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AIM: The primary therapeutic option for anal cancer treatment is chemoradiotherapy resulting in 80% survival. The aim of this study was to assess long-term bowel function impairment and anal pain at 3 and 6 years after anal cancer diagnosis, based on a hypothesis of an increase in impairment over time. A secondary aim was to investigate if chemoradiotherapy increased the risk for bowel impairment, compared to radiotherapy alone. METHOD: The ANal CAncer study (ANCA) consists of a national Swedish cohort of patients diagnosed with anal cancer between 2011-2013. Patients within the study were invited to respond to a study-specific questionnaire at 3- and 6-years after diagnosis. Descriptive analyses for the primary endpoint and ordinal logistic regressions for secondary endpoint were performed. RESULTS: A total of 388 patients (84%) were included in the study. At 3 years of follow-up, 264 patients were alive. A total of 195 of these patients (74%) answered a study specific questionnaire, and at 6 years 154 patients (67%). Fifty-seven percent experienced bowel urgency at both 3 and 6 years. There was an increased risk for repeated bowel movement within 1 h (OR 2.44 [95% CI: 1.08-5.61, p = 0.03]) at 3 years in patients who had been treated by chemoradiation compared to radiotherapy alone. CONCLUSIONS: Impairment in bowel function and anal pain after anal cancer treatment should be expected and remains after 6 years. This suggests that long-term follow-up may be necessary in some form after customary follow-up. The addition of chemotherapy increases long-term side effects of bowel function.
Assuntos
Neoplasias do Ânus , Sobreviventes de Câncer , Humanos , Defecação , Anticorpos Anticitoplasma de Neutrófilos , Suécia , Neoplasias do Ânus/terapia , Canal Anal , Medidas de Resultados Relatados pelo Paciente , DorRESUMO
AIM: The standard treatment for anal cancer is chemoradiotherapy. Most patients survive anal cancer but remain living with long-term side effects related to the treatment received. The aim of this study was to assess the occurrence of long-term impairment of urinary and sexual function at 3 and 6 years after diagnosis and to investigate the additive effect from chemotherapy in combined chemoradiotherapy on urinary incontinence, compared to radiotherapy alone. METHOD: The ANal CAncer study (ANCA) is based on a national Swedish cohort of patients diagnosed with anal cancer between 2011 and 2013. All identified patients within the study were invited to respond to a study-specific questionnaire at 3 and 6 years. Descriptive analyses for the primary endpoint were performed. To investigate a possible additional effect from chemotherapy logistic regression was used. RESULTS: A total of 388 patients were included in the study. At 3 years 264 patients were alive and invited to respond to an anal cancer specific questionnaire. The 3- and 6 year response rates were 195 (74%) and 155 patients (67%), respectively. The patient reported urinary function impairment at 3 years were urgency (63%), incomplete bladder emptying (47%), and incontinence (46%) and there was an absolute increase of the prevalence of urinary dysfunction in about 10% at 6 years. Three years after diagnosis, 77% reported that intercourse was not part of their sex life; this percentage increased at 6 years to 83%. We found no negative effect of chemotherapy in combined chemoradiotherapy versus radiotherapy alone on patient reported urinary incontinence. CONCLUSION: For anal cancer survivors, urinary function was impaired after 3 years and continued to deteriorate as measured at 6 years after diagnosis. Anal cancer and its treatment negatively affected sexual function for both men and women. This may explain why patients reported that sexual activity and frequency of intercourse was not of importance in their life.
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Neoplasias do Ânus , Sobreviventes de Câncer , Quimiorradioterapia , Disfunções Sexuais Fisiológicas , Incontinência Urinária , Humanos , Masculino , Feminino , Suécia/epidemiologia , Neoplasias do Ânus/terapia , Neoplasias do Ânus/complicações , Pessoa de Meia-Idade , Idoso , Sobreviventes de Câncer/estatística & dados numéricos , Quimiorradioterapia/efeitos adversos , Disfunções Sexuais Fisiológicas/etiologia , Disfunções Sexuais Fisiológicas/epidemiologia , Incontinência Urinária/etiologia , Incontinência Urinária/epidemiologia , Incontinência Urinária/terapia , Inquéritos e Questionários , Medidas de Resultados Relatados pelo Paciente , Fatores de Tempo , Adulto , Modelos LogísticosRESUMO
BACKGROUND: The societal cost associated with ovarian cancer (OC) is not well known. Increasing costs for new treatments and/or the impact of organizational changes motivates these costs to be described and communicated. This study aims to evaluate the cost of illness of OC in a population-based cohort. MATERIAL AND METHODS: All patients diagnosed with ovarian, fallopian tube, primary peritoneal cancer, and serous cancer of undesignated primary site (UPS) in 2011-2012 were followed for six years. Direct costs, i.e., costs for health care expenditures, were gathered from the regional healthcare database. Information on indirect costs, i.e., costs of loss of production due to sick leave, was retrieved from Statistics Sweden. Sub-group analyses were conducted regarding stage, income levels, residential area, and diagnosis. RESULTS: The cost of illness for all stages during the six years of follow-up was 201,086 per patient, where indirect costs constituted 43.7%. The mean cost of illness per year per patient for all stages was 33,514. Direct costs were higher in advanced stages compared to early stages for every year from diagnosis. During the first two years, there were no differences in indirect costs between early and advanced stages. However, during the third year there was a difference with higher indirect costs in advanced stages. There was no difference in direct costs depending on income levels. Regarding residential area, there was a difference in the outpatient cost during the index and second year with higher costs when chemotherapy and follow-up were provided at county hospitals, compared to at the tertiary hospital. CONCLUSIONS: Indirect costs constituted a large part of the cost of illness over 6 years from diagnosis. This could indicate that even though treatment costs can be expected to rise with the introduction of new therapies, the societal cost may decrease when survival increase.
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Custos de Cuidados de Saúde , Neoplasias Ovarianas , Humanos , Feminino , Gastos em Saúde , Estudos de Coortes , Neoplasias Ovarianas/terapia , Carcinoma Epitelial do Ovário/terapia , Efeitos Psicossociais da DoençaRESUMO
BACKGROUND: Squamous cell carcinoma of the anus is increasing in incidence but remains a rare disease with good 3- and 5-year recurrence free and overall survival rates of 63%-86%. The treatment includes chemoradiotherapy, mainly with 5-fluoruracil (5FU) and mitomycin. The aim of this study was to describe long-term (up to 9 years after treatment) oncological outcome and the types of treatments given, in a Swedish national cohort of patients diagnosed with anal cancer between 2011 and 2013. METHOD: Patients were identified in the Swedish Cancer Registry. Patients still alive were contacted and asked for consent. Clinical data were retrieved from National Patient Register at the Swedish National Board of Health and Welfare and from medical records. Unadjusted and adjusted analyses were performed for overall survival. RESULTS: Three hundred and eighty-eight patients were included in the study of which 338 patients (87%) received treatment with a curative intent. Follow up was 85 months (0-113 months) for patients treated with curative intent (information missing in one patient) 7.5 months (0-55) for patients with treated with a palliative intent. Curative treatment varied and consisted of both chemoradiotherapy and radiotherapy (46-64 Gy) alone. 5-FU, mitomycin and cisplatin were the most used chemotherapy agents. Five-year overall survival for patients treated with curative intent was 73%. In an adjusted analysis 5-FU and mitomycin is associated with a lower mortality than 5-FU and cisplatin but the association was weaker (HR 1.61 (95% CI: 0.904; 2.85) than in the unadjusted analysis. CONCLUSIONS: In this national cohort overall five-year survival was 73% for patients treated with curative intent. As reported by others our results indicate that 5-FU and mitomycin C should be the preferred chemotherapy in treatment for cure.
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Anticorpos Anticitoplasma de Neutrófilos , Neoplasias do Ânus , Anticorpos Anticitoplasma de Neutrófilos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Ânus/patologia , Quimiorradioterapia/métodos , Cisplatino , Estudos de Coortes , Fluoruracila/uso terapêutico , Humanos , Mitomicina , Suécia/epidemiologia , Resultado do TratamentoRESUMO
PURPOSE: The impact of anal cancer treatment for the patients is best evaluated by the patients themselves. The purpose of this study was to investigate quality of life (QoL) in patients with anal cancer at 3 and 6 years after treatment. METHODS: A Swedish national cross-sectional prospective cohort study with patients diagnosed with anal cancer between 2011 and 2013. Patients were invited to respond to a QoL questionnaire at 3 and 6 years, with focus on bowel, urinary and sexual function, social and mental function, co-morbidity, lifestyle, daily activities, personal characteristics, and perceived QoL. It also contained questions on the severity of the symptoms regarding occurrence, frequency, and duration and the level of "bother" experienced related to functional symptoms. QoL and prevalence of bother with urinary, sexual, bowel dysfunction, and anal pain were described. The prevalence of impaired QoL was compared with a healthy reference population. The association between QoL and experiencing bother was quantified by regression models. RESULTS: From an original cohort of 464 patients with anal cancer, 264 (57%) were alive and contacted at 3 years and 230 (50%) at 6 years. One hundred ninety-five (74%) patients responded to the 3-year and 152 (66%) to the 6-year questionnaire. Sixty percent reported low QoL at both 3 and 6 years. Impaired QoL was more prevalent among patients with major bother due to bowel dysfunction (at 3 years RR 1.42, 95% CI (1.06-1.9) p-value 0.020, at 6 years RR 1.52, 95% CI (1.03-2.24) p-value 0.034) and urinary dysfunction (at 6 years RR 1.44, 95% CI (1.08-1.91) p-value 0.013). There was a tendency to a positive relationship between the number of bodily functions causing bother and risk for impaired QoL. CONCLUSION: Patients treated for anal cancer reported bother regarding several bodily functions as well as poor QoL both at 3 and 6 years without much improvement. Bother was also associated with low QoL indicating that function-related bother should be addressed.
Assuntos
Neoplasias do Ânus , Sobreviventes de Câncer , Anticorpos Anticitoplasma de Neutrófilos , Estudos Transversais , Humanos , Medidas de Resultados Relatados pelo Paciente , Estudos Prospectivos , Qualidade de Vida , Inquéritos e Questionários , Suécia/epidemiologiaRESUMO
INTRODUCTION: Surgical complications after primary or interval debulking surgery in advanced ovarian cancer were investigated and associations with patient characteristics and surgical outcomes were explored. MATERIAL AND METHODS: A population-based cohort study including all women with ovarian cancer, FIGO III-IV, treated with primary or interval debulking surgery, 2013-2017. Patient characteristics, surgical outcomes and complications according to the Clavien-Dindo (CD) classification system ≤30 days postoperatively, were registered. Uni- and multivariable regression analyses were performed with severe complications (CD ≥ III) as endpoint. PFS in relation was analyzed using the Kaplan-Meier method. RESULTS: The cohort included 384 women, where 304 (79%) were treated with primary and 80 (21%) with interval debulking surgery. Complications CD I-V were registered in 112 (29%) patients and CD ≥ III in 42 (11%). Preoperative albumin was significantly lower in the CD ≥ III cohort compared with CD 0-II (P = 0.018). For every increase per unit in albumin, the risk of complications decreased by a factor of 0.93. There was no significant difference in completed chemotherapy between the cohorts CD 0-II 90.1% and CD ≥ III 83.3% (P = 0.236). In the univariable analysis; albumin <30 g/L, primary debulking surgery, complete cytoreduction and intermediate/high surgical complexity score (SCS) were associated with CD ≥ III. In the following multivariable analysis, only intermediate/high SCS was found to be an independent significant prognostic factor. Low (n = 180) vs intermediate/high SCS (n = 204) showed a median PFS of 17.2 months (95% confidence interval [CI] 15.2-20.7) vs 21.5 months (95% CI 18.2-25.7), respectively, with a significant log-rank; P = 0.038. CONCLUSIONS: Advanced ovarian cancer surgery is associated with complications but no significant difference was seen in completion of adjuvant chemotherapy when severe complications occur. Importantly, our study shows that intermediate/high SCS is an independent prognostic risk factor for complications. Low albumin, residual disease and primary debulking surgery were found to be associated with severe complications. These results may facilitate forming algorithms in the decision-making procedure of surgical treatment protocols.
Assuntos
Terapia Neoadjuvante , Neoplasias Ovarianas , Albuminas/uso terapêutico , Carcinoma Epitelial do Ovário/patologia , Quimioterapia Adjuvante , Estudos de Coortes , Feminino , Humanos , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , Estudos RetrospectivosRESUMO
BACKGROUND: Dizziness is a common complaint among older adults and may affect quality of life in a negative way. The aim of this study was to assess health-related quality of life (HRQL), sense of coherence (SOC), self-rated health (SRH) and comorbidity in relation to dizziness, among older persons from an urban population. METHODS: The study is part of the Gothenburg H70 Birth Cohort Studies (H70). A cross-sectional population-based sample including 662 79-years-olds (404 women, 258 men, 62% response rate) were surveyed with questions regarding dizziness, imbalance, comorbidities and general health. HRQL was assessed using the 36-item Short Form-36 Health Survey (SF-36) and SOC with the 13-items questionnaire Sense of Coherence (SOC-13). RESULTS: Half of the participants reported problems with dizziness (54%). Dizziness was negatively associated with HRQL, including after adjusting for comorbidities, especially in the physical domains of SF-36. Having dizziness was also associated with poorer SRH, tiredness and comorbidity among both men and women. SOC (mean total score), however, did not differ between dizzy and non-dizzy participants. CONCLUSIONS: Dizziness was negatively associated with HRQL, also after adjusting for comorbidities. Identification and treatment of dizziness, when possible, are important because reduction of dizziness symptoms may potentially help to enhance overall well-being in this age group.
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Tontura , Qualidade de Vida , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Tontura/epidemiologia , Feminino , Humanos , Masculino , Inquéritos e Questionários , População UrbanaRESUMO
PURPOSE: Dizziness may affect quality of life in a negative way and contribute to falls. The aim of this study was to investigate and compare 75 years old with dizziness caused by benign paroxysmal positional vertigo (BPPV) to those with general dizziness/impaired balance (non-BPPV related) and to those reporting no dizziness, regarding health-related quality of life (HRQL), falls, tiredness, and walking speed in a population-based setting. METHOD: A cross-sectional population-based sample, including 671 75 years old (398 women, 273 men), was investigated for BPPV, dizziness symptoms, falls, and walking speed. HRQL was assessed using the 36-item Short Form-36 Health Survey (SF-36). RESULT: A total of 67 persons (10%) had symptoms of BPPV with 11 (1.6%) having nystagmus when tested for BPPV. Having BPPV as well as general dizziness/impaired balance was associated with reduced HRQL, more tiredness, enhanced number of falls, and lower walking speed. Furthermore, the risk of having BPPV increased fourfold if symptoms of dizziness when turning in bed was reported. CONCLUSION: Having problems with dizziness is common among senior citizens where BPPV can be an unrecognized cause of dizziness that may impact HRQL and overall well-being. As BPPV is common among older adults, and is potentially curable through reposition maneuvers, it is important to liberally test for, and treat the condition. Information about dizziness when turning in bed can help to pinpoint persons with enhanced risk for BPPV also on a population-based level.
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Nistagmo Patológico , Qualidade de Vida , Idoso , Vertigem Posicional Paroxística Benigna/epidemiologia , Estudos Transversais , Tontura/epidemiologia , Feminino , Humanos , MasculinoRESUMO
OBJECTIVE: To analyze 5-year disease-free survival (DFS) and relative survival (RS) before and after the 2011 implementation of centralized primary treatment of patients with advanced ovarian cancer. METHODS: A population-based cohort study using the Swedish Quality Registry for Gynecological Cancer (SQRGC). Women with FIGO stage III and IV epithelial ovarian and Fallopian tube cancers were divided into two cohorts: before and after centralization. We estimated RS using the Ederer II method, analyzed the difference in the excess mortality rate ratio (EMRR) and estimated 5-year DFS in a Cox proportional hazard regression model with centralization, age, primary treatment and complete cytoreduction as variables. RESULTS: A total of 495 women were identified with 244 women before (2008-2010) and 251 after (2011-2013) centralization. An increased 5-year RS from 24% (95%CI:19-31) to 37% (95%CI:31-44) and an increased median RS from 27 months (95%CI:23-34) to 44 months (95%CI:40-52), p < 0.001 (log-rank), were observed in the total cohort regardless of primary treatment. EMRR was found to be 0.62 (95%CI:0.51-0.76) in 2011-2013 compared to 2008-2010 for all patients. After centralization, 5-year DFS was significantly longer, hazard ratio of 0.77 (95%CI:0.64-0.93) and centralization was found to be an independent significant factor for both survival and DFS. Complete cytoreduction was found to be a significant independent factor associated with increased RS and DFS. CONCLUSION: Centralization of primary treatment of advanced ovarian cancer was associated with significantly increased complete cytoreduction, 5-year RS and DFS, and was found to be a significant independent factor for both RS and DFS.
Assuntos
Carcinoma Epitelial do Ovário/mortalidade , Neoplasias Ovarianas/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Epitelial do Ovário/terapia , Procedimentos Cirúrgicos de Citorredução , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Neoplasias Ovarianas/terapia , Intervalo Livre de Progressão , Sistema de Registros , Estudos Retrospectivos , SuéciaRESUMO
The formation of metastases is driven by the ability of cancer cells to disseminate from the site of the primary tumour to target organs. The process of dissemination is constrained by anatomical features such as the flow of blood and lymph in the circulatory system. We exploit this fact in a stochastic network model of metastasis formation, in which only anatomically feasible routes of dissemination are considered. By fitting this model to two different clinical datasets (tongue & ovarian cancer) we show that incidence data can be modelled using a small number of biologically meaningful parameters. The fitted models reveal site specific relative rates of dissemination and also allow for patient-specific predictions of metastatic involvement based on primary tumour location and stage. Applied to other data sets this type of model could yield insight about seed-soil effects, and could also be used in a clinical setting to provide personalised predictions about the extent of metastatic spread.
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Modelos Biológicos , Metástase Neoplásica/patologia , Biologia Computacional , Feminino , Humanos , Cinética , Metástase Linfática/patologia , Masculino , Invasividade Neoplásica/patologia , Inoculação de Neoplasia , Células Neoplásicas Circulantes/patologia , Neoplasias Ovarianas/patologia , Processos Estocásticos , Neoplasias da Língua/patologiaRESUMO
BACKGROUND: The aim of this study was to adapt the instrument and evaluate the psychometric properties of the Swedish version of the Swallowing Quality of Care questionnaire (S-SWAL-CARE) in patients with oropharyngeal dysphagia. METHODS: Translation and adaptation of the original SWAL-CARE into Swedish was performed according to established international guidelines. Field testing was performed using 100 patients with oropharyngeal dysphagia due to multiple reasons such as head and neck cancer and neurologic/neuromuscular disease, who had undergone swallowing evaluation within 6 months prior to the study. The patients answered the S-SWAL-CARE, the Quality from the Patient's Perspective (QPP) and the Swallowing Quality of Life (SWAL-QOL). Test-retest was performed in 20% of the participants. The reliability and validity of the S-SWAL-CARE were assessed by Pearson correlation coefficient and Cronbach's alpha as well as convergent and discriminative validity, respectively. RESULTS: The field testing of the S-SWAL-CARE resulted in sufficient reliability, with Cronbach's alpha values exceeding 0.90 for all domains. All items correlated strongly to their own domain, with weaker correlations to the other domains, indicating proper scale structure. Results also indicate sufficient convergent and discriminant validity when tested for association to the QPP domains and the SWAL-QOL Total score. The test-retest reliability of the S-SWAL-CARE demonstrated sufficient intraclass correlation coefficient (ICC) for the General advice domain (0.73) and Clinical advice domain (0.82). The ICC for the Patient satisfaction domain was lower (0.44). CONCLUSION: The S-SWAL-CARE can be considered a reliable and valid tool to assess the dysphagia-related quality of care in a mixed Swedish dysphagia patient population.
Assuntos
Transtornos de Deglutição/psicologia , Qualidade de Vida , Inquéritos e Questionários/normas , Adulto , Idoso , Idoso de 80 Anos ou mais , Transtornos de Deglutição/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Psicometria/instrumentação , Qualidade da Assistência à Saúde/normas , Reprodutibilidade dos Testes , Suécia , TraduçõesRESUMO
INTRODUCTION: Voice problems are common following radiotherapy for laryngeal cancer. Few studies exist covering the effect of voice rehabilitation, and no previous studies exist regarding the cost of said rehabilitation. This randomized controlled study aimed to analyze the cost-effectiveness of voice rehabilitation after radiotherapy for patients with laryngeal cancer. MATERIAL AND METHODS: A total of 66 patients with laryngeal cancer with follow-up data 12 months post-radiotherapy were included. Patients were randomized into receiving either voice rehabilitation (n = 32) or no voice rehabilitation (n = 34). The patient outcome was measured as quality-adjusted life years (QALYs). The index range between 0 and 1, where 0 equals death and 1 represents perfect health. The QALYs were assessed with the European Organization for Research and Treatment of Cancer questionnaire QLQ-C30 mapped to EuroQoL 5 Dimension values. The cost of rehabilitation and other healthcare visits was derived from hospital systems. The patients reported the total amount of sick leave days during the first 12 months following radiotherapy. The cost-effectiveness of the voice rehabilitation was compared with no rehabilitation intervention based on the incremental cost-effectiveness ratio. RESULTS: The cost per gained QALY with voice rehabilitation compared to no rehabilitation from a societal perspective was - 27,594 (SEK - 250,852) which indicates that the voice rehabilitation is a cost-saving alternative compared to no rehabilitation due to lower costs and a slightly better health outcome. From a healthcare perspective, the voice rehabilitation indicates a cost 60,800 (SEK 552,725) per gained QALY. CONCLUSION: From a societal perspective, i.e., including the costs of production loss, voice rehabilitation compared to no voice rehabilitation following radiotherapy for laryngeal cancer seems to be cost-saving. When analyzing only the healthcare costs in relation to health outcomes, voice rehabilitation indicates an incremental cost of 60,800 per gained QALY, which is just above the threshold of the maximum willingness to pay level.
Assuntos
Neoplasias Laríngeas/reabilitação , Lesões por Radiação/reabilitação , Distúrbios da Voz/reabilitação , Adulto , Análise Custo-Benefício , Feminino , Custos de Cuidados de Saúde , Humanos , Neoplasias Laríngeas/economia , Neoplasias Laríngeas/patologia , Neoplasias Laríngeas/radioterapia , Masculino , Pessoa de Meia-Idade , Anos de Vida Ajustados por Qualidade de Vida , Lesões por Radiação/etiologia , Lesões por Radiação/patologia , Inquéritos e Questionários , Suécia , Distúrbios da Voz/etiologia , Distúrbios da Voz/patologiaRESUMO
BACKGROUND: Dizziness is common among older people and falling is a feared complication. AIM: The purpose of this study was to investigate the presence of dizziness and its association with falls, walking speed and fear of falling, including sex differences, among 79-year-olds. Secondary purposes were to describe the relationship between dizziness and falls to number of medications and diseases. METHOD: The study consisted of the fifth cohort of Gothenburg's H70 birth cohort studies. A sample of 662 79-year-olds (404 women, 258 men) were investigated with questions regarding dizziness, previous falls and falls efficacy [estimated according to the falls efficacy scale Swedish version (FES (S))]. Functional tests included self-selected and maximal walking speed over 20 m. RESULTS: Dizziness was reported among 51% of the women and by 58% of the men (p = 0.12). Approximately, 40% had fallen during the past 12 months (41% women, 38% of the men, p = 0.48). Dizziness was related to a higher risk of falls among women (OR 2.63 (95% CI 1.67-4.14, p < 0.0001), but not among men (OR 1.07, 95% CI 0.63-1.82, p = 0.8). Dizzy individuals had lower scores on FES (S) (p < 0.01), more medications (p < 0.001) and diseases (p < 0.001) than those without dizziness. Participants who reported dizziness walked 10% slower than participants without dizziness (p < 0.001). CONCLUSION: Women with dizziness more often reported falls compared to women without dizziness-a trend that was not seen among men. Persons with dizziness walked slower. Many medications increased risk of falling; hence, number of medications alone might help pinpoint risk groups for falling.
Assuntos
Tontura , Velocidade de Caminhada , Acidentes por Quedas , Idoso , Estudos de Coortes , Tontura/epidemiologia , Medo , Feminino , Humanos , Masculino , Fatores de Risco , Suécia/epidemiologia , População UrbanaRESUMO
OBJECTIVE: It has been suggested that asthmatics are more susceptible than healthy individuals to airborne irritating chemicals in general. However, there is limited human data available to support this hypothesis due to ethical and practical difficulties. We explored a murine model of ovalbumin (OVA)-induced airway inflammation to study susceptibility during acute exposure to chemicals with chlorine as a model substance. METHODS: Naïve and OVA sensitized female BALB/c mice were exposed to chlorine at four different concentrations (0, 5, 30 and 80 ppm) for 15 minutes with online recording of the respiratory function by plethysmography. The specific effects on respiratory mechanics, inflammatory cells and inflammatory mediators (cytokines and chemokines) of the airways were measured 24 hours after the chlorine exposure as well as histopathological examination of the lungs. RESULTS: Similar concentration-dependent reductions in respiratory frequency were seen in the two groups, with a 50% reduction (RD50) slightly above 5 ppm. Decreased body weight 24 hours after exposure to 80 ppm was also observed in both groups. Naïve, but not OVA-sensitized, mice showed increased bronchial reactivity and higher number of neutrophils in bronchoalveolar lavage fluid at 80 ppm. CONCLUSIONS: The results do not support an increased susceptibility to chlorine among OVA-sensitized mice. This animal model, which represents a phenotype of eosinophilic airway inflammation, seems unsuitable to study susceptibility to inhalation of irritants in relation to asthma.
Assuntos
Alérgenos , Asma , Cloro/toxicidade , Irritantes/toxicidade , Ovalbumina , Administração por Inalação , Animais , Asma/sangue , Asma/imunologia , Asma/patologia , Asma/fisiopatologia , Líquido da Lavagem Broncoalveolar/imunologia , Citocinas/imunologia , Modelos Animais de Doenças , Feminino , Imunoglobulina E/sangue , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Mecânica Respiratória/efeitos dos fármacosRESUMO
BACKGROUND: Asthmatic individuals constitute a large sub-population that is often considered particularly susceptible to the deleterious effects of inhalation of airborne chemicals. However, for most such chemicals information on asthmatics is lacking and inter-individual assessment factors (AFs) of 3-25 have been proposed for use in the derivation of health-based guideline values. OBJECTIVE: To evaluate available information in attempt to determine whether a general difference in airway response during short-term exposure between healthy and asthmatic individuals can be identified, and whether current AFs for inter-individual variability provide sufficient protection for asthmatics. METHODS: After performing systematic review of relevant documents and the scientific literature estimated differential response factors (EDRF) were derived as the ratio between the lowest observed adverse effect levels for healthy and asthmatic subjects based on studies in which both groups were tested under the same conditions. Thereafter, the concentration-response relationships for healthy and asthmatic subjects exposed separately to four extensively tested chemicals (nitrogen dioxide, ozone, sulfuric acid, sulfur dioxide) were compared on the basis of combined data. Finally, a Benchmark Concentration (BMC) analysis was performed for sulfur dioxide. RESULTS: We found evidence of higher sensitivity among asthmatics (EDRF > 1) to 8 of 19 tested chemicals, and to 3 of 11 mixtures. Thereafter, we confirmed the higher sensitivity of asthmatics to sulfuric acid and sulfur dioxide. No difference was observed in the case of ozone and nitrogen dioxide. Finally, our BMC analysis of sulfur dioxide indicated a ninefold higher sensitivity among asthmatics. CONCLUSION: Although experimental data are often inconclusive, our analyses suggest that an AF of 10 is adequate to protect asthmatics from the deleterious respiratory effects of airborne chemicals.
Assuntos
Poluentes Atmosféricos/efeitos adversos , Asma/diagnóstico , Asma/induzido quimicamente , Asma/prevenção & controle , Bases de Dados Factuais , Humanos , Dióxido de Nitrogênio/toxicidade , Ozônio/toxicidade , Dióxido de Enxofre/toxicidade , Ácidos Sulfúricos/toxicidadeRESUMO
Asthma, a chronic respiratory disease, can be aggravated by exposure to certain chemical irritants. The objectives were first to investigate the extent to which experimental observations on asthmatic subjects are taken into consideration in connection with the registration process under the EU REACH regulation, and second, to determine whether asthmatics are provided adequate protection by the derived no-effect levels (DNELs) for acute inhalation exposure. We identified substances for which experimental data on the pulmonary functions of asthmatics exposed to chemicals under controlled conditions are available. The effect concentrations were then compared with DNELs and other guideline and limit values. As of April 2015, only 2.6% of 269 classified irritants had available experimental data on asthmatics. Fourteen of the 22 identified substances with available data were fully registered under REACH and we retrieved 114 reliable studies related to these. Sixty-three of these studies, involving nine of the 14 substances, were cited by the REACH registrants. However, only 17 of the 114 studies, involving four substances, were regarded as key studies. Furthermore, many of the DNELs for acute inhalation were higher than estimated effect levels for asthmatics, i.e., lowest observed adverse effect concentrations or no-observed adverse effect concentrations, indicating low or no safety margin. We conclude that REACH registrants tend to disregard findings on asthmatics when deriving these DNELs. In addition, we found examples of DNELs, particularly among those derived for workers, which likely do not provide adequate protection for asthmatics. Copyright © 2016 The Authors Journal of Applied Toxicology Published by John Wiley & Sons Ltd.
Assuntos
Poluentes Ocupacionais do Ar/toxicidade , Asma/induzido quimicamente , Exposição por Inalação/análise , Exposição Ocupacional/análise , Saúde Ocupacional/legislação & jurisprudência , União Europeia , Regulamentação Governamental , Humanos , Exposição por Inalação/legislação & jurisprudência , Exposição por Inalação/normas , Concentração Máxima Permitida , Nível de Efeito Adverso não Observado , Exposição Ocupacional/legislação & jurisprudência , Exposição Ocupacional/normas , Saúde Ocupacional/normas , Níveis Máximos Permitidos , Local de Trabalho/normasRESUMO
BACKGROUND: To provide further information about short-term effects on voice quality and health-related quality of life (HRQL) following radiotherapy for laryngeal cancer, comparing glottic and supraglottic tumours. MATERIAL AND METHODS: Sixty-seven male patients who received radiotherapy for glottic and supraglottic tumours were included. Voice recordings were performed and patient reported outcome questionnaires filled in before radiotherapy and one-month post-completion. Acoustic and temporal measures were produced from the recordings and compared to an age-matched, vocally healthy control group (n = 23). RESULTS: Deterioration of HRQL post-radiotherapy was noted for both the glottic and supraglottic cohort. Pre- radiotherapy the glottic cohort demonstrated acoustic and temporal measures that were statistically different from healthy controls, with improvements post-radiotherapy where several measures showed no statistically significant differences compared to healthy controls. The supraglottic cohort revealed voice measures comparable to the healthy controls but demonstrated statistically significant impairments in HRQL compared to the glottic cohort following radiotherapy. CONCLUSION: Patients with supraglottic tumours may experience more eating and swallowing related problems prior to radiotherapy compared to glottic tumours and demonstrate a more significant reduction in HRQL following treatment. However, in terms of voice measurements, subjective measures correlate poorly with objective acoustic parameters, thereby emphasising the importance of patient-reported outcomes as part of treatment evaluation.
Assuntos
Carcinoma de Células Escamosas/radioterapia , Nível de Saúde , Neoplasias Laríngeas/radioterapia , Qualidade de Vida , Qualidade da Voz/efeitos da radiação , Idoso , Estudos de Casos e Controles , Transtornos de Deglutição/etiologia , Glote/efeitos da radiação , Humanos , Neoplasias Laríngeas/patologia , Masculino , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Inquéritos e Questionários , Qualidade da Voz/fisiologiaRESUMO
OBJECTIVE: This study aims to assess the effect of voice rehabilitation on health-related quality of life (HRQL) and communication experience for laryngeal cancer patients treated with radiotherapy. METHOD: This prospective randomised controlled trial included 74 patients with Tis-T4 laryngeal cancer treated curatively by radiotherapy, of which 37 constituted the intervention group receiving voice rehabilitation and 37 patients as a control group. Patients were followed at one and six months post-radiotherapy, with voice rehabilitation conducted between these time-points. Endpoints included patient reported outcomes, including HRQL as measured by European Organisation for Research and Treatment of Cancer (EORTC) Core30 (C30) and Head & Neck35 (H&N35) as well as communication function as measured by Swedish Self-Evaluation of Communication Experiences after Laryngeal cancer (S-SECEL). RESULTS: The intervention group reported statistically significant improvements in communication experience as measured by S-SECEL environmental, attitudinal and total score domains compared to the control group. Similar improvements were seen in EORTC H&N35 Speech domain and the EORTC C30 domain Global quality of life. Moderate correlations were noted (r = 0.51-0.59) between three of four S-SECEL domains and the EORTC domains Speech and Global quality of life. CONCLUSION: Laryngeal cancer patients treated with radiotherapy who receive voice rehabilitation appear to experience beneficial effects on communication function and selected HRQL domains. Voice rehabilitation following radiotherapy is recommended but further research investigating potential target groups and long-term effects is required.
Assuntos
Neoplasias Laríngeas/radioterapia , Qualidade de Vida , Radioterapia/efeitos adversos , Distúrbios da Voz/reabilitação , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Distúrbios da Voz/etiologiaRESUMO
Intraperitoneal 211At-based targeted α-therapy (TAT) may hold great promise as an adjuvant therapy after surgery and chemotherapy in epithelial ovarian cancer to eradicate any remaining undetectable disease. This implies that it will also be delivered to patients possibly already cured by the primary treatment. An estimate of long-term risks is therefore sought to determine whether the treatment is justified. Methods: Baseline data for risk estimates of α-particle irradiation were collected from published studies on excess cancer induction and mortality for subjects exposed to either 224Ra treatments or Thorotrast contrast agent (25% ThO2 colloid, containing 232Th). Organ dosimetry for 224Ra and Thorotrast irradiation were taken from the literature. These organ-specific risks were then applied to our previously reported dosimetry for intraperitoneal 211At-TAT patients. Results: Risk could be estimated for 10 different organ or organ groups. The calculated excess relative risk per gray (ERR/Gy) could be sorted into 2 groups. The lower-ERR/Gy group, ranging up to a value of approximately 5, included trachea, bronchus, and lung, at 0.52 (95% CI, 0.21-0.82); stomach, at 1.4 (95% CI, -5.0-7.9); lymphoid and hematopoietic system, at 2.17 (95% CI, 1.7-2.7); bone and articular cartilage, at 2.6 (95% CI, 2.0-3.3); breast, at 3.45 (95% CI, -10-17); and colon, at 4.5 (95% CI, -3.5-13). The higher-ERR/Gy group, ranging from approximately 10 to 15, included urinary bladder, at 10.1 (95% CI, 1.4-23); liver, at 14.2 (95% CI, 13-16); kidney, at 14.9 (95% CI, 3.9-26); and lip, oral cavity, and pharynx, at 15.20 (95% CI, 2.73-27.63). Applying a typical candidate patient (female, age 65 y) and correcting for the reference population mortality rate, the total estimated excess mortality for an intraperitoneal 211At-monoclonal antibody treatment amounted to 1.13 per 100 treated. More than half this excess originated from urinary bladder and kidney, 0.29 and 0.34, respectively. Depending on various adjustments in calculation and assumptions on competing risks, excess mortality could range from 0.11 to 1.84 per 100 treated. Conclusion: Published epidemiologic data on lifelong detriment after α-particle irradiation and its dosimetry allowed calculations to estimate the risk for secondary cancer after 211At-based intraperitoneal TAT. Measures to reduce dose to the urinary organs may further decrease the estimated relative low risk for secondary cancer from 211At-monoclonal antibody-based intraperitoneal TAT.