Association between physical measures of spinopelvic alignment and physical functioning with patient reported outcome measures (PROMs) after total hip arthroplasty: Protocol for systematic review and meta-analysis.

INTRODUCTION: Prevalence of total hip arthroplasty (THA) has trended upwards over past decades and is projected to increase further. Optimizing outcomes after surgery is essential to avoid surgical revision and maximize outcomes. Low back pain is reported as a problem post THA. Patient-reported outcome measures (PROMs) are commonly used to evaluate THA outcomes but have limitations (e.g., ceiling effects). It is therefore important to assess a comprehensive range of outcomes. Physical outcome measures of spinopelvic alignment and physical functioning demonstrate potential value, but no evidence synthesis has investigated their association with PROMs. The objectives of this systematic review are to evaluate the association between spinopelvic alignment and physical outcome measures of physical functioning with PROMs and characteristics of low back pain after THA. METHODS AND ANALYSIS: This protocol is aligned with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. Cross-sectional and longitudinal cohort studies evaluating the association between the physical outcome measures and PROMs (any outcome measures reported) following THA by any approach/implant will be included except surface replacement and revision THA. Studies investigating THA for developmental pathology and inflammatory conditions will be excluded. A systematic search in MEDLINE (Ovid), Embase (Ovid), Scopus, Web of Science, CINAHL, and the grey literature will be carried out from inception to July 31, 2023. Two independent reviewers will evaluate eligibility of retrieved articles, extract data and assess risk of bias (NIH quality assessment tool) of included studies. A third reviewer will mediate disagreements. Random-effects meta-analyses will be conducted if studies are sufficiently homogeneous in design, population, physical measures and PROMs; reporting odds ratios and 95% confidence intervals. Where meta-analyses are not possible, a narrative synthesis will be conducted. Confidence in cumulative evidence will be assessed using a modified GRADE (Grading of Recommendations Assessment, Development, and Evaluation). PROSPERO REGISTRATION NUMBER: PROSPERO Registration number CRD42023412744.

Hip Labral and Capsular Repair Are Unable to Restore Distractive Stability in a Biomechanical Model.

PURPOSE: To evaluate the change in hip distractive stability after a capsulotomy, labral tear, and simultaneous repair of both the capsule and the labrum in a biomechanical model. METHODS: Ten fresh-frozen human cadaveric hips were analyzed using a materials testing system to measure the distractive force and distance required to disrupt the hip suction seal under the following conditions: (1) native intact capsule and labrum, (2) 2- or 4-cm interportal capsulotomy (IPC), (3) labral tear, (4) T extension, (5) labral repair, (6) T extension repair, and (7) IPC repair. Each specimen was retested at 0° of flexion, 45° of flexion, and 45° of flexion with 15° of internal rotation. RESULTS: A significantly higher distractive force was required to rupture the suction seal in the intact condition compared with IPC (P = .012; 95% confidence interval [CI], 4.9-42.4); IPC and labral tear (P = .002; 95% CI, 11.3-49.4); IPC, labral tear, and T extension (P = .001; 95% CI, 13.9-51.5); IPC, labral repair, and T extension (P < .001; 95% CI, 20.8-49.7); IPC, labral repair, and T extension repair (P = .002; 95% CI, 12.5-52.4); and IPC repair, labral repair, and T extension repair (P = .01; 95% CI, 5.8-46.1). The IPC condition required a higher distractive force in isolation than when combined with a labral tear (P = .14; 95% CI, 1.2-12.0), T extension (P = .005; 95% CI, 2.8-15.3), or labral repair (P = .002; 95% CI, 4.4-18.8). CONCLUSIONS: The distractive resistance of an intact hip capsule and labrum was not restored once the soft tissues were violated, despite labral repair with a loop technique and capsular repair with interrupted figure-of-8 sutures. CLINICAL RELEVANCE: Time-zero complete capsular repair with concomitant labral repair may not be adequate to restore distractive hip stability after hip arthroscopy, reinforcing the use of postoperative precautions in the early postoperative period.

Method for accurate removal of trabecular bone samples from a curved articulating surface of the distal femur.

BACKGROUND: Knowing the mechanical properties of trabecular bone is critical for many branches of orthopaedic research. Trabecular bone is anisotropic and the principal trabecular direction is usually aligned with the load it transmits. It is therefore critical that the mechanical properties are measured as close as possible to this direction, which is often perpendicular to a curved articulating surface. METHODS: This study presents a method to extract trabecular bone cores perpendicular to a curved articulating surface of the distal femur. Cutting guides were generated from computed tomography scans of 12 human distal femora and a series of cutting tools were used to release cylindrical bone cores from the femora. The bone cores were then measured to identify the angle between the bone core axis and the principal trabecular axis. FINDINGS: The method yielded an 83% success rate in core extraction over 10 core locations per distal femur specimen. In the condyles, 97% of extracted cores were aligned with the principal trabecular direction. INTERPRETATION: This method is a reliable way of extracting trabecular bone specimens perpendicular to a curved articular surface and could be useful across the field of orthopaedic research.

The Contribution of Soft Tissue and Bony Stabilizers to the Hip Suction Seal: A Systematic Review of Biomechanical Studies.

BACKGROUND: Previous biomechanical studies have identified capsular closure, labral repair or reconstruction, and osteochondroplasty as important surgical interventions to improve hip stability. PURPOSE: To investigate the outcome metrics used to quantify hip stability and assess and measure the relative contributions of the labrum, capsule, and bone to hip stability through a quantitative analysis. STUDY DESIGN: Systematic review and meta-analysis; Level of evidence, 4. METHODS: PubMed and Embase databases were searched using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Included studies evaluated cadaveric hip biomechanics related to capsular, labral, and bony management during hip arthroscopy. Studies were assessed for distraction force and distance, fluid measures, and contact forces used to quantify the suction seal. Exclusion criteria included open surgery, arthroplasty, reorientation osteotomy, or traumatic dislocation. RESULTS: A total of 33 biomechanical studies comprising 322 hips that evaluated 1 or more of the following were included: distraction force or distance (24 studies), fluid measures (10 studies), and contact forces (6 studies). Compared with a capsulotomy or capsulectomy, capsular repair or reconstruction demonstrated greater resistance to distraction (standardized mean difference [SMD], 1.13; 95% CI, 0.46-1.80; P = .0009). Compared with a labral tear, a labral repair or reconstruction demonstrated less resistance to distraction (SMD, -0.67; 95% CI, -1.25 to -0.09; P = .02). Compared with a labral debridement, repair or reconstruction demonstrated greater resistance to distraction (SMD, 1.74; 95% CI, 1.23 to 2.26; P < .00001). No quantitative analysis was feasible from studies evaluating the effect of osseous resection due to the heterogeneity in methodology and outcome metrics assessed. CONCLUSION: Most biomechanical evidence supports capsulotomy repair or reconstruction to improve hip distractive stability at the end of hip arthroscopic surgery. While the repair of a torn labrum does not improve distractive resistance, it is superior to labral debridement in most biomechanical studies.

Early Postoperative Activities of Daily Living Do Not Adversely Affect Joint Torques or Translation Regardless of Capsular Condition: A Cadaveric Study.

PURPOSE: To evaluate the impact of capsular management on joint constraint and femoral head translations during simulated activities of daily living (ADL). METHODS: Using 6 (n = 6) cadaveric hip specimens, the effect of capsulotomies and repair was then evaluated during simulated ADL. Joint forces and rotational kinematics associated with gait and sitting, adopted from telemeterized implant studies, were applied to the hip using a 6-degrees of freedom (DOF) joint motion simulator. Testing occurred after creation of portals, interportal capsulotomy (IPC), IPC repair, T-capsulotomy (T-Cap), partial T-Cap repair, and full T-Cap repair. The anterior-posterior (AP), medial-lateral (ML), and axial compression DOFs were operated in force control, whereas flexion-extension, adduction-abduction, and internal-external rotation were manipulated in displacement control. Resulting femoral head translations and joint reaction torques were recorded and evaluated. Subsequently, the mean-centered range of femoral head displacements and peak signed joint restraint torques were calculated and compared. RESULTS: During simulated gait and sitting, the mean range of AP femoral head displacements with respect to intact exceeded 1% of the femoral head diameter after creating portals, T-Caps, and partial T-Cap repair (Wilcoxon signed rank P < .05); the mean ranges of ML displacements did not. Deviations in femoral head kinematics varied by capsule stage but were never very large. No consistent trends with respect to alterations in peak joint restrain torques were observed. CONCLUSIONS: In this cadaveric biomechanical study, capsulotomy and repair minimally affected resultant femoral head translation and joint torques during simulated ADLs. CLINICAL RELEVANCE: The tested ADLs appear safe to perform after surgery, regardless of capsular status, because adverse kinematics were not observed. However, further study is required to determine the importance of capsular repair beyond time-zero biomechanics and the resultant effect on patient-reported outcomes.

Capsular Mechanics After Periacetabular Osteotomy for Hip Dysplasia.

BACKGROUND: Hip dysplasia is characterized by insufficient acetabular coverage around the femoral head, which leads to instability, pain, and injury. Periacetabular osteotomy (PAO) aims to restore acetabular coverage and function, but its effects on capsular mechanics and joint stability are still unclear. The purpose of this study was to examine the effects of PAO on capsular mechanics and joint range of motion in dysplastic hips. METHODS: Twelve cadaveric dysplastic hips (denuded to bone and capsule) were mounted onto a robotic tester and tested in multiple positions: (1) full extension, (2) neutral 0°, (3) flexion of 30°, (4) flexion of 60°, and (5) flexion of 90°. In each position, the hips underwent internal and external rotation, abduction, and adduction using 5 Nm of torque. Each hip then underwent PAO to reorient the acetabular fragment, preserving the capsular ligaments, and was retested. RESULTS: The PAO reduced internal rotation in flexion of 90° (∆IR = -5°; p = 0.003), and increased external rotation in flexion of 60° (∆ER = +7°; p = 0.001) and flexion of 90° (∆ER = +11°; p = 0.001). The PAO also reduced abduction in extension (∆ABD = -10°; p = 0.002), neutral 0° (∆ABD = -7°; p = 0.001), and flexion of 30° (∆ABD = -8°; p = 0.001), but increased adduction in neutral 0° (∆ADD = +9°; p = 0.001), flexion of 30° (∆ADD = +11°; p = 0.002), and flexion of 60° (∆ADD = +11°; p = 0.003). CONCLUSIONS: PAO caused reductions in hip abduction and internal rotation but greater increases in hip adduction and external rotation. The osseous acetabular structure and capsule both play a role in the balance between joint mobility and stability after PAO.

Biomechanics of Cam Femoroacetabular Impingement: A Systematic Review.

PURPOSE: To assess how biomechanical gait parameters (kinematics, kinetics, and muscle force estimations) differ between patients with cam-type femoroacetabular impingement (FAI) and healthy controls, through a systematic search. METHODS: A systematic review of the literature from PubMed, Scopus, and Medline and EMBASE via OVID SP was undertaken from inception to April 2020 using PRISMA guidelines. Studies that described kinematics, kinetics, and/or estimated muscle forces in cam-type FAI were identified and reviewed. RESULTS: The search strategy identified 404 articles for evaluation. Removal of duplicates and screening of titles and abstracts resulted in full-text review of 37 articles, with 12 meeting inclusion criteria. The 12 studies reported biomechanical data on a total of 173 cam-FAI (151 cam-specific, 22 mixed-type) patients and 177 healthy age-, sex-, and body mass index-matched controls. Patients with cam FAI had reduced hip sagittal plane range of motion (mean difference -3.00° [-4.10, -1.90], P < .001), reduced hip peak extension angles (mean difference -2.05° [-3.58, -0.53] , P = .008), reduced abduction angles in the terminal phase of stance, and reduced iliacus and psoas muscle force production in the terminal phase of stance compared to the control groups. Cam FAI cohorts walked at a slower speed compared with controls. CONCLUSIONS: In conclusion, patients with cam-type FAI exhibit altered sagittal and frontal plane kinematics as well as altered muscle force production during level gait compared to controls. These findings will help guide future research into gait alterations in FAI and how such alterations may contribute to pathologic progression and furthermore, how such alterations can be modified for therapeutic benefit. LEVEL OF EVIDENCE: Systematic review of Level III studies.

Cam Osteochondroplasty for Femoroacetabular Impingement Increases Microinstability in Deep Flexion: A Cadaveric Study.

PURPOSE: The purpose of this in vitro cadaveric study was to examine the contributions of each surgical stage during cam femoroacetabular impingement (FAI) surgery (i.e., intact-cam hip, T-capsulotomy, cam resection, and capsular repair) toward hip range of motion, translation, and microinstability. METHODS: Twelve cadaveric cam hips were denuded to the capsule and mounted onto a robotic tester. The hips were positioned in several flexion positions-full extension, neutral (0°), 30° of flexion, and 90° of flexion-and performed internal-external rotations to 5 Nm of torque in each position. The hips underwent a series of surgical stages (T-capsulotomy, cam resection, and capsular repair) and were retested after each stage. Changes in range of motion, translation, and microinstability (overall translation normalized by femoral head radius) were measured after each stage. RESULTS: Regarding range of motion, cam resection increased internal rotation at 90° of flexion (change in internal rotation = +6°, P = .001) but did not affect external rotation. Capsular repair restrained external rotation compared with the cam resection stage (change in external rotation = -8° to -4°, P ≤ .04). In terms of translation, the hip translated after cam resection at 90° of flexion in the medial-lateral plane (change in translation = +1.9 mm, P = .04) relative to the intact and capsulotomy stages. Regarding microinstability, capsulotomy increased microinstability in 30° of flexion (change in microinstability [ΔM] = +0.05, P = .003), but microinstability did not further increase after cam resection. At 90° of flexion, microinstability did not increase after capsulotomy (ΔM = +0.03, P = .2) but substantially increased after cam resection (ΔM = +0.08, P = .03), accounting for a 31% change with respect to the intact stage. CONCLUSIONS: Cam resection increased microinstability by 31% during deep hip flexion relative to the intact hip. This finding suggests that iatrogenic microinstability may be due to separation of the labral seal and resected contour of the femoral head. CLINICAL RELEVANCE: Our in vitro study showed that, at time zero and prior to postoperative recovery, excessive motion after cam resection could disrupt the labral seal. Complete cam resection should be performed cautiously to avoid disruption of the labral seal and postoperative microinstability.

Hip Muscle Forces and Contact Loading During Squatting After Cam-Type FAI Surgery.

BACKGROUND: The purpose of this study was to compare muscle forces and hip contact forces (HCFs) during squatting in patients with cam-type femoroacetabular impingement (cam-FAI) before and after hip corrective surgery and with healthy control participants. METHODS: Ten symptomatic male patients with cam-FAI performed deep squatting preoperatively and at 2 years postoperatively. Patients were matched by age and body mass index to 10 male control participants. Full-body kinematics and kinetics were computed, and muscle forces and HCFs were estimated using a musculoskeletal model and static optimization. Normalized squat cycle (%SC) trials were compared using statistical nonparametric mapping (SnPM). RESULTS: Postoperatively, patients with cam-FAI squatted down with higher anterior pelvic tilt, higher hip flexion, and greater hip extension moments than preoperatively. Preoperative patients demonstrated lower anterior pelvic tilt and lower hip flexion compared with the participants in the control group. Postoperative patients showed increased semimembranosus force compared with their preoperative values. Preoperative forces were lower than the control group for the adductor magnus, the psoas major, and the semimembranosus; however, the preoperative patients showed greater inferior gluteus maximus forces than the patients in the control group, whereas the postoperative patients did not differ from the control patients. Higher posterior, superior, and resultant HCF magnitudes were identified postoperatively in comparison with the preoperative values. Preoperative posterior HCF was lower than in the control group, whereas the postoperative posterior HCF did not differ from those in the control group. CONCLUSIONS: Higher postoperative anterior pelvic tilt was associated with an indication of return to closer to normal pelvic motion, which resembled data from the control group. Lower preoperative anterior pelvic tilt was associated with muscle force imbalance, indicated by decreased semimembranosus and increased gluteus maximus forces. The overall increased postoperative muscle forces were associated with improved pelvic mobility and increased HCFs that were comparable with the control-group standards. CLINICAL RELEVANCE: Muscle forces and HCFs may be indicative of postoperative joint health restoration and alleviated symptoms.

Effects of Senior Simulation Suit Programme on nursing students' attitudes towards older adults: A randomized controlled trial.

BACKGROUND: As populations age worldwide, nursing educational institutions need to train nurses not only to provide health care services specific to the elderly, but also to have a positive attitude as they work. The present study aimed to investigate the efficacy of a Senior Simulation Suit Programme (SSSP). The SSSP, which focused on mimicking the physiological experiences of an 80 year-old person, was hypothesized to increase the wearer's positive attitude towards older adult care. METHODS: A single-blinded, randomized controlled trial was used to evaluate the efficacies of SSSP. One hundred and thirty-nine (139) nursing students were randomly assigned to either SSSP group (n = 69) or to a control group (n = 70) with "placebo clothing", i.e. clothing that mimicked old age but did not actually impair faculties. Two instruments-Kogan Attitudes Towards Old People Scale (KAOP) and a 1-item scale on Willingness To Care for Older People Scale (WCOP)-were used for data collection at baseline and at completion of SSSP. A Chinese version of Palmore's Facts Aging Quiz (C-FAQ) was used to assess nursing students' knowledge about adult care, and a questionnaire was developed to collect demographic information at baseline. RESULTS: No significant difference between the two groups was found. A significant increase of positive attitudes and of willingness to serve older adults was found in both the control group and the group wearing SSSP. CONCLUSION: Both the SSSP and control intervention could improve the attitudes of nursing students towards older adult care. This study suggests that wearing whatever the nursing students associate with being old, will improve their attitude towards older adult care.

Cosmic-ray antinuclei as messengers of new physics: status and outlook for the new decade.

The precise measurement of cosmic-ray antinuclei serves as an important means for identifying the nature of dark matter and other new astrophysical phenomena, and could be used with other cosmic-ray species to understand cosmic-ray production and propagation in the Galaxy. For instance, low-energy antideuterons would provide a "smoking gun" signature of dark matter annihilation or decay, essentially free of astrophysical background. Studies in recent years have emphasized that models for cosmic-ray antideuterons must be considered together with the abundant cosmic antiprotons and any potential observation of antihelium. Therefore, a second dedicated Antideuteron Workshop was organized at UCLA in March 2019, bringing together a community of theorists and experimentalists to review the status of current observations of cosmic-ray antinuclei, the theoretical work towards understanding these signatures, and the potential of upcoming measurements to illuminate ongoing controversies. This review aims to synthesize this recent work and present implications for the upcoming decade of antinuclei observations and searches. This includes discussion of a possible dark matter signature in the AMS-02 antiproton spectrum, the most recent limits from BESS Polar-II on the cosmic antideuteron flux, and reports of candidate antihelium events by AMS-02; recent collider and cosmic-ray measurements relevant for antinuclei production models; the state of cosmic-ray transport models in light of AMS-02 and Voyager data; and the prospects for upcoming experiments, such as GAPS. This provides a roadmap for progress on cosmic antinuclei signatures of dark matter in the coming years.

The Design and In Vivo Testing of a Locally Stiffness-Matched Porous Scaffold.

An increasing volume of work supports utilising the mechanobiology of bone for bone ingrowth into a porous scaffold. However, typically during in vivo testing of implants, the mechanical properties of the bone being replaced are not quantified. Consequently there remains inconsistencies in the literature regarding 'optimum' pore size and porosity for bone ingrowth. It is also difficult to compare ingrowth results between studies and to translate in vivo animal testing to human subjects without understanding the mechanical environment. This study presents a clinically applicable approach to determining local bone mechanical properties and design of a scaffold with similar properties. The performance of the scaffold was investigated in vivo in an ovine model. The density, modulus and strength of trabecular bone from the medial femoral condyle from ovine bones was characterised and power-law relationships were established. A porous titanium scaffold, intended to maintain bone mechanical homeostasis, was additively manufactured and implanted into the medial femoral condyle of 6 ewes. The stiffness of the scaffold varied throughout the heterogeneous structure and matched the stiffness variation of bone at the surgical site. Bone ingrowth into the scaffold was 10.73±2.97% after 6 weeks. Fine woven bone, in the interior of the scaffold, and intense formations of more developed woven bone overlaid with lamellar bone at the implant periphery were observed. The workflow presented will allow future in vivo testing to test specific bone strains on bone ingrowth in response to a scaffold and allow for better translation from in vivo testing to commercial implants.

Modified gait patterns due to cam FAI syndrome remain unchanged after surgery.

BACKGROUND: In order to reduce the development of hip osteoarthritis related to cam-type femoroacetabular impingement syndrome (FAIS), corrective surgery has evolved to become a safe and effective treatment. Although corrective surgery produces high level of patient satisfaction, it is still unclear how it affects muscle and hip contact forces during level walking. RESEARCH QUESTION: The purpose was to compare the muscle force contributions and hip contact forces in patients before and after surgical correction for cam FAIS with healthy control (CTRL) individuals during level walking. METHODS: Eleven male patients with symptomatic cam-type morphology, who underwent hip osteochondroplasty, had their level walking recorded pre- and at 2-year postoperatively. The patients were sex-, age-, BMI-matched to 11 CTRL individuals. Sagittal and frontal hip kinematics and kinetics were computed and, subsequently, muscle and hip contact forces were estimated using musculoskeletal modelling and static optimization. RESULTS: Patient-reported outcomes improved postoperatively. The pre- and postoperative FAIS walked slower and with shorter steps than the CTRL. Postoperative biceps femoris (CTRL: 0.35 ±â€¯0.13 N/BW; pre-op: 0.28 ±â€¯0.11 N/BW; post-op: 0.20 ±â€¯0.07 N/BW) and semimembranosus forces (CTRL: 0.77 ±â€¯0.24 N/BW; pre-op: 0.66 ±â€¯0.24 N/BW; post-op: 0.41 ±â€¯0.14 N/BW) were lower at ipsilateral foot-strike. Postoperative rectus femoris force (CTRL: 1.73 ±â€¯0.35 N/BW; pre-op: 1.44 ±â€¯0.24 N/BW; post-op: 1.18 ±â€¯0.23 N/BW) was lower than the other two groups, and the pre- and postoperative FAIS had lower iliacus (CTRL: 1.17 ±â€¯0.18 N/BW; pre-op: 0.93 ±â€¯0.16 N/BW; post-op: 0.94 ±â€¯0.21 N/BW) and psoas (CTRL: 1.55 ±â€¯0.24 N/BW; pre-op: 1.14 ±â€¯0.38 N/BW; post-op: 1.10 ±â€¯0.46 N/BW) muscle forces at contralateral foot-strike compared with the CTRL. Pre- and postoperative FAIS demonstrated lower peak hip contact loading resultant than the CTRL. SIGNIFICANCE: The altered gait parameters observed in the preoperative FAIS was not restored after surgery, and was still away from the CTRL. It is possible that the reduced dynamic muscle forces of the biceps femoris, semimembranosus and rectus femoris postoperatively were associated with the protected mechanism that involved the iliopsoas preoperatively. This is an indication that the gait adaptations affected by the FAIS do not restore to normal after surgical correction at the 2-years follow-up.

Hip capsule biomechanics after arthroplasty: the effect of implant, approach, and surgical repair.

AIMS: The hip's capsular ligaments passively restrain extreme range of movement (ROM) by wrapping around the native femoral head/neck. We determined the effect of hip resurfacing arthroplasty (HRA), dual-mobility total hip arthroplasty (DM-THA), conventional THA, and surgical approach on ligament function. MATERIALS AND METHODS: Eight paired cadaveric hip joints were skeletonized but retained the hip capsule. Capsular ROM restraint during controlled internal rotation (IR) and external rotation (ER) was measured before and after HRA, DM-THA, and conventional THA, with a posterior (right hips) and anterior capsulotomy (left hips). RESULTS: Hip resurfacing provided a near-native ROM with between 5° to 17° increase in IR/ER ROM compared with the native hip for the different positions tested, which was a 9% to 33% increase. DM-THA generated a 9° to 61° (18% to 121%) increase in ROM. Conventional THA generated a 52° to 100° (94% to 199%) increase in ROM. Thus, for conventional THA, the capsule function that exerts a limit on ROM is lost. It is restored to some extent by DM-THA, and almost fully restored by hip resurfacing. In positions of low flexion/extension, the posterior capsulotomy provided more normal function than the anterior, possibly because the capsule was shortened during posterior repair. However, in deep flexion positions, the anterior capsulotomy functioned better. CONCLUSION: Native head-size and capsular repair preserves capsular function after arthroplasty. The anterior and posterior approach differentially affect postoperative biomechanical function of the capsular ligaments. Cite this article: Bone Joint J 2019;101-B:426-434.