ABSTRACT
BACKGROUND: Symptom assessment is key to effective symptom management and palliative care for patients with advanced cancer. Symptom prevalence and severity estimates vary widely, possibly dependent on the assessment tool used. Are symptoms specifically asked about or must the patients add them as additional symptoms? This study compared the prevalence and severity of patient-reported symptoms in two different versions of a multi-symptom assessment tool. In one version, three symptoms dry mouth, constipation, sleep problems were among those systematically assessed, while in the other, these symptoms had to be added as an "Other problem". METHODS: This retrospective cross-sectional study included adult patients with advanced cancer at an inpatient palliative care unit. Data were collected from two versions of the Edmonton Symptom Assessment System (ESAS): modified (ESAS-m) listed 11 symptoms and revised (ESAS-r) listed 9 and allowed patients to add one "Other problem". Seven similar symptoms were listed in both versions. RESULTS: In 2013, 184 patients completed ESAS-m, and in 2017, 156 completed ESAS-r. Prevalence and severity of symptoms listed in both versions did not differ. In ESAS-m, 83% reported dry mouth, 73% constipation, and 71% sleep problems, but on ESAS-r, these symptoms were reported by only 3%, 15% and < 1%, respectively. Although ESAS-r severity scores for these three symptoms were higher than on ESAS-m, differences did not reach statistical significance. CONCLUSION: We identified significant differences in patient symptom reporting based on whether symptoms like dry mouth, obstipation and sleep problems were specifically assessed or had to be added by patients as an "Other problem".
Subject(s)
Neoplasms , Sleep Wake Disorders , Adult , Humans , Palliative Care , Inpatients , Symptom Assessment , Prevalence , Cross-Sectional Studies , Retrospective Studies , Neoplasms/complications , Neoplasms/epidemiology , Neoplasms/therapy , Constipation/diagnosis , Constipation/epidemiologyABSTRACT
BACKGROUND: Patients with advanced cancer are prone to develop different opportunistic oral infection due to anti-cancer treatment or the malignancies themselves. Studies of oral fungal samples show an increased prevalence of non-Candida albicans species in mixed oral infections with Candida albicans. Non-C. albicans and C. albicans are associated with varying degrees of resistance to azoles, which may have implications for treatment. This study aimed to assess the diversity and antifungal susceptibility of Candida species detected in the oral cavity. METHODS: An observational study with microbiological analysis was conducted. Clinical fungal isolates were collected from patients in a hospice unit in 2014-2016. Isolates were re-grown on chromID® Candida plates in 2020. Single colony of each species was re-cultivated and prepared for biochemical identification with a VITEK2® system and verified by gene sequencing. Etest was performed on RPMI agar, and the antifungals fluconazole, amphotericin B, anidulafungin and nystatin were applied. RESULTS: Fifty-six isolates from 45 patients were identified. Seven different Candida species and one Saccharomyces species were detected. The results of biochemical identification were confirmed with sequencing analysis. Thirty-six patients had mono infection, and nine out of 45 patients had 2-3 different species detected. Of C. albicans strains, 39 out of 40 were susceptible to fluconazole. Two non-C. albicans species were resistant to fluconazole, one to amphotericin B and three to anidulafungin. CONCLUSION: C. albicans was the predominant species, with a high susceptibility to antifungal agents. Different Candida species occur in both mono and mixed infections. Identification and susceptibility testing may therefore lead to more effective treatment and may prevent the development of resistance among patients with advanced cancer. TRAIL REGISTRATION: The study Oral Health in Advanced Cancer was registered at ClinicalTrials.gov (#NCT02067572) in 20/02/2014.
Subject(s)
Candidiasis, Oral , Neoplasms , Humans , Candidiasis, Oral/microbiology , Fluconazole/pharmacology , Fluconazole/therapeutic use , Amphotericin B/pharmacology , Amphotericin B/therapeutic use , Anidulafungin/pharmacology , Anidulafungin/therapeutic use , Microbial Sensitivity Tests , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Candida , Candida albicans , Neoplasms/drug therapy , Drug Resistance, FungalABSTRACT
PURPOSE: To investigate oral and dental late effects in survivors of childhood brain tumors medulloblastoma (MB) and central nervous system supratentorial primitive neuroectodermal tumor (CNS-PNET). METHODS: This cross-sectional study assessed oral and dental late effects in MB/CNS-PNET survivors treated before 20 years of age, and with a minimum of 2 years since treatment. Participants went through an oral and radiographic examination. We assessed oral status using the decayed-missing-filled index (DMFT), oral dryness, maximum mouth opening (MMO), fungal infection, and registration of dental developmental disturbances (DDD) in the form of hypodontia, microdontia, and enamel hypoplasia. RESULTS: The 46 participants' mean age at enrolment was 27 ± 12.8 years and at treatment 8.5 ± 5.2 years, and the mean time since treatment was 18.9 ± 12 years. Over a third (35%) of survivors had reduced mouth opening (mean 29.3 ± 5.6 mm (range 16-35)). A significantly lower MMO was found in individuals treated ≤ 5 years compared to survivors treated > 5 years (p = 0.021). One or more DDD were registered in 30.4% of the survivors, with a significantly higher prevalence in individuals treated ≤ 5 years (p < 0.001). Hypodontia was the most prevalent type of DDD. There was no difference in DMFT score in relation to age at treatment. Oral dryness was not frequently reported or observed in these survivors. CONCLUSION: Survivors of childhood MB/CNS-PNET are at risk of oral and dental late effects including reduced mouth opening and DDD. The risk is highest in survivors treated before the age of 5.
Subject(s)
Anodontia , Brain Neoplasms , Dental Caries , Mouth Abnormalities , Neuroectodermal Tumors, Primitive , Humans , Cross-Sectional Studies , Survivors , Neuroectodermal Tumors, Primitive/pathology , Brain Neoplasms/epidemiology , Brain Neoplasms/therapy , PrevalenceABSTRACT
PURPOSE: Long-term survivors (LTSs) of allogeneic hematopoietic stem cell transplantation (allo-HCT) may experience oral long-term effects like chronic graft-versus-host disease (oral cGVHD). The aim of this study was to investigate oral cGVHD in patients treated at a young age (< 30 years) more than 5 years after allo-HCT without total body irradiation (TBI). METHODS: All 94 participants went through a semi-structured interview, and an oral examination. Diagnosis of oral cGVHD was based on the "National Institutes of Health (NIH) cGVHD diagnosis and staging consensus criteria" from 2014. RESULTS: Mean age at transplantation was 17.5 years (range 0.4-29.9 years), and mean time since transplantation was 16.7 years (range 6-26 years). Oral cGVHD was diagnosed in 26 (28%) of 94 LTSs. Of which 20 (21.5%) showed lichen planus-like (LPL) changes, and additionally six (6.5%) also fulfilled the diagnostic criteria of oral cGVHD since they had one or more distinctive signs and symptoms of oral cGVHD combined with definite cGVHD in another organ. No LTSs reported oral cGVHD (NIH) grade 3. There was a significant association between cGVHD in the oral cavity and cGVHD in another organ (77% vs 29%, p < 0.001). Out of 72 LTSs, who answered the questions regarding taste disturbances, 16 (22%) reported dysgeusia. No LTSs developed secondary malignancies in the oral cavity during follow-up time. CONCLUSION: Oral long-term effects, such as oral cGVHD, may persist for many years after allo-HCT without TBI-conditioning in patients treated at a young age.
Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Adolescent , Adult , Child , Child, Preschool , Chronic Disease , Graft vs Host Disease/pathology , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Infant , Survivors , Transplantation Conditioning/adverse effects , Transplantation, Homologous/adverse effects , Whole-Body Irradiation/adverse effects , Young AdultABSTRACT
PURPOSE: To investigate taste and smell function in survivors, with a minimum of 2 years since treatment of childhood medulloblastoma (MB)/central nervous system supratentorial primitive neuroectodermal tumor (CNS-PNET). METHODS: This cross-sectional study included 40 survivors treated ≤ 20 years of age. Taste strips with four concentrations of sweet, sour, salt, and bitter were used to assess taste function in all participants. Score from 0 to 16; ≥ 9 normogeusia, < 9 hypogeusia, and complete ageusia which equals no sensation. No sensation of a specific taste quality equals ageusia of that quality. Thirty-two participants conducted smell testing using three subtests of Sniffin' sticks: threshold, discrimination, and identification. Together they yield a TDI-score from 1 to 48; functional anosmia ≤ 16.00, hyposmia > 16.00- < 30.75, normosmia ≥ 30.75- < 41.50, and ≥ 41.50 hyperosmia. Results were compared with normative data. Survivors rated their taste and smell function using a numerical rating scale (NRS) score 0-10. RESULTS: Forty survivors with a mean time since treatment of 20.5 years, 13 (32.5%) were diagnosed with hypogeusia, nine (22.5%) of these being ageusic to one or more taste qualities. Seventeen (53%) of 32 participants were diagnosed with hyposmia. The mean scores of the olfactory subtests, and TDI score were significantly lower than normative data (P < 0.0001). The mean NRS scores of smell and taste function were 7.9 ± 1.5 and 8 ± 1.3, respectively. CONCLUSION: Our study showed impaired taste and smell function in survivors of childhood MB/CNS-PNET using objective measurements. However, subjective ratings did not reflect objective findings.
Subject(s)
Ageusia , Central Nervous System Neoplasms , Cerebellar Neoplasms , Medulloblastoma , Neoplasms, Germ Cell and Embryonal , Olfaction Disorders , Anosmia , Cross-Sectional Studies , Humans , Olfaction Disorders/diagnosis , Olfaction Disorders/etiology , Smell/physiology , Survivors , Taste/physiologyABSTRACT
PURPOSE: The aim of this study was to explore what methods should be used to determine the minimal important difference (MID) and minimal important change (MIC) in scores for the European Organisation for Research and Treatment of Cancer Head and Neck Cancer Module, the EORTC QLQ-HN43. METHODS: In an international multi-centre study, patients with head and neck cancer completed the EORTC QLQ-HN43 before the onset of treatment (t1), three months after baseline (t2), and six months after baseline (t3). The methods explored for determining the MID were: (1) group comparisons based on performance status; (2) 0.5 and 0.3 standard deviation and standard error of the mean. The methods examined for the MIC were patients' subjective change ratings and receiver-operating characteristics (ROC) curves, predictive modelling, standard deviation, and standard error of the mean. The EORTC QLQ-HN43 Swallowing scale was used to investigate these methods. RESULTS: From 28 hospitals in 18 countries, 503 patients participated. Correlations with the performance status were |r|< 0.4 in 17 out of 19 scales; hence, performance status was regarded as an unsuitable anchor. The ROC approach yielded an implausible MIC and was also discarded. The remaining approaches worked well and delivered MID values ranging from 10 to 14; the MIC for deterioration ranged from 8 to 16 and the MIC for improvement from - 3 to - 14. CONCLUSIONS: For determining MIDs of the remaining scales of the EORTC QLQ-HN43, we will omit comparisons of groups based on the Karnofsky Performance Score. Other external anchors are needed instead. Distribution-based methods worked well and will be applied as a starting strategy for analyses. For the calculation of MICs, subjective change ratings, predictive modelling, and standard-deviation based approaches are suitable methods whereas ROC analyses seem to be inappropriate.
Subject(s)
Deglutition , Head and Neck Neoplasms , Head and Neck Neoplasms/therapy , Humans , Quality of Life/psychology , Surveys and QuestionnairesABSTRACT
Patients with head and neck cancer (HNC) and patients with primary Sjögren's syndrome (pSS) may exhibit similar symptoms of dry mouth and dry eyes, as a result of radiotherapy (RT) or a consequence of disease progression. To identify the proteins that may serve as promising disease biomarkers, we analysed saliva and tears from 29 radiated HNC patients and 21 healthy controls, and saliva from 14 pSS patients by mass spectrometry-based proteomics. The study revealed several upregulated, and in some instances overlapping, proteins in the two patient groups. Histone H1.4 and neutrophil collagenase were upregulated in whole saliva of both patient groups, while caspase-14, histone H4, and protein S100-A9 were upregulated in HNC saliva only. In HCN tear fluid, the most highly upregulated protein was mucin-like protein 1. These overexpressed proteins in saliva and tears play central roles in inflammation, host cell injury, activation of reactive oxygen species, and tissue repair. In conclusion, the similarities and differences in overexpressed proteins detected in saliva from HNC and pSS patients may contribute to the overall understanding of the different pathophysiological mechanisms inducing dry mouth. Thus, the recurring proteins identified could possibly serve as future promising biomarkers.
Subject(s)
Head and Neck Neoplasms , Sjogren's Syndrome , Xerostomia , Biomarkers/metabolism , Head and Neck Neoplasms/metabolism , Head and Neck Neoplasms/radiotherapy , Histones/metabolism , Humans , Neoplasm Recurrence, Local/metabolism , Proteomics , Saliva/metabolism , Sjogren's Syndrome/metabolism , Tears/metabolism , Xerostomia/metabolismABSTRACT
BACKGROUND: Osteonecrosis of the jaw (ONJ) is an adverse effect of antiresorptive treatment. This study estimated incidence proportions and incidence rates of ONJ in cancer patients with bone metastases from solid tumors treated for the prevention of skeletal-related events in routine clinical practice. METHODS: This cohort study in Denmark, Norway, and Sweden in 2011-2018 included 3 treatment cohorts: a denosumab inception cohort (DEIC), a zoledronic acid inception cohort (ZAIC), and a denosumab-switch cohort (DESC). The authors estimated 1- to 5-year incidence proportions and incidence rates of ONJ overall, by cancer site (breast, prostate, or other solid tumor), and by country. ONJ diagnoses were confirmed by adjudication. RESULTS: There were 1340 patients in the DEIC, 1352 in the ZAIC, and 408 in the DESC. The median ages of the 3 cohorts were 70, 69, and 70 years, respectively; the proportions of men were 72.6%, 53.8%, and 48.3%, respectively; and the median follow-up was 19.8, 12.9, and 13.3 months, respectively. The 5-year incidence proportions of ONJ were 5.7% (95% confidence interval [CI], 4.4%-7.3%) in the DEIC, 1.4% (95% CI, 0.8%-2.3%) in the ZAIC, and 6.6% (95% CI, 4.2%-10.0%) in the DESC. The corresponding ONJ incidence rates per 100 person-years were 3.0 (95% CI, 2.3-3.7), 1.0 (95% CI, 0.6-1.5), and 4.3 (95% CI, 2.8-6.3). Incidence proportions and incidence rates were highest in patients with prostate cancer and in Denmark. CONCLUSIONS: This study provides estimates of the risk of medically confirmed ONJ among patients initiating denosumab or zoledronic acid in routine clinical practice in 3 Scandinavian countries. The results varied by cancer site and by country. LAY SUMMARY: Denosumab and zoledronic acid reduce the risk of bone fractures, pain, and surgery in patients with advanced cancers involving bone. Osteonecrosis of the jaw (ONJ)-death of a jawbone-is a known side effect of treatment with denosumab or zoledronic acid. The authors examined almost 2900 denosumab- or zoledronic acid-treated patients with cancer in Denmark, Norway, and Sweden. Over the course of 5 years, ONJ developed in 5.7% of the patients whose initial treatment was denosumab, in 1.4% of the patients whose initial treatment was zoledronic acid, and in 6.6% of the patients who switched from zoledronic acid to denosumab.
Subject(s)
Bisphosphonate-Associated Osteonecrosis of the Jaw , Bone Density Conservation Agents , Bone Neoplasms , Bisphosphonate-Associated Osteonecrosis of the Jaw/drug therapy , Bisphosphonate-Associated Osteonecrosis of the Jaw/epidemiology , Bisphosphonate-Associated Osteonecrosis of the Jaw/etiology , Bone Density Conservation Agents/adverse effects , Bone Neoplasms/secondary , Cohort Studies , Denmark/epidemiology , Denosumab/adverse effects , Diphosphonates/adverse effects , Humans , Male , Sweden , Zoledronic Acid/adverse effectsABSTRACT
BACKGROUND: Few clinical studies evaluate interventions to reduce oral discomfort among patients in palliative care. AIM: This study examines the efficacy of a Salvia officinalis (SO) based herbal mouth rinse compared to conventional normal saline (NS) in order to improve oral health. DESIGN: A block-randomized controlled trial. Data were collected before and after a 4-day intervention with either SO (n=44) or NS (n=44). Numerical rating scales (NRS, 0-10) and 12 items from the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Oral Health 17 (EORTC QLQ-OH17) measured patient-reported oral symptoms. An oral examination was performed before and after the intervention. SETTING/PARTICIPANTS: This study included adult patients with late-stage cancer in an inpatient hospice unit. RESULTS: Of the 88 patients included (mean age=63.9 years, SD=10.6), 73 (83%) completed the study. At baseline, 78% reported dry mouth on the EORTC QLQ-OH17, and 80% rated dry mouth ≥4 on the NRS. Total oral health scores based on the 12 EORTC QLQ-OH17 items improved similarly in both groups (p<0.001). However, dry mouth ratings on both the EORTC QLQ-OH17 (p=0.036) and NRS (p=0.045) improved more in the SO group than in the NS group. Plaque on the teeth improved in both the SO (p=0.008) and NS (p=0.018) groups, but plaque on the tongue and erythema only improved with NS. CONCLUSIONS: This study did not detect an overall significant difference between SO and NS. Both mouth rinses improved oral health parameters, indicating that systematic assessment and oral care may reduce oral discomfort. TRIAL REGISTRATION: NCT02067572.
Subject(s)
Neoplasms , Salvia officinalis , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Mouthwashes , Palliative Care , Quality of Life , Surveys and Questionnaires , TeaABSTRACT
PURPOSE: Factors associated with the long-term dental effects after chemotherapy for childhood malignancies have not been well described. The primary aims of this study were as follows: (1) to assess whether age at diagnosis and treatment-related factors are associated with dental defects in survivors of childhood acute lymphoblastic leukemia (ALL) and (2) to assess the survivors' annual expenses for dental treatment compared to reference data. METHODS: This cross-sectional study enrolled 111 Norwegian survivors of ALL diagnosed before the age of 16. All of the subjects completed a questionnaire and underwent medical and oral examinations. Dental defects were registered according to the individual defect index, with 0 = no defects and 140 = anodontia, and the caries experience was registered according to the decayed-missing-filled teeth index (DMFT). Age-matched reference data were drawn from a national general population survey (n = 555). RESULTS: The mean age at examination was 29.1 years (SD 7.2), and mean follow-up period was 22.9 years (SD 7.3). In a regression model, diagnoses occurring at ≤5 years of age (B = -9.6, p < 0.001) and a cumulative dose of anthracyclines >120 mg/m(2) (B = 11.5, p < 0.001) were strongly associated with more severe dental defects. Survivors treated after the age of 5 had experienced more caries than those treated at a younger age [DMFT 9.6 (SD 6.1) vs. 6.0 (SD 4.6), respectively; p = 0.001]. High annual expenses for dental treatment were reported by a larger percentage of the reference population compared to the survivor group (18 vs. 9 %, respectively; p = 0.02). CONCLUSIONS: The age at diagnosis and the dose of anthracyclines appear to be strongly associated with the severity of dental defects, although few survivors reported high annual expenses for dental treatment. The increased risk of dental defects during adulthood should be communicated to ALL survivors.
Subject(s)
Antineoplastic Agents/adverse effects , Dental Caries/etiology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Adolescent , Adult , Child , Cross-Sectional Studies , Dental Caries/epidemiology , Female , Humans , Male , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality , Survivors , Young AdultSubject(s)
Bisphosphonate-Associated Osteonecrosis of the Jaw/diagnosis , Bone Density Conservation Agents/adverse effects , Diphosphonates/adverse effects , Societies, Medical , Bisphosphonate-Associated Osteonecrosis of the Jaw/drug therapy , Bone Density Conservation Agents/therapeutic use , Bone Resorption/physiopathology , Diphosphonates/therapeutic use , Humans , Osteonecrosis/chemically induced , Osteonecrosis/diagnosisABSTRACT
BACKGROUND: Although dysphagia is a common side effect after radiotherapy (RT) of head and neck cancer (HNC), data on long-term dysphagia is scarce. We aimed to 1) compare radiation dose parameters in HNC survivors with and without dysphagia, 2) investigate factors associated with long-term dysphagia and its possible impact on health-related quality of life (HRQoL), and 3) investigate how our data agree with existing NTCP models. METHODS: This cross-sectional study conducted in 2018-2020, included HNC survivors treated in 2007-2013. Participants attended a one-day examination in hospital and filled in patient questionnaires. Dysphagia was measured with the EORTC QLQ-H&N35 swallowing scale. Toxicity was scored with CTCAE v.4. We contoured swallowing organs at risk (SWOAR) on RT plans, calculated dose-volume histograms (DVHs), performed logistic regression analyses and tested our data in established NTCP models. RESULTS: Of the 239 participants, 75 (31%) reported dysphagia. Compared to survivors without dysphagia, this group had reduced HRQoL and the DVHs for infrahyoid SWOAR were significantly shifted to the right. Long-term dysphagia was associated with age (OR 1.07, 95% CI 1.03-1.10), female sex (OR 2.75, 95% CI 1.45-5.21), and mean dose to middle pharyngeal constrictor muscle (MD-MPCM) (OR 1.06, 95% CI 1.03-1.09). NTCP models overall underestimated the risk of long-term dysphagia. CONCLUSIONS: Long-term dysphagia was associated with higher age, being female, and high MD-MPCM. Doses to distally located SWOAR seemed to be risk factors. Existing NTCP models do not sufficiently predict long-term dysphagia. Further efforts are needed to reduce the prevalence and consequences of this late effect.
Subject(s)
Deglutition Disorders , Head and Neck Neoplasms , Humans , Female , Male , Deglutition Disorders/epidemiology , Deglutition Disorders/etiology , Quality of Life , Cross-Sectional Studies , Head and Neck Neoplasms/radiotherapy , Deglutition/radiation effectsABSTRACT
BACKGROUND: There is lack of evidence on chronic fatigue (CF) following radiotherapy (RT) in survivors of head and neck cancer (HNC). We aimed to compare CF in HNC survivors > 5 years post-RT with a reference population and investigate factors associated with CF and the possible impact of CF on health-related quality of life (HRQoL). MATERIAL AND METHODS: In this cross-sectional study we included HNC survivors treated in 2007-2013. Participants filled in patient-reported outcome measures and attended a one-day examination. CF was measured with the Fatigue Questionnaire and compared with a matched reference population using t-tests and Cohen's effect size. Associations between CF, clinical and RT-related factors were investigated using logistic regression. HRQoL was measured with the EORTC Quality of Life core questionnaire. RESULTS: The median age of the 227 HNC survivors was 65 years and median time to follow-up was 8.5 years post-RT. CF was twice more prevalent in HNC survivors compared to a reference population. In multivariable analyses, female sex (OR 3.39, 95 % CI 1.82-6.31), comorbidity (OR 2.17, 95 % CI 1.20-3.94) and treatment with intensity-modulated RT (OR 2.13, 95 % CI 1.16-3.91) were associated with CF, while RT dose parameters were not. Survivors with CF compared to those without, had significantly worse HRQoL. CONCLUSIONS: CF in HNC survivors is particularly important for female patients, while specific factors associated with RT appear not to play a role. The high CF prevalence in long-term HNC survivors associated with impaired HRQoL is important information beneficial for clinicians and patients to improve patient follow-up.
Subject(s)
Cancer Survivors , Fatigue , Head and Neck Neoplasms , Quality of Life , Humans , Female , Male , Head and Neck Neoplasms/radiotherapy , Cross-Sectional Studies , Aged , Fatigue/etiology , Middle Aged , Chronic Disease , Surveys and Questionnaires , Patient Reported Outcome MeasuresABSTRACT
OBJECTIVE: To assess reported cases of bisphosphonate-related osteonecrosis of the jaw (BONJ) to Medicines Agencies (MAs) in four Nordic countries and to compare the Norwegian MA data with BONJ cases retrieved through an e-mail survey to Oral and Maxillofacial Surgeons (OMS) in Norway. MATERIAL AND METHODS: BONJ cases reported to the national MAs in each country from January 1st 2003 to September 30th 2010 were collected. An e-mail survey was sent to all active members of the Norwegian Association of Oral and Maxillofacial Surgeons (n = 54) included questions on total BONJ cases seen in practice and route of drug administration during January 1st 2003 to December 31st 2009. RESULTS: In total, 253 BONJ cases were reported to the MAs; 39 in Denmark, 44 in Finland, 51 in Norway and 119 in Sweden. These figures result in cumulative incidences (multiplied by 100,000) of 0.7, 0.8, 1.1 and 1.3, respectively. Intravenous administration was reported in 169 of the cases. The e-mail survey resulted in 35 responses reporting 214 BONJ cases, 4-times more cases than reported to the MA. CONCLUSIONS: Cumulative incidence of cases reported in this study differs to some degree in the four Nordic countries (Denmark < Finland < Norway < Sweden). In Norway, almost the same number of BONJ cases were reported through the questionnaire by OMS as in all four countries together (214 by OMSs vs 254 to MAs) and included a high number after per oral administration. The present results indicate a notable under-reporting in Norway and most likely in other Nordic countries.
Subject(s)
Bisphosphonate-Associated Osteonecrosis of the Jaw/epidemiology , Electronic Mail , Humans , Incidence , Scandinavian and Nordic Countries/epidemiology , Surveys and QuestionnairesABSTRACT
Patients undergoing intensity-modulated radiotherapy (IMRT) for head and neck cancer may have increased incidence of dry eye disease and the exact mechanism is unclear. The present study aims to assess tear film and meibomian gland (MG) features in patients who received IMRT for head and neck cancer not involving the orbital area. Twenty-seven patients (64.7 ± 9.8 years) and 30 age-matched controls (61.4 ± 11.0 years) underwent a comprehensive dry eye work-up. Compared to the control group, the patients had more lid margin abnormalities, and worse meibum quality. The MG loss, calculated as (tarsal area-MG area)/tarsal area, was higher in the patient group in both the upper (53.0 ± 12.0% vs. 35.1 ± 10.3%, p < 0.001) and lower lids (69.5 ± 12.6% vs. 48.5 ± 12.5%, p < 0.001). In the patient group, more MG loss in the lower lids correlated with worse meibum quality (r = 0.445, p = 0.029). In contrast, there was no significant difference in aqueous tear production level, measured with Schirmer test. Patients treated with IMRT for head and neck cancer seemed to have comparable lacrimal gland function to the controls despite more dry eye symptoms. However, the patients had MG functional and morphological changes, which may present a higher risk for developing dry eye disease.
Subject(s)
Dry Eye Syndromes/epidemiology , Dry Eye Syndromes/etiology , Head and Neck Neoplasms/radiotherapy , Meibomian Glands/radiation effects , Radiotherapy, Intensity-Modulated/adverse effects , Adult , Aged , Aged, 80 and over , Case-Control Studies , Cross-Sectional Studies , Female , Humans , Incidence , Male , Meibomian Glands/pathology , Middle Aged , Radiation Dosage , Risk Factors , Tear Gases , TearsABSTRACT
A broader understanding of oral and ocular late effects in head and neck cancer (HNC) patients who underwent intensity-modulated radiotherapy (IMRT) may provide valuable information in follow-up and improve quality of life. Twenty-nine HNC patients treated at least 6 months earlier and 30 age-matched controls were recruited. After completing several questionnaires: Oral Health Impact Profile-14 (OHIP-14), Shortened Xerostomia Inventory (SXI), Ocular Surface Disease Index (OSDI) and McMonnies Dry Eye questionnaire (MDEQ), participants underwent oral and ocular examinations. Oral examination included clinical oral dryness score (CODS) and secretion rates of unstimulated and stimulated saliva (UWS, SWS). Ocular examination included tear film break-up time, Schirmer test and ocular surface staining. The patients had more problems related to dry mouth than controls based on CODS and SXI, and more complaints of dry eye disease based on OSDI and MDEQ. UWS and SWS rates and oral health related quality of life were significantly lower in the patient group. Subjective oral dryness (SXI) correlated significantly with subjective ocular dryness (OSDI and MDEQ). Our study demonstrates that HNC patients treated with IMRT experience late effects in terms of xerostomia and ocular dryness underlining the importance of interdisciplinary approach in the evaluation and follow-up of HNC patients.
Subject(s)
Head and Neck Neoplasms/radiotherapy , Radiotherapy, Intensity-Modulated/adverse effects , Radiotherapy/adverse effects , Aged , Dry Eye Syndromes , Eye Diseases/etiology , Female , Humans , Male , Middle Aged , Norway , Quality of Life , Radiotherapy, Intensity-Modulated/methods , Saliva/chemistry , Salivary Gland Diseases/etiology , Salivation , Stomatognathic Diseases/etiology , Surveys and Questionnaires , XerostomiaABSTRACT
Although radiotherapy is a common form of treatment for head and neck cancer, it may lead to tissue damage in the salivary and lacrimal glands, possibly affecting cytokine expression in the gland fluid of treated individuals. Cytokine profiles in saliva and tear fluid of 29 radiated head and neck cancer patients and 20 controls were screened using a multiplex assay. Correlations between cytokine expression and clinical oral and ocular manifestations were examined, and cellular pathways influenced by these cytokines were assessed using the Functional Enrichment Analysis Tool. Significantly elevated cytokines identified in patient saliva were CCL21, IL-4, CX3CL1, CCL2, CXCL1 and CCL15. Many of these cytokines correlated positively with objective signs of oral dryness, and reduced saliva production in the patients. Although CCL21 and IL-4 levels were significantly lower in patient tear fluid, they correlated with subjective ocular symptoms. These increased salivary cytokines affected pro-inflammatory and apoptotic cellular pathways, including T cell signalling, several interleukin signalling pathways, TNF and TGF-ß receptor signalling, and the apoptotic p53 pathway. In conclusion, the upregulated salivary cytokines identified suggest an interplay between innate and adaptive immunity, affecting immunoregulatory cellular pathways. Whether this is due to late effects of radiotherapy or tissue repair remains to be investigated.
Subject(s)
Adaptive Immunity/immunology , Cytokines/metabolism , Neoplasms/immunology , Saliva/metabolism , Aged , Aged, 80 and over , Female , Humans , Male , Middle AgedSubject(s)
Bisphosphonate-Associated Osteonecrosis of the Jaw/prevention & control , Bone Density Conservation Agents/adverse effects , Diphosphonates/adverse effects , Bone Density Conservation Agents/therapeutic use , Breast Neoplasms/drug therapy , Diphosphonates/therapeutic use , Female , Humans , Oral HealthABSTRACT
Senses of smell and taste, saliva flow, and dental status are considered as important factors for the maintenance of a good nutritional status. Salivary secretory rates, chemosensory function, burning mouth sensation, halitosis and dental status were investigated in 58 primary Sjögren's syndrome (pSS) patients, 22 non-Sjögren's syndrome sicca (non-SS) patients, and 57 age-matched healthy controls. A significantly greater proportion of pSS and non-SS patients had ageusia, dysgeusia, burning mouth sensation, and halitosis compared to controls. Patients with pSS had significantly lower olfactory and gustatory scores, and significantly higher caries experience compared to controls. Patients with pSS and non-SS patients had significantly lower unstimulated and stimulated whole saliva secretory rates compared to controls. The findings indicated that several different aspects of oral health were compromised in both pSS and non-SS patients, and this may affect their food intake and, hence, their nutritional status. Although non-SS patients do not fulfill Sjögren's syndrome classification criteria, they have similar or, in some cases, even worse oral complaints than the pSS patients. Further studies are needed to investigate food preferences, dietary intake, and nutritional status in these two patient groups in relation to their health condition.
Subject(s)
Dental Caries/etiology , Dysgeusia/etiology , Halitosis/etiology , Sjogren's Syndrome/complications , Sjogren's Syndrome/physiopathology , Adult , Aged , Case-Control Studies , Dental Caries/epidemiology , Dysgeusia/epidemiology , Female , Halitosis/epidemiology , Humans , Male , Middle Aged , Nutritional Status , Oral Health , Sjogren's Syndrome/epidemiology , Young AdultABSTRACT
Investigating cytokines in tear fluid and saliva may offer valuable information for understanding the pathogenesis of primary Sjögren's syndrome (pSS). Cytokine profiles in both tear fluid and saliva of pSS patients, non-Sjögren's syndrome (non-SS) subjects with sicca symptoms, and healthy controls without sicca complaints were analysed. Furthermore, relationships associating the severity of clinical ocular and oral manifestations with the upregulated cytokines were assessed. In tear fluid, pSS patients showed elevated levels of IL-1ra, IL-2, IL-4, IL-8, IL-12p70, IL-17A, IFN-γ, IP-10, MIP-1b, and Rantes compared to non-SS subjects and healthy controls. The increased cytokine levels (except IP-10) correlated significantly with reduced tear production, less stable tear film, and greater ocular surface damage. In saliva, pSS patients had a higher IP-10 level, which correlated with higher candida score; and an elevated MIP-1a level, which correlated significantly with lower unstimulated and stimulated whole saliva secretion rates. The upregulated cytokines identified in tear fluid and saliva of pSS patients show a clear interplay between innate and adaptive immune responses that may contribute to disease pathogenesis. The increase of IP-10 and MIP in both tears and saliva further emphasises the essential role of macrophages and innate immunity in pSS.