Skeletal and genetic determinants of osteoporosis

Osteoporosis, one of the critical diseases facing the ageing population and along with cardiovascular disease, diabetes and cancer, is a major concern for public health in western countries. Fractures, the clinical endpoint of osteoporosis, contribute considerably to overall morbidity, mortality and healthcare costs. It has been estimated that the lifetime risk to suffer a fracture is 40% for a 50-year-old white woman and 15% for men. Of those who have suffered a fracture of the hip, 50% are subsequently unable to walk unassisted and 20 % die within the first year after the hip fracture occurred. The total health care expenditures attributable to osteoporotic fractures in the United States was estimated at US$ 13.8 billion in 1995. In the Netherlands direct medical cost of osteoporosis-related fractures was estimated to be over 400 million guilders each year. Due to ageing, fractures from osteoporosis occurring each year are projected to increase world-wide from 1.7 million in 1990 to 6.3 mil1ion in 2050. Osteoporosis is defined as a systemic skeletal disease, characterised by low bone mass and microarchitectural detoriation of bone tissue with a consequent increase in bone fragility and susceptibility to fracture

Work outcome in yet undiagnosed patients with non-radiographic axial spondyloarthritis and ankylosing spondylitis; results of a cross-sectional study among patients with chronic low back pain

Background: To understand the impact of yet undiagnosed non-radiographic axial spondyloarthritis (nr-axSpA) and ankylosing spondylitis (AS) on work outcomes in a cohort of patients with long-lasting chronic low back pain (CLBP). Methods: Data were used from a primary care CLBP cohort that was established to understand the prevalence of nr-axSpA and AS. Clinical characteristics comprised measures of back pain (visual analogue scale), inflammation (C-reactive protein) and physical functioning (Roland Morris Disability Questionnaire (RMDQ)). Worker outcomes comprised a question on employment and the Work Productivity and Activity Impairment (WPAI) questionnaire, distinguishing absenteeism, presenteeism, and overall work impairment in those employed and activity impairment in all patients. For each disease subgroup, employment ratio compared to the general population was assessed by indirect standardization. Factors associated with work productivity were explored by zero inflated negative binomial (ZINB) regression models. Results: Patients with CLBP (n = 579) were included (41% male, mean age 36 years), of whom 71 (12%) were identified as having nr-axSpA and 24 (4%) as having AS. The standardized employment ratios were 0.89 (95% CI 0.84-0.94), 0.97 (95% CI 0.85-1.09) and 0.81 (95% CI 0.56-1.06) for patients with CLBP, nr-axSpA and AS, respectively. Scores for the WPAI subdomains were not significantly different between patients with CLBP, nr-axSpA or AS. The ZINB models showed significant associations between visual analog scale (VAS) score for pain and RMDQ and work productivity. Conclusion: The impact of yet undiagnosed nr-axSpA and AS on patients' work outcomes was substantial but was not significantly different from those of patients with long-standing CLBP. Variables significantly associated with reduced work productivity were VAS for pain and RMDQ score

Capturing Patient Value in an Economic Evaluation

OBJECTIVE: Economic evaluations predominantly use generic outcomes, such as EuroQol-5 Dimension (EQ-5D), to assess the health status. However, because of the generic nature, they are less suitable to capture the quality of life of patients with specific conditions. Given the transition to patient-centered (remote) care delivery, this study aims to evaluate the possibility to use disease-specific measures in a cost-effectiveness analysis (CEA).METHODS: A real-life cohort from Maasstad Hospital (2020-2021) in the Netherlands, with 772 Rheumatoid Arthritis (RA) patients, was used to assess the cost-effectiveness of electronic consultations (e-consultations) compared with face-to-face consultations. The Incremental Cost-Effectiveness Ratio (ICER) based on the generic EQ-5D was compared with ICER's based on RA specific measures; Rheumatoid Arthritis Impact of Disease (RAID) and Health Assessment Questionnaire-Disability Index (HAQ-DI). To compare the cost-effectiveness of these different measures, HAQ-DI and RAID were expressed in QALYs via estimated conversion equations.CONCLUSIONS: The conventional ICER (e.g. EQ-5D) indicates that e-consultations are cost-effective with cost savings of - €161k per QALY gained for a prevalent RA cohort treated in a secondary trainee hospital. RA specific measures show similar results, with ICER's of - €163k per HAQ-DI(QALY) and - €223k per RAID(QALY) gained. RA specific measures capture patient-relevant domains and offer the opportunity to improve the assessment and treatment of the disease impact.DISCUSSION: Disease-specific patient-reported outcome measures (PROMs) offer a promising alternative for traditional measures in economic evaluations, capturing patient-relevant domains more comprehensively. As PROMs are increasingly applied in clinical practice, the next step entails modelling of a RA patient-wide conversion equation to implement PROMs in economic evaluations. This article is protected by copyright. All rights reserved.</p

Is the QCI framework suited for monitoring outcomes and costs in a teaching hospital using value-based healthcare principles?:A retrospective cohort study

Objectives The objective is to develop a pragmatic framework, based on value-based healthcare principles, to monitor health outcomes per unit costs on an institutional level. Subsequently, we investigated the association between health outcomes and healthcare utilisation costs.Design This is a retrospective cohort study.Setting A teaching hospital in Rotterdam, The Netherlands.Participants The study was performed in two use cases. The bariatric population contained 856 patients of which 639 were diagnosed with morbid obesity body mass index (BMI) &lt;45 and 217 were diagnosed with morbid obesity BMI ≥45. The breast cancer population contained 663 patients of which 455 received a lumpectomy and 208 a mastectomy.Primary and secondary outcome measures The quality cost indicator (QCI) was the primary measures and was defined asQCI = (resulting outcome * 100)/average total costs (per thousand Euros)where average total costs entail all healthcare utilisation costs with regard to the treatment of the primary diagnosis and follow-up care. Resulting outcome is the number of patients achieving textbook outcome (passing all health outcome indicators) divided by the total number of patients included in the care path.Results The breast cancer and bariatric population had the highest resulting outcome values in 2020 Q4, 0.93 and 0.73, respectively. The average total costs of the bariatric population remained stable (avg, €8833.55, min €8494.32, max €9164.26). The breast cancer population showed higher variance in costs (avg, €12 735.31 min €12 188.83, max €13 695.58). QCI values of both populations showed similar variance (0.3 and 0.8). Failing health outcome indicators was significantly related to higher hospital-based costs of care in both populations (p &lt;0.01).Conclusions The QCI framework is effective for monitoring changes in average total costs and relevant health outcomes on an institutional level. Health outcomes are associated with hospital-based costs of care.</div

Is the QCI framework suited for monitoring outcomes and costs in a teaching hospital using value-based healthcare principles?:A retrospective cohort study

Objectives The objective is to develop a pragmatic framework, based on value-based healthcare principles, to monitor health outcomes per unit costs on an institutional level. Subsequently, we investigated the association between health outcomes and healthcare utilisation costs.Design This is a retrospective cohort study.Setting A teaching hospital in Rotterdam, The Netherlands.Participants The study was performed in two use cases. The bariatric population contained 856 patients of which 639 were diagnosed with morbid obesity body mass index (BMI) &lt;45 and 217 were diagnosed with morbid obesity BMI ≥45. The breast cancer population contained 663 patients of which 455 received a lumpectomy and 208 a mastectomy.Primary and secondary outcome measures The quality cost indicator (QCI) was the primary measures and was defined asQCI = (resulting outcome * 100)/average total costs (per thousand Euros)where average total costs entail all healthcare utilisation costs with regard to the treatment of the primary diagnosis and follow-up care. Resulting outcome is the number of patients achieving textbook outcome (passing all health outcome indicators) divided by the total number of patients included in the care path.Results The breast cancer and bariatric population had the highest resulting outcome values in 2020 Q4, 0.93 and 0.73, respectively. The average total costs of the bariatric population remained stable (avg, €8833.55, min €8494.32, max €9164.26). The breast cancer population showed higher variance in costs (avg, €12 735.31 min €12 188.83, max €13 695.58). QCI values of both populations showed similar variance (0.3 and 0.8). Failing health outcome indicators was significantly related to higher hospital-based costs of care in both populations (p &lt;0.01).Conclusions The QCI framework is effective for monitoring changes in average total costs and relevant health outcomes on an institutional level. Health outcomes are associated with hospital-based costs of care.</div

Estrogen receptor polymorphism predicts the onset of natural and surgical menopause

Age at menopause and risk of hysterectomy have strong genetic components, but the genes involved remain ill defined. We investigated whether genetic variation at the estrogen receptor (ER) gene contributes to the variability in the onset of menopause in 900 postmenopausal women, aged 55-80 yr, of the Rotterdam Study, a population-based cohort study in The Netherlands. Gynecological information was obtained, and if women reported surgical menopause, validation of type and indication of surgery was accomplished by checking medical records. The ER genotypes (PP, Pp, and pp) were assessed by PCR using the PvuII endonuclease. Compared with women carrying the pp genotype, homozygous PP women had a 1.1-yr (P &lt; 0.02) earlier onset of menopause. Furthermore, an allele dose effect was observed, corresponding to a 0.5-yr (P &lt; 0.02) earlier onset of menopause per copy of the P allele. The risk of surgical menopause was 2.4 (95% confidence interval, 1.5-3.8) times higher for women carrying the PP genotype compared to those in the pp group, with the most prominent effect in women who underwent hysterectomy due to fibroids or menorrhagia. We conclude that genetic variations of the ER gene are related to the onset of natural menopause and the risk of surgical menopause, especially hysterectomy.</p

External validation of a referral rule for axial spondyloarthritis in primary care patients with chronic low back pain

Objectives To validate and optimize a referral rule to identify primary care patients with chronic low back pain (CLBP) suspected for axial spondyloarthritis (axSpA). Design Cross-sectional study with data from 19 Dutch primary care practices for development and 38 for validation. Participants Primary care patients aged 18-45 years with CLBP existing more than three months and onset of back pain started before the age of 45 years. Main Outcome The number of axSpA patients according to the ASAS criteria. Methods The referral rule (CaFaSpA referral rule) was developed using 364 CL

Diagnostic performance of the ACR/EULAR 2010 criteria for rheumatoid arthritis and two diagnostic algorithms in an early arthritis clinic (REACH)

Introduction: An ACR/EULAR task force released new criteria to classify rheumatoid arthritis at an early stage. This study evaluates the diagnostic performance of these criteria and algorithms by van der Helm and Visser in REACH. Methods: Patients with symptoms ≤12 months from REACH were used. Algorithms were tested on discrimination, calibration and diagnostic accuracy of proposed cut-points. Two patient sets were defi ned to test robustness; undifferentiated arthritis (UA) (n=231) and all patients including those without synovitis (n=513). The outcomes evaluated were methotrexate use and persistent disease at 12 months. Results: In UA patients all algorithms had good areas under the curve 0.79, 95% CI 0.73 to 0.83 for the ACR/EULAR criteria, 0.80, 95% CI 0.74 to 0.87 for van der Helm and 0.83, 95% CI 0.77 to 0.88 for Visser. All calibrated well. Sensitivity and specifi city were 0.74 and 0.66 for the ACR/EULAR criteria, 0.1 and 1.0 for van der Helm and 0.59 and 0.93 for Visser. Similar results were found in all patients indicating robustness. Conclusion: The ACR/EULAR 2010 criteria showed good diagnostic properties in an early arthritis cohort refl ecting daily practice, as did the van der Helm and Visser algorithms. All were robust. To promote uniformity and comparability the ACR/EULAR 2010 criteria should be used in future diagnostic studies. Copyright Article author (or their employer) 2011

Fatigue in early, intensively treated and tight-controlled rheumatoid arthritis patients is frequent and persistent: a prospective study

Fatigue has a large impact on quality of life and is still unmanageable for many patients. Study aims were describe (1) the prevalence and pattern of fatigue over time in patients with early rheumatoid arthritis under a treat-to-target strategy and (2) identify predictive factors for worsening and recovering of fatigue over time. Data from the tREACH study were used, comparing different treatment strategies with fatigue as secondary objective. Patient outcomes on fatigue, quality of life, depression, and coping were obtained every 6 months and clinically assessed every 3 months. Prediction of fatigue at 12 months was investigated with an ROC curve. Analysis was stratified into non-fatigue and fatigue at baseline. Logistic regression was used for the evolution of fatigue in relation with the covariates over time. Almost half of all patients (n = 246) had high fatigue levels at baseline, decreasing slightly over time. At 12 months, 43% of patients were fatigued; while 23% of the initially fatigued patients showed lower levels of fatigue

Estrogen receptor polymorphism predicts the onset of natural and surgical menopause

Age at menopause and risk of hysterectomy have strong genetic components, but the genes involved remain ill defined. We investigated whether genetic variation at the estrogen receptor (ER) gene contributes to the variability in the onset of menopause in 900 postmenopausal women, aged 55-80 yr, of the Rotterdam Study, a population-based cohort study in The Netherlands. Gynecological information was obtained, and if women reported surgical menopause, validation of type and indication of surgery was accomplished by checking medical records. The ER genotypes (PP, Pp, and pp) were assessed by PCR using the PvuII endonuclease. Compared with women carrying the pp genotype, homozygous PP women had a 1.1-yr (P < 0.02) earlier onset of menopause. Furthermore, an allele dose effect was observed, corresponding to a 0.5-yr (P < 0.02) earlier onset of menopause per copy of the P allele. The risk of surgical menopause was 2.4 (95% confidence interval, 1.5-3.8) times higher for women carrying the PP genotype compared to those in the pp group, with the most prominent effect in women who underwent hysterectomy due to fibroids or menorrhagia. We conclude that genetic variations of the ER gene are related to the onset of natural menopause and the risk of surgical menopause, especially hysterectomy