Inter-software and inter-threshold reliability of quantitative paraspinal muscle segmentation.

PURPOSE: Changes in the cross-sectional area (CSA) and functional cross-sectional area (FCSA) of the lumbar multifidus (MF) and erector spinae muscles (ES) are factors that can contribute to low back pain. For the assessment of muscle CSA and composition there are various software and threshold methods used for tissue segmentation in quantitative analysis. However, there is currently no gold standard for software as well as muscle segmentation. This study aims to analyze the measurement error between different image processing software and different threshold methods for muscle segmentation. METHODS: Magnetic resonance images (MRI) of 60 patients were evaluated. Muscle CSA and FCSA measurements were acquired from axial T2-weighted MRI of the MF and ES at L4/L5 and L5/S1. CSA, FCSA, and FCSA/CSA ratio were measured independently by two observers. The MRI images were measured using two different software programs (ImageJ and Amira) and with two threshold methods (Circle/Overlap method) for each software to evaluate FCSA and FCSA/CSA ratio. RESULTS: Inter-software comparisons revealed high inter-rater reliability. However, poor inter-rater reliability were obtained with different threshold methods. CSA, FCSA, and FCSA/CSA showed excellent inter-software agreement of 0.75-0.99 regardless of the threshold segmentation method. The inter-rater reliability between the two observers ranged between 0.75 and 0.99. Comparison of the two segmentation methods revealed agreement between 0.19 and 0.84. FCSA and FCSA/CSA measured via the Overlap method were significantly higher than those measured via the Circle method (P < 0.01). CONCLUSION: The present study showed a high degree of reliability with very good agreement between the two software programs. However, study results based on different threshold methods should not be directly compared.

A noninvasive method to quantify the impairment of spinal motion ability in Parkinson's disease.

PURPOSE: There is a high demand on spinal surgery in patients with Parkinson's disease (PD) but the results are sobering. Although detailed clinical and radiological diagnostics were carried out with great effort and expense, the biodynamic properties of the spine of PD patients have never been considered. We propose a noninvasive method to quantify the impairment of motion abilities in patients with PD. METHODS: We present an analytical cross-sectional study of 21 patients with severe PD. All patients underwent a biodynamic assessment during a standardized movement-choreography. Thus, individual spinal motion profiles of each patient were objectively assessed and compared with a large comparative cohort of individuals without PD. Moreover, clinical scores to quantify motor function and lumbar back pain were collected and X-ray scans of the spine in standing position were taken and analysed. RESULTS: Biodynamic measurement showed that 36.9% of the assessed motions of all PD patients were severely impaired. Men were generally more functionally impaired than women, in 52% of all motion parameters. The neurological and radiological diagnostics recorded pathological values, of which UPDRS-III ON correlated with findings of the biodynamics assessment (R = 0.52, p = 0.02). CONCLUSIONS: The decision to operate on a PD patient's spine is far-reaching and requires careful consideration. Neurological and radiological scores did not correlate with the biodynamics of the spine. The resulting motion profile could be used as individual predictive factor to estimate whether patients are eligible for spinal surgery or alternative therapies.

Spinal and Pelvic Kinematics During Prolonged Rowing on an Ergometer vs. Indoor Tank Rowing.

ABSTRACT: Trompeter, K, Weerts, J, Fett, D, Firouzabadi, A, Heinrich, K, Schmidt, H, Brüggemann, GP, and Platen, P. Spinal and pelvic kinematics during prolonged rowing on an ergometer vs. indoor tank rowing. J Strength Cond Res 35(9): 2622-2628, 2021-This investigation aimed to compare spinopelvic kinematics during rowing on an ergometer vs. in a rowing tank and to evaluate changes with progressing fatigue. Spinal and pelvic kinematics of 8 competitive scull rowers (19.0 ± 2.1 years, 179.9 ± 7.6 cm, and 74.8 ± 8.1 kg) were collected during 1 hour of rowing on an ergometer and in a rowing tank using a routine training protocol. Kinematics of the upper thoracic spine, lower thoracic spine, lumbar spine, and pelvis were determined using an infrared camera system (Vicon, Oxford, United Kingdom). There was a greater lumbar range of motion (ROM) and less posterior pelvic tilt at the catch during rowing on the ergometer compared with in the rowing tank (p = 0.001-0.048), but no differences in pelvic ROM. In the rowing tank, the pelvic ROM increased over time (p = 0.002) and the ROM of the lower thoracic spine decreased (p = 0.002). In addition, there was an extended drive phase (when the rower applies pressure to the oar levering the boat forward) and an abbreviated recovery phase (setting up the rower's body for the next stroke) in the rowing tank (p = 0.032). Different rowing training methods lead to differences in spinopelvic kinematics, which may lead to substantially different spinal loading situations. Greater pelvic rotation and lesser lumbar ROM are considered ideal; therefore, the present results indicate that rowing in the rowing tank might facilitate the maintenance of this targeted spinopelvic posture, which might help protect the lower back. Rowers, coaches, and researchers should consider the differences between rowing training methods, especially when giving training recommendations.

Psychometric properties of the St George's Respiratory Questionnaire in patients with idiopathic pulmonary fibrosis.

The St George's Respiratory Questionnaire (SGRQ) has been used to measure health-related quality of life (HRQoL) in patients with idiopathic pulmonary fibrosis (IPF).This analysis evaluated the psychometric properties of the SGRQ using data from 428 patients with IPF who participated in a 12-month, randomised, placebo-controlled phase II trial of nintedanib.Internal consistency (Cronbach's α) was 0.91 for SGRQ total and >0.70 for domain scores. Test-retest reliability (intraclass correlation coefficients) was 0.77, 0.77, 0.69 and 0.66 for SGRQ total, activity, impact and symptoms scores, respectively. Construct validity of SGRQ total and domain scores was supported by weak to moderate cross-sectional correlations with the Medical Research Council dyspnoea scale (0.32-0.55), 6-min walk test distance (-0.25- -0.34), percentage predicted forced vital capacity (-0.11- -0.15) and measures of gas exchange (-0.26-0.03). There was some evidence that the SGRQ total score was sensitive to detecting change.The reliability, construct validity and responsiveness of the SGRQ in patients with IPF suggest that this is an acceptable measure of HRQoL in patients with IPF.

Design of a randomised, placebo-controlled clinical trial of nintedanib in patients with systemic sclerosis-associated interstitial lung disease (SENSCIS™).

OBJECTIVES: Nintedanib is a tyrosine kinase inhibitor approved for the treatment of idiopathic pulmonary fibrosis (IPF). The pathological pathways involved in fibrogenesis in IPF and interstitial lung disease associated with systemic sclerosis (SSc-ILD) show commonalities; both involve fibroblast activation, myofibroblast accumulation and deposition of extracellular matrix. The SENSCIS™ trial is a randomised, placebo-controlled Phase III trial that will evaluate the efficacy and safety of nintedanib in patients with SSc-ILD (NCT02597933). METHODS: Approximately 520 patients with SSc (based on 2013 American College of Rheumatology/European League Against Rheumatism criteria) and ILD (≥10% fibrosis of the lungs, confirmed by central assessment of chest high resolution computed tomography), forced vital capacity (FVC) ≥40% predicted and diffusing capacity for carbon monoxide of 30-89% predicted will be enrolled. Patients will be randomised (1:1) to nintedanib 150 mg twice daily or placebo, stratified by the presence of anti-topoisomerase I antibody. To reflect real-world management, patients receiving prednisone (≤10 mg/day) and/or a stable dose of mycophenolate or methotrexate, will be eligible. The primary endpoint is the annual rate of decline in FVC (mL/ year) assessed over 52 weeks. Patients will remain on blinded study treatment until the last patient completes 52 weeks of treatment or for a maximum of 100 weeks of treatment. Key secondary endpoints are absolute changes from baseline in modified Rodnan skin score and St George's Respiratory Questionnaire at week 52. RESULTS: Recruitment for the trial began in November 2015. CONCLUSIONS: This trial will assess the efficacy and safety of nintedanib in patients with SSc-ILD.

Nuclear death receptor TRAIL-R2 inhibits maturation of let-7 and promotes proliferation of pancreatic and other tumor cells.

BACKGROUND & AIMS: Tumor necrosis factor-related apoptosis inducing ligand (TRAIL-R1) (TNFRSF10A) and TRAIL-R2 (TNFRSF10B) on the plasma membrane bind ligands that activate apoptotic and other signaling pathways. Cancer cells also might have TRAIL-R2 in the cytoplasm or nucleus, although little is known about its activities in these locations. We investigated the functions of nuclear TRAIL-R2 in cancer cell lines. METHODS: Proteins that interact with TRAIL-R2 initially were identified in pancreatic cancer cells by immunoprecipitation, mass spectrometry, and immunofluorescence analyses. Findings were validated in colon, renal, lung, and breast cancer cells. Functions of TRAIL-R2 were determined from small interfering RNA knockdown, real-time polymerase chain reaction, Drosha-activity, microRNA array, proliferation, differentiation, and immunoblot experiments. We assessed the effects of TRAIL-R2 overexpression or knockdown in human pancreatic ductal adenocarcinoma (PDAC) cells and their ability to form tumors in mice. We also analyzed levels of TRAIL-R2 in sections of PDACs and non-neoplastic peritumoral ducts from patients. RESULTS: TRAIL-R2 was found to interact with the core microprocessor components Drosha and DGCR8 and the associated regulatory proteins p68, hnRNPA1, NF45, and NF90 in nuclei of PDAC and other tumor cells. Knockdown of TRAIL-R2 increased Drosha-mediated processing of the let-7 microRNA precursor primary let-7 (resulting in increased levels of mature let-7), reduced levels of the let-7 targets (LIN28B and HMGA2), and inhibited cell proliferation. PDAC tissues from patients had higher levels of nuclear TRAIL-R2 than non-neoplastic pancreatic tissue, which correlated with increased nuclear levels of HMGA2 and poor outcomes. Knockdown of TRAIL-R2 in PDAC cells slowed their growth as orthotopic tumors in mice. Reduced nuclear levels of TRAIL-R2 in cultured pancreatic epithelial cells promoted their differentiation. CONCLUSIONS: Nuclear TRAIL-R2 inhibits maturation of the microRNA let-7 in pancreatic cancer cell lines and increases their proliferation. Pancreatic tumor samples have increased levels of nuclear TRAIL-R2, which correlate with poor outcome of patients. These findings indicate that in the nucleus, death receptors can function as tumor promoters and might be therapeutic targets.

Surface CD107a/LAMP-1 protects natural killer cells from degranulation-associated damage.

Cytotoxic lymphocytes are important for immune responses against viral infections and cancer. They are able to kill target cells through the release of cytotoxic granules (CGs) without being harmed in the process. Because the lysosomal-associated membrane proteins (LAMPs) appear on the cell surface after CG exocytosis, we hypothesized that some of these proteins might be involved in transiently protecting cytotoxic lymphocytes from self-destruction. Intracellular expression of CD107a/LAMP-1, and to a lesser extent that of CD107b/LAMP-2, correlated with lymphocyte CG content. Engineered surface expression of CD107a/LAMP-1, but not of CD107b/LAMP-2, reduced the granule-mediated killing of transfected target cells. This was dependent on glycosylation of the CD107a/LAMP-1 hinge. Moreover, surface expression of CD107a/LAMP-1 reduced binding of perforin to cells. Importantly, knockdown of CD107a/LAMP-1 in primary human natural killer (NK) cells and deficiency of CD107a/LAMP-1 in mice resulted in increased NK cell apoptosis upon target cell-induced degranulation. Thus, our data support a novel role of CD107a/LAMP-1 in the protection of NK cells from degranulation-associated suicide, which may represent a general mechanism to transiently limit self-destruction by cytotoxic lymphocytes upon target cell killing.

Application of a novel spinal posture and motion measurement system in active and static sitting.

The quantification of work-related musculoskeletal risk factors is of great importance; however, only a few tools allow objective, unrestricted measurements of spinal posture and motion in workplaces. This study was performed to evaluate the applicability of the Epionics system in a sedentary workplace. The system is mobile and wireless and assesses lumbar lordosis, pelvic orientation and spinal motion, without restricting subjects in their movements. In total, 10 males were monitored while sitting for 2 h on static and dynamic office chairs and on an exercise ball, to evaluate the effect of dynamic sitting. The volunteers were able to perform their work unhampered. No differences among the tested furniture could be detected with respect to either the lordosis or the number of spinal movements after habituation to the furniture; however, differences in pelvic orientation were statistically significant. The results of the present study indicate that Epionics may be useful for the quantitative assessment of work-related risk factors. Practitioner Summary: Only a few tools allow objective, unrestricted measurements of spinal posture and motion in the workplace. Epionics SPINE measures lumbar lordosis, pelvic orientation and spinal motion under nearly unrestricted conditions and can be used to quantify work-related musculoskeletal risk factors. We demonstrated the use of this tool in the workplace-analysis.

Tiotropium versus salmeterol for the prevention of exacerbations of COPD.

BACKGROUND: Treatment guidelines recommend the use of inhaled long-acting bronchodilators to alleviate symptoms and reduce the risk of exacerbations in patients with moderate-to-very-severe chronic obstructive pulmonary disease (COPD) but do not specify whether a long-acting anticholinergic drug or a ß(2)-agonist is the preferred agent. We investigated whether the anticholinergic drug tiotropium is superior to the ß(2)-agonist salmeterol in preventing exacerbations of COPD. METHODS: In a 1-year, randomized, double-blind, double-dummy, parallel-group trial, we compared the effect of treatment with 18 µg of tiotropium once daily with that of 50 µg of salmeterol twice daily on the incidence of moderate or severe exacerbations in patients with moderate-to-very-severe COPD and a history of exacerbations in the preceding year. RESULTS: A total of 7376 patients were randomly assigned to and treated with tiotropium (3707 patients) or salmeterol (3669 patients). Tiotropium, as compared with salmeterol, increased the time to the first exacerbation (187 days vs. 145 days), with a 17% reduction in risk (hazard ratio, 0.83; 95% confidence interval [CI], 0.77 to 0.90; P<0.001). Tiotropium also increased the time to the first severe exacerbation (hazard ratio, 0.72; 95% CI, 0.61 to 0.85; P<0.001), reduced the annual number of moderate or severe exacerbations (0.64 vs. 0.72; rate ratio, 0.89; 95% CI, 0.83 to 0.96; P=0.002), and reduced the annual number of severe exacerbations (0.09 vs. 0.13; rate ratio, 0.73; 95% CI, 0.66 to 0.82; P<0.001). Overall, the incidence of serious adverse events and of adverse events leading to the discontinuation of treatment was similar in the two study groups. There were 64 deaths (1.7%) in the tiotropium group and 78 (2.1%) in the salmeterol group. CONCLUSIONS: These results show that, in patients with moderate-to-very-severe COPD, tiotropium is more effective than salmeterol in preventing exacerbations. (Funded by Boehringer Ingelheim and Pfizer; ClinicalTrials.gov number, NCT00563381.).

In vivo measurements of the effect of whole body vibration on spinal loads.

PURPOSE: It is assumed that whole body vibration (WBV) improves muscle strength, bone density, blood flow and mobility and is therefore used in wide ranges such as to improve fitness and prevent osteoporosis and back pain. It is expected that WBV produces large forces on the spine, which poses a potential risk factor for the health of the spine. Therefore, the aim of the study was to measure the effect of various vibration frequencies, amplitudes, device types and body positions on the loads acting on a lumbar vertebral body replacement (VBR). METHODS: Three patients suffering from a fractured lumbar vertebral body were treated using a telemeterized VBR. The implant loads were measured during WBV while the patients stood on devices with vertically and seesaw-induced vibration. Frequencies between 5 and 50 Hz and amplitudes of 1, 2 and 4 mm were tested. The patients stood with their knees straight, slightly bent, or bent at 60°. In addition, they stood on their forefeet. RESULTS: The peak resultant forces on the implant increased due to vibration by an average of 24% relative to the forces induced without vibration. The average increase of the peak implant force was 27% for vertically induced vibration and 15% for seesaw vibration. The forces were higher when the legs were straight than when the knees were bent. Both the vibration frequency and the amplitude had only a minor effect on the measured forces. CONCLUSIONS: The force increase due to WBV is caused by an activation of the trunk muscles and by the acceleration forces. The forces produced during WBV are usually lower than those produced during walking. Therefore, the absolute magnitude of the forces produced during WBV should not be harmful, even for people with osteoporosis.

Measurement of the number of lumbar spinal movements in the sagittal plane in a 24-hour period.

PURPOSE: Little is known about the number of spinal movements in the sagittal plane in daily life, mainly due to the lack of adequate techniques to assess these movements. Our aim was to measure these movements in asymptomatic volunteers. METHODS: Two sensor strips based on strain gauge technology (Epionics SPINE system) were fixed on the skin surface of the back parallel to the spine on a total of 208 volunteers without back pain. First, the lordosis angle was determined during relaxed standing. The volunteers were then released to daily life. The increases and decreases in the back lumbar lordosis angle over a period of 24 h were determined and classified into 5° increments. Changes in the lordosis angle greater than 5° were considered. RESULTS: The median number of spinal movements performed within 24 h was approximately 4,400. Of these movements, 66 % were between 5° and 10°. The proportions of higher-magnitude lordosis angle changes were much lower (e.g., 3 % for the 20-25° movement bin). Surprisingly, the median total number of movements was significantly higher (29 %) in women than in men. Large inter-individual differences were observed in the number of movements performed. The volunteers spent a median of 4.9 h with the lumbar spine flexed between 20° and 30° and only 24 min with the spine extended relative to the reference standing position. A median of 50 movements reached or exceeded full-flexion angle and zero movements full-extension angle. CONCLUSIONS: These data illustrate the predominantly small range of movement of the spine during daily activities and the small amount of time spent in extension. These unique data strongly contribute to the understanding of patients' everyday behavior, which might affect the development and testing of spinal implants and the evaluation of surgical and nonsurgical treatments.

Effect of low back pain on the kinetics and kinematics of the lumbar spine - a combined in vivo and in silico investigation.

Lifting is a significant risk factor for low back pain (LBP). Different biomechanical factors including spinal loads, kinematics, and muscle electromyography (EMG) activities have previously been investigated during lifting activities in LBP patients and asymptomatic individuals to identify their association with LBP. However, the findings were contradictory and inconclusive. Accurate and subject-specific prediction of spinal loads is crucial for understanding, diagnosing, planning tailored treatments, and preventing recurrent pain in LBP patients. Therefore, the present study aimed to estimate the L5-S1 compressive and resultant shear loads in 19 healthy and 17 non-specific chronic LBP individuals during various static load-holding tasks (holding a 10 kg box at hip, chest, and head height) using full-body and personalized musculoskeletal models driven by subject-specific in vivo kinematic/kinetic, EMG, and physiological cross-sectional areas (PCSAs) data. These biomechanical characteristics were concurrently analyzed to identify potential differences between the two groups. Statistical analyses showed that LBP had almost no significant effect on the range of motion (trunk, lumbar, pelvis), PCSA, and EMG. There were no significant differences (p > 0.05) in the predicted L5-S1 loads. However, as the task became more demanding, by elevating the hand-load from hip to head, LBP patients experienced significant increases in both compressive (33 %, p = 0.00) and shear (25 %, p = 0.02) loads, while asymptomatic individuals showed significant increases only in compressive loads (30 %, p = 0.01). This suggests that engaging in more challenging activities could potentially magnify the effect of LBP on the biomechanical factors and increase their discrimination capacity between LBP and asymptomatic individuals.

In vivo load on knee, hip and spine during manual materials handling with two lifting techniques.

It is generally accepted that the lifting technique strongly influences physical loads within the human body and, thus, the risk of musculoskeletal disorders. However, there is a lack of knowledge regarding whether particular lifting techniques are effective in reducing loads. Hence, this retrospective study quantified (partly published) in vivo loads at joints within the human body during two typical lifting techniques, stoop lifting and squat lifting. Patients who had received instrumented implants underwent in vivo load measurements at either the knee (two patients), the hip (eight patients), or the upper lumbar spine (four patients) while lifting a 10 kg weight frontally with either straight (stoop) or bent (squat) knees. Contact forces and moments and the orientation of the contact force vector were determined and examined using the paired t test of Statistical Parametric Mapping. The two lifting techniques did not differ in terms of load magnitudes but did differ in terms of directions: (i) at the hip joint, the load vector varied significantly (p < 0.05) in the frontal and sagittal planes, (ii) at the knee joint, the load vector differed significantly (p < 0.05) in the sagittal plane (iii) while the load vector and magnitude did not differ at the upper lumbar spine (p > 0.05). Our findings indicate that the lifting technique causes changes in the orientation rather than the magnitude of lower extremity joint contact loads. Even though this quantification could only be performed in a small group of patients, the quantification of the relevance of such lifting technique recommendations will hopefully guide future recommendations towards a more scientific interpretation.

Influences of lumbo-sacral transitional vertebrae for anterior lumbar interbody fusion.

Lumbo-sacral transitional vertebrae (LSTV) are frequent congenital variances of the spine and are associated with increased spinal degeneration. Nevertheless, there is a lack of data whether bony alterations associated with LSTV result in reduced segmental restoration of lordosis when performing ALIF. 58 patients with monosegmental stand-alone ALIF in the spinal segment between the 24th and 25th vertebra (L5/S1)/(L5/L6) where included. Of these, 17 patients had LSTV and were matched to a control population by age and sex. Pelvic incidence, pelvic tilt, sagittal vertical axis, lumbar lordosis, segmental lordosis, disc height and depth were compared. LSTV-patients had a significantly reduced segmental lordosis L4/5 (p = 0.028) and L5/S1/(L5/L6) (p = 0.041) preoperatively. ALIF resulted in a significant increase in segmental lordosis L5/S1 (p < 0.001). Postoperatively, the preoperatively reduced segmental lordosis was no longer significantly different in segments L4/5 (p = 0.349) and L5/S1/(L5/6) (p = 0.576). ALIF is associated with a significant increase in segmental lordosis in the treated segment even in patients with LSTV. Therefore, ALIF is a sufficient intervention for restoring the segmental lordosis in these patients as well.

In idiopathic scoliosis distances of spinal cord to thoracic pedicle are within 2 mm in a large region of the thoracic apex.

Despite a 15% misplacement rate of screws in idiopathic scoliosis surgery, little is known about the relationship between pedicles and nerve structures in the entire thoracic curve. This study aimed to explore the spinal cord's proximity to the pedicle wall at each thoracic vertebra in the entire thoracic curve, while considering different anatomical changes. Spinal cord to medial pedicle distances were measured on magnetic resonance imaging in 73 patients who underwent posterior spinal fusion with pedicle screw instrumentation. Associations with different variables were examined. A total of 51 patients (69.9%) showed a distance within 2 mm at the apex vertebra on the concave side, more than 50% had a distance within 2 mm in the next thoracic vertebra level above and below, and more than 25% two levels above and below. Weak correlations were found between proximity of the spinal cord at the apex vertebra and vertebra's level and Cobb angle on the concave side (r = - 0.310, P = 0.008, r = 0.380, P = 0.001, respectively). These results emphasize the importance of thorough assessment when placing thoracic pedicle screws in idiopathic scoliosis patients. Further research is warranted to develop surgical strategies aimed at preventing potentially neurological complications resulting from screw misplacement.

Schober test is not a valid assessment tool for lumbar mobility.

The Schober test is considered reliable in evaluating lumbar mobility and its impairment. Especially in patients with chronic low back pain (cLBP) identification of functional restriction is important. We aimed to investigate whether the 5 cm Schober cut-off provides a valid distinction between unrestricted and restricted mobility in participants with and without cLBP (18-65 years). cLBP is defined as LBP persisting for ≥ 12 weeks. We analyzed agreement between the Schober test with two measurement devices (Epionics SPINE®; Idiag M360®) and the influence of lumbar lordosis (LL) on their agreement. Also, the sensitivity and specificity of the Schober test was evaluated. For 187 participants (49.6%) Epionics SPINE® RoF and Schober test matched (either ≥ 5 cm; > 40.8° RoF or ≤ 5 cm; < 40.8° RoF), for 190 participants (50.4%) the two measurements did not. Idiag M360® RoF of 190 participants (50.4%) showed corresponding results (either ≥ 5 cm; > 46.0° RoF or ≤ 5 cm; < 46.0° RoF). Non-agreement was seen in 187 participants (49.6%). LL differed significantly in the Epionics SPINE® cohort (p < 0.001). Regarding the Epionics SPINE® cohort, Schober test showed a sensitivity of 79.6% with a specificity of 36.1%. For the Idiag M360® cohort, Schober test showed a sensitivity of 68.2% and a specificity of 46.6%. Our results do not establish a consistent matching between Schober test and the device measurements. Therefore, Schober test may not be valid to predict impairment of lumbar mobility. We recommend Schober test as an add-on in monitoring of an individual relative to its case.

Cost-effectiveness of tiotropium versus salmeterol: the POET-COPD trial.

The aim of this study was to perform a 1-yr trial-based cost-effectiveness analysis (CEA) of tiotropium versus salmeterol followed by a 5-yr model-based CEA. The within-trial CEA, including 7,250 patients with moderate to very severe chronic obstructive pulmonary disease (COPD), was performed alongside the 1-yr international randomised controlled Prevention of Exacerbations with Tiotropium (POET)-COPD trial comparing tiotropium with salmeterol regarding the effect on exacerbations. Main end-points of the trial-based analysis were costs, number of exacerbations and exacerbation days. The model-based analysis was conducted to extrapolate results to 5 yrs and to calculate quality-adjusted life years (QALYs). 1-yr costs per patient from the German statutory health insurance (SHI) perspective and the societal perspective were €126 (95% uncertainty interval (UI) €55-195) and €170 (95% UI €77-260) higher for tiotropium, respectively. The annual number of exacerbations was 0.064 (95% UI 0.010-0.118) lower for tiotropium, leading to a reduction in exacerbation-related costs of €87 (95% UI €19-157). The incremental cost-effectiveness ratio was €1,961 per exacerbation avoided from the SHI perspective and €2,647 from the societal perspective. In the model-based analyses, the 5-yr costs per QALY were €3,488 from the SHI perspective and €8,141 from the societal perspective. Tiotropium reduced exacerbations and exacerbation-related costs, but increased total costs. Tiotropium can be considered cost-effective as the resulting cost-effectiveness ratios were below commonly accepted willingness-to-pay thresholds.

Characterisation of exacerbation risk and exacerbator phenotypes in the POET-COPD trial.

BACKGROUND: Data examining the characteristics of patients with frequent exacerbations of chronic obstructive pulmonary disease (COPD) and associated hospitalisations and mortality are scarce. METHODS: Post-hoc analysis of the Prevention Of Exacerbations with Tiotropium in COPD (POET-COPD) trial, targeting exacerbations as the primary endpoint. Patients were classified as non-, infrequent, and frequent exacerbators (0, 1, or ≥ 2 exacerbations during study treatment), irrespective of study treatment. A multivariate Cox regression model assessed the effect of covariates on time to first exacerbation. RESULTS: In total, 7376 patients were included in the analysis: 63.5% non-exacerbators, 22.9% infrequent, 13.6% frequent exacerbators. Factors significantly associated with exacerbation risk were age, sex, body mass index, COPD duration and severity, smoking history, baseline inhaled corticosteroid use, and preceding antibiotic or systemic corticosteroid courses. Frequent exacerbators had greater severity and duration of COPD, received more pulmonary medication, and ≥ 2 systemic corticosteroid or antibiotic courses in the preceding year, and were more likely to be female and ex-smokers. The small proportion of frequent exacerbators (13.6%) accounted for 56.6% of exacerbation-related hospitalisations, which, overall, were associated with a three-fold increase in mortality. CONCLUSION: The frequent exacerbator phenotype was closely associated with exacerbation-related hospitalisations, and exacerbation-related hospitalisations were associated with poorer survival. TRIAL REGISTRATION: NCT00563381; Study identifier: BI 205.389.

Parameters influencing the outcome after total disc replacement at the lumbosacral junction. Part 2: distraction and posterior translation lead to clinical failure after a mean follow-up of 5 years.

PURPOSE: The aim of the second part of the study was to investigate the influence of parameters that lead to increased facet joint contact or capsule tensile forces (disc height, lordosis, and sagittal misalignment) on the clinical outcome after total disc replacement (TDR) at the lumbosacral junction. METHODS: A total of 40 patients of a prospective cohort study who received TDR because of degenerative disc disease or osteochondrosis L5/S1 were invited to an additional follow-up for clinical (ODI and VAS for overall, back, and leg pain) and radiographic analysis (a change in disc height, lordosis, or sagittal vertebral misalignment compared with the preoperative state). Based on the final ODI, patients were retrospectively distributed into groups N (normal: <25 %) or F (failure ≥ 25 %) for radiographic parameter comparison. A correlation analysis was performed between the clinical and radiological results. RESULTS: A total of 34 patients were available at a mean follow-up of 59.5 months. Both groups (N = 24; F = 10 patients) presented a significant improvement in overall pain, back pain, and ODI over time. At the final follow-up, higher clinical scores correlated with a larger disc height, increased lordosis, and posterior translation of the superior vertebra, which was also reflected by significant differences in these parameters in the group comparison. CONCLUSIONS: Parameters associated with increased facet joint capsule tensile forces lead to an inferior clinical outcome at mid-term follow-up. When performing TDR, we therefore suggest avoiding iatrogenic posterior translation and overdistraction (and consecutive lordosis).