Dental age in patients with neurofibromatosis 1.

Neurofibromatosis type 1 (NF1) is a common, hereditary, neurocutaneous skeletal condition with a variety of osseous manifestations. Although NF1 also affects craniofacial structures, the literature has only limited information related to the effect of NF1 on dental development. In this study the dental age of 34 Finnish NF1 patients, 8-17 yr of age, was estimated using the Demirjian & Goldstein method. The dental age of children with NF1 was similar to that of a Finnish control population. The findings suggest that NF1 does not affect the timing of tooth development.

Radiographic findings in the jaws of patients with neurofibromatosis 1.

PURPOSE: Neurofibromatosis 1 (NF1) is a neurocutaneous-skeletal disorder with variable phenotypic expression and an incidence of 1:3,000 worldwide. The objective was to characterize the NF1-related radiologic alterations found in the jaws of these patients. PATIENTS AND METHODS: In total, 102 patients with NF1 were included in the present study. Six patients had a plexiform neurofibroma in the craniofacial region. RESULTS: Radiologic abnormalities in the jaws were found in 29 of 102 patients with NF1, including 6 patients with plexiform neurofibroma in the head and neck region. The most common radiologic finding was enlargement of the mandibular canal. The most prominent skeletal deformities and alterations of varying severity were detected in the jaws of 6 patients with plexiform neurofibroma. In these patients, the skeletal deformities were seen on the side affected by the tumor and possibly caused by the tumor. In 1 patient, however, the skeletal changes were on the opposite side. CONCLUSIONS: Radiologic abnormalities were found in 29 of 102 patients. The most significant findings were profound deformities of the mandible and maxilla in all 6 patients with plexiform neurofibroma, but not in the other patients. The facial bone deformities found in young patients did not progress markedly at older ages with cessation of the patients' growth.

Oral soft tissue alterations in patients with neurofibromatosis.

Our aim was to characterize the type and frequency of oral soft tissue alterations in neurofibromatosis. A total of 103 patients with neurofibromatosis 1 (NF1) and three patients with neurofibromatosis 2 (NF2) were clinically evaluated for their oral soft tissue alterations. Disturbing growths were removed from nine patients with NF1 and from one patient with NF2. The specimens were analyzed using routine histological methods and with immunohistochemistry using antibodies to S100, type IV collagen, CD34, neurofilament, and neuron-specific tubulin (TUBB3). Alterations including oral tumors, overgrowths of gingival soft tissue, and enlarged papillae of the tongue were discovered in 74% of NF1 patients. The results showed that three tumors clinically classified as plexiform neurofibromas and five out of six discrete mucosal tumors displayed histology and immunohistology consistent with that of neurofibroma. The histology of one palatal lesion resembled that of a scar, and the lesion removed from the patient with NF2 was classified as an amyloid tumor. To conclude, oral soft tissue growths are common findings in NF1, but most lesions do not require treatment and the patients may even not be aware of these alterations. Collagen IV, S100, and CD34 are useful biomarkers in the analysis of NF1-related oral soft tissue tumors. The clinicians should recognize that oral soft tissue alterations are relatively common in NF1. Some of the growths are disturbing, and plexiform neurofibromas may bear a risk of malignant transformation.

Short mandible, maxilla and cranial base are common in patients with neurofibromatosis 1.

Neurofibromatosis type 1 (NF1) is an autosomal-dominant neuro-cutaneous-skeletal syndrome. Neurofibromatosis type 1 is one of the Rasopathies, and at the cellular level NF1 results in a hyperactive Ras pathway. In the current investigation, our aim was to study lateral skull X-rays (cephalograms) to assess NF1-related craniofacial morphology. A total of 85 Finnish patients with NF1, including four patients with plexiform neurofibroma of the 5th cranial nerve, and their age- and gender-matched controls, were enrolled in the study. The results showed that patients with NF1 typically had a short mandible, maxilla, and cranial base compared with healthy controls, irrespective of age, but the results were statistically significant only in adults. The length of the mandible, the maxilla and the cranial base correlated with the height of patients under 19 yr of age, but this correlation was absent in adult patients. Thus, a tall adult patient with NF1 may have short jaws and a short cranial base. In conclusion, the NF1 gene apparently influences the growth of craniofacial bones, thus contributing to the craniofacial morphology in NF1.

Neurofibromatosis 1 and dental caries.

A total of 110 patients with neurofibromatosis 1 (NF1) were evaluated for their dental health. Appropriate cohorts from national Finnish databases were used as reference. The results showed that NF1 patients presented lower rate of caries compared to controls in age groups under 35 years. The differences between NF1 patients and the reference population diminished by age. In conclusion, (1) NF1 per se does not predispose to caries; and (2) even if NF1 had an adverse effect on dental health, poor outcome can be counteracted with good personal dental care supported by well organized primary health care. The results of the present study are important to report since a common anecdotal perception is that the rate of caries may be higher in NF1 compared to reference population.

Speech characteristics in neurofibromatosis type 1.

Neurofibromatosis 1 (NF1) is a neurocutaneous-skeletal disorder often accompanied with varying degrees of cognitive and motor problems that potentially affect speech and language. While previous studies have shown that NF1 may be associated with a variety of deviations in the patients' speech, they have not investigated the characteristics in phonetic detail. Our clinical observation that many patients share a distinct voice and manner of speaking led to the primary aim of this study, which was to present a comprehensive description of speech in NF1. A total of 62 patients with NF1 (age range 7-66 years), and a control group of 24 speakers (age range 7-62 years) were evaluated for their speech. The test sessions were recorded and the data were analyzed both by ear and by acoustic measurements. The data were analyzed separately by two trained phoneticians, and a summary was produced after comparing the two independent analyses. Various speech problems were observed among patients with NF1. Individual variation was remarkable, but the deviations were more common and severe in children than in adult patients. In addition, men with NF1 had more speech deviations than women with NF1. Findings include deviations in voice quality, problems in regulating pitch, deviant nasality, misarticulation, and disfluency. We suggest that difficulties in speech, particularly in regulating pitch, may have negative social implications. Our results highlight which components of speech require particular attention in speech therapy for patients with NF1.

Speech after radial forearm free flap reconstruction of the tongue: a longitudinal acoustic study of vowel and diphthong sounds.

The purpose of this study was to use acoustic analyses to describe speech outcomes over the course of 1 year after radial forearm free flap (RFFF) reconstruction of the tongue. Eighteen Canadian English-speaking females and males with reconstruction for oral cancer had speech samples recorded (pre-operative, and 1 month, 6 months, and 1 year post-operative). Acoustic characteristics of formants (F1, F2), fundamental frequency (F0), and duration of 699 vowel and diphthong tokens were analysed. Furthermore, the changes in size of the vowel space area were studied, as well as the effects of radiation therapy (RT) and inclusion of the floor of the mouth (FOM) in the reconstruction. RFFF reconstruction was found to affect several characteristics in males, and a minimal number of variables in females. General signs of reduced ability to articulate were not observed. RT and FOM had no differing effects compared to non-RT or non-FOM. There were individual differences between patients.

Development of a Patient-Centered Functional Outcomes Questionnaire in Head and Neck Cancer.

Importance: Incorporation of patient perspectives, or patient-reported outcomes, in functional outcome measures has been gaining prominence in the literature on reconstructive surgery. Objective: To create and validate an instrument for measuring the main functional areas of concern for patients with head and neck cancer. Design, Setting, and Participants: This 4-phase mixed-methods qualitative study was conducted from July 1, 2013, to June 30, 2016, in a quaternary head and neck oncology center in Edmonton, Alberta, Canada. Patients were recruited from 3 Head and Neck Research Network sites: University of Alberta (Edmonton, Canada), Mount Sinai Health Network (New York, New York), and University of Turku Hospital (Turku, Finland). The inclusion criteria included 18 years of age or older, diagnosis of squamous cell carcinoma involving the subsites of the head and neck (ie, oral cavity, oropharynx, hypopharynx, and larynx), and at least 1 year since treatment completion. Those patients who were undergoing additional active treatment or with evidence of disease recurrence were excluded. Data were analyzed from July 1, 2013, to June 30, 2016. Main Outcomes and Measures: The primary outcome measures were the clinical correlation of the Edmonton-33 instrument scores with swallowing, speech, dry mouth, and chewing assessment outcomes. Results: In total, 10 patients with head and neck cancer (mean age, 59.6 years; 6 men [60%]) were included in phase 1 of the study, 5 patients (mean age, 55.2 years) were included in phase 2, 10 patients were included in phase 3, and 25 patients with head and neck cancer (mean age, 62.6 years; 14 men [56%]) participated in the phase 4 validation. The Edmonton-33 instrument scores correlated strongly with the swallowing scores of the MD Anderson Dysphagia Inventory (r = 0.77; 95% CI, 0.49-1.0), the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Head and Neck 35 (EORTC QLQ-H&N35) (r = -0.73; 95% CI, -1.0 to -0.44), and the modified barium swallow test (r = -0.60; 95% CI, -0.94 to -0.25). The instrument scores were also strongly correlated with the Speech Handicap Index scores (r = -0.64; 95% CI, -0.97 to -0.31), word intelligibility scores (r = 0.61; 95% CI, 0.27-0.95), and sentence intelligibility scores (r = 0.55; 95% CI, 0.19-0.91). A moderate to strong correlation was observed between the Edmonton-33 instrument and the EORTC QLQ-H&N35 scores in the dry mouth (r = -0.54; 95% CI, -0.91 to -0.18) and chewing (r = -0.45; 95% CI, -0.84 to -0.06) domains. The factor loading values for the domains of swallowing, speech, dry mouth, and chewing were all greater than 0.3. The mean factor loading values for the items related to swallowing were 0.71 (95% CI, 0.62-0.80) and for the items related to speech were 0.76 (95% CI, 0.72-0.80). The mean factor loading values for the items related to dry mouth were 0.71 (95% CI, 0.59-0.83) and for those related to chewing were 0.77 (95% CI, 0.69-0.85). Conclusions and Relevance: The Edmonton-33 appears to be a validated instrument that will allow patients with head and neck cancer to assess and report their own functional outcomes. It could serve as a single comprehensive measure for functional outcomes.

Craniofacial and oral alterations in patients with Neurofibromatosis 1.

ABTSRACT: Neurofibromatosis type 1 (NF1) is one of the most common inherited syndromes. The literature on craniofacial alterations associated with NF1 has been limited and partially contradictory. This review is based on literature search and the results of the clinical study "Craniofacial and Oral Alterations and Speech in patients with Neurofibromatosis 1", carried out at the University of Turku and Turku University Hospital, Finland in 2006-2012. By the end of 2012, a total of 110 NF1 patients, 54 female and 56 male patients, were examined.A part of our results confirms pre-existing understanding, a part is contradictory to previous considerations based mainly on case reports, and some are entirely novel. Specifically, our results confirmed that enlargement the mandibular canal is the most common abnormality of the mandible in patients with NF1. It should be noted, however, that this finding does not require treatment. Caries was not a major problem. In fact, it was less frequent in NF1 patients compared to reference population. These findings abrogate some previous perceptions. Novel findings of our project include periapical cemental dysplasia in females; short jaws, a finding which usually does not affect bite; and immunohistological analysis of oral mucosal abnormalities. Pioneering study on speech showed that various deviations were very common: As many as 94% of the participants showed some alterations.To conclude, the awareness of craniofacial alterations common in NF1would help avoiding unnecessary and even harmful involvement, e.g. of periapical cemental dysplasia or enlarged mandibular canal which do not require treatment.

Periapical cemental dysplasia is common in women with NF1.

BACKGROUND: Neurofibromatosis type 1 (NF1) is a genetic disorder with skeletal involvement. Periapical cemental dysplasia is a rare finding in the normal population. METHOD: A total of 55 patients with NF1, 29 female and 26 male patients, were evaluated with orthopantomograms, supplemented with periapical radiographs if necessary. The vitality of the teeth was measured by two different testing methods. RESULTS: A novel finding was the occurrence of cemental dysplasia affecting the periapical area of vital mandibular teeth in 8 adult women with NF1. Thus, cemental dysplasia was detected in 34.8% of the adult female NF1 patients, while cemental dysplasia was not present in men or children with NF1. CONCLUSION: Periradicular cemental dysplasia is indeed a new NF1 related bone lesion type. Our finding suggests that this is the first reported sexual dimorphism in the manifestations of NF1. Cemental dysplasia of NF1 patients should not be confused with periapical findings caused by endodontic pathoses. The former do not require active therapy whereas in the latter root canal treatment is necessary.

Squamous cell carcinomas arising from different types of oral epithelia differ in their tumor and patient characteristics and survival.

A hypothesis that OSCCs originating from different types of oral epithelia may have different patient and tumor characteristics was evaluated in this retrospective analysis of 188 patients with primary OSCC treated at Turku University Central Hospital, Turku, Finland in 1988-1997. The tumors were categorized according to the type of oral epithelium from which they have originated: (1) specialized epithelium (dorsal tongue) (2) keratinized (masticatory) epithelium, (3) non-keratinized (lining) epithelium, and (4) tongue epithelium (epithelium on the lateral border of the tongue). The relevant clinical data, including age, sex, social status, and risk behavior of the patients and clinical presentation, histopathological grading, and treatment of the tumors, as well as the follow-up information, were collected from the patient charts of the hospital. In general, tumor and patient characteristics of OSCCs and survival rates were found to be in line with those of recent analyses reported from other industrialized countries. However, OSCCs in young patients (4.8%) seemed to be clinically at a lower stage and histologically more highly differentiated than those of the other patients. Eight out of 9 (89%) OSCCs in the young patients were located on the lateral tongue. The 5-year recurrence-free rates of the patients according to the epithelial origin of the tumors were as follows: masticatory epithelium 42%, lining epithelium 57%, and epithelium of the lateral border of the tongue 61%. In conclusion, the tumors originating from different types of oral epithelia may have distinct properties with regard to their clinical behavior and responsiveness to the different treatment modalities. It would seem to be meaningful to investigate the molecular characteristics of the different types of oral epithelium in order to elucidate possible differences in their susceptibility to malignant transformation.

Functional and quality of life outcomes after partial glossectomy: a multi-institutional longitudinal study of the head and neck research network.

BACKGROUND: While aggressive treatment for oral cancer may optimize survival, decrements in speech and swallowing function and quality of life often result. This exploratory study investigated how patients recover their communicative function, swallowing ability, and quality of life after primary surgery [with or without adjuvant (chemo)radiation therapy] for tongue cancer over the course of the first year post-operation. METHODS: Patients treated for oral cancer at three institutions (University of Alberta Hospital, Mount Sinai Beth Israel Medical Center, and Turku University Hospital) were administered patient-reported outcomes assessing speech [Speech Handicap Index (SHI)], swallowing [(M.D. Anderson Dysphagia Inventory (MDADI)] and quality of life [European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck Module (EORTC-H&N35)]. Outcome measures were completed pre-operatively and at 1-, 6-, and 12-months post-operatively. RESULTS: One hundred and seventeen patients undergoing partial glossectomy with reconstruction participated in this study. Results indicated no significant differences in swallowing function (MDADI and EORTC-H&N35 subscales) between baseline and 6 months post-surgery and no significant differences in speech function (SHI subscales) between baseline and 1 year post-surgery. Most quality of life domains (EORTC-H&N35 subscales) returned to baseline levels by 1 year post-operation, while difficulties with dry mouth and sticky saliva persisted. A clear time trend of adjuvant (chemo)radiation therapy negatively affecting dry mouth scores over time was identified in this study, while negative independent effects of chemoradiation on MDADI swallowing, and EORTC-H&N35 swallowing, eating, and opening mouth subscales were found. CONCLUSIONS: Assessment time influenced patient-reported speech, swallowing, and quality of life outcomes, while treatment (by time) effects were found for only swallowing and quality of life outcomes. Results of the present study will help guide clinical care and will be useful for patient counseling on expected short and long-term functional and quality of life outcomes of surgical and adjuvant treatment for oral cavity cancer.

Intraocular lens-capsular bag imaging with ultrahigh-resolution optical coherence tomography Pseudophakic human autopsy eyes.

PURPOSE: To compare in vitro ultrahigh-resolution optical coherence tomography (UHR OCT) cross-sectional images of the pseudophakic human autopsy eye with histology to evaluate the potential of this imaging technique for enhanced visualization of the anterior segment, especially the capsular bag, intraocular lens (IOL), and posterior capsule opacification (PCO) formation after cataract surgery. SETTING: Department of Medical Physics and Department of Ophthalmology, University of Vienna, Vienna, Austria, and Department of Oral and Maxillofacial Surgery Institute of Dentistry, University of Turku, Turku, Finland. METHODS: Ultrahigh-resolution OCT images were acquired from 7 pseudophakic human autopsy eyes using 1.4 microm axial x 3.0 microm transverse resolution. The axial resolution with UHR OCT is 1.4 microm compared to 10.0 microm with the commercially available OCT. Plastic-embedded histologic sections were obtained in precise alignment with the OCT tomograms. RESULTS: Ultrahigh-resolution OCT cross-sectional tomograms corresponded to the histologic sections. With the wavelength used (800 nm), the anterior and posterior capsules, area of lens epithelial cell growth and extracellular matrix proliferation, and IOL could be clearly visualized. The extent of capsular bag adhesion to the IOL could be detected, as well as the amount of PCO formation. CONCLUSIONS: The improved resolution makes UHR OCT a powerful tool in anterior segment imaging and evaluation of the capacity of IOL materials and models to induce capsular bag adhesion. Ultrahigh-resolution OCT may also help in determining the area of origin of PCO after cataract surgery.

Effects of genioglossal muscle advancement on speech: an acoustic study of vowel sounds.

OBJECTIVE: The effects of the genioglossal muscle advancement on phonetic quality of speech were studied analyzing the acoustic features of vowel sounds. STUDY DESIGN AND SETTING: The study group consisted of 5 men suffering from partial upper airway obstruction during sleep. To prevent tongue base collapse, genioglossal muscle advancement was made with chin osteotomy without hyoid myotomy and suspension. The speech material consisted of 8 vowels produced in sentence context repeated 10 times before the operation, and 10 days and 6 weeks after the operation. The acoustic features of vowels were analyzed. RESULTS: The operation had no significant effects on vowel quality. Only for 2 of the subjects the pitches changed systematically due to the operation. CONCLUSION: According to the acoustic analysis, genioglossal muscle advancement with chin osteotomy has no effects on vowel production. Some short-term changes were observed, but these changes were highly individual. SIGNIFICANCE: The operation seems to have no potential to change vowel production.

CD44v6 in developing, dysplastic and malignant oral epithelia.

The CD44v6 adhesion molecule has been linked to progression of various carcinomas, but its role in relation to oral-cancer development is not clear. The study was designed to determine whether CD44v6 levels were clinically significant in oral dysplasias. Twenty-nine oral dysplasias were immunostained with CD44v6 antibody on follow-up. Developing normal epithelia and adult normal epithelia and oral carcinomas were stained for comparison. Oral dysplasias and carcinomas exhibited heterogenous staining patterns. No statistically significant correlation between CD44v6 expression and outcome was found for dysplasia patients. The results show that in developing and healthy oral mucosa CD44v6 is associated with epithelium-specific differentiation but in dysplasias and carcinomas it mirrors disorderly epithelial maturation. The results also suggest that determination of CD44v6 levels is not helpful in judging the likely clinical behaviour of oral dysplasia.

The effects of irradiation and hyperbaric oxygen on bone formation during rabbit mandibular distraction.

[18F-]fluoride positron-emission tomography (PET) was used to assess bone formation during mandibular distraction osteogenesis. There were three study groups: irradiation, irradiation+hyperbaric oxygen and control. The two experimental groups received a tumoricidal dose of irradiation to the mandible, and one group was also given hyperbaric oxygen (2.5 ATA (atmospheres absolute) for 90 min) 18 times preoperatively. Control animals received neither irradiation nor oxygen. A unilateral osteotomy was made and, after a period of latency, bone distraction was started, continued for 2 weeks, and the distraction generated was then allowed to consolidate for 4 weeks. The first PET study was performed at the end of distraction and the second at the end of consolidation. At the end of distraction, the metabolic activity of bone in the distracted area was significantly higher in the controls than in either experimental group; differences between the experimental groups were not statistically significant. By the end of consolidation, activity in the control group had diminished to the same as in the two experimental groups, in which no significant change had occurred. Radioactivity was still significantly higher at second imaging on the distracted than non-distracted side in the control and irradiation+hyperbaric oxygen groups, but not in the group that was only irradiated. The results indicate that previous irradiation disturbs bone formation during mandibular distraction osteogenesis. Hyperbaric oxygen was not able to prevent the suppression of osteogenesis caused by radiotherapy but it might improve bone formation by prolonging high osteogenic activity.

Rehabilitation of patients with congenital unrepaired cleft palate defects using free iliac crest bone grafts and dental implants.

PURPOSE: To rehabilitate the mastication and speech of edentulous congenital cleft lip and palate patients with the use of endosseous implants in conjunction with bone augmentation. MATERIALS AND METHODS: Between 1992 and 1999, 6 partially and 4 completely edentulous adult patients with complex cleft palate defects were treated. Six patients had large, unrepaired defects of the hard and soft palate, whereas the other 4 had residual oronasal fistulas after failed palatoplasty and bone grafting. In 8 patients, free inlay-antral and simultaneous lateral-onlay bone grafts (3 patients) were obtained from the iliac crest, and dental implants were placed secondarily. In the other 2 patients, the implants were placed without grafting in recent extraction sites. Rigid bars with extensions over the defects were used to support obturator prostheses (n = 7), or patients were provided with fixed implant-supported prostheses (n = 3). In all, 50 cylindric, screw-type dental implants were placed and followed up for 1 to 8 years (mean, 5 years). RESULTS: Six implants were regarded as early failures and 1 was lost during the first year of loading; 1 patient lost all 5 implants. The cumulative success rate at 5 years was 85.7%. DISCUSSION AND CONCLUSION: All 9 successfully rehabilitated patients reported a remarkable functional and psychologic improvement after the treatment. The described treatment protocol also seemed to be effective for correcting velopharyngeal insufficiency in patients using an obturator prosthesis.

Functional outcomes for clinical evaluation of implant restorations.

The functional outcomes related to treating patients afflicted with tooth loss are an important hallmark in substantiating prosthodontic intervention. The Oral Rehabilitation Outcomes Network (ORONet) conducted two international workshops to develop a core set of outcome measures, including a functional domain. The process followed the general format used in the Outcome Measures in Rheumatology (OMERACT) workshops to develop consensus for clinical outcome measures in arthritis research, which included: developing a comprehensive list of potential outcomes in the literature; submitting them to a filter for validity, clinical discrimination, and feasibility; and ranking those measures meeting all the filter criteria for relative value. The search was conducted to include functional assessments of speech, swallowing, mastication, nutrition, sensation, and motor function as they relate to dental implant therapies. This literature review surveyed 173 papers that produced some result of these descriptors in the functional domain. Of these, 67 papers reported on functional assessments and further defined objective and subjective outcomes. Many of these results were patient-perceived improvements in function, while others were objective assessments based on established methodologies and instruments. Objective evaluations of masticatory function and speech may meet criteria for validity and discriminability for selected interventions, but are generally not feasible for routine use in clinical care settings. The current recommendation is to employ a well-validated survey instrument that covers mastication and speech, such as the Oral Health Impact Profile (OHIP-14, short form), recognizing that patient perceptions of function may differ from objective ability.

Psychologic outcomes in implant prosthodontics.

Consensus regarding outcomes of the treatment of tooth loss, especially the psychologic outcomes, is needed to guide discovery of best practices and enable a better understanding of patient management for this chronic condition. This paper presents the findings of the ORONet Psychological Working Group for prosthodontics and aims to identify psychologic outcomes with properties deemed critical to meet clinical trial and clinical practice needs for the future. References obtained using a PubMed/Medline search were reviewed for clinical outcomes measures of interest. Clinical outcomes measures were judged relative to the criteria of truth, discrimination, and feasibility. Of the psychologic outcome measures identified in this systematic review, only the OHIP-14 was thought to be suitable for use in general practice and multi-institutional outcome registries and clinical trials. Development of clinically useful psychologic outcomes for future use could benefit from developmental methods and tools outlined in the patient-related outcomes field of clinical care.

Economic outcomes in prosthodontics.

PURPOSE: A systematic literature review was conducted to identify the types of economic measures currently used in implant prosthodontics and determine the degree to which cost of care is considered in the context of any positive outcome of the care provided. MATERIALS AND METHODS: A literature search was conducted using the following set of terms plus some additional hand searching: "dental implants" (Mesh) AND ("cost") OR "maintenance" OR "healthcare policy" OR "access to care" OR "third party" OR "economic") AND (("1995/01/01"[PDat]:'2009/12/31"[PDat]) AND (Humans[Mesh]) AND (English[lang])). RESULTS: After a review of the 466 titles and abstracts identified by the search, 18 articles were accepted for further consideration, as some attempt at economic outcome measures was made. An additional four articles were identified by hand searching. The 22 accepted articles were grouped into four basic categories: (1) measure of costs of treatment (direct, indirect, and maintenance costs), (2) cost-effectiveness mathematical modeling applied to simulate the lifetime paths and cost of treatment, (3) cost-effectiveness analysis/cost minimization, and (4) willingness-to-pay, willingness-to-accept. Attempts at determining the costs of treatment varied widely. When the OMERACT filters were applied to the various measures it was felt that discrimination and/or feasibility was a problem for most of the current economic outcome measures. CONCLUSIONS: Measures of cost-benefit, cost-effectiveness, and cost-utility are currently the gold standard; however, feasibility of such analyses is an issue. Collaboration with health economists to guide future research is highly recommended.