Aims. The main objective of this study was to examine whether the Oxford Shoulder Score (OSS) demonstrated floor or ceiling effects when used to measure outcomes following shoulder arthroplasty in a large national cohort. Secondary objectives were to assess its pain and function subscales, and to identify independent predictors for patients achieving a postoperative ceiling score following shoulder arthroplasty. Methods. Secondary database analysis of the National Joint Registry (NJR), which included 48,270 patients undergoing shoulder arthroplasty, was conducted. The primary outcome measure was the OSS. Secondary outcome measures were the OSS-Function Component Subscale and OSS-Pain Component Subscale. Floor and ceiling effects were considered to be present if > 15% of patients scored either the lowest or highest possible score.
Aims. The aim of this study was to explore why some calcar screws are malpositioned when a proximal humeral fracture is treated by internal fixation with a locking plate, and to identify risk factors for this phenomenon. Some suggestions can be made of ways to avoid this error. Methods. We retrospectively identified all proximal humeral fractures treated in our institution between October 2016 and October 2018 using the hospital information system. The patients’ medical and radiological data were collected, and we divided potential risk factors into two groups: preoperative factors and intraoperative factors. Preoperative factors included age, sex, height, weight, body mass index, proximal humeral bone mineral density, type of fracture, the condition of the medial hinge, and medial metaphyseal head extension. Intraoperative factors included the grade of surgeon, neck-shaft angle after reduction, humeral head height, restoration of medial support, and quality of reduction. Adjusted binary
Aims. The aim of this study is to report the implant survival and factors associated with revision of total elbow arthroplasty (TEA) using data from the Dutch national registry. Methods. All TEAs recorded in the Dutch national registry between 2014 and 2020 were included. The Kaplan-Meier method was used for survival analysis, and a
Aims. The current evidence comparing the two most common approaches for reverse total shoulder arthroplasty (rTSA), the deltopectoral and anterosuperior approach, is limited. This study aims to compare the rate of loosening, instability, and implant survival between the two approaches for rTSA using data from the Dutch National Arthroplasty Registry with a minimum follow-up of five years. Methods. All patients in the registry who underwent a primary rTSA between January 2014 and December 2016 using an anterosuperior or deltopectoral approach were included, with a minimum follow-up of five years. Cox and
Aims. The aim of this study was to identify risk factors for recurrent instability of the shoulder and assess the ability to return to sport in patients with engaging Hill-Sachs lesions treated with arthroscopic Bankart repair and Hill-Sachs remplissage (ABR-HSR). Methods. This retrospective study included 133 consecutive patients with a mean age of 30 years (14 to 69) who underwent ABR-HSR; 103 (77%) practiced sports before the instability of the shoulder. All had large/deep, engaging Hill-Sachs lesions (Calandra III). Patients were divided into two groups: A (n = 102) with minimal or no (< 10%) glenoid bone loss, and B (n = 31) with subcritical (10% to 20%) glenoid loss. A total of 19 patients (14%) had undergone a previous stabilization, which failed. The primary endpoint was recurrent instability, with a secondary outcome of the ability to return to sport. Results. At a mean follow-up of four years (1.0 to 8.25), ten patients (7.5%) had recurrent instability. Patients in group B had a significantly higher recurrence rate than those in group A (p = 0.001). Using a multivariate
Aims. The purpose of this study was to identify the changes in untreated long head of the biceps brachii tendon (LHBT) after a rotator cuff tear and to evaluate the factors related to the changes. Methods. A cohort of 162 patients who underwent isolated supraspinatus with the preservation of LHBT was enrolled and evaluated. The cross-sectional area (CSA) of the LHBT on MRI was measured in the bicipital groove, and preoperative to postoperative difference was calculated at least 12 months postoperatively. Second, postoperative changes in the LHBT including intratendinous signal change, rupture, dislocation, or superior labral lesions were evaluated with seeking of factors that were correlated with the changes or newly developed lesions after rotator cuff repair. Results. The postoperative CSA (12.5 mm. 2. (SD 8.3) was significantly larger than preoperative CSA (11.5 mm. 2. (SD 7.5); p = 0.005). In total, 32 patients (19.8%) showed morphological changes in the untreated LHBT 24 months after rotator cuff repair. Univariate regression analysis revealed that the factor chiefly related to the change in LHBT status was an eccentric LHBT position within the groove found on preoperative MRI (p = 0.011). Multivariate analysis using
Aims. This study aimed to determine the minimal detectable change (MDC), minimal clinically important difference (MCID), and substantial clinical benefit (SCB) under distribution- and anchor-based methods for the Mayo Elbow Performance Index (MEPI) and range of movement (ROM) after open elbow arthrolysis (OEA). We also assessed the proportion of patients who achieved MCID and SCB; and identified the factors associated with achieving MCID. Methods. A cohort of 265 patients treated by OEA were included. The MEPI and ROM were evaluated at baseline and at two-year follow-up. Distribution-based MDC was calculated with confidence intervals (CIs) reflecting 80% (MDC 80), 90% (MDC 90), and 95% (MDC 95) certainty, and MCID with changes from baseline to follow-up. Anchor-based MCID (anchored to somewhat satisfied) and SCB (very satisfied) were calculated using a five-level Likert satisfaction scale. Multivariate
Aims. To compare complication-related reoperation rates following primary arthroplasty for proximal humerus fractures (PHFs) versus secondary arthroplasty for failed open reduction and internal fixation (ORIF). Patients and Methods. We identified patients aged 50 years and over, who sustained a PHF between 2004 and 2015, from linkable datasets. We used intervention codes to identify patients treated with initial ORIF or arthroplasty, and those treated with ORIF who returned for revision arthroplasty within two years. We used multilevel
We assessed the age-related differences in the
use of total shoulder arthroplasty (TSA) and outcomes, and associated
time-trends using the United States Nationwide Inpatient Sample
(NIS) between 1998 and 2010. Age was categorised as <
50, 50
to 64, 65 to 79 and ≥ 80 years. Time-trends in the use of TSA were
compared using
Aims. The aim of the study was to develop a quantitative scoring system
to predict whether a large-to-massive rotator cuff tear was arthroscopically
reparable prior to surgery. Patients and Methods. We conducted a retrospective review of the pre-operative MR imaging
and surgical records of 87 patients (87 shoulders) who underwent
arthroscopic repair of a large-to-massive rotator cuff tear. Patients
were divided into two groups, based on the surgical outcome of the
repair. Of the 87 patients, 53 underwent complete repair (Group
I) and 34 an incomplete repair (Group II). Pre-operative MR images
were reviewed to quantify several variables. Between-group differences
were evaluated and multiple
Corticosteroid injections are often used to manage glenohumeral arthritis in patients who may be candidates for future total shoulder arthroplasty (TSA) or reverse shoulder arthroplasty (rTSA). In the conservative management of these patients, corticosteroid injections are often provided for symptomatic relief. The purpose of this study was to determine if the timing of corticosteroid injections prior to TSA or rTSA is associated with changes in rates of revision and periprosthetic joint infection (PJI) following these procedures. Data were collected from a national insurance database from January 2006 to December 2017. Patients who underwent shoulder corticosteroid injection within one year prior to ipsilateral TSA or rTSA were identified and stratified into the following cohorts: < three months, three to six months, six to nine months, and nine to 12 months from time of corticosteroid injection to TSA or rTSA. A control cohort with no corticosteroid injection within one year prior to TSA or rTSA was used for comparison. Univariate and multivariate analyses were conducted to determine the association between specific time intervals and outcomes.Aims
Methods
The aim of this study was to determine whether there is a correlation between the grade of humeral osteoarthritis (OA) and the severity of glenoid morphology according to Walch. We hypothesized that there would be a correlation. Overal, 143 shoulders in 135 patients (73 females, 62 males) undergoing shoulder arthroplasty surgery for primary glenohumeral OA were included consecutively. Mean age was 69.3 years (47 to 85). Humeral head (HH), osteophyte length (OL), and morphology (transverse decentering of the apex, transverse, or coronal asphericity) on radiographs were correlated to the glenoid morphology according to Walch (A1, A2, B1, B2, B3), glenoid retroversion, and humeral subluxation on CT images.Aims
Methods
This study compared patients who underwent arthroscopic repair of large to massive rotator cuff tears (LMRCTs) with isolated incomplete repair of the tear and patients with incomplete repair with biceps tendon augmentation. We aimed to evaluate the additional benefit on clinical outcomes and the capacity to lower the re-tear rate. We retrospectively reviewed 1,115 patients who underwent arthroscopic rotator cuff repair for full-thickness tears between October 2011 and May 2019. From this series, we identified 77 patients (28 male, 49 female) with a mean age of 64.1 years (50 to 80). Patients were classified into groups A (n = 47 incomplete) and B (n = 30 with biceps augmentation) according to the nature of their reconstruction. Clinical scores were checked preoperatively and at six months, one year, and two years postoperatively. In preoperative MRI, we measured the tear size, the degree of fatty infiltration, and muscle volume ratio of the supraspinatus. In postoperative MRI, the integrity of the repaired rotator cuff tendon was assessed using the Sugaya classification. Tendon thickness at the footprint was evaluated on T2-weighted oblique coronal view.Aims
Methods
This study aimed to assess the impact of using the metal-augmented glenoid baseplate (AGB) on improving clinical and radiological outcomes, as well as reducing complications, in patients with superior glenoid wear undergoing reverse shoulder arthroplasty (RSA). From January 2016 to June 2021, out of 235 patients who underwent primary RSA, 24 received a superior-AGB after off-axis reaming (Group A). Subsequently, we conducted propensity score matching in a 1:3 ratio, considering sex, age, follow-up duration, and glenoid wear (superior-inclination and retroversion), and selected 72 well-balanced matched patients who received a standard glenoid baseplate (STB) after eccentric reaming (Group B). Superior-inclination, retroversion, and lateral humeral offset (LHO) were measured to assess preoperative glenoid wear and postoperative correction, as well as to identify any complications. Clinical outcomes were measured at each outpatient visit before and after surgery.Aims
Methods
Metal and ceramic humeral head bearing surfaces are available choices in anatomical shoulder arthroplasties. Wear studies have shown superior performance of ceramic heads, however comparison of clinical outcomes according to bearing surface in total shoulder arthroplasty (TSA) and hemiarthroplasty (HA) is limited. This study aimed to compare the rates of revision and reoperation following metal and ceramic humeral head TSA and HA using data from the National Joint Registry (NJR), which collects data from England, Wales, Northern Ireland, Isle of Man and the States of Guernsey. NJR shoulder arthroplasty records were linked to Hospital Episode Statistics and the National Mortality Register. TSA and HA performed for osteoarthritis (OA) in patients with an intact rotator cuff were included. Metal and ceramic humeral head prostheses were matched within separate TSA and HA groups using propensity scores based on 12 and 11 characteristics, respectively. The primary outcome was time to first revision and the secondary outcome was non-revision reoperation.Aims
Methods
The aim of this study was to develop and internally validate a prognostic nomogram to predict the probability of gaining a functional range of motion (ROM ≥ 120°) after open arthrolysis of the elbow in patients with post-traumatic stiffness of the elbow. We developed the Shanghai Prediction Model for Elbow Stiffness Surgical Outcome (SPESSO) based on a dataset of 551 patients who underwent open arthrolysis of the elbow in four institutions. Demographic and clinical characteristics were collected from medical records. The least absolute shrinkage and selection operator regression model was used to optimize the selection of relevant features. Multivariable logistic regression analysis was used to build the SPESSO. Its prediction performance was evaluated using the concordance index (C-index) and a calibration graph. Internal validation was conducted using bootstrapping validation.Aims
Methods
Despite recent advances in arthroscopic rotator cuff repair, re-tear rates remain high. New methods to improve healing rates following rotator cuff repair must be sought. Our primary objective was to determine if adjunctive bone marrow stimulation with channelling five to seven days prior to arthroscopic cuff repair would lead to higher Western Ontario Rotator Cuff (WORC) scores at 24 months postoperatively compared with no channelling. A prospective, randomized controlled trial was conducted in patients undergoing arthroscopic rotator cuff repair. Patients were randomized to receive either a percutaneous bone channelling of the rotator cuff footprint or a sham procedure under ultrasound guidance five to seven days prior to index surgery. Outcome measures included the WORC, American Shoulder and Elbow Surgeons (ASES), and Constant scores, strength, ultrasound-determined healing rates, and adverse events.Aims
Methods
The impact of tobacco use on readmission and medical and surgical complications has been documented in hip and knee arthroplasty. However, there remains little information about the effect of smoking on the outcome after total shoulder arthroplasty (TSA). We hypothesized that active smokers are at an increased risk of poor medical and surgial outcomes after TSA. Data for patients who underwent arthroplasty of the shoulder in the USA between January 2011 and December 2015 were obtained from the National Readmission Database, and 90-day readmissions and complications were documented using validated coding methods. Multivariate regression analysis was performed to quantify the risk of smoking on the outcome after TSA, while controlling for patient demographics, comorbidities, and hospital-level confounding factors.Aims
Methods
A pragmatic multicentre randomized controlled trial, UK FROzen Shoulder Trial (UK FROST), was conducted in the UK NHS comparing the cost-effectiveness of commonly used treatments for adults with primary frozen shoulder in secondary care. A cost utility analysis from the NHS perspective was performed. Differences between manipulation under anaesthesia (MUA), arthroscopic capsular release (ACR), and early structured physiotherapy plus steroid injection (ESP) in costs (2018 GBP price base) and quality adjusted life years (QALYs) at one year were used to estimate the cost-effectiveness of the treatments using regression methods.Aims
Methods
The aim of this study was to define the complications and long-term outcome following adolescent mid-shaft clavicular fracture. We retrospectively reviewed a consecutive series of 677 adolescent fractures in 671 patients presenting to our region (age 13 to 17 years) over a ten-year period (2009 to 2019). Long-term patient-reported outcomes (abbreviated version of the Disabilities of the Arm, Shoulder and Hand (QuickDASH) score and EuroQol five-dimension three-level (EQ-5D-3L) quality of life score) were undertaken at a mean of 6.4 years (1.2 to 11.3) following injury in severely displaced mid-shaft fractures (Edinburgh 2B) and angulated mid-shaft fractures (Edinburgh 2A2) at a minimum of one year post-injury. The median patient age was 14.8 years (interquartile range (IQR) 14.0 to 15.7) and 89% were male (n = 594/671).Aims
Methods
The purpose of this study was to report bone adaptive changes after anatomical total shoulder arthroplasty (TSA) using a standard-length hydroxyapatite (HA)-coated humeral component, and to report on a computer-based analysis of radiographs to determine changes in peri-implant bone density objectively. A total of 44 TSAs, performed between 2011 and 2014 using a cementless standard-length humeral component proximally coated with HA, were included. There were 23 males and 21 females with a mean age of 65 years (17 to 65). All shoulders had good quality radiographs at six weeks and five years postoperatively. Three observers graded bone adaptive changes. All radiographs were uploaded into a commercially available photographic software program. The grey value density of humeral radiological areas was corrected to the grey value density of the humeral component and compared over time.Aims
Methods
Conservative treatment of moderately displaced proximal humeral head fractures yields good clinical results, but secondary fragment displacement may occur. Identification of those fractures at risk of displacement may influence initial decision-making. A total of 163 shoulders in 162 patients with conservatively treated isolated proximal humeral fractures were included. The fractures occurred between January 2015 and May 2018. The mean age of the patients was 69 years (26 to 100) and the mean follow-up was 144 days (42 to 779). The fractures were classified according to Neer. Scores for osteoporosis (Tingart, Deltoid Tuberosity Index (DTI)) and osteoarthritis (OA) of the glenohumeral joint were assessed. Translation of the head on follow-up radiographs of more than 10 mm was defined as displacement. Eccentric head index (EHI) describes the offset of the humeral head centre in relation to the diaphyseal axis. The ratio was estimated on anteroposterior (AP) and Neer views. Medial hinge was considered intact if the medial cortex proximal and distal to the fracture was in line on AP view.Aims
Methods
Patient-specific instrumentation has been shown to increase a surgeon’s precision and accuracy in placing the glenoid component in shoulder arthroplasty. There is, however, little available information about the use of patient-specific planning (PSP) tools for this operation. It is not known how these tools alter the decision-making patterns of shoulder surgeons. The aim of this study was to investigate whether PSP, when compared with the use of plain radiographs or select static CT images, influences the understanding of glenoid pathology and surgical planning. A case-based survey presented surgeons with a patient’s history, physical examination, and, sequentially, radiographs, select static CT images, and PSP with a 3D imaging program. For each imaging modality, the surgeons were asked to identify the Walch classification of the glenoid and to propose the surgical treatment. The participating surgeons were grouped according to the annual volume of shoulder arthroplasties that they undertook, and responses were compared with the recommendations of two experts.Aims
Methods
The primary aim of this study was to evaluate the efficacy of distension arthrography in the treatment of adhesive capsulitis of the shoulder. The secondary aim was to assess which patient and procedural factors predicted the recurrence of symptoms after the procedure. All patients referred to our shoulder clinic over a ten-year period, between 2008 and 2018, with a clinical diagnosis of capsulitis and symptoms persisting for more than six months, were offered treatment with a distension arthrogram. All procedures were performed by one of five musculoskeletal radiologists, with a combination of steroid, local anaesthetic, and a distention volume of 10 ml, 30 ml, or 50 ml. Patient demographics, procedural details, recurrence of symptoms, and the need for further intervention were evaluated.Aims
Methods
Heterotopic ossification (HO) is a potentially devastating complication of the surgical treatment of a proximal humeral fracture. The literature on the rate and risk factors for the development of HO under these circumstances is lacking. The aim of this study was to determine the incidence and risk factors for the development of HO in these patients. A retrospective analysis of 170 patients who underwent operative treatment for a proximal humeral fracture between 2005 and 2016, in a single institution, was undertaken. The mean follow-up was 18.2 months (1.5 to 140). The presence of HO was identified on follow-up radiographs.Aims
Methods
The aim of this study was to investigate the effects of preoperative bisphosphonate treatment on the intra- and postoperative outcomes of arthroplasty of the shoulder. The hypothesis was that previous bisphosphonate treatment would adversely affect both intra- and postoperative outcomes. A retrospective cohort study was conducted involving patients undergoing arthroplasty of the shoulder, at a single institution. Two patients with no previous bisphosphonate treatment were matched to each patient who had received this treatment preoperatively by gender, age, race, ethnicity, body mass index (BMI), and type of arthroplasty. Previous bisphosphonate treatment was defined as treatment occurring during the three-year period before the arthroplasty. The primary outcome measure was the incidence of intraoperative complications and those occurring at one and two years postoperatively. A total of 87 patients were included: 29 in the bisphosphonates-exposed (BP+) group and 58 in the non-exposed (BP-) group. In the BP+ group, there were 26 female and three male patients, with a mean age of 71.4 years (51 to 87). In the BP- group, there were 52 female and six male patients, with a mean age of 72.1 years (53 to 88).Aims
Patients and Methods
We assessed the long-term (more than ten-year) outcomes of the
Kudo type-5 elbow prosthesis in patients with rheumatoid arthritis
(RA). We reviewed 41 elbows (Larsen Grade IV, n = 21; Grade V, n =
20) in 31 patients with RA who had undergone a Kudo type-5 total
elbow arthroplasty (TEA) between 1994 and 2003, and had been followed
up for more than ten years. The humeral component was cementless
and the all-polyethylene ulnar component cemented in every patient. Clinical
outcome was assessed using the Mayo elbow performance score. We
calculated the revision rate and evaluated potential risk factors
for revision. The duration of follow-up was a mean 141 months (120
to 203).Aims
Materials and Methods
The aim of the present study was to compare the 30- and 90-day
re-admission rates and complication rates of outpatient and inpatient
total shoulder arthroplasty (TSA). The United States Medicare Standard Analytical Files database
was questioned to identify patients who had undergone outpatient
or inpatient TSA between 2005 and 2012. Patient characteristics
were compared between the two groups using chi-squared analysis. Multivariate
logistic regression analysis was used to control for differences
in baseline patient characteristics and to compare the two groups
in terms of post-operative complications within 90 days and re-admission
within 30 days and 90 days.Aims
Patients and Methods
The goal of this study is to investigate the relation between indicators of osteoporosis (i.e., bone mineral density (BMD), and Cortical Index (CI)) and the complexity of a fracture of the proximal humerus as a result of a low-energy trauma. A retrospective chart review of 168 patients (mean age 67.2 years, range 51 to 88.7) with a fracture of the proximal humerus between 2007 and 2011, whose BMD was assessed at the Fracture Liaison Service with Dual Energy X-ray Absorptiometry (DXA) measurements of the hip, femoral neck (FN) and/or lumbar spine (LS), and whose CI and complexity of fracture were assessed on plain anteroposterior radiographs of the proximal humerus.Objectives
Methods
The factors that predispose to recurrent instability and revision
stabilization procedures after arthroscopic Bankart repair for anterior
glenohumeral instability remain unclear. We sought to determine
the rate and risk factors associated with ongoing instability in
patients undergoing arthroscopic Bankart repair for instability
of the shoulder. We used the Statewide Planning and Research Cooperative System
(SPARCS) database to identify patients with a diagnosis of anterior
instability of the shoulder undergoing arthroscopic Bankart repair
between 2003 and 2011. Patients were followed for a minimum of three
years. Baseline demographics and subsequent further surgery to the ipsilateral
shoulder were analyzed. Multivariate analysis was used to identify
independent risk factors for recurrent instability.Aims
Materials and Methods
Radiostereometric analysis (RSA) allows an extremely accurate
measurement of early micromotion of components following arthroplasty. In this study, RSA was used to measure the migration of 11 partially
cemented fluted pegged glenoid components in patients with osteoarthritis
who underwent total shoulder arthroplasty using an improved surgical
technique (seven men, four women, mean age 68). Patients were evaluated
clinically using the American Shoulder and Elbow Surgeons (ASES)
and Constant-Murley scores and by CT scans two years post-operatively. Aims
Patients and Methods
In the initial development of total shoulder arthroplasty (TSA),
the humeral component was usually fixed with cement. Cementless
components were subsequently introduced. The aim of this study was
to compare the long-term outcome of cemented and cementless humeral
components in arthroplasty of the shoulder. All patients who underwent primary arthroplasty of the shoulder
at our institution between 1970 and 2012 were included in the study.
There were 4636 patients with 1167 cemented humeral components and
3469 cementless components. Patients with the two types of fixation
were matched for nine different covariates using a propensity score
analysis. A total of 551 well-balanced pairs of patients with cemented
and cementless components were available after matching for comparison
of the outcomes. The clinical outcomes which were analysed included loosening
of the humeral component determined at revision surgery, periprosthetic
fractures, post-operative infection and operating time.Aims
Patients and Methods
We retrospectively reviewed 89 consecutive patients
(45 men and 44 women) with a mean age at the time of injury of 58
years (18 to 97) who had undergone external fixation after sustaining
a unilateral fracture of the distal humerus. Our objectives were
to determine the incidence of heterotopic ossification (HO); identify
risk factors associated with the development of HO; and characterise
the location, severity and resultant functional impairment attributable
to the presence of HO. HO was identified in 37 elbows (42%), mostly around the humerus
and along the course of the medial collateral ligament. HO was hazy
immature in five elbows (13.5%), mature discrete in 20 (54%), extensive
mature in 10 (27%), and complete bone bridges were present in two
elbows (5.5%). Mild functional impairment occurred in eight patients,
moderate in 27 and severe in two. HO was associated with less extension
(p = 0.032) and less overall flexion-to-extension movement (p =
0.022); the flexion-to-extension arc was <
100º in 21 elbows
(57%) with HO compared with 18 elbows (35%) without HO (p = 0.03).
HO was removed surgically in seven elbows. The development of HO was significantly associated with sustaining
a head injury (p = 0.015), delayed internal fixation (p = 0.027),
the method of fracture fixation (p = 0.039) and the use of bone
graft or substitute (p = 0.02).HO continues to be a substantial
complication after internal fixation for distal humerus fractures. Cite this article:
Depression can significantly affect quality of life and is associated
with higher rates of medical comorbidities and increased mortality
following surgery. Although depression has been linked to poorer
outcomes following orthopaedic trauma, total joint arthroplasty
and spinal surgery, we wished to examine the impact of depression
in elective total shoulder arthroplasty (TSA) as this has not been
previously explored. The United States Nationwide Inpatient Sample (NIS) was used
to identify patients undergoing elective TSA over a ten-year period.
Between 2002 and 2012, 224 060 patients underwent elective TSA.Aims
Patients and Methods
To compare radiographic failure and re-operation rates of anatomical
coracoclavicular (CC) ligament reconstructional techniques with
non-anatomical techniques after chronic high grade acromioclavicular
(AC) joint injuries. We reviewed chronic AC joint reconstructions within a region-wide
healthcare system to identify surgical technique, complications,
radiographic failure and re-operations. Procedures fell into four
categories: Aims
Patients and Methods