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BACKGROUND: Dysphagia is a consequence of oropharyngeal squamous cell carcinoma (OPSCC) treatments and often results in a devastating reduction in quality of life (QoL; Nguyen et al., 2005; Pauloski, 2008). OBJECTIVES: This study aimed to report temporal trends in swallowing outcomes using the Modified Barium Swallow Impairment Profile (MBSImP) and the M.D. Anderson Dysphagia Inventory (MDADI) and to study the relationship between these two measures. METHOD: This was a retrospective review of clinical data collected in January 2013 to December 2017 from a tertiary care center. MBSImP PI scores and MDADI composite scores were collected pretreatment and 1, 6, and 12 months posttreatment. Data were analyzed in aggregate and stratified by treatment modality. To address the primary objective, descriptive statistics were used. To address the secondary objective, four Spearman tests were run between MBSImP PI and MDADI composite scores. RESULTS: A total of 123 OPSCC participants were included. With respect to trends, MBSImP PI scores worsened 1 month posttreatment and remained impaired at 6 and 12 months. For MDADI composite scores, patient reports worsened 1 month posttreatment and subsequently improved at 6 and 12 months. MBSImP PI and MDADI composite scores were weakly negatively correlated (i.e., in agreement) at the pre- and 12-month posttreatment appointments. CONCLUSIONS: Swallowing outcomes in OPSCC patients have distinct yet predictable trends for both clinician-assessed and patient-reported swallowing outcomes during the first year following cancer treatment. However, unlike previous findings, these two types of measures were in agreement at the pretreatment and 12 months posttreatment appointments.
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Transtornos de Deglutição , Neoplasias Orofaríngeas , Humanos , Deglutição , Transtornos de Deglutição/diagnóstico , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/terapia , Qualidade de Vida , Neoplasias Orofaríngeas/complicações , Neoplasias Orofaríngeas/diagnóstico , Neoplasias Orofaríngeas/terapia , Medidas de Resultados Relatados pelo PacienteRESUMO
PURPOSE: Mobile health (mHealth) technologies for dysphagia management may allow patients to complete rehabilitation exercises from home and their clinicians to remotely monitor them. However, clinicians are rarely formally consulted in the early stages of ideation. This study aimed to determine necessary elements to be included in a clinician web portal that would allow for remote monitoring of patients completing dysphagia exercises using mHealth equipped with surface electromyography (sEMG). METHOD: Ten dysphagia clinicians were consulted individually using convergent interviewing. Interviews were transcribed and analysed using thematic analysis to identify themes and sub-themes. RESULT: Themes identified included: perceived benefits of an mHealth system; clinical uptake of an mHealth system; clinical targets desired; preferred communication method; notification style and frequency; and user interface considerations. There was no consensus regarding clinical targets to display, notification frequency, method of clinician-patient communication, or layout for the user interface. Agreement existed on the importance of the simplicity and customisability for the clinician web portal user interface. CONCLUSION: Lack of consensus on specific elements to be included in a clinician web portal could reflect low clinical exposure to sEMG. This study provides an example of formal end user feedback in the ideation phase of design.
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Purpose A large knowledge gap related to dysphagia treatment adherence was identified by a recent systematic review: Few existing studies report on adherence, and current adherence tracking relies heavily on patient self-report. This study aimed to report weekly adherence and dysphagia-specific quality of life following home-based swallowing therapy in head and neck cancer (HNC). Method This was a quasi-experimental pretest-posttest design. Patients who were at least 3 months post-HNC treatment were enrolled in swallowing therapy using a mobile health (mHealth) swallowing system equipped with surface electromyography (sEMG) biofeedback. Participants completed a home dysphagia exercise program across 6 weeks, with a target of 72 swallows per day split between three different exercise types. Adherence was calculated as percent trials completed of trials prescribed. The M. D. Anderson Dysphagia Inventory (MDADI) was administered before and after therapy. Results Twenty participants (75% male), with an average age of 61.9 years (SD = 8.5), completed the study. The majority had surgery ± adjuvant (chemo)radiation therapy for oral (10%), oropharyngeal (80%), or other (10%) cancers. Using an intention-to-treat analysis, adherence to the exercise regimen remained high from 84% in Week 1 to 72% in Week 6. Radiation therapy, time since cancer treatment, medical difficulties, and technical difficulties were all found to be predictive of poorer adherence at Week 6. A statistically significant improvement was found for composite, emotional, and physical MDADI subscales. Conclusions When using an mHealth system with sEMG biofeedback, adherence rates to home-based swallowing exercise remained at or above 72% over a 6-week treatment period. Dysphagia-specific quality of life improved following this 6-week treatment program.
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Transtornos de Deglutição , Neoplasias de Cabeça e Pescoço , Deglutição , Transtornos de Deglutição/diagnóstico , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/terapia , Feminino , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , SobreviventesRESUMO
OBJECTIVES: Purpose: Dysphagia affects a wide cross-section of society. Reports of stigma and missed diagnoses suggest limited public awareness of this prevalent condition, exacerbating the hidden disability stemming from this impairment. This study explored the public awareness of dysphagia among people both with and without occupational ties to healthcare to assess the level of awareness and identify topics where public knowledge may be deficient. METHODS: Method: An online purpose-built survey was administered to determine self-assessed awareness of dysphagia, and researcher-assessed understanding of the causes, symptoms, assessment and treatment of swallowing disorders. Survey answers (n = 374) were grouped by healthcare (n = 105) and non-healthcare (n = 269) respondents. Responses were analysed using both qualitative and quantitative methods. RESULTS: Result: Self-assessed respondent awareness was low among 71% of non-healthcare and 29% of healthcare respondents, corroborating the limited demonstrated knowledge of the causes, symptoms, assessment and treatment of dysphagia. Self-assessed and researcher-assessed awareness was more limited among non-healthcare respondents. CONCLUSIONS: Conclusion: Survey results confirm limited public knowledge of dysphagia and demonstrate the need for greater public awareness of this largely invisible disorder.
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Transtornos de Deglutição , Transtornos de Deglutição/diagnóstico , Humanos , Estigma Social , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Dysphagia is one consequence of head and neck cancer that has a significant impact on quality of life for head and neck cancer survivors. While survival rates continue to improve, focus has shifted to maximizing long-term function, with prevention or prehabilitation programs becoming more common. Prehabilitation programs typically include an exercise regime that specifies the exercise type, the number of repetitions to complete per set, the number of sets of each exercise to complete per day, as well as the length of the treatment block. Ideally, exercise programs are designed with principles of neuromuscular plasticity in mind. METHODS: Twenty-nine original research articles published between 2006 and 2020 were included in this state-of-the-art review and examined for program timing and details. RESULTS: Two definitions for prehabilitation were noted: one third of the studies defined prehabilitation as preventative exercises prior to the start of acute cancer treatment; the remaining two thirds defined prehabilitation as treatment concurrent prehabilitation. Exercises prescribed ranged from general stretching and range of motion exercises, to trismus and swallowing specific exercises. The most common swallowing specific exercise was the Mendelsohn's maneuver, followed by the effortful swallow, Shaker, and Masako maneuver. The most common dose was 10 repetitions of an exercise, three times per day for the duration of radiation therapy. The most common measures were questionnaires, followed by g-tube dependence, mouth opening, and MBS reports. CONCLUSION: This review of the literature has shed light on the variability of prehabilitation timing, exercise type, dose, duration of treatment, and outcomes associated with prehabilitation, making the selection of an optimal prehabilitation program difficult at this time.
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Transtornos de Deglutição/prevenção & controle , Neoplasias de Cabeça e Pescoço/terapia , Exercício Pré-Operatório , Quimiorradioterapia , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Complicações Pós-Operatórias/prevenção & controleRESUMO
BACKGROUND: The tongue is an essential organ for human interaction, communication and survival. To date, there is a paucity of objective functional, patient reported, or quality of life outcomes of patients undergoing a total glossectomy with preservation of the larynx (TGLP). OBJECTIVE: To examine prospectively collected objective, self-reported functional and quality of life (QOL) data in patients undergoing TGLP and free flap reconstruction. METHODS: Sixteen TGLP patients were identified in the prospective head and neck cancer and functional outcomes database between January of 2009 and December 2017. Data collection included patient age, sex, performance status, TNM staging, diagnosis and adjuvant treatment. Swallowing and speech functions were measured and prospectively recorded pre- and postoperatively. Patient reported outcomes were measured with the Speech Handicap Index (SHI) and the M.D. Anderson Dysphagia Inventory (MDADI). RESULTS: All patients had a significant reduction in their objective swallowing (P = 0.035), sentence (P = 0.001) and word intelligibility (P < .001) scores. There was no significant reduction in SHI or total MDADI scores. All patients maintained their QOL in the post-treatment time frame. There was no relationship between free-flap type and outcome. CONCLUSION: Total glossectomy with laryngeal sparing and free flap reconstruction results in significant reduction in objective functional measurements, but patients report stable functional and quality of life outcomes after treatment.
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Over the last two decades, dysphagia is increasingly recognized as a significant short-term and long-term issue in oropharyngeal cancer patients. However, there remains a lack of standardization and agreement about reporting swallowing outcomes in studies that assess treatment outcomes in this population. A systematic review was performed following PRISMA Guidelines by searching Pubmed (MEDLINE) and Scopus. The inclusion criteria used included (1) prospective and retrospective clinical studies involving adult patients with oropharyngeal cancer, (2) reports swallowing outcomes, (3) English studies or studies with English translation, (4) full text retrievable and (5) publication between 1990 and 2016. 410 unique studies were identified, and 106 were analyzed. A majority (> 80%) of studies that reported swallowing outcomes were published after 2010. While 75.4% of studies reported subjective outcomes (e.g., patient-reported or clinician-reported outcome measures), only 30.2% of studies presented results of objective instrumental assessment of swallowing. The majority (61%) of studies reported short-term swallowing outcomes at 1 year or less, and only 10% of studies examined 5-year swallowing comes. One study examined late-dysphagia (> 10 years) in the oropharyngeal cancer population. Considerable heterogeneity remains in the reporting of swallowing outcomes after treatment of oropharyngeal cancer despite its importance for quality of life. Studies reporting long-term swallowing outcomes are lacking in the literature, and objective measures of swallowing function remain underutilized and nonstandardized.
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Confiabilidade dos Dados , Transtornos de Deglutição/terapia , Neoplasias Orofaríngeas/complicações , Avaliação de Resultados em Cuidados de Saúde/tendências , Adulto , Transtornos de Deglutição/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde/normas , Resultado do TratamentoRESUMO
The objective of this study was to conduct the first patient usability testing of a mobile health (mHealth) system for in-home swallowing therapy. Five participants with a history of head and neck cancer evaluated the mHealth system. After completing an in-application (app) tutorial with the clinician, participants were asked to independently complete five tasks: pair the device to the smartphone, place the device correctly, exercise, interpret progress displays, and close the system. Quantitative and qualitative methods were used to evaluate the effectiveness, efficiency, and satisfaction with the system. Critical changes to the app were found in three of the tasks, resulting in recommendations for the next iteration. These issues were related to ease of Bluetooth pairing, placement of device, and interpretation of statistics. Usability testing with patients identified issues that were essential to address prior to implementing the mHealth system in subsequent clinical trials. Of the usability methods used, video observation (synced screen capture with videoed gestures) revealed the most information.
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Transtornos de Deglutição/terapia , Neoplasias de Cabeça e Pescoço , Autocuidado , Sobreviventes , Telemedicina , Interface Usuário-Computador , Adulto , Idoso , Feminino , Letramento em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Aplicativos MóveisRESUMO
BACKGROUND: To determine the impact of Human Papillomavirus (HPV) status on speech, swallowing, and quality of life (QOL) outcomes after surgical treatment of oropharyngeal cancer (OPSCC). METHODS: A retrospective review of a prospectively collected database of all patients with OPSCC diagnosed and treated from 1998 to 2009. Speech, swallowing, and quality of life data were gathered at 3 different evaluation points. HPV status was determined using p16 positivity as a surrogate marker. Univariate and multivariate statistical analyses were performed to identify whether p16 status is a significant predictor of functional outcome and QOL. RESULTS: One hundred twelve patients with OPSCC and known p16 status were treated with primary surgery between 1998 and 2009, with mean age of 56 years. Out of those patients 63 (56%) were p16 positive. Speech intelligibility remained high at 1-year post operation (95.4%). Only 11.5% of the patients required a feeding tube at 1 year after surgery to maintain their daily caloric requirements and the risk of aspiration after surgery was not significant (p = 0.097). There was no statistically or clinically significant difference in speech, swallowing ability, swallowing safety and QOL outcomes between p16-positive and negative OPSCC. CONCLUSIONS: Surgically treated OPSCC patients demonstrate excellent swallowing function and can achieve excellent speech perception. P16 status may not be predictive of functional outcomes or QOL in surgically treated OPSCC.
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Carcinoma de Células Escamosas/cirurgia , Retalhos de Tecido Biológico , Papillomavirus Humano 16/genética , Neoplasias Orofaríngeas/cirurgia , Infecções por Papillomavirus/virologia , Procedimentos de Cirurgia Plástica/métodos , Qualidade de Vida , Carcinoma de Células Escamosas/fisiopatologia , Carcinoma de Células Escamosas/psicologia , DNA Viral/análise , Deglutição , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/fisiopatologia , Neoplasias Orofaríngeas/psicologia , Infecções por Papillomavirus/cirurgia , Período Pós-Operatório , Estudos RetrospectivosRESUMO
Mobile health (mHealth) technologies may offer an opportunity to address longstanding clinical challenges, such as access and adherence to swallowing therapy. Mobili-T® is an mHealth device that uses surface electromyography (sEMG) to provide biofeedback on submental muscles activity during exercise. An automated swallow-detection algorithm was developed for Mobili-T®. This study evaluated the performance of the swallow-detection algorithm. Ten healthy participants and 10 head and neck cancer (HNC) patients were fitted with the device. Signal was acquired during regular, effortful, and Mendelsohn maneuver saliva swallows, as well as lip presses, tongue, and head movements. Signals of interest were tagged during data acquisition and used to evaluate algorithm performance. Sensitivity and positive predictive values (PPV) were calculated for each participant. Saliva swallows were compared between HNC and controls in the four sEMG-based parameters used in the algorithm: duration, peak amplitude ratio, median frequency, and 15th percentile of the power spectrum density. In healthy participants, sensitivity and PPV were 92.3 and 83.9%, respectively. In HNC patients, sensitivity was 92.7% and PPV was 72.2%. In saliva swallows, HNC patients had longer event durations (U = 1925.5, p < 0.001), lower median frequency (U = 2674.0, p < 0.001), and lower 15th percentile of the power spectrum density [t(176.9) = 2.07, p < 0.001] than healthy participants. The automated swallow-detection algorithm performed well with healthy participants and retained a high sensitivity, but had lowered PPV with HNC patients. With respect to Mobili-T®, the algorithm will next be evaluated using the mHealth system.
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Sobreviventes de Câncer , Transtornos de Deglutição/diagnóstico , Deglutição/fisiologia , Eletromiografia/métodos , Telemedicina , Adulto , Idoso , Algoritmos , Biorretroalimentação Psicológica , Transtornos de Deglutição/terapia , Feminino , Neoplasias de Cabeça e Pescoço/complicações , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos TestesRESUMO
PURPOSE: Delivery of swallowing therapy is faced with challenges regarding access to in-clinic services and adherence to prescribed home programs. Mobile health (mHealth) technologies are being developed at a rapid pace to address these difficulties. Whereas some benefits to using these modern tools for therapy are obvious (e.g., electronic reminders), other advantages are not as well understood. One example is the potential for mHealth devices and apps to enhance adherence to treatment regimens. METHOD: This article introduces a number of psychological concepts that relate to adherence and that can be leveraged by mHealth. Elements that contribute to flow (optimal experience) during an activity and those that reinforce grit (perseverance to achieve a long-term goal) can be used to engage patients in their own rehabilitation. RESULTS: The experience of flow can be targeted by presenting the rehabilitation exercise as an optimally challenging game, one that offers a match between challenge and ability. Grit can be supported by reinforcing routine and by varying the therapy experience using different games. CONCLUSIONS: A combination of hardware and software design approaches have the potential to transform uninteresting and repetitive activities, such as those that make up swallowing therapy regimens, into engaging ones. The field of gamification, however, is still developing, and gamified mHealth apps will need to withstand scientific testing of their claims and demonstrate effectiveness in all phases of outcome research.
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Transtornos de Deglutição/terapia , Deglutição , Teoria dos Jogos , Cooperação do Paciente , Telemedicina/métodos , Jogos de Vídeo , Transtornos de Deglutição/diagnóstico , Transtornos de Deglutição/fisiopatologia , Transtornos de Deglutição/psicologia , Objetivos , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Aplicativos Móveis , Recuperação de Função Fisiológica , Autoeficácia , Design de Software , Resultado do TratamentoRESUMO
BACKGROUND: Adherence to swallowing rehabilitation exercises is important to develop and maintain functional improvement, yet more than half of head and neck cancer (HNC) patients report having difficulty adhering to prescribed regimens. Health apps with game elements have been used in other health domains to motivate and engage patients. Understanding the factors that impact adherence may allow for more effective gamified solutions. OBJECTIVE: The aim of our study was to (1) identify self-reported factors that influence adherence to conventional home therapy without a mobile device in HNC patients and (2) identify appealing biofeedback designs that could be used in a health app. METHODS: A total of 10 (4 females) HNC patients (mean=60.1 years) with experience completing home-based rehabilitation programs were recruited. Thematic analysis of semi-structured interviews was used to answer the first objective. Convergent interviews were used to obtain reactions to biofeedback designs. RESULTS: Facilitators and barriers of adherence to home therapy were described through 6 themes: patient perceptions on outcomes and progress, clinical appointments, cancer treatment, rehabilitation program, personal factors, and connection. App visuals that provide feedback on performance during swallowing exercises should offer an immediate representation of effort relative to a goal. Simple, intuitive graphics were preferred over complex, abstract ones. Continued engagement with the app could be facilitated by tracking progress and by using visuals that build structures with each use. CONCLUSIONS: This is a detailed documentation of the initial steps in designing a health app for a specific patient group. Results revealed the importance of patient engagement in early stages of app development.
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PURPOSE: Treatment for oral cancer can result in speech impairments that can have varying impacts on patient quality of life. This study explored the relationship between clinical measures of speech impairment and the perception that patients had of this change in the early stage of recovery. METHOD: This was a quasi-experimental 1-group pre-post study design carried out on 10 patients with surgical intervention for oral cancer. Two clinical measures (word intelligibility and consonant phoneme error) and 2 patient-perception measures (Speech Handicap Index total score and Speech Handicap Index patient criteria score) were collected at preoperative and 1-month postoperative appointments. RESULTS: Qualitative analysis revealed discordance between clinical and patient-perceived measures in 4 of 10 patients. Change in consonant phoneme error and change in word intelligibility were significantly correlated (r = .827). Furthermore, on average, statistically significant relationships were not found between clinical and patient-perceived measures or between the 2 patient-perception measures. CONCLUSIONS: Discordance between clinical and patient-perceived measures was observed in almost half of the sample, indicating that clinical tests did not fully explain the extent of impairment perceived by patients. Speech outcomes should focus on both types of measures, and patient perception outcomes should be carefully considered when recommending speech therapy.
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Neoplasias Bucais/cirurgia , Satisfação do Paciente , Complicações Pós-Operatórias/reabilitação , Autoimagem , Distúrbios da Fala/psicologia , Distúrbios da Fala/reabilitação , Adulto , Idoso , Alberta , Atitude do Pessoal de Saúde , Estudos de Avaliação como Assunto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/complicações , Fonética , Complicações Pós-Operatórias/psicologia , Psicometria/estatística & dados numéricos , Estudos Retrospectivos , Inteligibilidade da Fala , Estatística como Assunto , Inquéritos e Questionários , Qualidade da VozRESUMO
Surface electromyography (sEMG) is used as an adjuvant to dysphagia therapy to demonstrate the activity of submental muscles during swallowing exercises. Mechanomyography (MMG) has been suggested as a potential superior alternative to sEMG; however, this advantage is not confirmed for signal acquired from submental muscles. This study compared the signal-to-noise ratio (SNR) obtained from sEMG and MMG sensors during swallowing tasks, in healthy participants and those with a history of head and neck cancer (HNC), a population with altered anatomy and a high incidence of dysphagia. Twenty-two healthy adults and 10 adults with a history of HNC participated in this study. sEMG and MMG signals were acquired during dry, thin liquid, effortful, and Mendelsohn maneuver swallows. SNR was compared between the two sensors using repeated measures ANOVAs and subsequent planned pairwise comparisons. Test-retest measures were collected on 20 % of participants. In healthy participants, MMG SNR was higher than that of sEMG for dry [t(21) = -3.02, p = 0.007] and thin liquid swallows [t(21) = -4.24, p < 0.001]. Although a significant difference for sensor was found in HNC participants F(1,9) = 5.54, p = 0.043, planned pairwise comparisons by task revealed no statistically significant difference between the two sensors. sEMG also showed much better test-retest reliability than MMG. Biofeedback provided as an adjuvant to dysphagia therapy in patients with HNC should employ sEMG technology, as this sensor type yielded better SNR and overall test-retest reliability. Poor MMG test-retest reliability was noted in both healthy and HNC participants and may have been related to differences in sensor application.
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Transtornos de Deglutição/terapia , Deglutição/fisiologia , Eletromiografia/métodos , Neoplasias de Cabeça e Pescoço/fisiopatologia , Miografia/métodos , Adulto , Idoso , Sobreviventes de Câncer , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/fisiopatologia , Feminino , Neoplasias de Cabeça e Pescoço/complicações , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Razão Sinal-Ruído , Adulto JovemRESUMO
Head and neck cancer treatment alters the anatomy and physiology of patients. Resulting swallowing difficulties can lead to serious health concerns. Surface electromyography (sEMG) is used as an adjuvant to swallowing therapy exercises. sEMG signal collected from the area under the chin provides visual biofeedback from muscle contractions and is used to help patients perform exercises correctly. However, conventional sEMG adhesive pads are relatively thick and difficult to effectively adhere to a patient's altered chin anatomy, potentially leading to poor signal acquisition in this population. Here, the emerging technology of epidermal electronics is introduced, where ultra-thin geometry allows for close contouring of the chin. The two objectives of this study were to (1) assess the potential of epidermal electronics technology for use with swallowing therapy and (2) assess the significance of the reference electrode placement. This study showed comparative signals between the new epidermal sEMG patch and the conventional adhesive patches used by clinicians. Furthermore, an integrated reference yielded optimal signal for clinical use; this configuration was more robust to head movements than when an external reference was used. Improvements for future iterations of epidermal sEMG patches specific to day-to-day clinical use are suggested.
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Deglutição , Eletromiografia/instrumentação , Epiderme , Eletrodos , Feminino , HumanosRESUMO
Confounding effect is a critical issue in clinical research of otolaryngology because it can distort the research's conclusion. In this review, we introduce the definition of confounding effect, the methods of verifying and controlling the effect. Confounding effect can be prevented by research's design, and adjusted by data analysis. Clinicians would be aware and cautious about confounding effect in their research. They would be able to set up a research's design in which appropriate methods have been applied to prevent this effect.They would know how to adjust confounding effect after data collection. It is important to remember that sometimes it is impossible to eliminate confounding effect completely, and statistical method is not a master key. Solid research knowledge and critical thinking of our brain are the most important in controlling confounding effect.
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Otolaringologia , Projetos de Pesquisa , Viés , Humanos , Análise de Regressão , Estatística como AssuntoRESUMO
The use of imatinib mesylate (IM) (Gleevec, Novartis) in chronic myeloid leukemia (CML) and other neoplastic disorders is in a dramatic increase, inducing long-standing survival. Therefore, the interest in the associated events with this treatment is more and more manifest. We describe a case of CML in which, at the usual antileukemic dose, IM induced a rapid and persistent normalization of the levels of serum cholesterol, triglycerides, low- and high-density lipoproteins and glucose. In the present case report we confirm other observations on the hypolipemiant and antidiabetic effects, concomitant with that antileukemic, of IM.
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Antineoplásicos/uso terapêutico , Hipolipemiantes/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Adulto , Benzamidas , Humanos , Mesilato de Imatinib , MasculinoRESUMO
Cytotoxic lymphocytes employ Granzyme B as a potent initiator of apoptosis to cleave and activate effector caspases. Unexpectedly, cells transfected with Bcl-2 were resistant to granzyme B-induced killing, suggesting that a mitochondrial pathway was critical. Utilizing cells expressing a dominant-negative caspase 9, the current study demonstrated that caspase activation via the apoptosome was not required. Indeed, cleavage of caspase 3 to p20 still occurred in Bcl-2-transfectants but processing to p17 was blocked. This blockade was recapitulated by the Inhibitor-of-Apoptosis-Protein XIAP and relieved by Smac/DIABLO. Thus granzyme B mediates direct cleavage of caspase 3 and also activates mitochondrial disruption, resulting in the release of proapoptotic proteins that suppress caspase inhibition. Engagement of both pathways is critical for granzyme-induced killing.