Development and validation of a fall risk Questionnaire in Greek community-dwelling individuals over 60 years old.

Objectives: The purpose of this study was to develop a questionnaire that can reliably recognize Greek individuals over the age of 60 with increased risk of falls. Methods: An 11-item self-reported Questionnaire (LRMS) was developed and delivered to 200 individuals. Collected data were compared to Timed Up and Go (TUG), Falls Efficacy Scale-International (FES-I), Tinetti Assessment Tool, Geriatric Depression Scale-15 (GDS-15) and Morse fall scale. The results were statistically analyzed. Results: Correlation between LRMS and the examined tools was high TUG (r=0.831), FES-I (r=-0.820), Tinetti balance (r=-0.812), Tinetti gait (r=-0.789), GDS-15 (r=-0.562), and Morse fall scale (r=0.795). Cronbach's alpha for LRMS total score was 0.807. ICC of the LRMS total score was 0.991. The area under the curve of LRMS was 0.930 (cut-off point 10.5, 95% C.I. 0.88 - 0.98, p<0.001, sensitivity=86%, specificity=98%) with TUG as gold standard, 0.919 (cut-off point 11.5, 95% C.I. 0.88 - 0.96, p<0.001, sensitivity=85%, specificity=89%) with FES-I and 0.947 (cut-off point 10.5, 95% C.I. 0.91 - 0.98, p<0.001, sensitivity=93%, specificity=91%) with Tinetti. Conclusions: The LRMS Questionnaire showed sufficient internal consistency, excellent test-retest reliability and high correlation with the already established tools for fall risk assessment. It is short and easy to use without assistance from specially trained personnel.

Change in kyphosis does not affect the risk of falling in postmenopausal osteopenic and osteoporotic women.

OBJECTIVES: To examine the influence of the annual change in kyphosis on the risk of falling in postmenopausal osteopenic and osteoporotic women. METHODS: This prospective observational study included 498 postmenopausal Greek women over the age of 50, suffering from either osteoporosis or osteopenia. Data on age, height, weight, and self-reported falls were collected. Additionally, we evaluated the degree of the kyphosis angle, the balance, the mobility, the functionality and the handgrip strength on both hands of each subject using the Debrunner kyphometer, the Berg Balance Scale, the Timed-Up-and-Go test, the 30 Seconds Sit-to-Stand test and the Jamar Hydraulic Hand Dynamometer, respectively. All the above data were recorded at the baseline visit and the 12-month follow-up visit for each participant. RESULTS: All examined variables presented a statistically significant change at the 12-month follow-up visit. Nevertheless, the annual change in kyphosis did not show any association with the risk of falling. CONCLUSION: No association was shown between the annual change in kyphosis and the risk of falling in postmenopausal osteopenic and osteoporotic women, nor bears any substantial prognostic value for future falls.

Bone metabolism subgroups identified as hip fracture patients via clustering.

PURPOSE: The aim of the study was to describe the bone metabolism status that underlies a hip fracture. METHODS: Estimated glomerular filtration rate (e-GFR), calcium (Ca), phosphorus (P), total (ALP) and bone specific alkaline phosphatase (b-ALP), intact parathyroid hormone (i-PTH), 25-hydroxy-vitamin D (25OHD), total procollagen type I amino-terminal propeptide (PINP), and N-terminal peptide of collagen I (NTx), measured at admission in 272 hip fracture patients, were ex post analyzed by K-means clustering and principal component analysis and were evaluated by a clinician. RESULTS: Four components, mainly consisting of b-ALP, PINP, ALP, and NTx; e-GFR and P; i-PTH and 25OHD; and Ca explained about 70% of the variability. A total of 184 patients clustered around a centroid (A) with low 25OHD (13.2 ng/ml), well-preserved kidney function (e-GFR=67.19 ml/min/1.73m2), normal Ca, P, i-PTH and bone markers, with the exception of slightly increased NTx (24.82nMBCE). Cluster B (n=70) had increased i-PTH (93.38 pg/ml), moderately decreased e-GFR, very low 25OHD (8.68 ng/dl), and high bone turnover (b-ALP 28.46 U/L, PINP 69.87 ng/ml, NTx 31.3nMBCE). Cluster C (n=17) also had hyperparathyroidism (80.35 pg/ml) and hypovitaminosis D (9.15 ng/ml), low e-GFR(48.89 ml/min/1.73m2), and notably high ALP (173 U/L) and bone markers (b-ALP 44.64 U/L, PINP 186.98 ng/ml, NTx 38.28nMBCE). According to the clinician, 62 cases clearly had secondary hyperparathyroidism. CONCLUSIONS: Based on serum measurements, the dominant patterns of bone metabolism were normal bone turnover with high normal NTx, and secondary hyperparathyroidism related to chronic kidney disease and hypovitaminosis D. The bone formation markers, e-GFR, NTx, and P composed the most important factors.

Secondary Fracture Prevention: Consensus Clinical Recommendations from a Multistakeholder Coalition.

Osteoporosis-related fractures are undertreated, due in part to misinformation about recommended approaches to patient care and discrepancies among treatment guidelines. To help bridge this gap and improve patient outcomes, the American Society for Bone and Mineral Research assembled a multistakeholder coalition to develop clinical recommendations for the optimal prevention of secondary fractureamong people aged 65 years and older with a hip or vertebral fracture. The coalition developed 13 recommendations (7 primary and 6 secondary) strongly supported by the empirical literature. The coalition recommends increased communication with patients regarding fracture risk, mortality and morbidity outcomes, and fracture risk reduction. Risk assessment (including fall history) should occur at regular intervals with referral to physical and/or occupational therapy as appropriate. Oral, intravenous, andsubcutaneous pharmacotherapies are efficaciousandcanreduce risk of future fracture.Patientsneededucation,however, about thebenefitsandrisks of both treatment and not receiving treatment. Oral bisphosphonates alendronate and risedronate are first-line options and are generally well tolerated; otherwise, intravenous zoledronic acid and subcutaneous denosumab can be considered. Anabolic agents are expensive butmay be beneficial for selected patients at high risk.Optimal duration of pharmacotherapy is unknown but because the risk for second fractures is highest in the earlypost-fractureperiod,prompt treatment is recommended.Adequate dietary or supplemental vitaminDand calciumintake shouldbe assured. Individuals beingtreatedfor osteoporosis shouldbe reevaluated for fracture risk routinely, includingvia patienteducationabout osteoporosisandfracturesandmonitoringfor adverse treatment effects.Patients shouldbestronglyencouraged to avoid tobacco, consume alcohol inmoderation atmost, and engage in regular exercise and fall prevention strategies. Finally, referral to endocrinologists or other osteoporosis specialists may be warranted for individuals who experience repeated fracture or bone loss and those with complicating comorbidities (eg, hyperparathyroidism, chronic kidney disease).

Secondary Fracture Prevention: Consensus Clinical Recommendations from a Multistakeholder Coalition.

Osteoporosis-related fractures are undertreated, due in part to misinformation about recommended approaches to patient care and discrepancies among treatment guidelines. To help bridge this gap and improve patient outcomes, the American Society for Bone and Mineral Research assembled a multistakeholder coalition to develop clinical recommendations for the optimal prevention of secondary fracture among people aged 65 years and older with a hip or vertebral fracture. The coalition developed 13 recommendations (7 primary and 6 secondary) strongly supported by the empirical literature. The coalition recommends increased communication with patients regarding fracture risk, mortality and morbidity outcomes, and fracture risk reduction. Risk assessment (including fall history) should occur at regular intervals with referral to physical and/or occupational therapy as appropriate. Oral, intravenous, and subcutaneous pharmacotherapies are efficacious and can reduce risk of future fracture. Patients need education, however, about the benefits and risks of both treatment and not receiving treatment. Oral bisphosphonates alendronate and risedronate are first-line options and are generally well tolerated; otherwise, intravenous zoledronic acid and subcutaneous denosumab can be considered. Anabolic agents are expensive but may be beneficial for selected patients at high risk. Optimal duration of pharmacotherapy is unknown but because the risk for second fractures is highest in the early post-fracture period, prompt treatment is recommended. Adequate dietary or supplemental vitamin D and calcium intake should be assured. Individuals being treated for osteoporosis should be reevaluated for fracture risk routinely, including via patient education about osteoporosis and fractures and monitoring for adverse treatment effects. Patients should be strongly encouraged to avoid tobacco, consume alcohol in moderation at most, and engage in regular exercise and fall prevention strategies. Finally, referral to endocrinologists or other osteoporosis specialists may be warranted for individuals who experience repeated fracture or bone loss and those with complicating comorbidities (eg, hyperparathyroidism, chronic kidney disease). © 2019 American Society for Bone and Mineral Research.

Application of current sarcopenia definitions in spinal cord injury.

OBJECTIVE: Little is known about how appropriate the working definitions of sarcopenia are in subjects with spinal cord injury (SCI). This study aimed to evaluate the application of current sarcopenia definitions in SCI. METHODS: We compared 31 complete SCI men with 33 able-bodied age matched subjects. All were examined by whole body DXA (Norland XR 36, USA) regarding muscle and fat mass and by peripheral quantitative computed tomography (pQCT XCT-3000, Germany) in 66% of tibia's length (muscle cross sectional area, (CSA) in mm2). Low muscle mass was defined by skeletal muscle index, (SMI= appendicular lean mass (aLM)/height2 in Kg/m2) and by the residual method: relative aLM, 20th percentile of the distribution of residuals as the cutoff point, (RASM), respectively. CSA is a surrogate for force. RESULTS: We found lower values on RASM (p<0.001), and SMI (p<0.001) compared to controls in SCI and difference in the rate of sarcopenia according to sarcopenia definitions. CSA was significantly decreased in SCI (p<0.001) and correlation with duration of paralysis was weak. CONCLUSION: Current functional definitions of sarcopenia classify different individuals as sarcopenic. Sarcopenia was more prevalent in SCI. The sensitivity and specificity of using these measurements in SCI remain unclear.

Evaluation of physical performance in musculoskeletal and rheumatic diseases with jumping mechanography.

OBJECTIVE: Low muscle function is a component of sarcopenia. Rheumatic and musculoskeletal diseases are related to increased muscle loss and decreased muscle performance. Our purpose was to study muscle function among pre and postmenopausal women and women with rheumatic diseases. METHODS: Two hundred fifty seven women were included in the study: Group POST OST included 61 osteoporotic postmenopausal women under treatment with osteoporotic drugs and calcium/vitamin D supplements (mean age 65±9.6 years), group POST HEALTH consisted of 117 healthy postmenopausal women (mean age 62.9±9.8 yrs), Group RHEUM included 20 women with rheumatic diseases (mean age 58.85±13yrs), and group PRE included 59 healthy premenopausal women (mean age 35±7.6 yrs). For the measurement of objective parameters of movement (Force, velocity, Power), we used the mechanography system in Leonardo platform (Novotec, Germany). Personal Power (Power/Weight) was also calculated. RESULTS: Height was decreased with age, while body mass index (BMI) and weight were significantly increased. In groups POST OST, POST HEALTH, RHEUM, all measured parameters were statistically decreased in comparison with group PRE. No statistical significance was found among POST HEALTH and POST OST women. CONCLUSIONS: Jumping mechanography can be proposed as a novel tool to assess physical performance in musculoskeletal and rheumatic diseases. It offers to the clinician additional information, while quantitatively assesses muscle function, for assessing sarcopenia.

Clinical manifestations of osteoarthritis in osteoporotic and osteopenic postmenopausal women.

OBJECTIVE: We investigated the frequency of clinical manifestations of osteoarthritis in women with low BMD. METHODS: This prospective epidemiological study investigated the degree of osteoarthritic pain and functional disability in symptomatic joints of a randomly selected population of postmenopausal Greek women aged >45 years with osteoporosis or osteopenia. Degree of osteoarthritic impairment (none, mild, moderate or severe) was classified at the knee, hip, neck or hand using a site-specific internationally validated osteoarthritis questionnaire. RESULTS: 3000 women were included with mean age of 66.7 years. Osteoporosis was more common than osteopenia. Mild osteoarthritic impairment was most prevalent. An inverse relationship between severity of osteoarthritic impairment and mean femoral neck T-score was observed, regardless of site. There was a significant difference in mean femoral neck T-score between patients with severe osteoarthritic impairment and those with no, mild, or moderate impairment. This was also observed when lumbar spine BMD results were pooled. CONCLUSIONS: Most postmenopausal women with low BMD suffer from osteoarthritic impairment, with an inverse association between severity of osteoarthritic impairment and mean femoral neck T-score. Mean lumbar spine or femoral neck T-scores of patients with severe osteoarthritic impairment were significantly lower than those of patients with less impairment.

A contemporary therapeutic approach to bone disease in beta-thalassemia - a review.

Homozygous beta-thalassemia represents a serious hemoglobinopathy, in which an amazing prolongation in the survival rate of patients has been achieved over recent decades. A result of this otherwise positive evolution is the fact that bone problems have become a major issue in this group of patients. Through an in-depth review of the related literature, the purpose of this study is to present and comment on the totality of the data that have been published to date pertaining to the prevention and treatment of thalassemia bone-disease, focusing on: the contribution of diet and lifestyle, the treatment of hematologic disease and its complications, the management of hypercalciuria, the role of vitamins and minerals and the implementation of anti-osteoporosis medical regimen. In order to comprehensively gather the above information, we mainly reviewed the international literature through the PubMed database, searching for the preventive and therapeutic data that have been published pertaining to thalassemia bone-disease over the last twenty-nine years. There is no doubt that thalassemia bone-disease is a complication of a multi-factorial etiopathology, which does not follow the rules of classical postmenopausal osteoporosis. Bisphosphonates have been the first line of treatment for many years now, with varied and usually satisfactory results. In addition, over the last few years, more data have arisen for the use of denosumab, teriparatide, and other molecules that are in the clinical trial phase, in beta-thalassemia.

Degenerative inter-vertebral disc disease osteochondrosis intervertebralis in Europe: prevalence, geographic variation and radiological correlates in men and women aged 50 and over.

Objectives: To assess the prevalences across Europe of radiological indices of degenerative inter-vertebral disc disease (DDD); and to quantify their associations with, age, sex, physical anthropometry, areal BMD (aBMD) and change in aBMD with time. Methods: In the population-based European Prospective Osteoporosis Study, 27 age-stratified samples of men and women from across the continent aged 50+ years had standardized lateral radiographs of the lumbar and thoracic spine to evaluate the severity of DDD, using the Kellgren-Lawrence (KL) scale. Measurements of anterior, mid-body and posterior vertebral heights on all assessed vertebrae from T4 to L4 were used to generate indices of end-plate curvature. Results: Images from 10 132 participants (56% female, mean age 63.9 years) passed quality checks. Overall, 47% of men and women had DDD grade 3 or more in the lumbar spine and 36% in both thoracic and lumbar spine. Risk ratios for DDD grades 3 and 4, adjusted for age and anthropometric determinants, varied across a three-fold range between centres, yet prevalences were highly correlated in men and women. DDD was associated with flattened, non-ovoid inter-vertebral disc spaces. KL grade 4 and loss of inter-vertebral disc space were associated with higher spine aBMD. Conclusion: KL grades 3 and 4 are often used clinically to categorize radiological DDD. Highly variable European prevalences of radiologically defined DDD grades 3+ along with the large effects of age may have growing and geographically unequal health and economic impacts as the population ages. These data encourage further studies of potential genetic and environmental causes.

Assessment of the antiosteoporotic treatment initiation: A retrospective observational study in Greece.

OBJECTIVE: A study to retrospectively assess the decision to implement treatment for osteoporosis based on Greek version of FRAX tool. METHODS: The study population was 1000 postmenopausal women aged 45 or above, excluding those with medical conditions demanding specific osteoporosis management. Data were collected regarding their medical history and additionally, risk factors incorporated in FRAX questionnaire. FRAX score was estimated at the time of the anti-osteoporotic treatment initiation. RESULTS: The mean age of the study sample was 58.5±8.79 years. 46.8% of the participating osteopenic women had initiated treatment for osteoporosis at their first consultation while the 80.6% met the current national intervention threshold of FRAX tool. CONCLUSION: Stemming from our results there is an indication that women who are borderline eligible for treatment and seek consultation for osteoporosis are likely to be given treatment regardless of the potential benefit. One cannot ignore the fact that a clinician's good clinical judgment is of the utmost importance and under no circumstances can be replaced by any prognostic assessment tool.

Evaluation of commonly used nutritional assessment methods in hip fracture patients.

OBJECTIVE: Malnutrition is a common problem in hip fracture patients. The prevalence of malnutrition and available nutritional markers for use for nutritional assessment in this population group was investigated. METHODS: This is a case control study including 214 patients with a hip fracture from "KAT" Hospital in Athens, Greece, and 108 controls from three Elderly Open Protection Centers. Main outcome measures were anthropometric [Body Mass Index (BMI), triceps skinfold thickness (TST) and mid-arm muscle circumference (MAMC)] and biochemical parameters (serum albumin and serum cholesterol). Mini Nutritional Assessment (MNA) was used for malnutrition assessment. RESULTS: Based on MNA score only, we found 19.5 % vs. 0.9% malnourished, 54.6% vs. 32.4% at risk and 25.9% vs. 66.7% well-nourished, in hip fracture group and controls, respectively. All anthropometric parameters of malnutrition were significantly lower in the hip fracture patients compared to controls (p value<0.05). Serum albumin and serum-cholesterol levels correlated negatively significantly with s-CRP levels (R2=0.247, p<0.001 and R2=0.06, p<0.001, respectively) in the hip fracture group. CONCLUSIONS: Hip fracture patients are often malnourished. MNA application may be helpful in identifying malnourished hip fracture patients. Moreover, serum cholesterol may be a useful marker of malnutrition in hip fracture patients.

Evaluation of the first fracture liaison service in the Greek healthcare setting.

We evaluated the first implementation of FLS in the Greek healthcare setting, at the 251 Hellenic Air Force and VA General Hospital of Athens. Participation rate was moderate (54.5%) and needs improvement; osteoporosis medication was either suggested or reviewed in 74 out of the 116 patients recruited. PURPOSE: The purpose of this study was to evaluate the first implementation of a fracture liaison service (FLS) in Greece, at the 251 Hellenic Air Force and VA General Hospital, Athens. METHODS: Single-center, prospective study from May 1, 2013 to April 30, 2015 (first year-second year follow-up) was conducted. Patients of both genders aged 40-90 years old, with a history of a low trauma fracture and willing to participate, were included after identification by an FLS nurse. Following recruitment, osteoporosis risk factors were assessed, FRAX score was calculated for treatment-naïve patients, bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA), and osteoporosis treatment was suggested where applicable. The rate of participation, the indication of osteoporosis treatment, and the difficulties met were evaluated. RESULTS: Of the eligible 213 patients, 97 (45.5%) were reluctant to participate for personal reasons. From the 116 initially recruited patients (mean age 74.8 ± 12 years), 77 (66.4%) discontinued their participation at some point for various reasons and 39 patients concluded the study. All 116 patients were assessed for osteoporosis risk factors and given a tailor-made exercise and education program, while FRAX score was assessed in all treatment-naïve patients (74 patients, 63.8%). Osteoporosis medication was suggested or reviewed in 74 patients; however, an adherence rate of 100% is only available for the 24 who concluded the study. CONCLUSIONS: We report the first implementation of FLS in the Greek healthcare setting. The participation rate is moderate and definitely needs improvement.

Development and validation of an osteoporosis treatment questionnaire (OSTREQ) evaluating physicians' criteria in the choice of treatment.

OBJECTIVE: This article describes the development and validation of the osteoporosis treatment questionnaire (OSTREQ), which is a physician-reported outcome tool aiming to evaluate physicians' criteria in the choice of osteoporosis treatment. DESIGN: The questionnaire -named OSTREQ- consisting of 17 questions that were divided into eight sections "Health Care System", "Patients' Preference in administration routes", "Usage, Cost", "Severity of Disease", "Treatment Efficacy", "Safety Profile", "Pharmaceutical Industry", affecting the decision and overall execution of a therapeutic approach, was developed by an expert panel and was later officially translated into English. In the second phase, orthopedic surgeons were asked to complete OSTREQ. Six indirect methods to evaluate validity were adopted: exploratory factor analysis, confirmatory factor analysis, subscale validity, known group validity, floor or ceiling effects, interpretability. To assess the reliability of the questionnaire, internal consistency validity as well as test-retest and parallel forms were calculated. RESULTS: One hundred seventy-two orthopedic surgeons were interviewed with an average period of experience in clinical practice of 10.5 years (SD ±8.9 years). The factors "Severity of Disease" and "Treatment Efficacy" were the most important in the choice of osteoporosis treatment, while the factor "Pharmaceutical Industry" had the least impact. The methodology of validation proved that the questionnaire possesses construct validity, discriminate ability, reliability, and sensitivity to change. CONCLUSIONS: OSTREQ represents a comprehensive and focused tool that, for the first time, assesses physicians' criteria in the choice of osteoporosis treatment. This tool could assist health care systems and pharmaceutical companies to be aware which parameters drive physicians' preferences regarding osteoporosis treatment.

Prospective study of spinal orthoses in women.

BACKGROUND: There are not many clinical trials investigating the efficiency and compliance of using spinal orthoses in the management of osteoporosis. OBJECTIVES: The purpose of this study was to investigate the effect of long-term use and the compliance of spinal orthoses in postmenopausal women with vertebral fractures. STUDY DESIGN: Clinical trial of spinal orthoses in postmenopausal women. METHODS: Women were separated into groups wearing different types of orthoses (Spinomed, Osteomed, Spinomed active, and Spine-X). Isometric maximum strength of trunk muscles (F/Wabdominals-extensors) was calculated and back pain was assessed in all women. In addition, women completed a compliance questionnaire about the use of the orthoses. RESULTS: Spinomed decreased pain (p = 0.001) and increased trunk muscle strength (F/Wabdominals, p = 0.005 and F/Wextensors, p = 0.003, respectively). The compliance of wearing an orthosis for 6 months was 66%. CONCLUSION: The results suggest that orthoses could be an effective intervention for back pain and muscle strengthening in osteoporotic women. CLINICAL RELEVANCE: In women with established osteoporosis, wearing Spinomed orthosis for at least 2 h/day for 6 months decreased back pain significantly and increased personal isometric trunk muscle strength. All spinal orthoses could be valuable instruments to help all requested rehabilitation programs like spine muscles' strengthening and postural correct behavior, but only when used properly.

Smoking is a significant determinant of low serum vitamin D in young and middle-aged healthy males.

OBJECTIVE: We aimed to determine the prevalence of 25(OH)D (D2 and D3 independently) inadequacy in healthy young/middle-aged men and to investigate its relationship with BMD, bone markers, demographic and lifestyle parameters such as age, BMI, smoking, alcohol consumption and dietary calcium intake. DESIGN: We determined 25(OH)D levels using LC-MS/MS, a robust method for measurement of both 25(OH)D3 and 25(OH)D2, iPTH, osteocalcin, beta C terminal cross-linked telopeptides of type I collagen (b-CTXs), procollagen type 1 amino-terminal propeptide (PINP), BMD at L2-L4 and proximal femur, smoking habits, daily dietary calcium intake and alcohol consumption in 181 randomly selected healthy men aged 20-50y. RESULTS: The prevalence of vitamin D deficiency (25(OH)D < 20 ng/ml) was 50.3%. Only 8.8% of the participants had vitamin D sufficiency (25(OH)D ≥ 30 ng/ml). We found a strong correlation between 25(OH)D and smoking in the totality of participants (p<0.001). 25(OH)D level was lower by approximately 4.3 ng/dl (p<0.001) in a smoker compared to a non-smoker among the totality of participants, while this value increased to 9.2 ng/ml in the 40-50y subgroup (p=0.003). A multinomial logistic regression model demonstrated that a young smoker (20-29y) had 58% increased likelihood of having vitamin D deficiency compared to a non-smoker of the same age group (p=0.041). CONCLUSIONS: A high prevalence of vitamin D deficiency was identified in a young and middle-aged male population. Smoking is a significant determinant of serum 25(OH)D, while it increases significantly the likelihood of having vitamin D deficiency. In our hands, vitamin D levels are not a determinant of bone turnover and BMD in this population.

Bone disease in anorexia nervosa.

Anorexia nervosa is a serious psychiatric disorder accompanied by high morbidity and mortality. It is characterized by emaciation due to self-starvation and displays a unique hormonal profile. Alterations in gonadal axis, growth hormone resistance with low insulin-like growth factor I levels, hypercortisolemia and low triiodothyronine levels are almost universally present and constitute an adaptive response to malnutrition. Bone metabolism is likewise affected resulting in low bone mineral density, reduced bone accrual and increased fracture risk. Skeletal deficits often persist even after recovery from the disease with serious implications for future skeletal health. The pathogenetic mechanisms underlying bone disease are quite complicated and treatment is a particularly challenging task.