RESUMEN
BACKGROUND: Preclinical data suggest that combined gamma-tocotrienol with pentoxifylline ameliorates radiotherapy-induced gastrointestinal damage. AIM: To test whether gastrointestinal symptoms arising after radiotherapy, and persisting after maximal medical therapy, can be improved using Tocovid SupraBio 200 mg and pentoxifylline 400 mg orally twice daily for one year. Patients stratified by severity of symptoms, and randomised to active treatment or matched placebo were assessed after 12 months. The primary end point was improvement in gastrointestinal symptoms measured using the Inflammatory Bowel Disease Questionnaire, bowel subset score. Changes in bio-markers of fibrosis were assessed. RESULTS: 62 patients, median age 66, 34(55%) treated for prostate, 21(34%) gynaecological, 6(10%) anal and one(1%) rectal cancer were recruited; 40(65%) randomised to treatment, 22(35%) to placebo, 39 months (median) after radiotherapy completion. Gamma tocotrienol was not detected in serum in 41% of treated patients, despite good compliance with study medication. Treatment was completed in 28(70%) and 17(77%) patients in the treatment and placebo groups respectively. No improvement in symptom scores nor in quality of life was identified. Thirteen serious adverse events occurred. A transient ischaemic attack, was possibly related to pentoxifylline, others were assessed as unlikely to be related to treatment. Levels of EGF, PDGF and FGF were significantly reduced and consistent trends in reduced inflammation were seen during treatment but were not sustained once treatment ended. SUMMARY: This single centre study closed prematurely and therefore data interpretation is of necessity limited. No clinical benefit was demonstrated. However, biochemical data suggest that this intervention does have anti-inflammatory and anti-fibrotic effects.
Asunto(s)
Neoplasias Pélvicas , Pentoxifilina , Tocotrienoles , Método Doble Ciego , Humanos , Masculino , Neoplasias Pélvicas/radioterapia , Pentoxifilina/uso terapéutico , Calidad de Vida , Resultado del TratamientoRESUMEN
With the global COVID-19 pandemic, many public health services were severely disrupted. Estimating the overall health effects of this is difficult as most disease surveillance systems have also been substantially affected during the pandemic. For some diseases, this effect is mitigated by the methods enacted to fight the pandemic, such as use of facial coverings, social distancing and quarantine, but measles is infectious to the degree that this mitigation is likely to be limited. Thus, outbreaks and an increase in global measles mortality are expected. However, the severity of this impact is not yet known. In early 2020, a study by Roberton and colleagues predicted an additional 12,360 to 37,920 deaths in children under-five worldwide from measles over the coming year based on three potential levels of vaccine coverage reductions ranging from 18.5 to 51.9%. Our study investigates the magnitude of the increase in measles mortality due to decreased vaccine coverage because of COVID-19, based on official estimates of 2020 measles vaccine coverage from WHO/UNICEF released in July 2021. Using the Lives Saved Tool (LiST), an interventions modeling program, we estimated measles mortality for low/middle income countries (LMICs) based on the 2020 WHO/UNICEF estimates of national immunization coverage (WUENIC). Because these calculations use actual reported vaccine coverage, they provide a more accurate picture of measles mortality related to COVID-19 disruptions in 2020. Using the WUENIC data, LiST predicted fewer additional deaths in 2020 due to decreases in measles vaccine coverage than estimations made by LiST based on Roberton, 2020 due to remarkable recovery efforts by national immunization programmes in the second half of 2020.
RESUMEN
PURPOSE: Hydrogen peroxide (H2O2) plays a vital role in normal cellular processes but at supraphysiological concentrations causes oxidative stress and cytotoxicity, a property that is potentially exploitable for the treatment of cancer in combination with radiation therapy (RT). We report the first phase 1 trial testing the safety and tolerability of intratumoral H2O2 + external beam RT as a novel combination in patients with breast cancer and exploratory plasma marker analyses investigating possible mechanisms of action. METHODS AND MATERIALS: Twelve patients with breast tumors ≥3 cm (surgically or medically inoperable) received intratumoral H2O2 with either 36 Gy in 6 twice-weekly fractions (n = 6) or 49.5 Gy in 18 daily fractions (n = 6) to the whole breast ± locoregional lymph nodes in a single-center, nonrandomized study. H2O2 was mixed in 1% sodium hyaluronate gel (final H2O2 concentration 0.5%) before administration to slow drug release and minimize local discomfort. The mixture was injected intratumorally under ultrasound guidance twice weekly 1 hour before RT. The primary endpoint was patient-reported maximum intratumoral pain intensity before and 24 hours postinjection. Secondary endpoints included grade ≥3 skin toxicity and tumor response by ultrasound. Blood samples were collected before, during, and at the end of treatment for cell-death and immune marker analysis. RESULTS: Compliance with H2O2 and RT was 100%. Five of 12 patients reported moderate pain after injection (grade 2 Common Terminology Criteria for Adverse Events v4.02) with median duration 60 minutes (interquartile range, 20-120 minutes). Skin toxicity was comparable to RT alone, with maintained partial/complete tumor response relative to baseline in 11 of 12 patients at last follow-up (median 12 months). Blood marker analysis highlighted significant associations of TRAIL, IL-1ß, IL-4, and MIP-1α with tumor response. CONCLUSIONS: Intratumoral H2O2 with RT is well tolerated with no additional toxicity compared with RT alone. If efficacy is confirmed in a randomized phase 2 trial, the approach has potential as a cost-effective radiation response enhancer in multiple cancer types in which locoregional control after RT alone remains poor.
Asunto(s)
Neoplasias de la Mama/terapia , Quimioradioterapia/métodos , Peróxido de Hidrógeno/administración & dosificación , Oxidantes/administración & dosificación , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/sangre , Neoplasias de la Mama/sangre , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Neoplasias de la Mama Masculina/sangre , Neoplasias de la Mama Masculina/patología , Neoplasias de la Mama Masculina/terapia , Quimiocina CCL3/sangre , Fraccionamiento de la Dosis de Radiación , Femenino , Humanos , Ácido Hialurónico/administración & dosificación , Peróxido de Hidrógeno/efectos adversos , Inyecciones Intralesiones/efectos adversos , Inyecciones Intralesiones/métodos , Interleucina-1beta/sangre , Interleucina-4/sangre , Irradiación Linfática , Masculino , Persona de Mediana Edad , Oxidantes/efectos adversos , Dimensión del Dolor , Dolor Asociado a Procedimientos Médicos/inducido químicamente , Radiodermatitis/patología , Piel/efectos de los fármacos , Ligando Inductor de Apoptosis Relacionado con TNF/sangre , Ultrasonografía Intervencional , Viscosuplementos/administración & dosificaciónRESUMEN
In the genetic counselling setting it is not uncommon for a client and genetic counsellor to be faced with uncertainty surrounding the exact diagnostic label to be assigned to the client's symptoms. The huge range of possible conditions/syndromes and the lack of definitive evidence available often combine to create diagnostic uncertainty or non-diagnosis (the assessment given where a genetic diagnosis of the client's symptoms cannot be confirmed at that point). This paper aims to explore the interactional management and negotiation of diagnostic uncertainty in the genetic counselling clinic in the UK. Through the application of discourse analytic tools (including reported speech, contrast and hedging) to transcripts of actual clinical interactions, the participants' use of evidence, and professional and client expertise, are examined and found to be key in the negotiation of diagnostic uncertainty. The complete data set for this research consists of transcripts of 18 clinical encounters between genetic counsellor and client. Two client cases are identified and analysed in detail in order to follow the pattern of interactional management of diagnostic uncertainty throughout the whole interaction. The findings suggest that, unlike other medical settings, clients within genetic counselling are able to actively participate in talk about diagnosis allowing, for the extent of non-diagnosis to be negotiated. This is particularly so during two moments in the interaction: the beginning of the clinic where the agenda is set, and towards the end of the clinic when a form of diagnostic assessment must be made. By providing an insight into the problematic interactional activity of giving a non-diagnosis this paper can contribute to discussions on genetic counselling practice. The analysis in this paper demonstrates how a genetic counsellor can manage the balance between accurate information-giving and empathy towards individual client needs for a diagnosis.