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OBJECTIVES:As tumours of bone and soft tissue are rare, multicentre prospective collaboration is essential for meaningful research and evidence-based advances in patient care. The aim of this study was to identify barriers and facilitators encountered in large-scale collaborative research by orthopaedic oncological surgeons involved or interested in prospective multicentre collaboration. METHODS:All surgeons who were involved, or had expressed an interest, in the ongoing Prophylactic Antibiotic Regimens in Tumour Surgery (PARITY) trial were invited to participate in a focus group to discuss their experiences with collaborative research in this area. The discussion was digitally recorded, transcribed and anonymised. The transcript was analysed qualitatively, using an analytic approach which aims to organise the data in the language of the participants with little theoretical interpretation. RESULTS:The 13 surgeons who participated in the discussion represented orthopaedic oncology practices from seven countries (Argentina, Brazil, Italy, Spain, Denmark, United States and Canada). Four categories and associated themes emerged from the discussion: the need for collaboration in the field of orthopaedic oncology due to the rarity of the tumours and the need for high level evidence to guide treatment; motivational factors for participating in collaborative research including establishing proof of principle, learning opportunity, answering a relevant research question and being part of a collaborative research community; barriers to participation including funding, personal barriers, institutional barriers, trial barriers, and administrative barriers and facilitators for participation including institutional facilitators, leadership, authorship, trial set-up, and the support of centralised study coordination. CONCLUSIONS:Orthopaedic surgeons involved in an ongoing international randomised controlled trial (RCT) were motivated by many factors to participate. There were a number of barriers to and facilitators for their participation. There was a collective sense of fatigue experienced in overcoming these barriers, which was mirrored by a strong collective sense of the importance of, and need for, collaborative research in this field. The experiences were described as essential educational first steps to advance collaborative studies in this area. Knowledge gained from this study will inform the development of future large-scale collaborative research projects in orthopaedic oncology.Cite this article: J. S. Rendon, M. Swinton, N. Bernthal, M. Boffano, T. Damron, N. Evaniew, P. Ferguson, M. Galli Serra, W. Hettwer, P. McKay, B. Miller, L. Nystrom, W. Parizzia, P. Schneider, A. Spiguel, R. Vélez, K. Weiss, J. P. Zumárraga, M. Ghert. Barriers and facilitators experienced in collaborative prospective research in orthopaedic oncology: A qualitative study. Bone Joint Res 2017;6:-314. DOI: 10.1302/2046-3758.65.BJR-2016-0192.R1.

Chondrosarcoma is the second most common surgically treated primary bone sarcoma. Despite a large number of scientific papers in the literature, there is still significant controversy about diagnostics, treatment of the primary tumour, subtypes, and complications. Therefore, consensus on its day-to-day treatment decisions is needed. In January 2024, the Birmingham Orthopaedic Oncology Meeting (BOOM) attempted to gain global consensus from 300 delegates from over 50 countries. The meeting focused on these critical areas and aimed to generate consensus statements based on evidence amalgamation and expert opinion from diverse geographical regions. In parallel, periprosthetic joint infection (PJI) in oncological reconstructions poses unique challenges due to factors such as adjuvant treatments, large exposures, and the complexity of surgery. The meeting debated two-stage revisions, antibiotic prophylaxis, managing acute PJI in patients undergoing chemotherapy, and defining the best strategies for wound management and allograft reconstruction. The objectives of the meeting extended beyond resolving immediate controversies. It sought to foster global collaboration among specialists attending the meeting, and to encourage future research projects to address unsolved dilemmas. By highlighting areas of disagreement and promoting collaborative research endeavours, this initiative aims to enhance treatment standards and potentially improve outcomes for patients globally. This paper sets out some of the controversies and questions that were debated in the meeting., Competing Interests: A. Puri is a member of the editorial board of The Bone & Joint Journal. P. Ruggieri reports consulting fees from Exactech and Stryker, unrelated to this study. M. T. Houdek reports consulting fees from Link Orthopedics, unrelated to this study. E. Botello reports consulting fees, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events, and support for attending meetings and/or travel from Zimmer Biomet, all of which are unrelated to this study. G. V. Morris reports consulting fees, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events, and support for attending meetings and/or travel from Implantcast, all of which are unrelated to this study., (© 2024 Jeys et al.)

Background: Intramedullary nail fixation is commonly used for prophylactic stabilization of impending and fixation of complete pathological fractures of the long bones. However, metallic artifacts complicate imaging evaluation for bone healing or tumor progression and postoperative radiation planning. Carbon-fiber implants have gained popularity as an alternative, given their radiolucency and superior axial bending. This study evaluates incidences of mechanical and nonmechanical complications., Methods: Adult patients (age 18 years and older) treated with carbon-fiber nails for impending/complete pathological long bone fractures secondary to metastases from 2013 to 2020 were analyzed for incidences and risk factors of mechanical and nonmechanical complications. Mechanical complications included aseptic screw loosening and structural failures of host bone and carbon-fiber implants. Deep infection and tumor progression were considered nonmechanical. Other complications/adverse events were also reported., Results: A total of 239 patients were included; 47% were male, and 53% were female, with a median age of 68 (IQR, 59 to 75) years. Most common secondary metastases were related to breast cancer (19%), lung cancer (19%), multiple myeloma (18%), and sarcoma (13%). In total, 17 of 30 patients with metastatic sarcoma received palliative intramedullary nail fixation for impending/complete pathological fractures, and 13 of 30 received prophylactic nail stabilization of bone radiated preoperatively to manage juxta-osseous soft-tissue sarcomas, where partial resection of the periosteum or bone was necessary for negative margin resection. 33 (14%) patients had complications. Mechanical failures included 4 (1.7%) structural host bone failures, 7 (2.9%) implant structural failures, and 1 (0.4%) aseptic loosening of distal locking screws. Nonmechanical failures included 8 (3.3%) peri-implant infections and 15 (6.3%) tumor progressions with implant contamination. The 90-day and 1-year mortalities were 28% (61/239) and 53% (53/102), respectively. The literature reported comparable failure and mortality rates with conventional titanium treatment., Conclusions: Carbon-fiber implants might be an alternative for treating impending and sustained pathological fractures secondary to metastatic bone disease. The seemingly comparable complication profile warrants further cohort studies comparing carbon-fiber and titanium nail complications., Competing Interests: Conflict of interest by the authors: Each author certifies that there are no funding or commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article related to the author or any immediate family members., (Copyright © 2023 by the American Academy of Orthopaedic Surgeons.)

Purpose: the evaluation of body image perception, pain coping strategies, and dream content, together with phantom limb and telescoping phenomena in patients with sarcoma who underwent surgery for limb amputation., Material and Methods: consecutive outpatients were evaluated at T0 (within 3 weeks after surgery) and T1 (4-6 months after surgery) as follows: demographic and clinical data collection; the Groningen Questionnaire Problems after Arm Amputation; the West Haven-Yale Multidimensional Pain Inventory; the Body Image Concern Inventory, a clinical trial to identify telescoping; and a weekly diary of dreams. Dream contents were coded according to the Hall and Van de Castle coding system., Results: Twenty patients completed the study (15 males and 5 females, mean age: 53.9 ± 24.6, education: 7.8 ± 3.4). All subjects experienced phantom limb and 35% of them experienced telescoping soon after surgery, and 25% still after 4-6 months. Both at T0 and T1, that half of the subjects reported dreams about still having their missing limbs. At T1 the patients' perceptions of being able to deal with problems were lower, and pain and its interference in everyday life were higher yet associated with significant engagement in everyday activities and an overall good mood. The dream content analysis highlighted that males were less worried about health problems soon after amputation, and women showed more initial difficulties that seemed to be resolved after 4-6 months after surgery., Conclusions: The dream content analysis may improve clinicians' ability to support their patients during their therapeutic course.

Introduction: Bone metastases are frequent in patients with cancer. Electrochemotherapy (ECT) is a minimally invasive treatment. Preclinical and clinical studies supported the use of ECT in patients with metastatic bone disease (MBD). The purposes of this multicentre study are to confirm the safety and efficacy of ECT, and to identify appropriate operating procedures in different MBD conditions., Materials and Methods: 102 patients were treated in 11 Centres and recorded in the REINBONE registry (a shared database protected by security passwords): clinical and radiological information, ECT session, adverse events, response, quality of life indicators and duration of follow-up were registered., Results: 105 ECT sessions were performed (one ECT session in 99 patients, two ECT sessions in 3 patients). 24 patients (23.5%) received a programmed intramedullary nail after ECT, during the same surgical procedure. Mean follow-up was 5.9 ± 5.1 months (range 1.5-52). The response to treatment by RECIST criteria was 40.4% objective responses, 50.6% stable disease and 9% progressive disease. According to PERCIST criteria the response was: 31.4% OR; 51.7% SD, 16.9% PD with no significant differences between the 2 criteria. Diagnosis of breast cancer and ECOG values 0-1 were significantly associated to objective response. A significant decrease in pain intensity and significant better quality of life was observed after ECT session at follow-up., Conclusion: The results are encouraging on pain and tumour local control. ECT proved to be an effective and safe treatment for MBD and it should be considered as an alternative treatment as well as in combination with radiation therapy., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest with the trademarks included in the manuscript. All authors disclose no personal, financial or non-financial competing interests. Francesca de Terlizzi and Matteo Cadossi are IGEA employers. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (Copyright © 2021 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Gait alterations have been studied with computer-assisted gait analysis after megaprosthetic replacement for tumors around the knee. It has never been proven that megaprostheses affects gait more than total knee arthroplasty (TKA); this study aims to compare via gait analysis patients who underwent megaprosthesis with patients with TKA., Methods: We analyzed 26 patients with a megaprosthetic replacement of the distal femur and 21 patients with a standard TKA. For each subject computerized gait analysis was performed. Range of motion (ROM) of the knee was recorded, Quality of Life and functional evaluation in the oncologic group were assessed with the Musculoskeletal Tumor Society (MSTS) questionnaire, while Short Form-36 (SF-36) scores were calculated for both groups., Results: All patients walked slower than healthy people (P < 0.05). Gait analysis showed a lower cadence than in the healthy population but no significant difference between the two groups. A longer swing and a shorter stance phase were detected in the megaprosthetic sample. The osteoarthritis group showed greater flexion during the phase of loading response, even if this was lower than the contralateral limb or healthy population. There was a statically significant difference between the healthy limb and the operated one in both groups regarding ROM, but no significant difference was registered between the two implants. MSTS score and most of SF-36 parameters showed no significant differences compared with literature data., Conclusions: Gait analysis shows little discrepancy between the two groups; gait pattern abnormalities do not affect patients with a megaprosthetic replacement more significantly than patients undergoing TKA., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Both non-rapid eye movements and rapid eye movements sleep facilitate the strengthening of newly encoded memory traces, and dream content reflects this process. Numerous studies evaluated the impact of diseases on dream content, with particular reference to cancer, and reported the presence of issues related to death, negative emotions, pain and illness. This study investigates death and illness experiences in 13 consecutive patients with sarcoma compared to paired controls, early after diagnosis, evaluating dream contents, fear of death, mood and anxiety, distress, and severity of disease perception (perceived and communicated). Ten patients and 10 controls completed the study. Dream contents were significantly different between patients and normative data (DreamSat) and patients and controls (higher presence of negative emotions, low familiar settings and characters and no success involving the dreamer). Illness and death were present in 57% of patients' dreams (0% among controls), but no differences emerged between patients and controls in regard to anxiety and depression, distress and fear of death, even if the severity of illness was correctly perceived. The appearance of emotional elements in dreams and the absence of conscious verbalization of distress and/or depressive or anxious symptoms by patients could be ascribed to the time required for mnestic elaboration (construction/elaboration phase) during sleep.

Several bone grafts are available for clinical use, each with their own peculiar biological and mechanical properties. A new bone graft was obtained by combining mineral structures from natural bovine bones with bioresorbable polymers and cellular nutrients. The study aims to evaluate the clinical, biological and structural properties of this bone graft and its reliability in orthopedic oncology. 23 adult patients (age range 18-85 years) were treated between October 2016 and December 2018; the oncologicdiagnoses were heterogeneous. After surgical curettage and bone grafting, a clinical-radiological follow up was conducted. Radiographs were used to evaluate graft integration according to the usual bone healing and oncologic follow up. Local complications (infection, local recurrence, wound dehiscence, fracture or early reabsorption) were evaluated. The mean followup was of 18.34 ± 4.83 months. No fracture or infection occurred. One case of patellar Giant Cell Tumor (GCT) and one of proximal tibia low-grade chondrosarcoma recurred after about one year. Two wound dehiscences occurred (one required a local flap). Follow-up X-rays showed good to excellent graft integration in most patients (20 out of 21). The investigated graft has a mechanical and structural function that can allow early weight-bearing and avoid a preventive bone fixation (only needed in four patients in this series). The graft blocks are different for shapes and dimensions, but they can be customized by the producer or sawcut by the surgeon in the operating theatre to fit the residual bone cavity. The complication rate was low, and a rapid integration was observed with no inflammatory reaction in the surrounding tissues. Further studies are mandatory to confirm these promising results.

Primitive myxoid mesenchymal tumor of infancy is a rare soft tissue tumor. The present case is one of the most invasive primitive myxoid mesenchymal tumor of infancy reported to date. To our knowledge, it is the first case described with extensive involvement of pelvis and the third described developing metastasis and with an invasion of the spinal canal without evidence of transformation into undifferentiated sarcoma. The patient failed to respond to chemotherapy (CHT). According to the few available data, CHT seems to be more effective in the presence of metastatic disease or increased cellularity. However, CHT, including high-dose ifosfamide, resulted ineffective even after lung metastasis development with pathologic evidence of increased mitotic rate. The management of this case and the data in the literature confirm surgery as the gold standard treatment in this pathology.

Introduction: Pelvic and sacral tumor surgery is traditionally characterized by several major complications. Bleeding is probably the most feared and dreadful complication. The aim of the study was to evaluate whether the intraoperative use of the intra-aortic balloon occlusion technique could decrease the perioperative blood loss. A secondary aim was to assess aortic balloon-related complications., Materials and Methods: From January 2014 to December 2017 15 patients (Group 1) treated with intra-aortic balloon inflation were prospectively enrolled and compared to a historical control group (Group 2) of 11 patients with similar surgeries. Number of blood units transfused, perioperative hemoglobin values, hours spent in intensive care unit (ICU), length of inpatient stay, and perioperative complications were evaluated., Results: Intraoperatively, a mean of 6.1 blood units per patient (BUPP) was used in Group 1 and 16.2 BUPP in Group 2. Postoperatively the averages were 2,8 and 5,4 BUPP in Group 1 and 2, respectively. Patients in Group 1 had a faster recovery in hemoglobin values, as well as a shorter length of overall inpatient stay (28,9 vs 59 days) and of ICU stay (33.9 vs 74.6 h). The most relevant complications observed in Group 1 were two thrombosis at the incannulation site that required a surgical arterial thrombectomy., Conclusion: The intra-aortic balloon occlusion is an effective technique to control bleeding during the resections of huge pelvic and sacral tumors. A proper training of a multidisciplinary team and an accurate patient selection are required to prevent major complications., Competing Interests: Declaration of competing interest None, (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background and Objectives: Limb salvage surgery remains the standard treatment in bone and soft tissue tumors. Toronto Extremity Salvage Score (TESS) is the most used quality of life measure. Our objective was to perform cross-cultural adaptation and validation in Italian, testing test-retest reliability, construct validity, and responsiveness., Methods: We interviewed patients already treated for content validity. A total of 124 patients completed TESS and other questionnaires presurgery, at 3 months, 3 months + 2 weeks, and 6 months follow-up. We calculated intraclass correlation coefficients (ICCs) for reliability, associations with Pearson's r, and change over time with paired T tests., Results: A new item regarding touch-screen devices was added to the upper extremity (UE) questionnaire. ICC resulted of 0.99 for lower extremity (LE) and 0.98 for UE patients, Pearson's r between TESS and Musculoskeletal Tumor Society was .66 and .64, EuroQol-5D-5L r was .62 and .61, and r between TESS and short form-36 physical function subscale was .76 and .71 for LE and UE groups, respectively. Paired T test results were statistically significant to detect change over time (0.03, 0.04, and 0.04 for LE groups and 0.03, 0.01, and 0.04 for UE groups)., Conclusion: The Italian version of TESS can be used for the bone and soft tissue sarcoma population in clinical trials in Italy and with Italian speaking patients abroad to ensure patients' perspectives for efficacy and efficiency of treatments., (© 2020 Wiley Periodicals, Inc.)

Case: A 35-year-old man with a giant cell tumor involving the lateral condyle and trochlea of the right distal femur underwent curettage of the lesion and cement grafting, which resulted in symptomatic patellofemoral osteoarthritis after more than 4 years. A standard follow-up excluded recurrence, whereas infection was ruled out while investigating the symptoms. Finally, a patellofemoral resurfacing prosthesis was implanted while filling the bone defects with tantalum cones., Conclusion: A "tailored" surgical technique with a selected patellofemoral joint arthroplasty could be used in oncologic setting to save further bone stock for possible revisions while permitting full and quick clinical recovery.

Acromioclavicular joint (ACJ) injuries are common, but their incidence is probably underestimated. As the treatment of some sub-types is still debated, we reviewed the available literature to obtain an overview of current management.We analysed the literature using the PubMed search engine.There is consensus on the treatment of Rockwood type I and type II lesions and for high-grade injuries of types IV, V and VI. The treatment of type III injuries remains controversial, as none of the studies has proven a significant benefit of one procedure when compared with another.Several approaches can be considered in reaching a valid solution for treating ACJ lesions. The final outcome is affected by both vertical and horizontal post-operative ACJ stability. Synthetic devices, positioned using early open or arthroscopic procedures, are the main choice for young people.Type III injuries should be managed surgically only in cases with high-demand sporting or working activities. Cite this article: EFORT Open Rev 2017;2:432-437. DOI: 10.1302/2058-5241.2.160085., Competing Interests: ICMJE Conflict of interest statement: None declared.

Shoulder joint dislocation is the most common joint dislocation seen in the emergency department.Traumatic dislocation may cause damage to the soft-tissues surrounding the shoulder joint and sometimes to the bone. The treatment, which aims at restoration of a fully functioning, pain-free and stable shoulder, includes either conservative or surgical management preceded by closed reduction of the acute dislocation.Conservative management usually requires a period of rest, generally involving immobilisation of the arm in a sling, even though it is still debated whether to immobilise the shoulder in internal or external rotation.Operative management, with no significant differences in term of re-dislocation rates between open and arthroscopic repair, incorporates soft-tissue reconstructions and/or bony procedures and is recommended in young male adults engaged in highly demanding physical activities.At our institution, non-operative management is favoured particularly for patients with multi-directional instability or soft-tissue laxity. Conservative measures are often preferred in older patients or younger patients that are not actively engaged in overhead activities. Immediate surgery on all first-time dislocations may subject many patients to surgery who would not have had any future subluxation.For these reasons, initially we will always try physical therapy and activity modification for the vast majority of our patients. Cite this article: EFORT Open Rev 2017;2:35-40.DOI: 10.1302/2058-5241.2.160018., Competing Interests: ICMJE Conflict of interest statement: None

Objectives: Soft tissue tumours (STT) require accurate diagnosis in order to identify potential malignancies. Preoperative planning is fundamental to avoid inadequate treatments. The role of contrast-enhanced computed tomography (CT) for local staging remains incompletely assessed. Aims of the study were to evaluate CT accuracy in discriminating active from aggressive tumours compared to histology and evaluate the role of CT angiography (CTA) in surgical planning., Materials and Methods: This retrospective cohort series of 88 cases from 1200 patients (7 %) was locally studied by contrast-enhanced CT and CTA in a referral centre: 74 malignant tumours, 14 benign lesions. Contrast-enhancement patterns and relationship of the mass with major vessels and bone were compared with histology on surgically excised samples. Sensitivity, specificity, positive and negative predictive values (PPV, NPV) were evaluated in discriminating active from aggressive tumours., Results: Sensitivity in differentiating aggressive tumours from active lesions was 89 %, specificity 84 %, PPV 90 %, NPV 82 %. The relationship between mass and major vessels/bone was fundamental for surgical strategy respectively in 40 % and in 58 % of malignant tumours., Conclusion: Contrast-enhanced CT and CTA are effective in differentiating aggressive masses from active lesions in soft tissue and in depicting the relationship between tumour and adjacent bones and major vessels., Key Points: • Accurate delineation of vascular and bony involvement preoperatively is fundamental for a correct resection. • CT plays a critical role in differential diagnosis of soft tissue masses. • Contrast-enhanced CT and CT angiography are helpful in depicting tumoral vascular involvement. • CT is optimal for characterization of bone involvement in soft tissue malignancies.

Background: Microorganism adhesion on polyethylene for total joint arthroplasty is a concern. Many studies have focused on vitamin E-stabilized ultrahigh-molecular-weight polyethylene (UHMWPE), whereas first-generation, highly crosslinked UHMWPE, which is the most commonly used in clinical practice, has been scarcely evaluated., Questions/purposes: We aimed (1) to compare the adherence of Staphylococcus epidermidis, Staphylococcus aureus, Escherichia coli, and Candida albicans with virgin (untreated) UHMWPE (PE) and crosslinked UHMWPE (XLPE); (2) to correlate the results with the biomaterial surface properties; and (3) to determine whether the decreased adhesion on vitamin E-stabilized UHMWPE (VE-PE) previously recorded for bacteria can also be confirmed for C albicans., Methods: Microbial adhesion of biofilm-producing American Type Culture Collection (ATCC) and clinical strains on XLPE and VE-PE were compared with PE at 3, 7, 24, and 48 hours of incubation and quantified, as colony forming units (CFU)/mL, using a sonication protocol. Sample surfaces were characterized by scanning electron microscopy, roughness and contact angle measurements, attenuated total reflection-Fourier transform infrared spectroscopy, and x-ray photoelectron spectroscopy (XPS) to reveal qualitative differences in surface composition and topography that could influence the microbial adhesion. The results were analyzed by descriptive statistics and tested by unpaired t-tests., Results: All microorganisms, both ATCC and clinical strains, showed lower adhesion (p < 0.05) on XLPE with adhesion percentages ranging from 18% to 25%, compared with PE with adhesion percentages ranging from 51% to 55%, after 48 hours. Only the ATCC S epidermidis showed a reduced adhesion profile even at 3 hours (adhesion ratio of 14% on XLPE versus 50% on PE) and 24 hours (19% on XLPE versus 55% on PE) of incubation. ATCC and clinical C albicans were less adherent to XLPE than to PE (p < 0.05) showing even at the earlier incubation time points adhesion values always of 10(3) CFU/mL and 10(4) CFU/mL, respectively. Roughness and contact angle were 0.8 ± 0.2 μm and 92° ± 3°, respectively, with no differences among samples. Qualitative differences in the surface chemical composition were revealed by XPS only. A confirmation of the decreased adhesion on VE-PE respect to PE was also registered here for C albicans strains (p < 0.05)., Conclusions: Vitamin E stabilization and crosslinking of UHMWPE are capable of reducing microbial adhesion. Further studies are needed to fully elucidate the mechanisms of modulation of microbial adhesion to medical-grade UHMWPE., Clinical Relevance: Our results suggest that VE-PE and XLPE may have an added benefit of being more resistant to bacterial adhesion, even fungal strains.

Primary synovial chondromatosis (SC) is a rare proliferative disorder that causes pain, swelling, and restriction of movement to the joints it affects. The disease frequently runs a protracted course, often requiring multiple surgical procedures to obtain some control. Few reports exist detailing the natural history of SC, although malignant transformation to synovial chondrosarcoma (CHS) is recognized to be a rare event. The aim of our study was to review a large orthopaedic oncology database in order to evaluate the incidence of CHS arising from SC. We identified 78 patients who have presented to our centre with primary synovial chondromatosis (SC). Of those patients, 5 went on to develop malignant change. This represents a 6.4% incidence of developing synovial chondrosarcoma (CHS) within preexisting primary synovial chondromatosis. The patients had a mean age of 28 years at first diagnosis with synovial chondromatosis with the median time from original diagnosis to malignant transformation being 20 years (range 2.7-39 yrs).