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1.
Cancer ; 130(4): 497-504, 2024 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-37941524

RESUMO

There is growing interest in cannabis use for cancer pain. This commentary aims to discuss the evidence surrounding cannabis use for cancer pain in the context of the long-racialized landscape of cannabis policies and the disparity in pain control among cancer patients holding minoritized racial identities. Much evidence surrounding both the benefits and harms of cannabis use in cancer patients, and all patients in general, is lacking. Although drawing on the research in cancer that is available, it is also important to illustrate the broader context about how cannabis' deep roots in medical, political, and social history impact patient use and health care policies. There are lessons we can learn from the racialized disparities in opioid risk mitigation strategies, so they are not replicated in the settings of cannabis for cancer symptom management. Additionally, the authors intentionally use the term "cannabis" here rather than "marijuana.: In the early 1900s, the lay press and government popularized the use of the word "marijuana" instead of the more common "cannabis" to tie the drug to anti-Mexican prejudice.


Assuntos
Dor do Câncer , Cannabis , Dor Crônica , Maconha Medicinal , Neoplasias , Humanos , Dor do Câncer/tratamento farmacológico , Maconha Medicinal/uso terapêutico , Dor/tratamento farmacológico , Dor/induzido quimicamente , Analgésicos Opioides/uso terapêutico , Neoplasias/complicações , Neoplasias/epidemiologia , Neoplasias/terapia
2.
BMJ Open ; 13(12): e078645, 2023 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-38072483

RESUMO

INTRODUCTION: Almost all patients receiving mechanical ventilation (MV) in intensive care units (ICUs) require analgesia and sedation. The most widely used sedative drug is propofol, but there is uncertainty whether alpha2-agonists are superior. The alpha 2 agonists for sedation to produce better outcomes from critical illness (A2B) trial aims to determine whether clonidine or dexmedetomidine (or both) are clinically and cost-effective in MV ICU patients compared with usual care. METHODS AND ANALYSIS: Adult ICU patients within 48 hours of starting MV, expected to require at least 24 hours further MV, are randomised in an open-label three arm trial to receive propofol (usual care) or clonidine or dexmedetomidine as primary sedative, plus analgesia according to local practice. Exclusions include patients with primary brain injury; postcardiac arrest; other neurological conditions; or bradycardia. Unless clinically contraindicated, sedation is titrated using weight-based dosing guidance to achieve a Richmond-Agitation-Sedation score of -2 or greater as early as considered safe by clinicians. The primary outcome is time to successful extubation. Secondary ICU outcomes include delirium and coma incidence/duration, sedation quality, predefined adverse events, mortality and ICU length of stay. Post-ICU outcomes include mortality, anxiety and depression, post-traumatic stress, cognitive function and health-related quality of life at 6-month follow-up. A process evaluation and health economic evaluation are embedded in the trial.The analytic framework uses a hierarchical approach to maximise efficiency and control type I error. Stage 1 tests whether each alpha2-agonist is superior to propofol. If either/both interventions are superior, stages 2 and 3 testing explores which alpha2-agonist is more effective. To detect a mean difference of 2 days in MV duration, we aim to recruit 1437 patients (479 per group) in 40-50 UK ICUs. ETHICS AND DISSEMINATION: The Scotland A REC approved the trial (18/SS/0085). We use a surrogate decision-maker or deferred consent model consistent with UK law. Dissemination will be via publications, presentations and updated guidelines. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT03653832.


Assuntos
Dexmedetomidina , Propofol , Adulto , Humanos , Propofol/uso terapêutico , Dexmedetomidina/uso terapêutico , Análise Custo-Benefício , Clonidina/uso terapêutico , Estado Terminal/terapia , Qualidade de Vida , Agonistas de Receptores Adrenérgicos alfa 2/uso terapêutico , Hipnóticos e Sedativos/uso terapêutico , Dor/induzido quimicamente , Unidades de Terapia Intensiva , Reino Unido , Respiração Artificial , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto , Ensaios Clínicos Fase III como Assunto
3.
Libyan J Med ; 18(1): 2275417, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37905304

RESUMO

This study aimed to evaluate the anti-inflammatory and analgesic properties of the methanolic extract of Opuntia ficus indica L. in small animal (rats and mice model). The current treatment for febrile conditions often involves the use of non-steroidal anti-inflammatory drugs (NSAIDs), which can have adverse effects, particularly gastrointestinal ulcers. Therefore, there is a growing need to explore natural alternatives with fewer side effects. The study utilized various experimental models to assess the effects of the extract. The results demonstrated a significant analgesic effect of the extract, as evidenced by a reduction in pain induced by acetic acid and hot plate tests. Additionally, the extract exhibited anti-inflammatory effects, as indicated by a decrease in carrageenan-induced paw edema and dextran-induced inflammation. To gain insights into the chemical composition of the extract, HPLC analysis was conducted. The analysis successfully identified and quantified 20 compounds, including luteolin, galangin, catechin, thymol, methylated quercetin, quercetin, rutin, acacetin, hesperidin, apigenin, kaempferol, pinocembrin, chrysin, gallic acid, caffeic acid, ascorbic acid, ferulic acid, m-coumaric acid, rosmarinic acid, and trans-cinnamic acid.The findings suggest that Opuntia ficus indica L. extract holds promise as an effective and reasonably priced natural remedy for pain and inflammation in rats and mice model. The comprehensive chemical composition analysis provided valuable insights into the presence of various bioactive compounds, which may contribute to the observed therapeutic effects. Further research and exploration of the extract's mechanisms of action are warranted to fully understand its potential in small animal healthcare.


Assuntos
Opuntia , Camundongos , Ratos , Animais , Opuntia/química , Quercetina/efeitos adversos , Quercetina/análise , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Anti-Inflamatórios/efeitos adversos , Analgésicos/efeitos adversos , Inflamação/tratamento farmacológico , Dor/tratamento farmacológico , Dor/induzido quimicamente
4.
Cancer Res Commun ; 3(9): 1917-1926, 2023 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-37772996

RESUMO

Symptoms such as pain, nausea, and anxiety are common in individuals with cancer. Treatment of these issues is often challenging. Cannabis products may be helpful in reducing the severity of these symptoms. While some studies include data on the prevalence of cannabis use among patients with cancer, detailed data remain limited, and none have reported the prevalence of cannabidiol (CBD) use in this population. Adult patients with cancer attending eight clinics at a large, NCI-designated Comprehensive Cancer Center completed a detailed, cannabis-focused questionnaire between 2021 and 2022. Eligible participants were diagnosed with invasive cancer and treated in the past 12 months. Summary statistics were calculated to describe the sample regarding cannabis use. Approximately 15% (n = 142) of consented patients (n = 934) reported current cannabis use (defined as use within the past 12 months). Among which, 75% reported cannabis use in the past week. Among current cannabis users, 39% (n = 56; 6% overall) used CBD products. Current users reported using cannabis a median of 4.5 (interquartile range: 0.6­7.0) days/week, 2.0 (1.0­3.0) times per use/day, and for 3 years (0.8­30.0). Use patterns varied by route of administration. Patients reported moderate to high relief of symptoms with cannabis use. This study is the most detailed to date in terms of cannabis measurement and provides information about the current state of cannabis use in active cancer. Future studies should include complete assessments of cannabis product use, multiple recruitment sites, and diverse patient populations. SIGNIFICANCE: Clinicians should be aware that patients are using cannabis products and perceive symptom relief with its use.


Assuntos
Canabidiol , Cannabis , Alucinógenos , Maconha Medicinal , Neoplasias , Adulto , Humanos , Cannabis/efeitos adversos , Canabidiol/uso terapêutico , Maconha Medicinal/uso terapêutico , Prevalência , Dor/induzido quimicamente , Agonistas de Receptores de Canabinoides , Neoplasias/tratamento farmacológico
5.
J Oncol Pharm Pract ; 27(1): 253-257, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32611269

RESUMO

INTRODUCTION: Immune thrombocytopenia is an autoimmune disorder associated with increased thrombocyte destruction and impaired production in the bone marrow. Proposed mechanisms include an antibody or autoreactive T-cell-associated autoimmunity and thrombopoietin deficiency among others. Clinical manifestations are predominantly mucocutaneous hemorrhages including petechiae, purpura, mucosal bleeding in the urinary or the gastrointestinal tracts, menorrhagia, and epistaxis. The purpose of the treatment is to prevent bleeding rather than normalizing the platelet counts. First-line treatments include corticosteroids ± intravenous immunoglobulin and Anti-D which mainly decrease antibody-mediated platelet destruction and increase the number of peripheral Tregs. Second-line and subsequent therapies include splenectomy, chimeric anti-CD20 antibody (rituximab), which eliminates B cells and act as an immunomodulatory agent, and Thrombopoietin receptor agonists (romiplostim), which promote platelet production. CASE REPORT: We describe a 40-year-old male patient diagnosed with immune thrombocytopenia that was refractory to first-line corticosteroid and intravenous immunoglobulin and second-line romiplostim monotherapy treatments.Management and outcome: The patient was given the romiplostim and rituximab combination which not only successfully treated thrombocytopenia but also resulted in grade 3 bone pains and the patient's subsequent refusal to continue therapy. DISCUSSION: Common adverse effects of rituximab are infusion reactions and prolonged immunosuppression; those of romiplostim include thrombosis, headaches, arthralgia-myalgia, and gastrointestinal symptoms. This case shows that romiplostim has not caused any discernible side effects when given alone, while combination with rituximab resulted in severe bone and joint pains. We hypothesize that this combination regimen shows a synergistic effect both in terms of efficacy and adverse-effect probability and/or severity.


Assuntos
Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Receptores Fc/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Rituximab/administração & dosagem , Trombopoetina/administração & dosagem , Adulto , Síndrome Antifosfolipídica/tratamento farmacológico , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Masculino , Dor/induzido quimicamente , Contagem de Plaquetas , Rituximab/uso terapêutico
6.
Cancer Med ; 9(8): 2723-2731, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32090502

RESUMO

PURPOSE: The purpose of this analysis was to determine the cost-effectiveness of a Collaborative Care Model (CCM)-based, centralized telecare approach to delivering rehabilitation services to late-stage cancer patients experiencing functional limitations. METHODS: Data for this analysis came from the Collaborative Care to Preserve Performance in Cancer (COPE) trial, a randomized control trial of 516 patients assigned to: (a) a control group (arm A), (b) tele-rehabilitation (arm B), and (c) tele-rehabilitation plus pharmacological pain management (arm C). Patient quality of life was measured using the EQ-5D-3L at baseline, 3-month, and 6-month follow-up. Direct intervention costs were measured from the experience of the trial. Participants' hospitalization data were obtained from their medical records, and costs associated with these encounters were estimated from unit cost data and hospital-associated utilization information found in the literature. A secondary analysis of total utilization costs was conducted for the subset of COPE trial patients for whom comprehensive cost capture was possible. RESULTS: In the intervention-only model, tele-rehabilitation (arm B) was found to be the dominant strategy, with an incremental cost-effectiveness ratio (ICER) of $15 494/QALY. At the $100 000 willingness-to-pay threshold, this tele-rehabilitation was the cost-effective strategy in 95.4% of simulations. It was found to be cost saving compared to enhanced usual care once the downstream hospitalization costs were taken into account. In the total cost analysis, total inpatient hospitalization costs were significantly lower in both tele-rehabilitation (arm B) and tele-rehabilitation plus pain management (arm C) compared to control (arm A), (P = .048). CONCLUSION: The delivery of a CCM-based, centralized tele-rehabilitation intervention to patients with advanced stage cancer is highly cost-effective. Clinicians and care teams working with this vulnerable population should consider incorporating such interventions into their patient care plans.


Assuntos
Análise Custo-Benefício , Neoplasias/economia , Manejo da Dor/economia , Dor/economia , Qualidade de Vida , Telemedicina/economia , Telerreabilitação/economia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Estudos de Casos e Controles , Técnicas de Apoio para a Decisão , Feminino , Seguimentos , Humanos , Masculino , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Neoplasias/reabilitação , Dor/induzido quimicamente , Dor/patologia , Dor/prevenção & controle , Prognóstico
7.
Support Care Cancer ; 28(8): 3781-3789, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31832824

RESUMO

BACKGROUND: The Universal Health Coverage goals call for access to affordable palliative care to reduce inequities in "total pain" and suffering. To achieve this, a patient-centred understanding of these inequities is required. AIM: To assess association of total pain and suffering (i.e. physical, psychological, social, and spiritual health outcomes) and perceived health care quality with financial difficulties among stage IV solid malignancy patients. DESIGN: Using baseline data from the COMPASS cohort study, we assessed total pain and suffering including physical (physical and functional well-being, pain, symptom burden), psychological (anxiety, depression, emotional well-being), social (social well-being), and spiritual (spiritual well-being, hope) outcomes and perceived health care quality (physician communication, nursing care, and coordination/responsiveness). Financial difficulties were scored by assessing patient perception of the extent to which their resources were meeting expenses for their treatments, daily living, and other obligations. We used multivariable linear/logistic regression to test association between financial difficulties and each patient-reported outcome. SETTING/PARTICIPANTS: Six hundred stage IV solid malignancy patients in Singapore. RESULTS: Thirty-five percent reported difficulty in meeting expenses. A higher financial difficulties score was associated with worse physical, psychological, social, spiritual outcomes, and lower perceived quality of health care coordination and responsiveness (i.e. greater total pain and suffering) (all p < 0.05). These associations persisted after adjustment for socio-economic indicators. CONCLUSION: Results identify advanced cancer patients with financial difficulties to be a vulnerable group with greater reported total pain and suffering. A holistic patient-centred approach to care at end-of-life may help meet goals for Universal Health Coverage.


Assuntos
Neoplasias/economia , Dor/induzido quimicamente , Dor/economia , Dor/enfermagem , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/psicologia , Dor/psicologia , Qualidade de Vida/psicologia
8.
Am J Clin Dermatol ; 20(5): 711-723, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31264114

RESUMO

BACKGROUND: Atopic dermatitis is highly prevalent in black/African American, Asian, and Hispanic patients, making assessment of these populations in clinical trials important. Crisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild-to-moderate atopic dermatitis. In two pivotal phase III clinical trials in patients aged ≥ 2 years, crisaborole was superior to vehicle in reducing global disease severity. The most common treatment-related adverse event was application site pain. OBJECTIVE: The objective of this study was to investigate the efficacy and safety of crisaborole according to patient race and ethnicity. METHODS: A pooled post hoc analysis by race and ethnicity of the two pivotal trials and a safety extension trial was performed. Race included white or nonwhite (encompassing Asian/native Hawaiian/other Pacific Islander, black/African American, and other/American Indian/Alaskan native); ethnicity included Hispanic/Latino or not Hispanic/Latino. RESULTS: In white, nonwhite, Hispanic/Latino, and not Hispanic/Latino groups at day 29, more crisaborole- than vehicle-treated patients achieved improvements in global disease severity [Investigator's Static Global Assessment of clear/almost clear with a ≥ 2-grade improvement (white: 33.5% vs. 22.3%, nominal p < 0.001; nonwhite: 30.0% vs. 21.3%, nominal p < 0.05; Hispanic/Latino: 35.4% vs. 18.2%, nominal p < 0.01; not Hispanic/Latino: 31.3% vs. 22.8%, nominal p < 0.01)]. Crisaborole treatment also improved atopic dermatitis signs/symptoms and quality of life. Frequency of crisaborole-related adverse events was 7.1-8.5% in the pivotal trials. CONCLUSION: Across races and ethnicities, crisaborole demonstrated efficacy for the treatment of mild-to-moderate atopic dermatitis, with a low frequency of treatment-related adverse events.


Assuntos
Compostos de Boro/administração & dosagem , Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem , Dermatite Atópica/tratamento farmacológico , Fármacos Dermatológicos/administração & dosagem , Disparidades nos Níveis de Saúde , Dor/epidemiologia , Administração Cutânea , Adolescente , Adulto , Idoso , Compostos de Boro/efeitos adversos , Compostos Bicíclicos Heterocíclicos com Pontes/efeitos adversos , Criança , Pré-Escolar , Dermatite Atópica/diagnóstico , Dermatite Atópica/etnologia , Fármacos Dermatológicos/efeitos adversos , Etnicidade/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pomadas , Dor/induzido quimicamente , Dor/diagnóstico , Medição da Dor , Qualidade de Vida , Grupos Raciais/estatística & dados numéricos , Índice de Gravidade de Doença , Pele/efeitos dos fármacos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
9.
Pharm Biol ; 57(1): 432-436, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31242794

RESUMO

Context: Since there is still a great need to search for plant species with antinociceptive and anti-inflammatory activities, Diploptropis purpurea (Rich.) Amshoff (Fabaceae) is studied for the first time. Objective: This evaluates the analgesic and anti-inflammatory activities of the stem methanol extract of Diplotropis purpurea (MEDP). Material and methods: The anti-inflammatory and analgesic effects of MEDP of D. purpurea were evaluated in vivo. The antinociceptive activity was assessed in CD1 male mice were treated by oral gavage with 500 mg/kg of MEDP 30 min before submitting to acetic acid-induced abdominal writhing, hot-plate, and formalin tests. Paws oedema induced by carrageenan, histamine or serotonin were performed in male Sprague-Dawley rats to determinate the anti-inflammatory activity. Results: Oral administration of MEDP produced significant antinociceptive effects on the inflammatory phase in the formalin test [12.0 s versus 72.5 s in carboxymethyl cellulose (CMC) control group]. MEDP produced an analgesic effect in the hot-plate model, although the effect was modest compared to tramadol (40 and 60%, respectively). The oral administration of MEDP in a dose of 500 mg/kg showed maximum inhibition (75.1%) after 0.5 h in carrageenan-induced oedema, but it did not modify histamine or serotonin-induced oedemas. Discussion and conclusion: In the peripheral nociception model, acetic acid-induced abdominal writhing, the MEDP did not show a protective effect, but its analgesic effects were evident in the inflammatory phase of the formalin test and in the hot-plate model. These results show that the anti-inflammatory effect was accompanied by a reduction in the perception of painful stimuli.


Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Edema/tratamento farmacológico , Fabaceae/química , Dor/tratamento farmacológico , Extratos Vegetais/farmacologia , Animais , Edema/induzido quimicamente , Inflamação/tratamento farmacológico , Masculino , Metanol/química , Camundongos , Dor/induzido quimicamente , Medição da Dor , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Ratos , Ratos Sprague-Dawley
10.
J Am Assoc Lab Anim Sci ; 58(3): 373-379, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30857577

RESUMO

The AVMA Guidelines for the Euthanasia of Animals considers injection of barbiturates to be an acceptable method of euthanasia in rodents but states there is a potential for pain when administered intraperitoneally. This study examined the potential for pain in mice by assessing visceral pain after intraperitoneal administration and acute pain by using a paw-lick test. Male and female mice (n = 160) intraperitoneally received a euthanizing dose of sodium pentobarbital at a concentration of 5, 50, or 390 mg/mL and were observed for writhing, peritoneum-directed behaviors (PDB), loss of righting reflex, and time to death. Writhing was not observed in any animal. There was no significant difference in the number of mice exhibiting PDB or in the rate of PDB for responders receiving either saline or the 390-mg/mL solution. There was a significant treatment effect on time, with greater concentration and dose resulting in more rapid loss of righting reflex and death. In the second set of experiments, the same solutions were injected subcutaneously into the plantar hindpaw of male and female mice (n = 84). The number of responders, latency until the first lick, and the number of licks per responder were recorded. The number of responders was increased in the 50-mg/mL group; however, there was no difference in latency or the number of licks per responder. These results show that intraperitoneal injection of sodium pentobarbital for euthanasia in mice did not result in increased behavioral signs of pain, and animals lose consciousness more rapidly than the onset of pain seen in the pawlick test. Therefore, although sodium pentobarbital is capable of inducing inflammation, euthanasia through intraperitoneal administration is rapid and does not result in overt signs of pain when compared with injection of saline.


Assuntos
Hipnóticos e Sedativos/efeitos adversos , Dor/veterinária , Pentobarbital/efeitos adversos , Animais , Eutanásia Animal/métodos , Feminino , Hipnóticos e Sedativos/administração & dosagem , Injeções Intraperitoneais/efeitos adversos , Injeções Intraperitoneais/veterinária , Ciência dos Animais de Laboratório , Masculino , Camundongos , Dor/induzido quimicamente , Medição da Dor , Pentobarbital/administração & dosagem
11.
Br J Dermatol ; 180(2): 289-296, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-29947134

RESUMO

BACKGROUND: Bakuchiol is a phytochemical that has demonstrated cutaneous antiageing effects when applied topically. Early studies have suggested that bakuchiol is a functional analogue of topical retinoids, as both compounds have been shown to induce similar gene expression in the skin and lead to improvement of cutaneous photodamage. No in vivo studies have compared the two compounds for efficacy and side-effects. OBJECTIVES: To compare the clinical efficacy and side-effect profiles of bakuchiol and retinol in improving common signs of cutaneous facial ageing. METHODS: This was a randomized, double-blind, 12-week study in which 44 patients were asked to apply either bakuchiol 0·5% cream twice daily or retinol 0·5% cream daily. A facial photograph and analytical system was used to obtain and analyse high-resolution photographs of patients at 0, 4, 8 and 12 weeks. Patients also completed tolerability assessment questions to review side-effects. During study visits, a board-certified dermatologist, blinded to study group assignments, graded pigmentation and redness. RESULTS: Bakuchiol and retinol both significantly decreased wrinkle surface area and hyperpigmentation, with no statistical difference between the compounds. The retinol users reported more facial skin scaling and stinging. CONCLUSIONS: Our study demonstrates that bakuchiol is comparable with retinol in its ability to improve photoageing and is better tolerated than retinol. Bakuchiol is promising as a more tolerable alternative to retinol.


Assuntos
Fenóis/administração & dosagem , Envelhecimento da Pele/efeitos dos fármacos , Luz Solar/efeitos adversos , Vitamina A/administração & dosagem , Adulto , Método Duplo-Cego , Face , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/induzido quimicamente , Dor/epidemiologia , Medição da Dor , Fenóis/efeitos adversos , Estudos Prospectivos , Pele/efeitos dos fármacos , Pele/efeitos da radiação , Envelhecimento da Pele/efeitos da radiação , Creme para a Pele/administração & dosagem , Creme para a Pele/efeitos adversos , Pigmentação da Pele/efeitos dos fármacos , Pigmentação da Pele/efeitos da radiação , Resultado do Tratamento , Vitamina A/efeitos adversos
12.
J Pharmacol Toxicol Methods ; 88(Pt 1): 100-108, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28797764

RESUMO

Temporomandibular joint (TMJ) disorders are a group of conditions that result in TMJ pain, which frequently limits basic daily activities. Experimental models that allow the study of the mechanisms underlying these inflammatory and pain conditions are of great clinical relevance. The aim of this study was to evaluate nociception, inflammation and participation of the macrophage/microglia cells in the arthritis of the TMJ induced by two phlogistic agents. 84 rats were divided into 2 groups: Zy, which received zymosan intra-articularly, or Cg, which received carrageenan intra-articularly. Mechanical nociception, total leukocyte influx to the synovial fluid and histopathological analyses were evaluated in the TMJ. The participation of macrophage/microglia located in trigeminal ganglia (TG) and in the subnucleus caudalis (V-SnC) was assessed immunohistochemically. Both agents induced mechanical hyperalgesia 6h after the induction, but a more persistent algesic state was perceived in the Cg group, which lasted for 120h. Even though both groups presented increased leukocyte influx, the Zy-group presented a more intense influx. Zymosan recruited resident macrophage in the trigeminal ganglia 24h after the injection. In the V-SnC, the group Cg presented a more prolonged immunolabeling pattern in comparison with the group Zy. It can be concluded that zymosan induced a more intense infiltrate and peripheral nervous changes, while Cg lead to a moderate TMJ inflammation with prominent changes in the V-SnC.


Assuntos
Artrite/fisiopatologia , Hiperalgesia/fisiopatologia , Medição da Dor/métodos , Dor/fisiopatologia , Transtornos da Articulação Temporomandibular/fisiopatologia , Animais , Artrite/induzido quimicamente , Artrite/diagnóstico , Artrite/patologia , Carragenina/farmacologia , Modelos Animais de Doenças , Hiperalgesia/induzido quimicamente , Hiperalgesia/patologia , Injeções Intra-Articulares , Macrófagos/efeitos dos fármacos , Macrófagos/patologia , Masculino , Microglia/efeitos dos fármacos , Microglia/patologia , Nociceptividade/efeitos dos fármacos , Nociceptividade/fisiologia , Dor/induzido quimicamente , Dor/patologia , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Transtornos da Articulação Temporomandibular/induzido quimicamente , Transtornos da Articulação Temporomandibular/patologia , Gânglio Trigeminal/citologia , Gânglio Trigeminal/efeitos dos fármacos , Zimosan/farmacologia
13.
Eur J Contracept Reprod Health Care ; 22(3): 207-211, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28447484

RESUMO

OBJECTIVES: Although medical abortion with home use of misoprostol has been shown to be safe and acceptable, there are few data about the experience of pain during the procedure. The aims of this study were to assess the intensity of pain associated with home use of misoprostol for medical abortion and to identify variables associated with severe pain. METHODS: This was an observational study using an anonymous web-based questionnaire in patients having a medical abortion at home in France between 1 December 2013 and 30 April 2014. RESULTS: The questionnaire was completed by 232 women and the results of 193 were retained for analysis. The average pain score was 5.6 on a 10 point scale. A pain score ≥6 was rated as severe and was reported by 105 patients (54%). Nulliparity (odds ratio [OR] 4.10; 95% confidence interval [CI] 2.04, 8.22; p < .0001), lack of choice regarding the method of abortion (OR 2.32; 95% CI 1.13, 4.78; p = .0218) and lack of information about the level of pain associated with the procedure (OR 3.27; 95% CI 1.09, 9.74; p = .0334) were significantly correlated with severe pain. Analgesic prescriptions were very heterogeneous. CONCLUSIONS: Pain remains the main side effect of medical abortion. More studies are needed on pain assessment and the effectiveness of analgesic treatments in women using misoprostol at home for medical abortion, in order to improve their care and improve evidence-based guidelines.


Assuntos
Abortivos não Esteroides/efeitos adversos , Aborto Induzido/efeitos adversos , Misoprostol/efeitos adversos , Medição da Dor , Dor/induzido quimicamente , Abortivos não Esteroides/administração & dosagem , Aborto Induzido/métodos , Adulto , Analgésicos/uso terapêutico , Feminino , França , Humanos , Misoprostol/administração & dosagem , Dor/tratamento farmacológico , Gravidez , Autoadministração , Inquéritos e Questionários , Adulto Jovem
14.
Acta Anaesthesiol Scand ; 60(7): 842-51, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26991481

RESUMO

BACKGROUND: Assessment and reporting of adverse events (AEs) in studies of perioperative interventions is critical given the potential for unintended and preventable iatrogenic morbidity and mortality. This focused review evaluated the quality of AE assessment and reporting in acute post-operative pain treatment trials. Since older analgesics (e.g., opioids, NSAIDs) already have a well-characterized safety profile, we concentrated on trials of pregabalin and gabapentin as a representative sample of studies where the perioperative safety profile was relatively unknown. METHODS: We reviewed primary reports of trials of pregabalin and gabapentin for treatment of acute post-operative pain for: (1) adherence to the 10 recommendations from the 'CONSORT Extension for Harms,' (2) AE assessment method, (3) timing of AE assessment and reporting, and (4) assessment and reporting of AE severity. RESULTS: We identified 31 trials of pregabalin and 59 of gabapentin. The median number of CONSORT harms recommendations that were satisfied was 7 of 10. The most common (41%) method of AE assessment was direct questioning about specific AEs by investigators. However, AE assessment method was not described in 18% of trials. AE assessments were reported for specified perioperative time points in only 24% of trials. Of greatest concern, no AE data were reported whatsoever in 8 of the included publications. CONCLUSIONS: Considerable widespread improvements are needed in AE reporting for post-operative pain treatment trials. In addition to heightened awareness among clinical investigators, mandatory journal editorial policies may further facilitate improvements in safety assessment and reporting.


Assuntos
Analgésicos , Pregabalina , Humanos , Dor/induzido quimicamente , Relatório de Pesquisa
15.
CNS Neurosci Ther ; 22(2): 88-101, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26663896

RESUMO

While acute inflammation is a natural physiological response to tissue injury or infection, chronic inflammation is maladaptive and engenders a considerable amount of adverse pain. The chemical mediators responsible for tissue inflammation act on nociceptive nerve endings to lower neuronal excitation threshold and sensitize afferent firing rate leading to the development of allodynia and hyperalgesia, respectively. Animal models have aided in our understanding of the pathophysiological mechanisms responsible for the generation of chronic inflammatory pain and allowed us to identify and validate numerous analgesic drug candidates. Here we review some of the commonly used models of skin, joint, and gut inflammatory pain along with their relative benefits and limitations. In addition, we describe and discuss several behavioral and electrophysiological approaches used to assess the inflammatory pain in these preclinical models. Despite significant advances having been made in this area, a gap still exists between fundamental research and the implementation of these findings into a clinical setting. As such we need to characterize inherent pathophysiological pathways and develop new endpoints in these animal models to improve their predictive value of human inflammatory diseases in order to design safer and more effective analgesics.


Assuntos
Modelos Animais de Doenças , Medição da Dor/métodos , Dor/diagnóstico , Animais , Adjuvante de Freund/toxicidade , Humanos , Inflamação/induzido quimicamente , Inflamação/diagnóstico , Inflamação/metabolismo , Dor/induzido quimicamente , Dor/metabolismo
16.
Physiol Behav ; 149: 229-38, 2015 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-26074204

RESUMO

INTRODUCTION: Assessment of oral motor behavior in a mouse is challenging due to the lack of currently available techniques that are non-invasive and allow long-term assessment in a home cage environment. The purpose of this study was to evaluate incising behavior using mouse chow attached to a three-dimensional force transducer that was mounted on the existing home cage. In addition, a persistent hyperalgesia condition was introduced to evaluate the sensitivity of the technique to identify incising behavioral changes. METHODS: Incising activity of CD-1 male and female mice (n=48) was evaluated over a 24 hour recording session during four baseline and six longitudinal hyperalgesia assessment sessions using custom written software. A pre-clinical persistent pain model was used to induce hyperalgesia in the masseter muscle by repetitive acidic saline injections. Sex and age differences were evaluated for multiple incising variables during both light and dark cycles during baseline and hyperalgesia conditions. RESULTS: Significant sex differences were found for multiple incising variables but not for age. Discrete incising frequencies were identified in the range of 4.6-10.4 Hz and were reproducibly found in both female and male mice. A significant shift to lower incising frequencies was observed after repetitive acidic saline injections compared to neutral saline injections. This shift to lower frequencies of incising returned to baseline levels after approximately four weeks but was statistically longer in female compared to male mice. Significant differences were also found for chow intake (reduced) and weight change during the hyperalgesia condition. No significant differences were found for total number of incisions or number of incising episodes per day or incising force. CONCLUSIONS: The findings from this study support the use of recording three dimensional incising forces as a sensitive measure of incising behavior. This novel technique allowed the identification of specific incising variables that were differentially affected in female and male mice during a persistent hyperalgesia. The data were collected in the home cage environment with minimal bias such as experimenter interaction. Similar to other dental pain studies, mice were able to maintain normal incising activity levels per day (total incisions, total number of incising episodes) even in the presence of hyperalgesia.


Assuntos
Meio Ambiente , Etologia , Hiperalgesia/etiologia , Hiperalgesia/patologia , Músculo Masseter/fisiopatologia , Mastigação/fisiologia , Ácidos/toxicidade , Animais , Peso Corporal/efeitos dos fármacos , Peso Corporal/fisiologia , Modelos Animais de Doenças , Ingestão de Alimentos , Feminino , Masculino , Camundongos , Dor/induzido quimicamente , Dor/complicações , Medição da Dor , Limiar da Dor , Caracteres Sexuais , Cloreto de Sódio/administração & dosagem , Fatores de Tempo
17.
Oncol Nurs Forum ; 41(5): E282-9, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25158665

RESUMO

PURPOSE/OBJECTIVES: To describe the experience of chemotherapy-induced premature menopause (CIPM) among Latinas, explore how CIPM was assimilated into the breast cancer experience, and relate measured acculturation levels to the CIPM experience. RESEARCH APPROACH: Interpretive descriptive method from a feminist inquiry lens. SETTING: Telephone interviews with participants from 12 states in the United States. PARTICIPANTS: 20 Latinas who experienced CIPM after treatment for breast cancer. METHODOLOGIC APPROACH: In-depth interviews and the Brief Acculturation Scale for Hispanics were used to elicit data, with interpreter assistance as needed. FINDINGS: One overarching theme, Bigger Than Menopause, and three subthemes, Experiencing Menopause, Ever-Changing Landscape, and Working Through the Experience, were found. PARTICIPANTS' ability to assimilate CIPM into the breast cancer experience was affected by the magnitude of physiologic and psychosocial effects, access to health care, information and support, sense of control, and acculturation level. CONCLUSIONS: The CIPM experience for Latinas with breast cancer is multifaceted, with less acculturated Latinas facing multiple barriers in accessing health care, treatment, information, and support. INTERPRETATION: PARTICIPANTS described CIPM as part of a larger context that included physiologic and psychosocial effects and affected participants' ability to assimilate CIPM into the breast cancer experience. The impact of low acculturation and barriers experienced were elucidated as factors associated with assimilating CIPM into the breast cancer experience.


Assuntos
Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Hispânico ou Latino , Menopausa Precoce/etnologia , Insuficiência Ovariana Primária/induzido quimicamente , Aculturação , Adulto , Atitude Frente a Saúde , Neoplasias da Mama/complicações , Neoplasias da Mama/psicologia , Cultura , Feminino , Feminismo , Filgrastim , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Acessibilidade aos Serviços de Saúde , Necessidades e Demandas de Serviços de Saúde , Disparidades em Assistência à Saúde , Hispânico ou Latino/psicologia , Humanos , Menopausa Precoce/psicologia , Pessoa de Meia-Idade , Dor/induzido quimicamente , Educação de Pacientes como Assunto , Polietilenoglicóis , Insuficiência Ovariana Primária/etnologia , Insuficiência Ovariana Primária/psicologia , Pesquisa Qualitativa , Proteínas Recombinantes/efeitos adversos , Fatores Socioeconômicos , Avaliação de Sintomas , Telefone , Estados Unidos , Aumento de Peso/efeitos dos fármacos
18.
Catheter Cardiovasc Interv ; 84(6): 1019-25, 2014 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-24478190

RESUMO

OBJECTIVES: To assess and compare the intra-arterial injection-associated discomfort of iodinated contrast media (CM) and the impact on diagnostic efficacy in diabetics with critical limb ischemia (CLI). BACKGROUND: Arterial revascularization is a mainstay in patients with CLI. Previous diagnostic angiography is a crucial step that can be affected by CM injection discomfort compromising the revascularization results, and it could vary related to the CM agents. METHODS: One hundred forty-eight patients received Iodixanol 270 mg iodine pro ml or Ioversol 320 mg iodine pro ml in a prospective, double-blind, randomized, parallel-group clinical trial. Injection-associated discomfort was assessed by Visual Analogic Scale (VAS). Diagnostic efficacy and safety up to 1 week were evaluated. RESULTS: The incidence of pain has been around 50% of the all population in study, with lesser incidence of pain (25.7% vs 74.3%; P < 0.0001) and of heat sensation (55.4% vs 85.1%; P < 0.0001), after Iodixanol than after Ioversol injection. Discomfort mean score, according to VAS assessment, was less in the Iodixanol group (8.1 ± 15.3) than in the Ioversol group (36.0 ± 29.7), after first injection (P < 0.001) and for all injections (P < 0.001). A significant difference was also observed in favor of Iodixanol (P < 0.001), respect to mean score of discomfort and heat sensation, assessed by the operators after all the CM injections. CONCLUSIONS: Iodixanol caused less frequent and severe discomfort, characterized as pain and heat during intra-arterial administration compared with Ioversol. The pain severity is tightly related to image and diagnosis quality with an impact on the patients for additional injections and larger CM volumes.


Assuntos
Meios de Contraste/efeitos adversos , Angiopatias Diabéticas/diagnóstico por imagem , Isquemia/diagnóstico por imagem , Extremidade Inferior/irrigação sanguínea , Dor/induzido quimicamente , Doença Arterial Periférica/diagnóstico por imagem , Ácidos Tri-Iodobenzoicos/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Meios de Contraste/administração & dosagem , Estado Terminal , Angiopatias Diabéticas/terapia , Método Duplo-Cego , Procedimentos Endovasculares , Feminino , Humanos , Incidência , Injeções Intra-Arteriais , Isquemia/terapia , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Dor/diagnóstico , Dor/epidemiologia , Medição da Dor , Doença Arterial Periférica/terapia , Estudos Prospectivos , Radiografia , Fatores de Tempo , Ácidos Tri-Iodobenzoicos/administração & dosagem
19.
Int J Gynecol Cancer ; 23(8): 1520-7, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24257567

RESUMO

PURPOSE: In this prospective study, symptoms were assessed in patients with locally advanced cervical cancer undergoing concurrent chemoradiotherapy (CTRT) with either weekly cisplatin (WP) or every-3-week cisplatin/5-fluorouracil (PF). MATERIALS AND METHODS: Patients with 1994 International Federation of Gynecology and Obstetrics stage IIB to IVA disease, biopsy-proven involved pelvic nodes, or gross tumor size greater than 5 cm were eligible. Patients requiring paraaortic radiotherapy were excluded. With the use of a modified Edmonton Symptom Assessment Scale, patients reported symptom severity on an 11-point scale 3 times per week during CTRT and at the first follow-up. The Wilcoxon rank sum test and multilevel mixed-effects linear regression were used to assess the effect of chemotherapy regimen on symptoms. RESULTS: Among the 52 patients included in the final analysis, 37 received WP, 13 received PF, and 2 received 1 cycle of PF followed by WP. Overall compliance with completion of Edmonton Symptom Assessment Scale questionnaires was 75%. There were significant differences in symptom scores for well-being, anorexia, fatigue, diarrhea, and stomatitis favoring the WP regimen. All symptoms except diarrhea were stable and of low intensity in the WP group. In the PF group, symptoms had a cyclical pattern with an initial rise followed by a gradual fall during the 3-week period after chemotherapy. For the 29 patients (56%) who completed the follow-up surveys, scores for all symptoms improved to baseline levels 4 to 6 weeks after treatment. CONCLUSIONS: This analysis provides important patient-reported data regarding the rates and timing of acute symptoms during CTRT that can help clinicians better manage symptoms that impact patients' quality of life.


Assuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Carcinoma/tratamento farmacológico , Cisplatino/efeitos adversos , Fluoruracila/efeitos adversos , Neoplasias do Colo do Útero/tratamento farmacológico , Adulto , Idoso , Anorexia/induzido quimicamente , Antimetabólitos Antineoplásicos/administração & dosagem , Ansiedade/induzido quimicamente , Carcinoma/radioterapia , Quimiorradioterapia/efeitos adversos , Cisplatino/administração & dosagem , Depressão/induzido quimicamente , Diarreia/induzido quimicamente , Fadiga/induzido quimicamente , Feminino , Fluoruracila/administração & dosagem , Humanos , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Dor/induzido quimicamente , Estudos Prospectivos , Estomatite/induzido quimicamente , Neoplasias do Colo do Útero/radioterapia , Adulto Jovem
20.
J Pain ; 14(6): 628-37, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23578956

RESUMO

UNLABELLED: Neurofibromatosis type 1 (NF1) is characterized primarily by tumor formation in the nervous system, but patients report other neurological complications including pain and itch. Individuals with NF1 harbor 1 mutated NF1 allele causing heterozygous expression in all of their cells. In mice, Nf1 heterozygosity leads to hyperexcitability of sensory neurons and hyperproliferation of mast cells, both of which could lead to increased hypersensitivity and scratching in response to noxious and pruritic stimuli. To determine whether Nf1 heterozygosity may increase pain and itch behaviors independent of secondary effects of tumor formation, we used mice with a targeted, heterozygous Nf1 gene deletion (Nf1±) that lack tumors. Nf1± mice exhibited normal baseline responses to thermal and mechanical stimuli. Moreover, similar to wild-type littermates, Nf1± mice developed inflammation-induced heat and mechanical hypersensitivity, capsaicin-induced nocifensive behavior, histamine-dependent or -independent scratching, and chronic constriction injury-induced cold allodynia. However, Nf1± mice exhibited an attenuated first phase of formalin-induced spontaneous behavior and expedited resolution of formalin-induced heat hypersensitivity. These results are not consistent with the hypothesis that Nf1 heterozygosity alone is sufficient to increase pain and itch sensation in mice, and they suggest that additional mechanisms may underlie reports of increased pain and itch in NF1 patients. PERSPECTIVE: This study assessed whether Nf1 heterozygosity in mice increased hypersensitivity and scratching following noxious and pruritic stimuli. Using Nf1± mice lacking tumors, this study finds no increases in pain or itch behavior, suggesting that there is no predisposition for either clinical symptom solely due to Nf1 heterozygosity.


Assuntos
Neurofibromatose 1/complicações , Dor/diagnóstico , Dor/etiologia , Prurido/diagnóstico , Prurido/etiologia , Animais , Capsaicina/efeitos adversos , Cloroquina/toxicidade , Constrição , Modelos Animais de Doenças , Lateralidade Funcional , Histamina/toxicidade , Hiperalgesia/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neurofibromatose 1/genética , Neurofibromatose 1/metabolismo , Dor/induzido quimicamente , Medição da Dor , Limiar da Dor/fisiologia , Prurido/induzido quimicamente , p-Metoxi-N-metilfenetilamina/toxicidade
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