Meaning, Truth, and Physics

A physical theory is a partially interpreted axiomatic formal system (L,S), where L is a formal language with some logical, mathematical and physical axioms, and with some derivation rules, and the semantics S is a relationship between the formulas of L and some states of affairs in the physical world. In our ordinary discourse, the formal system L is regarded as an abstract object or structure, the semantics S as something which involves the mental/conceptual realm. This view is of course incompatible with physicalism. How can physical theory be accommodated in a purely physical ontology? The aim of this paper is to outline an account for meaning and truth of physical theory, within the philosophical framework spanned by three doctrines: physicalism, empiricism, and the formalist philosophy of mathematics

Consequences of different diagnostic ‘gold standards' in test accuracy research: Carpal Tunnel Syndrome as an example

Test accuracy studies assume the existence of a well-defined illness definition and clear-cut diagnostic gold standards or reference standards. However, in clinical reality illness definitions may be vague or a mere description of a set of manifestations, mostly clinical signs and symptoms. This can lead to disagreements among experts about the correct classification of an illness and the adequate reference standard. Using data from a diagnostic accuracy study in carpal tunnel syndrome, we explored the impact of different definitions on the estimated test accuracy and found that estimated test performance characteristics varied considerably depending on the chosen reference standard. In situations without a clear-cut illness definition, randomized controlled trials may be preferable to test accuracy studies for the evaluation of a novel test. These studies do not determine the diagnostic accuracy, but the clinical impact of a novel test on patient management and outcom

Incidence of Atypical Femoral Fractures in Patients on Osteoporosis Therapy-A Registry-Based Cohort Study.

Atypical femoral fractures (AFFs) have been reported in patients taking bisphosphonates (BPs) for osteoporosis therapy but also in patients with no exposure to these drugs. In contrast, less is known about the incidence of AFFs in patients taking denosumab. This registry-based cohort study analyzed the incidence of AFFs in patients with suspected or confirmed osteoporosis who were included in the osteoporosis register of the Swiss Society of Rheumatology between January 2015 and September 2019. Statistical analyses included incidence rates, rate ratios, and hazard ratios for AFFs, and considered sequential therapies and drug holidays as time-dependent covariates. Among the 9956 subjects in the cohort, 53 had subtrochanteric or femoral shaft fractures. Ten fractures occurred under BP or denosumab treatment and two under teriparatide therapy. Five fractures were classified as AFFs based on the revised American Society of Bone and Mineral Research case definition of AFFs from 2014. Three AFFs occurred in women being treated with denosumab at the time of diagnosis, all with prior BP use (10, 7, and 1 years, respectively). One AFF developed in a woman receiving ibandronate and one arose in a woman receiving glucocorticoids rather than antiresorptive therapy. The incidence of AFFs per 10,000 observed patient-years was 7.1 in patients receiving denosumab and 0.9 in patients with BP-associated AFFs, yielding a rate ratio of 7.9 (95% confidence interval [CI] 0.63-413), p = 0.073. The risk of AFFs was not significantly higher in patients receiving denosumab therapy compared with BP therapy (hazard ratio = 7.07, 95% CI 0.74-68.01, p = 0.090). We conclude that the risk of AFFs is low in patients taking BPs, denosumab, or both sequentially. All three patients with AFFs under denosumab therapy had undergone prior BP therapy. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research

Comparison of anti-fracture effectiveness of zoledronate, ibandronate and alendronate versus denosumab in a registry-based cohort study.

UNLABELLED This registry-based study of 3068 patients with osteoporosis compared the anti-fracture effectiveness of denosumab versus bisphosphonates. Denosumab was associated with significantly greater risk reduction than alendronate or ibandronate for vertebral and any fractures. No difference in fracture risk reduction was found between zoledronate and denosumab. PURPOSE To analyse the fracture risk of patients with osteoporosis receiving bisphosphonates or denosumab in a real-world setting. METHODS This registry-based cohort study evaluated patients taking denosumab, bisphosphonates or both sequentially. Fractures were analysed using rates, rate ratios and hazard ratios (HR), including both therapies as time-varying co-variates. Fracture risk hazards were adjusted (aHR) for baseline T-Scores and trabecular bone score (TBS) and were additionally analysed with inverse probability treatment weighting. RESULTS A total of 3068 patients (89% female; median age at treatment onset, 69 years [63 to 76]) received denosumab (median duration 2.8 years, [2.2 to 4.7]), bisphosphonates (3.4 years, [2.1 to 5.7]) or both sequentially. Thus, 11,078 subject-years were assessed for bisphosphonates (41% alendronate, 36% ibandronate, 23% zoledronate) and 4216 for denosumab. Moreover, 48,375 subject-years were observed before treatment onset, in addition to 2593 years of drug holidays. A total of 1481 vertebral fractures (435 under therapy), 1508 non-vertebral fractures (499 under therapy) and 202 hip fractures (67 under therapy) occurred after age 50. The risks of vertebral, non-vertebral and hip fractures were significantly lower under all bisphosphonates, denosumab and drug holidays than before treatment onset (all p < 0.001). After adjusting for age, baseline T-scores and TBS, denosumab was associated with lower risk than alendronate or ibandronate for vertebral fractures (aHR 0.47 (0.35 to 0.64) and 0.70 [0.53 to 0.91], p < 0.001 and p = 0.009, respectively) and any fractures (aHR 0.62 [0.51 to 0.76] and 0.77 [0.64 to 0.92], p < 0.001 and p = 0.004). With propensity weighting, denosumab was associated with a lower hip fracture risk compared to alendronate (HR 0.54 [0.29 to 0.98], p = 0.044). No difference in fracture risk reduction (vertebral, non-vertebral or hip) was found between zoledronate and denosumab. CONCLUSIONS When adjusting for disease severity, denosumab was associated with significantly greater risk reduction than alendronate and ibandronate for vertebral fractures. No difference in fracture risk reduction was found between zoledronate and denosumab

The effect of romosozumab on bone mineral density depending on prior treatment: a prospective, multicentre cohort study in Switzerland.

SUMMARY This multicentre, prospective cohort study measured the effect of romosozumab for 12 months on bone mineral density, taking into account prior therapies. Prior antiresorptive therapy blunted the BMD response to romosozumab, and the duration was correlated with BMD changes at both the lumbar spine and total hip. INTRODUCTION In Switzerland, romosozumab is administered to high-risk osteoporosis patients. Our study aimed to assess the effect of romosozumab on bone mineral density (BMD), taking into account prior therapies. METHODS This multicentre, prospective cohort study measured the effect of romosozumab for 12 months in patients in a nationwide Swiss osteoporosis registry. BMD and bone turnover marker (P1NP and CTX) changes were measured and compared between pre-treated and treatment naïve patients. RESULTS Ninety-nine patients (92 women and 7 men, median age 71 years [65, 76]) were enrolled from January 2021 to December 2023. Among them, 22 had no prior treatment before romosozumab, while 77 had previous therapy (including 23 with a history of prior teriparatide therapy), with a median duration of 6 years [4, 11] of cumulative antiresorptive treatment. Over 12 months, romosozumab led to BMD changes of 10.3% [7.5, 15.5] at the lumbar spine, 3.1% [1.1, 5.8] at the total hip and 3.1% [0.5, 5.3] at the femoral neck, indicating notable variability. Significantly lower BMD responses were observed in pre-treated patients, with the duration of prior antiresorptive therapy inversely associated with BMD increases at the lumbar spine and hip. Other predictors of BMD changes at the total hip included baseline T-scores at the hip, body mass index and baseline CTX level, while the BMD response at the lumbar spine was associated with the lumbar spine T-score at baseline, age and baseline CTX level. CONCLUSION Prior antiresorptive therapy blunted the BMD response to romosozumab, and the duration was correlated with BMD changes at both the lumbar spine and total hip

Meaning, Truth, and Physics

A physical theory is a partially interpreted axiomatic formal system (L,S), where L is a formal language with some logical, mathematical and physical axioms, and with some derivation rules, and the semantics S is a relationship between the formulas of L and some states of affairs in the physical world. In our ordinary discourse, the formal system L is regarded as an abstract object or structure, the semantics S as something which involves the mental/conceptual realm. This view is of course incompatible with physicalism. How can physical theory be accommodated in a purely physical ontology? The aim of this paper is to outline an account for meaning and truth of physical theory, within the philosophical framework spanned by three doctrines: physicalism, empiricism, and the formalist philosophy of mathematics