Ir(III) Half-Sandwich Photosensitizers with a π-Expansive Ligand for Efficient Anticancer Photodynamic Therapy.

One approach to reduce the side effects of chemotherapy in cancer treatment is photodynamic therapy (PDT), which allows spatiotemporal control of the cytotoxicity. We have used the strategy of coordinating π-expansive ligands to increase the excited state lifetimes of Ir(III) half-sandwich complexes in order to facilitate the generation of 1O2. We have obtained derivatives of formulas [Cp*Ir(C∧N)Cl] and [Cp*Ir(C∧N)L]BF4 with different degrees of π-expansion in the C∧N ligands. Complexes with the more π-expansive ligand are very effective photosensitizers with phototoxic indexes PI > 2000. Furthermore, PI values of 63 were achieved with red light. Time-dependent density functional theory (TD-DFT) calculations nicely explain the effect of the π-expansion. The complexes produce reactive oxygen species (ROS) at the cellular level, causing mitochondrial membrane depolarization, cleavage of DNA, nicotinamide adenine dinucleotide (NADH) oxidation, as well as lysosomal damage. Consequently, cell death by apoptosis and secondary necrosis is activated. Thus, we describe the first class of half-sandwich iridium cyclometalated complexes active in PDT.

Ferrozoles: Ferrocenyl derivatives of letrozole with dual effects as potent aromatase inhibitors and cytostatic agents.

In the treatment of hormone-dependent cancers, aromatase inhibitors (AI) are receiving increased attention due to some undesirable effects such as the risk of endometrial cancer and thromboembolism of SERMs (selective estrogen receptor modulators). Letrozole is the most active AI with 99% aromatase inhibition. Unfortunately, this compound also exhibits some adverse effects such as hot flashes and fibromyalgias. Therefore, there is an urgent need to explore new types of AIs that retain the same-or even increased-antitumor ability. Inspired by the letrozole structure, a set of new derivatives has been synthesized that include a ferrocenyl moiety and different heterocycles. The derivative that contains a benzimidazole ring, namely compound 6, exhibits a higher aromatase inhibitory activity than letrozole and it also shows potent cytostatic behavior when compared to other well-established aromatase inhibitors, as demonstrated by dose-response, cell cycle, apoptosis and time course experiments. Furthermore, 6 promotes the inhibition of cell growth in both an aromatase-dependent and -independent fashion, as indicated by the study of A549 and MCF7 cell lines. Molecular docking and molecular dynamics calculations on the interaction of 6 or letrozole with the aromatase binding site revealed that the ferrocene moiety increases the van der Waals and hydrophobic interactions, thus resulting in an increase in binding affinity. Furthermore, the iron atom of the ferrocene fragment can form a metal-acceptor interaction with a propionate fragment, and this results in a stronger coupling with the heme group-a possibility that is consistent with the strong aromatase inhibition of 6.

Complications of Small Aperture Intracorneal Inlays: A Literature Review.

Presbyopia can be defined as the refractive state of the eye in which, due to a physiological decrease in the ability to accommodate, it is not possible to sustain vision without fatigue in a prolonged manner, along with difficulty focusing near vision. It is estimated that its prevalence in 2030 will be approximately 2.1 billion people. Corneal inlays are an alternative in the correction of presbyopia. They are implanted beneath a laser-assisted in situ keratomileusis (LASIK) flap or in a pocket in the center of the cornea of the non-dominant eye. The purpose of this review is to provide information about intraoperative and postoperative KAMRA inlay complications in the available scientific literature. A search was conducted on PubMed, Web of Science, and Scopus with the following search strategy: ("KAMRA inlay" OR "KAMRA" OR "corneal inlay pinhole" OR "pinhole effect intracorneal" OR "SAICI" OR "small aperture intracorneal inlay") AND ("complication" OR "explantation" OR "explanted" OR "retired"). The bibliography consulted shows that the insertion of a KAMRA inlay is an effective procedure that improves near vision with a slight decrease in distance vision. However, postoperative complications such as corneal fibrosis, epithelial iron deposits, and stromal haze are described.

[Referral criteria to clinical genetics from primary care: Consensus document]. / Criterios de derivación a genética clínica desde Atención Primaria. Documento de consenso.

INTRODUCTION: Primary care (PC) is the first contact between the patient and the doctor, so it is essential to be clear about the criteria for suspecting a genetic disease and where it should be referred for study. MATERIAL AND METHODS: Four scientific societies: the Spanish Society of Family and Community Medicine (semFYC), the Spanish Association of Human Genetics (AEGH), the Spanish Association of Pediatrics (AEP) and the Spanish Society of Medical Oncology (SEOM), have reviewed the criteria for referral to the clinical genetics services of the different published guidelines with the purpose of define the recommendations for PC. CONCLUSIONS: With this consensus document, the PC doctor and pediatrician will know when, how and where to refer their patients with hereditary and/or genetic pathology to clinical genetics services.

Elimination of punitive outcomes and criminalization of medical errors.

PURPOSE OF REVIEW: The penalization of error in the health field continues to be one of the main barriers in the notification, analysis and proposals for measures to improve adverse events. Strategies should be established in order to develop a nonpunitive culture with the sole purpose of learning from mistakes and improving patient safety. RECENT FINDINGS: Strategies are established for the development of a nonpunitive culture, such as promoting confidentiality and data protection in the notification and analysis of adverse events. SUMMARY: Despite education, improvements in quality and safety in healthcare, mistakes will undoubtedly occur. The creation of a protected, blame-free environment that promotes systematic reporting of adverse events will provide valuable information for preventive work and the desired improvement in patient and health team safety.

Physician treatment preferences for relapsed/refractory multiple myeloma: a discrete choice experiment.

Aim: This study aimed to assess physician preferences for later lines (third to fifth) of therapy in patients with relapsed/refractory multiple myeloma (RRMM) in the USA. Materials & methods: Factors relevant to physicians' treatment preferences for RRMM were identified from a literature search and refined in a qualitative phase. Preferences were quantitatively assessed using a discrete choice experiment. Physicians (n = 227) made choices regarding treatment scenarios for RRMM. Results: Efficacy had the highest mean relative importance, with overall survival valued as most important when making treatment decisions for patients with RRMM. Reduced incidences of keratopathy and thrombocytopenia had similar relative importance in later-line treatment. Conclusion: Greater understanding of physicians' criteria for clinical decision-making may help inform wider adoption of new treatments.

When deciding which treatment patients with relapsed or refractory multiple myeloma should receive, physicians have to weigh the benefits of each treatment against the risk of side effects. This study required physicians to complete a survey on aspects involved in their treatment decisions and identified those of highest importance. Physicians chose patient survival as the most important factor and minimization of side effects as less important considerations. Reducing patients' risk of developing corneal conditions or low platelet (a type of blood cell) count were of equal importance to doctors. Understanding physicians' treatment preferences and the reasons behind them will help identify gaps in education about new therapies as they become available.

Microglia at the Crossroads of Pathogen-Induced Neuroinflammation.

Microglia are the resident tissue macrophages of the central nervous system (CNS). Recent findings point out that in the steady state the major role of microglia, is to instruct and regulate the correct function of the neuronal networks and different components of the neurovascular unit in the adult CNS, while providing immune surveillance. Paradoxically, during CNS infection immune activation of microglia generates an inflammatory milieu that contributes to the clearance of the pathogen but can, in the process, harm nearby cells of CNS. Most of the knowledge about the harmful effects of activated microglia on CNS has arisen from studies on neurodegenerative diseases. In this review we will focus on the beneficial role and detrimental functions of microglial cells on the neighboring cells of the CNS upon infection.

Mesenchymal Stem Cell Therapy Awareness, Knowledge, and Use for the Treatment of Fistulizing Crohn's Disease: An International Survey Among Gastroenterologists and Colorectal Surgeons.

INTRODUCTION: Mesenchymal stem (or stromal) cells are a promising therapy for the treatment of various inflammatory and autoimmune diseases. This study aimed to understand awareness, knowledge, and perception of mesenchymal stem cells among gastroenterologists and colorectal surgeons, with particular focus on the perianal fistulizing Crohn's disease indication. METHODS: A web-based questionnaire was distributed to currently practicing and registered gastroenterologists and colorectal surgeons across 15 countries in North America, Europe, and Asia Pacific. RESULTS: Of 146 clinicians, 115 (79%) were aware of mesenchymal stem cells. The majority were moderately to largely interested in this therapy (87%), willing to use it in patients with perianal fistulizing Crohn's disease (82%), and believed it addresses unmet needs for these patients (93%). However, most responders reported having limited or no knowledge of this therapy (64%) or its efficacy (51%), safety (53%), and mechanism of action (65%) in perianal fistulizing Crohn's disease. Many clinicians (46%) also expressed concerns about using this therapy in these patients. Attending discussions and presentations on mesenchymal stem cells and seeing more patients with Crohn's disease were associated with increased awareness (both P < 0.001). CONCLUSIONS: Many clinicians demonstrated an interest in mesenchymal stem cells in general and a willingness to use them to treat perianal fistulizing Crohn's disease, but this survey showed suboptimal knowledge of what mesenchymal stem cells are and how they work in this indication. This may explain clinicians' concerns about use of this therapy and calls out for education activities.

Targets, Mechanisms and Cytotoxicity of Half-Sandwich Ir(III) Complexes Are Modulated by Structural Modifications on the Benzazole Ancillary Ligand.

Cancers are driven by multiple genetic mutations but evolve to evade treatments targeting specific mutations. Nonetheless, cancers cannot evade a treatment that targets mitochondria, which are essential for tumor progression. Iridium complexes have shown anticancer properties, but they lack specificity for their intracellular targets, leading to undesirable side effects. Herein we present a systematic study on structure-activity relationships of eight arylbenzazole-based Iridium(III) complexes of type [IrCl(Cp*)], that have revealed the role of each atom of the ancillary ligand in the physical chemistry properties, cytotoxicity and mechanism of biological action. Neutral complexes, especially those bearing phenylbenzimidazole (HL1 and HL2), restrict the binding to DNA and albumin. One of them, complex 1[C,NH-Cl], is the most selective one, does not bind DNA, targets exclusively the mitochondria, disturbs the mitochondria membrane permeability inducing proton leak and increases ROS levels, triggering the molecular machinery of regulated cell death. In mice with orthotopic lung tumors, the administration of complex 1[C,NH-Cl] reduced the tumor burden. Cancers are more vulnerable than normal tissues to a treatment that harnesses mitochondrial dysfunction. Thus, complex 1[C,NH-Cl] characterization opens the way to the development of new compounds to exploit this vulnerability.

Evaluación de los factores de riesgo vasculares convencionales en pacientes con ataque cerebrovascular isquémico en un hospital de Uruguay / Evaluation of conventional vascular risk factors in patients with ischemic cerebrovascular attack in a hospital in Uruguay

Resumen El ataque cerebrovascular es la segunda causa de muerte en adultos en el mundo occidental. Con el objetivo de conocer el estado actual de los factoresde riesgo vasculares convencionales (FRC) para el ataque cerebrovascularisquémico (ACVi) -hipertensión arterial (HTA), dislipemia, diabetes mellitus (DM), tabaquismo, arritmias, antecedentes de ataque cerebrovascular (ACV),edad y sexo- y de valorar el cumplimiento de las medidas de prevención, se analizó la distribución de éstos según etiología y topografía en un hospital público de Montevideo, Uruguay. Se estudiaron 114 pacientes de 25-97 años con ACVi. Se aplicó un protocolo para recolectar variables afines a la investigación utilizando criterios del Trial of Org 10172 in Acute Stroke Treatment y Oxfordshire Community Stroke Project para la clasificación etiológica y topográfica respectivamente. Se consideró la presencia de HTA y DM según criterios dela Organización Mundial de la Salud, de dislipemia según el Adult Treatment Panel III, de tabaquismo por haber fumado como mínimo un cigarrillo/día en el último trimestre y de arritmia a la alteración de la frecuencia cardíaca. Se observó un aumento de la frecuencia de ACVi con la edad, mayor proporción del sexo masculino respecto a la población general hasta los 64 años y frecuencia relativa etiológica y topográfica similar a la descripta en la bibliografía. La HTA fue el FRC de mayor frecuencia, tanto único como en concomitancia con otros,seguida de dislipemia y DM. Estos fueron superiores respecto de publicaciones nacionales previas. Se corroboró la implicancia de los FRC en el ACVi y la inadecuada prevención de los factores de riesgo modificables.

Abstract Stroke is the second leading cause of death in adults in the western world. Inorder to know the current status of conventional risk factors (CRF) for ischs emic stroke (IS) hypertension (HBP), dyslipidemia, diabetes mellitus, smoking, arrhythmias, history of stroke,age and sex- and to assess compliance with prevention measures, their distribution was analysed according toetiology and topography in a public hospital in Montevideo, Uruguay. One hundred fourteen IS patients aged 25-97 years were studied. A protocol was applied to collect variables related to the research using the Trial of Org 10172 in Acute Stroke Treatment and Oxfordshire Community Stroke Project criteria for etiological andtopographic classification, respectively. The presence of hypertension (HBP) and diabetes according to World Health Organization criteria, dyslipidemia according to the criteria of the Adult Treatment Panel III, smoking having smoked at least one cigarette/day in the last trimester and arrhythmia according to the alterationof the heart rate were considered. An increased in the frequency of stroke with age, a higher proportionin men compared to the general population up to 64 years of age and relative etiological and topographic frequency like bibliography were obserbed. HBP was the most frequent CRF, both alone and in concomitance with others, followed by dyslipidemia and diabetes, these being higher to than previous national publications.The implication of CRFs in stroke and the inadequate prevention of modifiable risk factors were corroborated.

Resumo O acidente vascular-cerebral é a segunda causa de morte em adultos no mundo ocidental. Para conhecer ostatus atual dos fatores de risco vasculares convencionais (FRC) para acidente vascular-cerebral isquêmico(ACVi) -hipertensão arterial (HTA), dislipidemia, diabetes mellitus (DM), tabagismo, arritmias, antecedentesde ACVi, idade e sexo- e para avaliar o cumprimento das medidas de prevenção, sua distribuição foi analisadade acordo com a etiologia e a topografia em um hospital público de Montevidéu, Uruguai. Foram estudados114 pacientes com ACVi com idades entre 25 e 97 anos. Um protocolo foi aplicado para coletar variáveis vinculadas à pesquisa usando os critérios do Trial of Org 10172 in Acute Stroke Treatment e Oxfordshire Community Stroke Project para classificação etiológica e topográfica, respectivamente. Considerou-se apresença de HTA e DM de acordo com os critérios da Organização Mundial da Saúde, dislipidemia de acordocom o Adult Treatment Panel III, tabagismo tendo fumado pelo menos um cigarro/dia no último trimestree arritmia conforme a alteração da frequência cardíaca. Observa-se aumento da frequência de AVCi com aidade, maior proporção de homens em relação à população geral até 64 anos e frequência relativa etiológicae topográfica semelhante à bibliografia. A HTA foi o FRC mais frequente, tanto única quanto em concomitância com outras, seguida de dislipidemia e DM. Eles foram superiores às publicações prévias. O envolvimentodos FRCs no ACVi e a prevenção inadequada dos fatores de risco modificáveis foram confirmadas.

Melanoma Targeted Therapies beyond BRAF-Mutant Melanoma: Potential Druggable Mutations and Novel Treatment Approaches.

Melanomas exhibit the highest rate of somatic mutations among all different types of cancers (with the exception of BCC and SCC). The accumulation of a multimode of mutations in the driver oncogenes are responsible for the proliferative, invasive, and aggressive nature of melanomas. High-resolution and high-throughput technology has led to the identification of distinct mutational signatures and their downstream alterations in several key pathways that contribute to melanomagenesis. This has enabled the development of individualized treatments by targeting specific molecular alterations that are vital for cancer cell survival, which has resulted in improved outcomes in several cancers, including melanomas. To date, BRAF and MEK inhibitors remain the only approved targeted therapy with a high level of evidence in BRAFV600E/K mutant melanomas. The lack of approved precision drugs in melanomas, relative to other cancers, despite harboring one of the highest rates of somatic mutations, advocates for further research to unveil effective therapeutics. In this review, we will discuss potential druggable mutations and the ongoing research of novel individualized treatment approaches targeting non-BRAF mutations in melanomas.

Role of diagnostic imaging in psoriatic arthritis: how, when, and why.

Psoriasis is a common skin disease. Up to 30% of patients with psoriasis develop psoriatic arthritis (PsA) resulting, by far, the most prevalent coexisting condition. Heterogeneity of clinical and radiological presentation is a major challenge to diagnosis of PsA. Initial reports about PsA emphasized a benign course in most patients, but it is now recognized that psoriatic arthritis often leads to impaired function and a reduced quality of life. PsA is a progressive disease characterized by diverse clinical features, often resulting in diagnostic delay and treatment that are associated with poor clinical and structural outcomes. New effective treatments may halt PsA progression, and consequently, treatment goals have evolved from simple reduction of pain to achieving full remission or minimal disease activity. This emerging treat-to-target strategy paradigm emphasize a need for early diagnosis; sensitive imaging techniques may be of value in this process. While radiography and CT depict structural damage, US and MRI have emerged as helpful tools to evaluate magnitude and severity of active inflammatory lesions. This review aims to describe the role of imaging modalities in diagnosis, follow-up and prognosis of PsA.

Chronic Unilateral Uveitis as a Manifestation of Leprosy: A Case Report and Literature Review.

Purpose: To describe a case of leprosy presenting chronic anterior uveitis associated with other systemic lesions.Methods: Case report and systematic literature review.Results: We describe the case of a 65-year-old patient presenting clinical features of chronic uveitis and poor response to topical and intravitreal steroid treatment. Upon ocular examination, diffuse iris atrophy and macular edema were observed and laboratory tests for autoimmune and infectious diseases were within normal range. Physical examination revealed the presence of skin lesions on trunk and extremities, which were biopsied and identified as positive for leprosy.Conclusion: The case reported herein presented atypical characteristics of uveitis due to the involvement of the posterior segment of the eye. Leprosy diagnosis could be a challenge, a systematic approach is mandatory to achieve adequate treatment.

Mujeres y cuidado: disputas y negociaciones en el espacio académico / Mulheres e cuidado: disputas e negociações no espaço acadêmico / Femmes et soin : competitions et negociations dans le contexte universitaire / Women and care: disputes and negotiations in academic space

Resumen El presente artículo ofrece insumos, tanto empíricos como teóricos, que evidencian cómo opera el vínculo entre el espacio y el género en la academia de ciencias sociales y humanidades de Bogotá, Colombia. A través de 10 historias de vida de mujeres que trabajan en distintas universidades, afirmamos que la academia es un espacio hostil para las mujeres que la habitan, en tanto que se reproducen en su interior lógicas dualistas, coloniales, heteropatriarcales y capitalistas, que afectan de manera particular las experiencias de mujeres y cuerpos no heteronormativos. Encontramos que el cuidado es una noción central y conflictiva en dicha experiencia de la academia, pues opera tanto como forma de opresión, al anular la participación y visibilidad de las mujeres, como de resistencia, negociación y potencia política para transformar la universidad.

Resumo O presente artigo oferece insumos tanto empíricos quanto teóricos que evidenciam a forma como opera o vínculo entre o espaço e o gênero na academia de ciências sociais e humanas de Bogotá, Colômbia. Com base em dez histórias de vida de mulheres que trabalham em diferentes universidades, afirmamos que a academia é um espaço hostil para as mulheres que o habitam, pois em seu interior são reproduzidas lógicas dualistas, coloniais, heteropatriarcais e capitalistas, que afetam de maneira particular as experiências de mulheres e corpos não heteronormativos. Verificamos que o cuidado é uma noção central e conflituosa nessa experiência acadêmica, pois opera tanto como forma de opressão, ao anular a participação e a visibilidade das mulheres, quanto como de resistência, negociação e potência política para transformar a universidade.

Résumé Cet article offre des données empiriques aussi bien que théoriques qui mettent en évidence comment fonctionne le lien entre l'espace et le genre dans le contexte universitaire de sciences sociales et humaines de Bogota, Colombie. A l'appui de dix histoires de s vie de femmes qui travaillent dans différentes universités, on affirme que l'académie est un espace hostile aux femmes, car à son intérieur se reproduisent des logiques dualistes, colonialistes, capitalistes et heteropatriacales qui affectent de façon particulière les expériences des femmes et des corps non heteronormatifs. On a vérifié que le soin est une notion centrale et conflictuelle dans cette expérience académique, car elle opère comme mode d'oppression, lorsqu'on annule la participation et la visibilité des femmes, aussi bien que comme résistance, négociation et force politique pour transformer l'université.

Abstract This article offers both empirical and theoretical resources that demonstrate how the link between space and gender operates in academic life in social sciences and humanities in Bogotá, Colombia. By examining ten life stories of women who work in different universities, we affirm that academia is a hostile space for the women who inhabit it, as it reproduces dualist, colonial, hetero-patriarchal and capitalist logics within it; these particularly affect the experiences of women and non-heteronormative bodies. Care is found to be a central and conflictive notion in this experience of academia, as it operates both as a form of oppression, by nullifying women's participation and visibility, and as a form of resistance, negotiation and political power to transform the university.

Alta prevalencia de dos o más intentos de suicidio asociados con ideación suicida y enfermedad mental en Colombia en 2016 / High Prevalence of Two or More Suicide Attempts Associated with Suicidal Ideation and Mental Disease in Colombia 2016

RESUMEN Introducción: La ideación suicida y los intentos son muy predictivos de muerte por suicidio. Además, los intentos de suicidio causan a la sociedad una carga financiera de millones de dólares. Objetivo: Establecer los factores asociados con más de un intento de suicidio registrado en 2016 en la población colombiana. Métodos: Se realizó un estudio trasversal de 18.763 reportes consignados en la base de datos del Sistema Nacional de Vigilancia en Salud Pública del Instituto Nacional de Salud de Colombia durante 2016. Resultados: Del total de reportes, 11.738 (62,6%) corresponden al sexo femenino; la media de edad fue 25,0 (IC95%, 24,9-25,2) arios; el 46% de todos los casos corresponden a personas entre 10 y 20 años. Refirieron 2 o más intentos de suicidio 5.734 (30,6%). Las prevalencias de alguna enfermedad mental y de ideación suicida persistente fueron del 48,5 y el 16,4% respectivamente. Tras realizar el ajuste mediante regresión logística, el factor más asociado con más de 1 intento suicida, fue la ideación suicida persistente: OR bruta = 5,5 (IC95%, 5,0-5,9) y ORa = 4,0 (IC95%, 3,6-4,3). Conclusiones: Los pacientes con ideación suicida persistente tienen una probabilidad 4 veces mayor de hacer 2 o más intentos suicidas. Otros factores, como el uso de arma cortopunzante como mecanismo para ejecutar el intento y el antecedente de trastorno afectivo bipolar y/o depresión, también se asociaron con más de 1 intento de suicidio.

ABSTRACT Introduction: Suicidal ideation and attempts are strongly predictive of suicide deaths. Furthermore, suicide attempts exert a financial burden of millions of dollars on society. Objective: To establish the factors associated with more than one suicide attempt in the Colombian population that was reported in 2016. Methods: A cross-sectional study of 18,763 reports entered in the database of the National Public Health Surveillance of the National Institute of Health of Colombia during 2016 was performed. Results: 11,738 (62.6%) of the total number of reports were female, the mean age was 25.0 (95% CI, 24.9-25.2) years, 46% of all cases were individuals between 10- and 20-years-old; 5,734 (30.6%) reported 2 or more suicide attempts and the prevalence of a mental disorder and persistent suicidal ideation were 48.5% and 16.4%, respectively. The factor most strongly associated with more than one suicide attempt, after adjusting for logistic regression, was persistent suicide ideation with crude OR = 5.5 (95% CI, 5.0-5.9), and ORa = 4.0 (95% CI, 3.6-4.3). Conclusions: Patients with persistent suicidal ideation were 4 times more likely to have 2 or more suicide attempts. Other factors such as the use of a sharp weapon as a mechanism to perform the attempt and the history of bipolar affective disorder and/or depression were also associated with more than one suicide attempt.

Immunogenicity and Safety of the Adjuvanted Recombinant Zoster Vaccine in Chronically Immunosuppressed Adults Following Renal Transplant: A Phase 3, Randomized Clinical Trial.

BACKGROUND: The incidence of herpes zoster is up to 9 times higher in immunosuppressed solid organ transplant recipients than in the general population. We investigated the immunogenicity and safety of an adjuvanted recombinant zoster vaccine (RZV) in renal transplant (RT) recipients ≥18 years of age receiving daily immunosuppressive therapy. METHODS: In this phase 3, randomized (1:1), observer-blind, multicenter trial, RT recipients were enrolled and received 2 doses of RZV or placebo 1-2 months (M) apart 4-18M posttransplant. Anti-glycoprotein E (gE) antibody concentrations, gE-specific CD4 T-cell frequencies, and vaccine response rates were assessed at 1M post-dose 1, and 1M and 12M post-dose 2. Solicited and unsolicited adverse events (AEs) were recorded for 7 and 30 days after each dose, respectively. Solicited general symptoms and unsolicited AEs were also collected 7 days before first vaccination. Serious AEs (including biopsy-proven allograft rejections) and potential immune-mediated diseases (pIMDs) were recorded up to 12M post-dose 2. RESULTS: Two hundred sixty-four participants (RZV: 132; placebo: 132) were enrolled between March 2014 and April 2017. gE-specific humoral and cell-mediated immune responses were higher in RZV than placebo recipients across postvaccination time points and persisted above prevaccination baseline 12M post-dose 2. Local AEs were reported more frequently by RZV than placebo recipients. Overall occurrences of renal function changes, rejections, unsolicited AEs, serious AEs, and pIMDs were similar between groups. CONCLUSIONS: RZV was immunogenic in chronically immunosuppressed RT recipients. Immunogenicity persisted through 12M postvaccination. No safety concerns arose. CLINICAL TRIALS REGISTRATION: NCT02058589.

A scoping review of rehabilitation interventions for survivors of head and neck cancer.

Purpose: The objectives of this scoping review were to summarize, understand, and disseminate findings from a broad body of literature on rehabilitation interventions used with survivors of head and neck cancer. Method: Searches were conducted in six databases. Inclusion criteria were studies of adult head and neck cancer survivors with a predefined primary rehabilitation outcome as a result of an intervention. Excluded were studies not written in English, opinion papers, or studies where the intervention was not carried out by a rehabilitation healthcare service. A second level, full-text review of the studies was conducted. A thematic analysis was used to examine and combine study findings. Results: A total of 3804 results were retrieved from all sources resulting in 39 papers that were analyzed. The thematic analysis of the included papers represented interventions focusing on swallowing and nutrition, speech, physical therapy, assistive devices, complementary and alternative modalities, comprehensive interdisciplinary programs, and preventive rehabilitation programs. Conclusion: This review has provided an overview of the scope of rehabilitation interventions available for survivors of head and neck cancer and preliminary information about their efficacy. This is foundational information for the development and refinement of rehabilitation interventions and programs for head and neck cancer survivors. Implications for Rehabilitation The existing evidence suggests that survivors of head and neck cancer can benefit from early screening of potential rehabilitation needs and being involved in preventive rehabilitation programs pre-surgery when possible. Rehabilitation programs should consider swallowing interventions for patients as evidence reports improved swallowing function, decreased pain and discomfort, and reduced duration of feeding tube use. Rehabilitation programs should consider nutritional interventions after radiotherapy: Patients benefited from stabilized weights, improved nutritional status, and an improved quality of life. Physical exercise interventions demonstrated improvements in physical function, muscular endurance, range of motion, overall quality of life, and showed reductions in pain, and fatigue.

Development and validation of the McGill body image concerns scale for use in head and neck oncology (MBIS-HNC): A mixed-methods approach.

OBJECTIVE: The aim of this study was to develop and validate a patient-reported outcome measure to evaluate body image concerns in head and neck cancer (HNC) patients. METHODS: Items were created using a combination of deductive (eg, US Food and Drug Administration Qualification of Clinical Outcome Assessments, literature review) and inductive approaches (eg, subject matter experts, HNC patients). Items were translated for use in both Canadian English and Canadian French using back-translation. A two-step empirical validation process using the Classical Test Theory (CTT) and Rasch Measurement Theory (RMT) was conducted with 224 and 258 HNC patients, respectively, having undergone disfiguring surgery within the past 3 years. RESULTS: Analyses suggest two subscales for MBIS-HNC: social discomfort (10 items) and negative self-image (11 items). The McGill Body Image Concerns Scale-Head and Neck Cancer (MBIS-HNC) is reliable with high internal consistency (0.98), high test-retest reliability over a two-week period (ICC = 0.88), moderate to high convergent validity (range r = 0.43-0.81), and divergent validity (range r = 0.12-0.15). RMT was used in addition to CTT. Disordered thresholds led to the modification of the number of response options, and items were deleted based on differential item functioning and high local dependency. Unidimensionality of both subscales and supporting a total score was confirmed. The measure was however characterized by the presence of an important floor effect, confirmed with poor targeting as demonstrated by the person-item threshold distribution. CONCLUSION: Evidence gathered from our theory-driven validation study using CTT and RMT provides practitioners and researchers with a useful and easy to use self-report measure.