stroke (59.8% males, mean age 71+12.8 years) were included. Headache at onset or at the first 72 hours was present in 23.2% and 12.5% of them presented persistent headache attributed to ischemic stroke. Only 62.5% of the headaches at stroke onset fulfilled the diagnostic criteria of ICHD-III. Conclusion: Headache after ischemic stroke is a common symptom. It was associated with female sex, posterior circulation stroke and low scores on the National Institutes of Health Stroke Scale (NIHSS). The current diagnostic criteria should be reviewed.

El bloqueo del hematoma no es suficiente como método de anestesia en la reducción de fracturas desplazadas de radio distal / The hematoma block is not enough as method of anesthesia in reduction of displaced distal radius fractures

Antecedentes y objetivo: Dos de cada tres fracturas de muñeca están desplazadas pero la mayoría pueden tratarse de forma conservadora tras una reducción cerrada. El dolor que refieren los pacientes durante la reducción cerrada de estas fracturas es variable y el mejor método para controlarlo no está bien establecido. El objetivo de este estudio fue evaluar el dolor durante la reducción cerrada de fracturas de radio distal tras utilizar el bloqueo del hematoma como método anestésico. Material y método: Estudio clínico transversal que incluyó a todos los pacientes que presentaron una fractura aguda de radio distal que requirió reducción cerrada e inmovilización durante un periodo de seis meses en dos Hospitales Universitarios. Se registraron datos demográficos, clasificación de la fractura, dolor percibido mediante una escala visual analógica en diferentes momentos de la reducción y complicaciones. Resultados: Se incluyeron 94 pacientes consecutivos. La edad media fue de 61 años. La puntuación media del dolor en la evaluación inicial fue de seis puntos. Tras realizar el bloqueo del hematoma, el dolor percibido durante la maniobra de reducción descendió a 5,1 puntos en la muñeca, pero aumentó a 7,3 puntos en los dedos. El dolor disminuyó a 4,9 puntos durante la colocación del yeso y alcanzó 1,4 puntos tras la colocación del cabestrillo. El dolor referido fue mayor en las mujeres en todos los momentos. No hubo diferencias significativas según el tipo de fractura. No se observaron complicaciones neurológicas ni cutáneas. Conclusiones: El bloqueo del hematoma es un método solo ligeramente efectivo para reducir el dolor en la muñeca durante la reducción cerrada de las fracturas de muñeca. Esta técnica disminuye ligeramente el dolor percibido en la muñeca y no reduce el dolor en los dedos. Otros métodos de reducción u otras técnicas analgésicas pueden ser opciones más efectivas.(AU)

Background: Two out of three wrist fractures seen in the emergency are displaced but most can be treated conservatively after closed reduction. Patient-reported pain during closed reduction of distal radius fractures varies widely and the best method to decrease the perceived pain has not been well established. The purpose of this study was to assess the pain during closed reduction of distal radius fractures after using the hematoma block as method of anaesthesia. Patients and methods: Cross-sectional clinical study including all patients who presented an acute fracture of the distal radius requiring closed reduction and immobilization during a six-month period in two University Hospitals. Demographic data, fracture classification, perceived pain using a visual analog scale at different times of reduction and complications were registered. Results: Ninety-four consecutive patients were included. Mean age was 61 years. Mean pain score at initial assessment was 6 points. After the hematoma block, the perceived pain during the reduction manoeuvre improved to 5.1 points at the wrist, but increased to 7.3 points at the fingers. Pain decreased to 4.9 points during cast placement and reached 1.4 point after sling placement. The reported pain was higher in women at all times. There were no significant differences according to the according to the type of fracture. No neurological or skin complications were observed. Conclusions: The hematoma block is only a mild effective method to reduce the wrist pain during closed reduction of distal radius fractures. This technique decreases slightly the perceived pain in the wrist and does not reduce the pain in the fingers. Other reduction methods or other analgesic techniques may be more effective options.(AU)

[Translated article] The haematoma block is not enough as method of anaesthesia in reduction of displaced distal radius fractures / El bloqueo del haematoma no es suficiente como método de anestesia en la reducción de fracturas desplazadas de radio distal

Antecedentes y objetivo: Dos de cada tres fracturas de muñeca están desplazadas pero la mayoría pueden tratarse de forma conservadora tras una reducción cerrada. El dolor que refieren los pacientes durante la reducción cerrada de estas fracturas es variable y el mejor método para controlarlo no está bien establecido. El objetivo de este estudio fue evaluar el dolor durante la reducción cerrada de fracturas de radio distal tras utilizar el bloqueo del hematoma como método anestésico. Material y método: Estudio clínico transversal que incluyó a todos los pacientes que presentaron una fractura aguda de radio distal que requirió reducción cerrada e inmovilización durante un periodo de seis meses en dos Hospitales Universitarios. Se registraron datos demográficos, clasificación de la fractura, dolor percibido mediante una escala visual analógica en diferentes momentos de la reducción y complicaciones. Resultados: Se incluyeron 94 pacientes consecutivos. La edad media fue de 61 años. La puntuación media del dolor en la evaluación inicial fue de seis puntos. Tras realizar el bloqueo del hematoma, el dolor percibido durante la maniobra de reducción descendió a 5,1 puntos en la muñeca, pero aumentó a 7,3 puntos en los dedos. El dolor disminuyó a 4,9 puntos durante la colocación del yeso y alcanzó 1,4 puntos tras la colocación del cabestrillo. El dolor referido fue mayor en las mujeres en todos los momentos. No hubo diferencias significativas según el tipo de fractura. No se observaron complicaciones neurológicas ni cutáneas. Conclusiones: El bloqueo del hematoma es un método solo ligeramente efectivo para reducir el dolor en la muñeca durante la reducción cerrada de las fracturas de muñeca. Esta técnica disminuye ligeramente el dolor percibido en la muñeca y no reduce el dolor en los dedos. Otros métodos de reducción u otras técnicas analgésicas pueden ser opciones más efectivas.(AU)

Background: Two out of three wrist fractures seen in the emergency are displaced but most can be treated conservatively after closed reduction. Patient-reported pain during closed reduction of distal radius fractures varies widely and the best method to decrease the perceived pain has not been well established. The purpose of this study was to assess the pain during closed reduction of distal radius fractures after using the hematoma block as method of anaesthesia. Patients and methods: Cross-sectional clinical study including all patients who presented an acute fracture of the distal radius requiring closed reduction and immobilization during a six-month period in two University Hospitals. Demographic data, fracture classification, perceived pain using a visual analog scale at different times of reduction and complications were registered. Results: Ninety-four consecutive patients were included. Mean age was 61 years. Mean pain score at initial assessment was 6 points. After the hematoma block, the perceived pain during the reduction manoeuvre improved to 5.1 points at the wrist, but increased to 7.3 points at the fingers. Pain decreased to 4.9 points during cast placement and reached 1.4 point after sling placement. The reported pain was higher in women at all times. There were no significant differences according to the according to the type of fracture. No neurological or skin complications were observed. Conclusions: The hematoma block is only a mild effective method to reduce the wrist pain during closed reduction of distal radius fractures. This technique decreases slightly the perceived pain in the wrist and does not reduce the pain in the fingers. Other reduction methods or other analgesic techniques may be more effective options.(AU)

Cuidados enfermeros en el duelo perinatal. Una revisión sistemática y crítica de las actitudes y los conocimientos en la práctica clínica / Nursing care in perinatal grief. A systematic and critical review of attitudes and knowledge in clinical practice

Objetivo: Revisar y sintetizar la evidencia disponible sobre las actitudes y conocimientos de las enfermeras ante el duelo perinatal de los progenitores. Método: Se realizó una revisión sistemática de artículos originales publicados desde enero del 2016 hasta febrero del 2023, sin límite de idioma, en las bases de datos Scopus, PubMed, Cinahl, PsycINFO, ScienceDirect y Web Of Science. Se utilizó el marco metodológico de la Declaración Preferred Reporting Items for Systematic reviews and Meta-Analyse (PRISMA) para revisiones sistemáticas y metaanálisis. Todo el proceso se efectuó por pares, siendo solventadas las discrepancias por un tercer revisor. Se evaluó la calidad de los artículos siguiendo los criterios Critical Appraisal Skills Programme Español (CASPe). Resultados: Se obtuvieron 12 artículos en esta revisión tras aplicar los criterios de inclusión, de los cuales, salvo un estudio cuantitativo transversal (8,33%), los demás eran análisis cualitativos realizados mediante entrevistas (75%) o grupos de discusión (16,66%). Se destaca que existen diferentes problemas biopsicosociales relacionados con las necesidades de cuidado que demanda la familia y que, por escasa formación o cultura del profesional sanitario, no se abordan de una manera adecuada. Los estudios encontrados muestran diversos recursos para atender adecuadamente el duelo perinatal, existiendo discrepancias en relación con permitir o no que se muestre y/o coja el cuerpo del bebé fallecido; existen también desacuerdos respecto a si el equipo asistencial debe fundamentar su práctica en protocolos o teorías como la del duelo de Kübler-Ross. La mayoría de los estudios (75%) consideran necesarias más formación y sensibilización contemplando la naturaleza biopsicosocial del usuario.(AU)

Aim: To review and synthesize the available evidence on the attitudes and knowledge of nurses regarding the perinatal grief of the parents. Methods: A systematic review of original articles published from January 2016 to February 2023 without language limit in the Scopus, PubMed, Cinahl, PsycINFO, ScienceDirect and Web Of Science databases was carried out. The PRISMA Statement methodological framework was used for systematic reviews and meta-analyses. The entire process was carried out in pairs, with discrepancies being resolved by a third reviewer. The quality of the articles was evaluated following the Critical Appraisal Skills Program Spanish (CASPe criteria). Results: Twelve articles were obtained in this review after applying the inclusion criteria, of which. Except for one cross-sectional quantitative study (8.33%), the rest were qualitative studies carried out through interviews (75%) or discussion groups (16.66%). It is highlighted that there are different biopsychosocial problems related to the care needs demanded by the family and that, due to poor training or culture of the health professional, are not adequately addressed. The studies found show various resources to adequately attend to perinatal grief, there being discrepancies in relation to allowing or not allowing the body of the deceased baby to be shown and/or taken; There are also disagreements regarding whether the healthcare team should base its practice on protocols or theories such as the Kübler-Ross theory of grief. Most of the studies (75%) consider that more training and awareness is necessary, contemplating the biopsychosocial nature of the user.(AU)

La transición posquirúrgica en adolescentes que padecen escoliosis idiopática. Un estudio cualitativo / The post-surgical transition in adolescents who have idiopathic scoliosis. A qualitative study

Objetivo: Conocer el proceso que viven las y los adolescentes que padecen escoliosis idiopática al intervenirse quirúrgicamente para corregir la deformidad física. Método: Estudio cualitativo con enfoque interaccionismo simbólico. Se realizaron 22 entrevistas semiestructuradas a adolescentes intervenidos de fusión espinal posterior en un hospital de tercer nivel de Madrid entre mayo de 2019 y enero de 2021. Se llevó a cabo análisis en progreso de Taylor y Bogdan. Resultados: Los pacientes con escoliosis idiopática del adolescente presentan una transición compleja simultánea de tipo salud/enfermedad y de desarrollo. Las principales condiciones inhibidoras de la transición son los significados sobre: su identidad, sociales, creencias sobre la cirugía, el desconocimiento sobre la patología, el proceso quirúrgico y su recuperación. Como condiciones facilitadoras encontramos: la actitud positiva hacia el cambio físico, estético, social, el nivel socioeconómico y el apoyo familiar. Conclusiones: Los informantes de este estudio refieren que la afectación estética y las limitaciones físicas son los principales elementos que les causan disconfort. La intervención quirúrgica se presenta como la solución a esta situación. La recuperación es un punto crítico en el proceso de transición debido principalmente al dolor. Aceptan el malestar sufrido durante la recuperación porque esperan obtener una mejora en la imagen y las limitaciones físicas. Los cambios y diferencias que experimentan durante la transición les hace pensar que van a poder llevar una «vida normal» a la que se refieren constantemente en los discursos.(AU)

Objective: To know the process experienced by adolescents suffering from idiopathic scoliosis when undergoing surgery to correct the physical deformity. Method: Qualitative study with a symbolic interactionism approach. 22 semi-structured interviews were conducted with adolescents who underwent posterior spinal fusion in a third-level hospital in Madrid between May 2019 and January 2021. Taylor and Bogdan's analysis in progress was carried out. Results: Patients with adolescent idiopathic scoliosis present with a complex simultaneous health/illness and developmental transition. The main inhibitory conditions of the transition are the meanings about: their identity, social, beliefs about surgery, ignorance about the pathology, the surgical process, and their recovery. As facilitating conditions, we find: a positive attitude towards physical, aesthetic, and social change, socioeconomic level, and family support. Conclusions: The informants of this study refer that aesthetic affectation and physical limitations are the main elements that cause them discomfort. Surgical intervention is presented as the solution to this situation. Recovery is a critical point in the transition process mainly due to pain. They accept the discomfort suffered during the recovery because they hope to obtain an improvement in the image and physical limitations. The changes and differences they experience during the transition make them think that they will be able to lead a «normal life» to which they constantly refer in their speeches.(AU)

Bone Remodeling in Osteoarthritis-Biological and Radiological Aspects.

Among available papers published on the given subject over the last century, various terms have been used as synonyms for one, now generally accepted-osteoarthritis, in some countries called "wear and tear" or "overload arthritis". The opsolent terms-hypertrophic arthritis, degenerative arthritis, arthritis deformans and osteoarthrosis-sought to highlight the dominant clinical signs of this ubiquitous, polymorph disease of the whole osteochondral unit, which by incidence and prevalence represents one of the leading chronic conditions that cause long-term pain and incapacity for work. Numerous in vitro and in vivo research resulted in broadened acknowledgments about osteoarthritis pathophysiology and pathology on both histological and cellular levels. However, the cause of osteoarthritis is still unknown and is currently the subject of a hypothesis. In this paper, we provide a review of recent findings on biological phenomena taking place in bone tissue during osteoarthritis to the extent useful for clinical practice. Choosing a proper radiological approach is a conditio sine qua non to the early diagnosis of this entity.

Recent Development of Novel Aminoethyl-Substituted Chalcones as Potential Drug Candidates for the Treatment of Alzheimer's Disease.

No drug on the market, as a single entity, participates in different pathways involved in the pathology of Alzheimer's disease. The current study is aimed at the exploration of multifunctional chalcone derivatives which can act on multiple targets involved in Alzheimer's disease. A series of novel aminoethyl-substituted chalcones have been developed using in silico approaches (scaffold morphing, molecular docking, and ADME) and reported synthetic methods. The synthesized analogs were characterized and evaluated biologically using different in vitro assays against AChE, AGEs, and radical formation. Among all compounds, compound PS-10 was found to have potent AChE inhibitory activity (IC50 = 15.3 nM), even more than the standard drug (IC50 = 15.68 nM). Further, the in vivo evaluation of PS-10 against STZ-induced dementia in rats showed memory improvement (Morris Water Maze test) in rats. Also, PS-10 inhibited STZ-induced brain AChE activity and oxidative stress, further strengthening the observed in vitro effects. Further, the molecular dynamic simulation studies displayed the stability of the PS-10 and AChE complex. The novel aminoethyl-substituted chalcones might be considered potential multifunctional anti-Alzheimer's molecules.

A randomized interventional clinical trial assessing the safety and effectiveness of PeaNoc XL tablets in managing joint pain and inflammation in arthritis patients.

Background: Globally, alternative medicine is used widely by most patients for several health challenges. To evaluate the effectiveness and safety of PeaNoc XL Tablet in managing pain and inflammation, a randomized clinical trial and systematic study was designed. PeaNoc XL Tablet has been widely utilized for pain and inflammation management, but no previous studies have examined its efficacy and safety. The aim of this study was to determine the clinical effectiveness and safety profile of PeaNoc XL in patients with arthritis experiencing joint pain and inflammation. Methods: A randomized, controlled, and an open-label trial was conducted. A total of 155 patients (18 to 60 years) with arthritis were enrolled for participation. Using computer-generated random sequences, the study population was divided into two groups in a randomized manner. Group A received Standard therapy and Group B received Standard therapy with PeaNoc XL Tablet 400mg (two tablets OD after food). Results: Out of 155 patients, a total of 83 individuals were excluded from the study, leaving 72 patients who were randomly assigned to either Group A (n=36) or Group B (n=36). The administration of PeaNoc XL as an adjunct to standard therapy resulted in a significant reduction in levels of TNF-α (P<0.01), IL-1ß (P<0.001), IL-6 (P<0.01), and CRP (P<0.01) in arthritis patients experiencing joint pain and inflammation. Conversely, no notable differences were observed from the baseline in the standard therapy group. Conclusions: After 12 weeks of supplementation of PeaNoc XL tablets, as an add-on therapy helps in the reduction of pain score, joint stiffness, and physical stiffness. Trial registration:  CTRI/2022/10/046693.

2023 AAFP/IAAHPC feline hospice and palliative care guidelines.

The '2023 AAFP/IAAHPC Feline Hospice and Palliative Care Guidelines' are authored by a Task Force of experts in feline hospice and palliative care convened by the American Association of Feline Practitioners and the International Association for Animal Hospice and Palliative Care. They emphasize the specialized communication skills and ethical considerations that are associated with feline hospice and palliative care, with references to other feline practice guidelines for a more complete discussion of specific diseases, feline pain management best practices and cat friendly interactions. A comprehensive, multi-step hospice consultation allows for tailoring the approach to both the cat and the family involved in the care. The consultation includes establishing 'budgets of care', a concept that greatly influences what can be done for the individual cat. The Guidelines acknowledge that each cat and caregiver will be different in this regard; and establishing what is reasonable, practical and ethical for the individual cat and caregiver is important. A further concept of the 'care unit' is introduced, which is extrapolated from human hospice and palliative care, and encourages and empowers the caregiver to become a part of the cat's care every step of the way. Ethical considerations include a decision-making framework. The importance of comfort care is emphasized, and the latest information available about how to assess the quality of a cat's life is reviewed. Emotional health is as equally important as physical health. Hence, it is fundamental to recognize that compromised physical health, with pain and/or illness, impairs emotional health. A limited discussion on euthanasia is included, referring to the AAFP's End of Life Educational Toolkit for recommendations to help the caregiver and the veterinary professional ensure a peaceful passing and transition - one that reflects the best interests of the individual cat and caregiver.

A randomized trial: The safety, pharmacokinetics and preliminary pharmacodynamics of ropivacaine oil delivery depot in healthy subjects.

INTRODUCTION: Ropivacaine oil delivery depot (RODD) can slowly release ropivacaine and block nerves for a long timejavascript:;. The aim of the present work was to investigate the safety, pharmacokinetics, and preliminary pharmacodynamics of RODD in subcutaneous injection among healthy subjects. METHODS: The abdomens of 3 subjects were subcutaneously administered with a single-needle RODD containing 12~30 mg of ropivacaine. The irritation, nerve blocking range and optimum dose were investigated. Forty-one subjects were divided into RODD groups containing 150, 230, 300, 350 and 400 mg of ropivacaine and a ropivacaine hydrochloride injection (RHI) 150 mg group. Multineedle subcutaneous injection of RODD or RHI was performed in the abdomens of the subjects. The primary endpoint was a safe dose or a maximum dose of ropivacaine (400 mg). Subjects' vital signs were observed; their blood was analyzed; their cardiovascular system and nervous systems were monitored, and their dermatological reactions were observed and scored. Second, the ropivacaine concentrations in plasma were determined, pharmacokinetic parameters were calculated, and the anesthetic effects of RODD were studied, including RODD onset time, duration and intensity of nerve block. RESULTS: Single-needle injection of RODD 24 mg was optimal for 3 subjects, and the range of nerve block was 42.5±20.8 mm. Multineedle subcutaneous injection of RODD in the abdomens of subjects was safe, and all adverse events were no more severe than grade II. The incidence rate of grade II adverse events, such as pain, and abnormal ST and ST-T segment changes on electrocardiography, was approximately 1%. The incidence rate of grade I adverse events, including erythema, papules, hypertriglyceridemia, and hypotension was greater than 10%. Erythema and papules were relieved after 24 h and disappeared after 72 h. Other adverse reactions disappeared after 7 days. The curve of ropivacaine concentration-time in plasma presented a bimodal profile. The results showed that ropivacaine was slowly released from the RODD. Compared with the 150 mg RHI group, Tmax was longer in the RODD groups. In particular, Tmax in the 400 mg RODD group was longer than that in the RHI group (11.8±4.6 h vs. 0.77±0.06 h). The Cmax in the 150 mg RODD group was lower than that in the 150 mg RHI group (0.35±0.09 vs. 0.58±0.13 µg·mL-1). In particular, the Cmax increased by 48% when the dose was increased by 2.6 times in the 400 mg group. Cmax, the AUC value and the intensity of the nerve block increased with increasing doses of RODD. Among them, the 400 mg RODD group presented the strongest nerve block (the percentage of level 2 and 3, 42.9%). The corresponding median onset time was 0.42 h, and the duration median was 35.7⁓47.7 h. CONCLUSIONS: RODD has a sustained release effect. Compared with the RHI group, Tmax was delayed in the RODD groups, and the duration of nerve block was long. No abnormal reaction was found in the RODD group containing 400 mg of ropivacaine after subcutaneous injection among healthy subjects, suggesting that RODD was adequately safe. TRIAL REGISTRATION: Chictr.org: CTR2200058122; Chinadrugtrials.org: CTR20192280.

Evidencing general acceptability of open-label placebo use for tackling overtreatment in primary care: a mixed methods study.

BACKGROUND: Overtreatment poses a challenge to healthcare systems due to harmful consequences of avoidable side-effects and costs. This study presents the first account for examining the feasibility of placebo use for reducing overtreatment in primary care, including whether public attitudes support the use of different placebo types in place of inappropriate prescriptions of antibiotics, antidepressants, or analgesics. METHODS: We used a multi-study, mixed-methods design, including patient and public (PPI) consultations, focus groups (Study 1) and two pre-registered online experiments (Studies 2 and 3). RESULTS: Study 1 (N = 16) explored everyday conceptions and practicalities of potential placebo use in the context of respiratory infections. Findings highlighted the importance of trusting doctor-patient relationships and safety-netting. Study 2 employed a randomised experiment with a representative UK sample (N = 980), investigating attitudes towards 5 different treatment options for respiratory infections: (1) blinded + pure placebo, (2) open-label + pure placebo, (3) open-label + impure placebo, (4) antibiotic treatment, and (5) no treatment. Study 2 also examined how attitudes varied based on wording and individual differences. Findings indicated general support (ηp2 = .149, large effect size) for replacing inappropriate antibiotics with open-label + impure placebos, although personal placebo acceptability was lower. Also, older people, individuals suffering from chronic illness or those showing higher levels of health anxiety appeared less amenable to placebo use. Study 3 (N = 1177) compared attitudes towards treatment options across three clinical scenarios: respiratory infection, depression and pain. Findings suggested significant differences in the acceptability of placebo options based on the clinical context. In the infection scenario, options for open-label + pure placebos, open-label + impure placebos and no treatment were rated significantly more acceptable (ηp2 = .116, medium effect size) compared to the depression and pain scenarios. Again, general support for placebos was higher than placebo acceptability for personal use. CONCLUSIONS: Findings from PPI and three studies indicate general support for combatting overprescribing in primary care through clinical placebo use. This is an indicator for wider UK public support for a novel, behavioural strategy to target a long-standing healthcare challenge. General acceptability appears to be highest for the use of open-label + impure placebos in the context of antibiotic overprescribing.

Investigation of an outbreak of disease compatible with scurvy in a male penitentiary in the state of Ceará, Brazil, 2019-2020: a case-control study.

MAIN RESULTS: An outbreak of illness compatible with scurvy occurred among male prison inmates; most frequent signs/symptoms were edema and pain in lower limbs, difficulty in walking and hematoma/ecchymosis; the associated factor was age > 40 years. IMPLICATIONS FOR SERVICES: The results can contribute to the identification and description of scurvy outbreaks in other contexts and territories. Epidemiological studies of events like this enhance the practice of field epidemiology in health services. PERSPECTIVES: It is expected that the prevention of hypovitaminosis, such as scurvy, will be based on public policies aimed at the population deprived of liberty; and that the capabilities of health services to detect and respond to cases of the disease will be improved. OBJECTIVE: to identify the occurrence of an outbreak compatible with scurvy and exposure factors associated with typical signs/symptoms of hypovitaminosis that occurred in a male penitentiary in Ceará, Brazil between 2019-2020. METHODS: this was a population-based case-control study; we used clinical records and interviews with compatible cases - based on sign/symptom onset during the study period - and with controls; we carried out multivariate analysis. RESULTS: out of 62 cases, mean age was 40.6 years (SD = 10.8); main signs/symptoms were edema and pain in the lower limbs (100.0%), difficulty in walking (91.9%), hematoma/ecchymosis in the lower limbs (90.3%) and fever (88.7%); we identified being over 40 years old as an associated factor (aOR = 1.10; 95%CI 1.05;1.17; p-value = 0.001); and as protective factors: working (aOR = 0.11; 95%CI 0.03;0.36; p-value < 0.001) and taking part in classes (aOR = 0.21; 95%CI 0.08;0.59; p-value = 0.003) in the prison. CONCLUSION: we considered the penitentiary outbreak to be compatible with scurvy due to characteristic signs/symptoms, associated with the identified factors; we recommended regular provision of a diet rich in vitamin C to all male inmates and clinical follow-up of cases.

Implementation of coordinated spontaneous awakening and breathing trials using telehealth-enabled, real-time audit and feedback for clinician adherence (TEACH): a type II hybrid effectiveness-implementation cluster-randomized trial.

BACKGROUND: Intensive care unit (ICU) patients on mechanical ventilation often require sedation and analgesia to improve comfort and decrease pain. Prolonged sedation and analgesia, however, may increase time on mechanical ventilation, risk for ventilator associated pneumonia, and delirium. Coordinated interruptions in sedation [spontaneous awakening trials (SATs)] and spontaneous breathing trials (SBTs) increase ventilator-free days and improve mortality. Coordination of SATs and SBTs is difficult with substantial implementation barriers due to difficult-to-execute sequencing between nurses and respiratory therapists. Telehealth-enabled remote care has the potential to overcome these barriers and improve coordinated SAT and SBT adherence by enabling proactive high-risk patient monitoring, surveillance, and real-time assistance to frontline ICU teams. METHODS: The telehealth-enabled, real-time audit and feedback for clinician adherence (TEACH) study will determine whether adding a telehealth augmented real-time audit and feedback to a usual supervisor-led audit and feedback intervention will yield higher coordinated SAT and SBT adherence and more ventilator-free days in mechanically ventilated patients than a usual supervisor-led audit and feedback intervention alone in a type II hybrid effectiveness-implementation cluster-randomized clinical trial in 12 Intermountain Health hospitals with 15 ICUs. In the active comparator control group (six hospitals), the only intervention is the usual supervisor-led audit and feedback implementation. The telehealth-enabled support (TEACH) intervention in six hospitals adds real-time identification of patients eligible for a coordinated SAT and SBT and consultative input from telehealth respiratory therapists, nurses, and physicians to the bedside clinicians to promote adherence including real-time assistance with execution. All intubated and mechanically ventilated patients ≥ 16 years of age are eligible for enrollment except for patients who die on the day of intubation or have preexisting brain death. Based on preliminary power analyses, we plan a 36-month intervention period that includes a 90-day run-in period. Estimated enrollment in the final analysis is up to 9900 mechanically ventilated patients over 33 months. DISCUSSION: The TEACH study will enhance implementation science by providing insight into how a telehealth intervention augmenting a usual audit and feedback implementation may improve adherence to coordinated SAT and SBT and increase ventilator-free days. TRIAL REGISTRATION: Clinicaltrials.gov, NCT05141396 , registered 12/02/2021.

Prevalence and characteristics of pain in moderate-to-severe obstructive sleep apnea patients and effect of CPAP treatment.

Pain problems are common in patients with obstructive sleep apnea (OSA), but few studies have thoroughly evaluated pain in these patients. The objective of this study was to examine the prevalence and characteristics of pain in moderate-to-severe OSA patients and the effect of continuous positive airway pressure (CPAP) treatment. Moderate-to-severe OSA patients and healthy controls (HC) completed the Short Form McGill Pain Questionnaire (SF-MPQ) and a portion of the Brief Pain Inventory (BPI) Short Form to assess pain characteristics. The Epworth Sleepiness Scale (ESS), the Short Form-36 (SF-36), and the Hospital Anxiety and Depression Scale (HADS) were used to measure daytime sleepiness, health-related quality of life (HRQoL), and psychological status, respectively. The OSA patients with pain were divided into a CPAP-treated group and a CPAP-untreated group based on their adherence to CPAP. The subjects' pain intensity was reassessed after 3 months. The prevalence of pain was 57.5% in OSA versus 27.1% in HC (p < 0.001). Head (39.0%) accounted for the highest proportion of overall pain locations in subjects with OSA, with 28.8% of OSA patients experiencing headaches. Pain in OSA was associated with impaired HRQoL and psychological problems. Patients with very severe OSA had an increased risk for pain problems (OR: 7.000, p = 0.041). Associated factors for pain intensity in OSA included age, ESS ≥ 9.0, and lowest pulse oximetry (LSpO2) < 80.0%. Pain intensity in OSA decreased significantly after CPAP treatment (p < 0.001). Pain was prevalent among patients with moderate-to-severe OSA and was associated with depression, anxiety, and a lower HRQoL. Patients with very severe OSA had an increased risk for pain problems. The intensity of pain in OSA can be predicted by age, ESS ≥ 9.0, and LSpO2 < 80.0%, and it can be alleviated through CPAP treatment.

Neuromas cause severe residual problems at long-term despite surgery.

Pain, and disabilities after neuroma surgery, using patient reported outcome measurements (PROMs), were evaluated by QuickDASH and a specific Hand Questionnaire (HQ-8). The 69 responding individuals (response rate 61%; 59% women; 41% men; median follow up 51 months) reported high QuickDASH score, pain on load, cold sensitivity, ability to perform daily activities and sleeping difficulties. Individuals reporting impaired ability to perform daily activities and sleeping problems had higher scores for pain, stiffness, weakness, numbness/tingling, cold sensitivity and QuickDASH. Only 17% of individuals reported no limitations at all. No differences were observed between sexes. Surgical methods did not influence outcome. Symptoms and disabilities correlated moderately-strongly to each other and to ability to perform regular daily activities as well as to sleeping difficulties. Pain, cold sensitivity, sleeping difficulties and limitation to perform daily activities were associated to higher QuickDASH. A weak association was found between follow up time and QuickDASH score as well as pain on load, but not cold sensitivity. A major nerve injury was frequent among those with limitations during work/performing other regular daily activities. Despite surgical treatment, neuromas cause residual problems, which affect the capacity to perform daily activities and ability to sleep with limited improvement in long-term.

[vNOTES hysterectomy - a new minimally invasive method for gynecologic surgery]. / vNOTES ­ en ny minimalinvasiv metod för gynekologisk kirurgi.

vNOTES hysterectomy is a scarless minimally invasive method with a vaginal approach to the abdominal cavity combined with endoscopic overview. Studies have shown that patients who underwent vNOTES hysterectomy had less pain and shorter hospital stay than after laparoscopic hysterectomy.

Different sedation profiles with ciprofol compared to propofol represented by objective sedation level assessments by BIS and its acute hemodynamic impact in 3 escalated doses of ciprofol and propofol in healthy subjects: a single-center, open-label, randomized, 2-stage, 2-way crossover trial.

OBJECTIVE: To compare the sedation profiles and the pharmacokinetic, pharmacodynamic and safety characteristics of ciprofol and propofol at 3 escalated dose levels in healthy Chinese male subjects. PATIENTS AND METHODS: Eighteen subjects were planned to be enrolled into 3 dose groups in turn: group 1 (ciprofol-0.4 mg/kg vs. propofol-2.0 mg/kg), group 2 (ciprofol-0.6 mg/kg vs. propofol-3.0 mg/kg) and group 3 (ciprofol-0.8 mg/kg vs. propofol-4.0 mg/kg). They were randomly assigned into a ciprofol or propofol group in a ratio of 1:1, with sequences of ciprofol-propofol or propofol-ciprofol, separated with a washout period of at least 48 h. RESULTS: A total of 19 subjects were enrolled and 18 completed the trial. The median time to being fully alert after induction by ciprofol was longer than for propofol. The bispectral index (BIS) recovered significantly slower with ciprofol than with propofol 5 min and 10 min after reaching its lowest points. Systolic blood pressure (group 1: p=0.041; group 2: p=0.015; group 3: p=0.004) and mean arterial pressures (group 1: p=0.026; group 2: p=0.015; group 3: p=0.004) measured by the area under the curve below the baseline during the 2 min after induction were significantly less for ciprofol compared to propofol, but a significant change in diastolic blood pressure was only observed in group 3 (p=0.002). Eighteen (100.0%) subjects experienced 47 ciprofol-related treatment emergent adverse events (TEAEs) and 17 (94.4%) subjects had 54 propofol-related TEAEs, which were mainly hypotension, involuntary movements, respiratory depression, and pain at the injection site with severity of grade 1 or 2. CONCLUSIONS: Ciprofol may be well tolerated at higher doses in the clinical practice and exhibited significantly different sedation profiles to propofol.