Large- and medium-sized arterial aneurysms in two patients with SMAD4-related juvenile polyposis syndrome.

Germline SMAD4 pathogenic variants (PVs) cause juvenile polyposis syndrome (JPS), which is known for an increased risk of gastrointestinal juvenile polyps and gastrointestinal cancer. Many patients with SMAD4 PV also show signs of hereditary hemorrhagic telangiectasia (HHT) and some patients have aneurysms and dissections of the thoracic aorta. Here we describe two patients with a germline SMAD4 PV and a remarkable clinical presentation including multiple medium-sized arterial aneurysms. More data are needed to confirm whether the more extensive vascular phenotype and the other described features in our patients are indeed part of a broader JPS spectrum.

Short versus conventional straight stem in uncemented total hip arthroplasty: functional outcomes up to 5 years and survival up to 12 years: secondary results of a randomized controlled trial.

BACKGROUND AND PURPOSE: To date, the mid- and long-term outcomes of the Collum Femoris Preserving (CFP) stem compared with conventional straight stems are unknown. We aimed to compare physical function at a 5-year follow-up and implant survival at an average of 10-year follow-up in an randomized controlled trial (RCT). METHODS: This is a secondary report of a double-blinded RCT in 2 hospitals. Patients aged 18-70 years with hip osteoarthritis undergoing an uncemented primary THA were randomized to a CFP or a Zweymüller stem. Patient-reported outcomes, clinical tests, and radiographs were collected at baseline, 2, 3, 4, and 5 years postoperatively. Primary outcome was the Hip disability and Osteoarthritis Outcome Score (HOOS) function in activities of daily living (ADL) subscale. Secondary outcomes were other patient-reported outcomes, clinical tests, adverse events, and implant survival. Kaplan-Meier and competing risk survival analyses were performed with data from the Dutch Arthroplasty Registry. RESULTS: We included 150 patients. Mean difference between groups on the HOOS ADL subscale at 5 years was -0.07 (95% confidence interval -5.1 to 4.9). Overall survival was 92% for the CFP and 96% for the Zweymüller stem. No significant difference was found. CONCLUSION: No significant differences were found in physical function at 5-year and implant survival at 10-year follow-up between the CFP and Zweymüller stems. When taking cup revisions into account, the CFP group showed clinically inferior survival.

A comparison of uncemented short versus standard stem length in total hip arthroplasty: results from the Dutch Arthroplasty Register.

BACKGROUND AND PURPOSE: We aimed to compare revision rates between uncemented short and standard stems in total hip arthroplasties (THAs) and the corresponding patient-reported outcome measures (PROMs). PATIENTS AND METHODS: We included all short (C.F.P., Fitmore, GTS, Metha, Nanos, Optimys, Pulchra, and Taperloc Microplasty) and standard stems in uncemented THAs registered between 2009 and 2021 in the Dutch Arthroplasty Register. Kaplan-Meier survival and multivariable Cox regression analyses were performed with overall and femoral stem revision as endpoints. RESULTS: Short stems were used in 3,352 and standard stems in 228,917 hips. 10-year overall revision rates (4.8%, 95% confidence interval [CI] 3.7-6.3 vs. 4.5%, CI 4.4-4.6) and femoral stem revision rates (3.0%, CI 2.2-4.2 vs. 2.3%, CI 2.2-2.4) were comparable for short- and standard-stem THAs. Today's predominant short stems (Fitmore and Optimys) showed short-term revision rates similar to that of standard-stem THAs. Other, less frequently used short stems had higher 10-year overall (6.3%, CI 4.7-8.5) and femoral stem (4.5%, CI 3.1-6.3) revision rates. Multivariable Cox regression also showed a higher risk for overall (HR 1.7, CI 1.0-2.9) and femoral stem revision (HR 2.0, CI 1.1-3.5) using the latter short stems compared with standard stems. An exploratory analysis of PROMs showed no difference. CONCLUSION: There was no overall difference in revision rates but a tendency toward increased revision of short stems both for the whole THA and for the stem itself. The less frequently used short stems had increased revision risk. No difference in PROMs was shown.

Risk for re-revision and type of antibiotic-loaded bone cement in hip or knee arthroplasty revisions: report of the Dutch Arthroplasty Register.

BACKGROUND AND PURPOSE: High-dose dual antibiotic-loaded bone cement (ALBC) may reduce the risk of revision after total hip and knee replacements. The aim of our study therefore was to determine the risk of re-revision following first time aseptic hip or knee revision using single versus dual ALBC. PATIENTS AND METHODS: Patients from the Dutch Arthroplasty Register treated from 2007 to 2018 with first time cemented aseptic hip (n = 2,529) or knee revisions (n = 7,124) were incorporated into 2 datasets. The primary endpoint of this observational cohort study was subsequent all-cause re-revision. Multivariable Cox proportional hazard and competing risk was analyzed for both groups. RESULTS: There was no difference in re-revision rate (any reason) with single versus dual ALBC (hazard ratio 1.06, 95% confidence interval [CI] 0.83-1.35 for hip and 0.93, CI 0.80-1.07 for knee revisions). The 10-year crude cumulative re-revision rate also showed no differences for single versus dual ALBC use. The crude cumulative 7-year THA re-revision and 9-year TKA re-revision rates did not show any difference in implant survival for common cement types used. CONCLUSION: We could not confirm the potential benefit of using dual ALBC compared with single ALBC for aseptic hip and knee revisions.

Increased Persistent Mid-Thigh Pain After Short-Stem Compared With Wedge-Shaped Straight-Stem Uncemented Total Hip Arthroplasty at Medium-Term Follow-Up: A Randomized Double-Blinded Cross-Sectional Study.

BACKGROUND: Femoral prosthesis design may impact the frequency of mid-thigh pain. We compared current, incidental, and persistent mid-thigh pain between the short-stem, Collum Femoris femur prosthesis, and the wedge shaped straight-stem, Zweymüller femur prosthesis and studied the associations between demographics, radiographic measurements, and mid-thigh pain. METHODS: We contacted patients from a randomized controlled trial who underwent uncemented total hip arthroplasty (THA) for hip osteoarthritis at a mean follow-up of 44 months (range 24-64 months). Patients were specifically assessed for current (during assessment), incidental (any time postoperatively for >1 week) mid-thigh pain, and persistent (any time postoperatively for >2 years) mid-thigh pain. Furthermore, we used regression analysis to study associations between demographics, radiographic measurements, and mid-thigh pain. RESULTS: One hundred forty of 150 patients (93%) responded to our assessment. Mean age at the time of operation was 62 years (±7.0). Current mid-thigh pain occurred in 16 patients (23%) in the Collum Femoris Preserving (CFP) group compared with 10 patients (14%) in the Zweymüller group (P = .192). Incidental mid-thigh pain occurred in 24 patients (34%) in the CFP group compared with 15 patients (21%) in the Zweymüller group (P = .090). Persistent mid-thigh pain was found in 13 patients (19%) in the CFP group compared with five patients (7%) in the Zweymüller group (P = .043). Varus malalignment (odds ratio 1.819 [95% confidence interval 1.034-3.200]) and leg lengthening (odds ratio 1.107 per cm lengthening [95% confidence interval 1.026-1.195]) showed significant associations with mid-thigh pain. CONCLUSIONS: We found more persistent mid-thigh pain after short-stem uncemented THA compared to wedge-shaped straight-stem uncemented THA during medium-term follow-up. Varus malalignment and leg lengthening were associated with mid-thigh pain.

Revision rate after short-stem total hip arthroplasty: a systematic review of 49 studies.

BACKGROUND AND PURPOSE: The aim of short-stem total hip arthroplasty is to preserve proximal bone stock for future revisions, to improve biomechanical reconstruction, and to make minimally invasive approaches easier. It is therefore being increasingly considered to be a sound alternative to conventional total hip arthroplasty, especially for young and active patients. However, it is still unknown whether survival rates of short-stem hips match current standards. We made a systematic summary of reported overall survival after short-stem total hip arthroplasty. MATERIALS AND METHODS: We conducted a systematic review of English, French, German, and Dutch literature. 2 assessors independently identified clinical studies on short-stem hip arthroplasty. After recalculating reported revision rates, we determined whether each implant had a projected revision rate of 10% or less at 10 years of follow-up or a revision rate per 100 observed component years of 1 or less. Stems were classified as "collum", "partial collum", or "trochanter-sparing". RESULTS AND INTERPRETATION: We found 49 studies, or 51 cohorts, involving 19 different stems. There was a large increase in recent publications. The majority of studies included had a follow-up of less than 5 years. We found a large number of observational studies on "partial collum" and "trochanter-sparing" stems, demonstrating adequate survival rates at medium-term follow-up. Clinical evidence from "collum stem" studies was limited to a small number of studies with a medium-term follow-up period. These studies did not show a satisfactory overall survival rate.

Intraoperative application of three-dimensional printed guides in total hip arthroplasty: A systematic review.

BACKGROUND: Acetabular component positioning in total hip arthroplasty (THA) is of key importance to ensure satisfactory post-operative outcomes and to minimize the risk of complications. The majority of acetabular components are aligned freehand, without the use of navigation methods. Patient specific instruments (PSI) and three-dimensional (3D) printing of THA placement guides are increasingly used in primary THA to ensure optimal positioning. AIM: To summarize the literature on 3D printing in THA and how they improve acetabular component alignment. METHODS: PubMed was used to identify and access scientific studies reporting on different 3D printing methods used in THA. Eight studies with 236 hips in 228 patients were included. The studies could be divided into two main categories; 3D printed models and 3D printed guides. RESULTS: 3D printing in THA helped improve preoperative cup size planning and post-operative Harris hip scores between intervention and control groups (P = 0.019, P = 0.009). Otherwise, outcome measures were heterogeneous and thus difficult to compare. The overarching consensus between the studies is that the use of 3D guidance tools can assist in improving THA cup positioning and reduce the need for revision THA and the associated costs. CONCLUSION: The implementation of 3D printing and PSI for primary THA can significantly improve the positioning accuracy of the acetabular cup component and reduce the number of complications caused by malpositioning.

Evaluating the Clinical Relevance of Routine Sonication for Periprosthetic Hip or Knee Joint Infection Diagnosis.

Periprosthetic joint infection (PJI) is a serious complication after joint arthroplasty. PJI screening and conventional cultures may be inconclusive. Sonication fluid culturing stands out as a valuable adjunct technique for PJI diagnosis. This study aims to determine the clinical relevance of routine sonication for all (a)septic revisions. All patients who underwent (partial) hip or knee revision arthroplasty between 2012 and 2021 were retrospectively reviewed. We formed three groups based on the European Bone and Joint Society PJI criteria: infection confirmed, likely, and unlikely. We analyzed clinical, laboratory, and radiological screening. Sensitivity and specificity were calculated for synovial fluid (preoperative), tissue, and sonication fluid cultures. We determined the clinical relevance of sonication as the percentage of patients for whom sonication confirmed PJI; 429 patients who underwent (partial) revision of hip or knee arthroplasty were included. Sensitivity and specificity were 69% and 99% for synovial fluid cultures, 76% and 92% for tissue cultures, and 80% and 89% for sonication fluid cultures, respectively. Sonication fluid cultures improved tissue culture sensitivity and specificity to 83% and 99%, respectively. In 11% of PJIs, sonication fluid cultures were decisive for diagnosis. This is applicable to acute and chronic infections. Sonication fluid cultures enhanced the sensitivity and specificity of PJI diagnostics. In 11% of PJI cases, causative pathogens were confirmed by sonication fluid culture results. Sonication fluid culture should be performed in all revision arthroplasties.

Effect of Bisphosphonates on Skeletal Related Events in Long Bone Metastases of Renal Cell Carcinoma: A Systematic Review.

Bone metastases (BMs) in patients with renal cell carcinoma (RCC) are lytic lesions which are prone to skeletal related events (SREs) such as (pending) pathological fractures or bone pain requiring radiotherapy or surgery. The aim of this review is to assess whether the use of bisphosphonates in patients with RCC and BMs in the long bones results in reduced SRE rate. A systematic review of literature was conducted, using PubMed, Embase, Medline, Web of Science, Cochrane, and Google Scholar (date 1971 till June 2021). All clinical studies on bisphosphonates in patients with RCC and BMs in long bones were retrieved. Primary outcome measure was SRE rate of BMs in long bones. Secondary outcome was fracture rate of BMs in long bones. Fourteen relevant articles were selected. Bisphosphonates reduced the mean skeletal morbidity rate by 0.4-0.95 SREs/year and had a pooled SRE rate of 38.3% (95% confidence interval [CI] 28.4%-49.3%). When bisphosphonates were added to radiotherapy the pooled SRE rate was 18.4% (95% CI, 10.5%-30.3%). In addition, pooled effect sizes showed a significant SRE risk reduction (RR 0.45, 95% CI, 0.24-0.85) in the bisphosphonates combined with radiotherapy group. There was limited reported data on rate of pathological fractures. In general, bisphosphonates reduce the SRE rate in RCC patients with BMs. The level of evidence for the effect of bisphosphonates on the rate of pathological fractures in patients with long BMs of RCC is low.

Best practices, implementation and challenges of outpatient parenteral antimicrobial therapy: results of a worldwide survey among healthcare providers.

Background: Outpatient Parenteral Antimicrobial Therapy (OPAT) is considered a patient-friendly and cost-effective practice. Patients in the OPAT service can be at risk for developing adverse events. Due to extensive variations in practice, guidelines have been developed to minimize the risks. Objectives: In this first worldwide survey on OPAT, we explored the current OPAT services around the world, adherence to recommendations and identified best practices and challenges from different perspectives. Methods: An e-survey was conducted and consisted of questions about demographics, characteristics of the OPAT service, role of pharmacy, future developments, and respondents' views on improvements as well as best practices. Results: A total of 126 responses from 28 countries were included. Seventy-eight percent (78%) of the respondents stated that their facility provides antimicrobial therapy in the outpatient setting, whereas 22% did not. Forty-two percent (42%) of the hospitals with OPAT services had a specialized OPAT service, while 14% lacked specialized services and 22% had a partially specialized team in place. In facilities with a specialized OPAT service, the number of mandatory infectious disease (ID) consultations before discharge and clinical monitoring by an ID specialist or OPAT team member, the frequency of monitoring, and the availability of an OPAT registry were higher. A multidisciplinary team's presence was commonly noted as best practices. On the other hand, respondents experienced difficulties with reimbursement and lack of standardization in the screening, follow-up and monitoring of patients. Conclusion: This survey provides a better understanding of the implementation and practices of OPAT services globally and describes best practices and the challenges from different professionals.

Background: Outpatient parenteral antimicrobial therapy (OPAT) is defined as 'the administration of parenteral antimicrobial therapy in at least 2 doses on different days without intervening hospitalization'National and continental studies show a great proportion of unregulated OPAT services with the implementation of a specialized OPAT team varying extensively.Besides the perspectives of infectious disease specialists, the perspectives of other healthcare workers involved with OPAT is under investigated. Method: An electronic e-survey was conducted with questions about demographics, characteristics of OPAT service, the role of the pharmacy in OPAT, future developments and best-practices and challenges. Results: OPAT services have a high global adoption rate of 78%, however only 42% of healthcare facilities offer formal OPAT servicesFacilities with formal OPAT services have higher requirements for infectious disease consultation before discharge, clinical monitoring by an OPAT team member, monitoring frequency, and availability of an OPAT registryBest practices include a multidisciplinary OPAT team and the use of elastomer pumpsCommon challenges in OPAT involve reimbursement issues and lack of standardization in patient screening, follow-up, and monitoring. Conclusion: This is the first worldwide study exploring the implementation of OPAT services and perspectives of different professionals.

Best practices, implementation and challenges of outpatient parenteral antimicrobial therapy: results of a worldwide survey among healthcare providers.

The mysteries of target site concentrations of antibiotics in bone and joint infections: what is known? A narrative review.

INTRODUCTION: Currently, antibiotic treatment is often a standard dosing regimen in bone and joint infections (BJI). However, it remains unknown if exposure at the target-site is adequate. The aim of this review is to gain more insight in the relationship between the target site concentration of antibiotic and the minimal inhibitory concentration to target the bacteria in bone and joint infections (BJI). AREAS COVERED: A literature search was performed by Erasmus MC Medical library. Bone, bone tissue and synovial concentration of antibiotics were covered in humans. In addition, we reported number of patients, dose, sampling method, analytical method and tissue and plasma concentrations. We used the epidemiological cutoff value (ECOFF) values of the targeted micro-organisms. If more than 3 publications were available on the antibiotic, we graphically presented ECOFFS values against reported antibiotic concentrations. EXPERT OPINION: For most antibiotics, the literature is sparse. In addition, a lot of variable and total antibiotic concentrations are published. Ciprofloxacin, cefazolin, cefuroxime, vancomycin and linezolid seem to have adequate average exposure if correlating total concentration to ECOFF, when standard dosing is used. With regard to other antibiotics, results are inconclusive. More extensive pharmacokinetic/pharmacodynamic modeling in BJI is needed.

Timing of debridement, antibiotics, and implant retention (DAIR) for early post-surgical hip and knee prosthetic joint infection (PJI) does not affect 1-year re-revision rates: data from the Dutch Arthroplasty Register.

Debridement, antibiotics, and implant retention (DAIR) is a procedure to treat a periprosthetic joint infection (PJI) after total hip arthroplasty (THA) or total knee arthroplasty (TKA). The timing between the primary procedure and the DAIR is likely a determinant for its successful outcome. However, the optimal timing of a DAIR and the chance of success still remain unclear. We aimed to assess the risk of re-revision within 1 year after a DAIR procedure and to evaluate the timing of the DAIR in primary THA and TKA. We used data from the Dutch Arthroplasty Register (LROI) and selected all primary THA and TKA in the period 2007-2016 which underwent a DAIR within 12 weeks after primary procedure. A DAIR was defined as a revision for infection in which only modular parts were exchanged. A DAIR was defined as successful if not followed by a re-revision within 1 year after DAIR; 207 DAIRs were performed < 4  weeks after THA, of which 16 (8 %) received a complete revision within 1 year. DAIR procedures performed between 4 and 12 weeks ( n = 98 ) had a failure rate of 9 % ( n = 9 ). After TKA 126 DAIRs were performed in less than 4  weeks, of which 11 (9 %) received a complete revision within 1 year; 83 DAIRs were performed between 4 and 12 weeks, of which 14 (17 %) were revised. There was no significant difference in 1-year re-revision rate after a DAIR procedure by timing of the DAIR procedure for total hip and knee arthroplasty based on Dutch registry data.

First validation of the PASSPORT training environment for arthroscopic skills.

The demand for high quality care is in contrast to reduced training time for residents to develop arthroscopic skills. Thereto, simulators are introduced to train skills away from the operating room. In our clinic, a physical simulation environment to Practice Arthroscopic Surgical Skills for Perfect Operative Real-life Treatment (PASSPORT) is being developed. The PASSPORT concept consists of maintaining the normal arthroscopic equipment, replacing the human knee joint by a phantom, and integrating registration devices to provide performance feedback. The first prototype of the knee phantom allows inspection, treatment of menisci, irrigation, and limb stressing. PASSPORT was evaluated for face and construct validity. Construct validity was assessed by measuring the performance of two groups with different levels of arthroscopic experience (20 surgeons and 8 residents). Participants performed a navigation task five times on PASSPORT. Task times were recorded. Face validity was assessed by completion of a short questionnaire on the participants' impressions and comments for improvements. Construct validity was demonstrated as the surgeons (median task time 19.7 s [8.0-37.6]) were more efficient than the residents (55.2 s [27.9-96.6]) in task completion for each repetition (Mann-Whitney U test, P < 0.05). The prototype of the knee phantom sufficiently imitated limb outer appearance (79%), portal resistance (82%), and arthroscopic view (81%). Improvements are required for the stressing device and the material of cruciate ligaments. Our physical simulation environment (PASSPORT) demonstrates its potential to evolve as a training modality. In future, automated performance feedback is aimed for.

Novel metallic implantation technique for osteochondral defects of the medial talar dome. A cadaver study.

BACKGROUND AND PURPOSE: A metallic inlay implant (HemiCAP) with 15 offset sizes has been developed for the treatment of localized osteochondral defects of the medial talar dome. The aim of this study was to test the following hypotheses: (1) a matching offset size is available for each talus, (2) the prosthetic device can be reproducibly implanted slightly recessed in relation to the talar cartilage level, and (3) with this implantation level, excessive contact pressures on the opposite tibial cartilage are avoided. METHODS: The prosthetic device was implanted in 11 intact fresh-frozen human cadaver ankles, aiming its surface 0.5 mm below cartilage level. The implantation level was measured at 4 margins of each implant. Intraarticular contact pressures were measured before and after implantation, with compressive forces of 1,000-2,000 N and the ankle joint in plantigrade position, 10 dorsiflexion, and 14 plantar flexion. RESULTS: There was a matching offset size available for each specimen. The mean implantation level was 0.45 (SD 0.18) mm below the cartilage surface. The defect area accounted for a median of 3% (0.02-18) of the total ankle contact pressure before implantation. This was reduced to 0.1% (0.02-13) after prosthetic implantation. INTERPRETATION: These results suggest that the implant can be applied clinically in a safe way, with appropriate offset sizes for various talar domes and without excessive pressure on the opposite cartilage.

Soft tissue damage after minimally invasive THA.

BACKGROUND AND PURPOSE: Minimally invasive surgery (MIS) for hip replacement is thought to minimize soft tissue damage. We determined the damage caused by 4 different MIS approaches as compared to a conventional lateral transgluteal approach. METHODS: 5 surgeons each performed a total hip arthroplasty on 5 fresh frozen cadaver hips, using either a MIS anterior, MIS anterolateral, MIS 2-incision, MIS posterior, or lateral transgluteal approach. Postoperatively, the hips were dissected and muscle damage color-stained. We measured proportional muscle damage relative to the midsubstance cross-sectional surface area (MCSA) using computerized color detection. The integrity of external rotator muscles, nerves, and ligaments was assessed by direct observation. RESULTS: None of the other MIS approaches resulted in less gluteus medius muscle damage than the lateral transgluteal approach. However, the MIS anterior approach completely preserved the gluteus medius muscle in 4 cases while partial damage occurred in 1 case. Furthermore, the superior gluteal nerve was transected in 4 cases after a MIS anterolateral approach and in 1 after the lateral transgluteal approach. The lateral femoral cutaneous nerve was transected once after both the MIS anterior approach and the MIS 2-incision approach. INTERPRETATION: The MIS anterior approach may preserve the gluteus medius muscle during total hip arthroplasty, but with a risk of damaging the lateral femoral cutaneous nerve.

Time-action analysis (TAA) of the surgical technique implanting the collum femoris preserving (CFP) hip arthroplasty. TAASTIC trial identifying pitfalls during the learning curve of surgeons participating in a subsequent randomized controlled trial (an observational study).

BACKGROUND: Two types of methods are used to assess learning curves: outcome assessment and process assessment. Outcome measures are usually dichotomous rare events like complication rates and survival or require an extensive follow-up and are therefore often inadequate to monitor individual learning curves. Time-action analysis (TAA) is a tool to objectively determine the level of efficiency of individual steps of a surgical procedure. METHODS/DESIGN: We are currently using TAA to determine the number of cases needed for surgeons to reach proficiency with a new innovative hip implant prior to initiating a multicentre RCT. By analysing the unedited video recordings of the first 20 procedures of each surgeon the number and duration of the actions needed for a surgeon to achieve his goal and the efficiency of these actions is measured. We constructed a taxonomy or list of actions which together describe the complete surgical procedure. In the taxonomy we categorised the procedure in 5 different Goal Oriented Phases (GOP): 1. the incision phase. 2. the femoral phase. 3. the acetabulum phase. 4. the stem phase. 5. the closure pase. Each GOP was subdivided in Goal Oriented Actions (GOA) and each GOA is subdivided in Separate Actions (SA) thereby defining all the necessary actions to complete the procedure. We grouped the SAs into GOAs since it would not be feasible to measure each SA. Using the video recordings, the duration of each GOA was recorded as well as the amount of delay. Delay consists of repetitions, waiting and additional actions. The nett GOA time is the total GOA time - delay and is a representation of the level of difficulty of each procedure. Efficiency is the percentage of nett GOA time during each procedure. DISCUSSION: This allows the construction of individual learning curves, assessment of the final skill level for each surgeon and comparison of different surgeons prior to participation in an RCT. We believe an objective and comparable assessment of skill level by process assessment can improve the value of a surgical RCT in situations where a learning curve is expected.

Perforation of the ileum after a stab wound of the gluteal region: a case report.

We present a case of a patient with a seemingly insignificant single gluteal stab wound which led to a solitary perforation of the ileum and delayed peritonitis. This case report illustrates that, despite the absence of any signs of bowel perforation on presentation, a patient may deteriorate gradually in the subsequent hours. This demonstrates the role of clinical observation in high risk gluteal stab wound patients.

Is statistical significance clinically important?--A guide to judge the clinical relevance of study findings.

In this paper we describe several issues that influence the reporting of statistical significance in relation to clinical importance, since misinterpretation of p values is a common issue in orthopaedic literature. Orthopaedic research is tormented by the risks of false-positive (type I error) and false-negative (type II error) inferences, due to multiple testing and small sample sizes. Strict vigilance is required for interpretation of results and their accompanying p values to determine whether the results are of any clinical importance. To prevent type I and type II errors, primary and secondary outcome measures should be clearly defined and a sample size calculation should be performed on solely the primary outcome parameter. Analysis of multiple secondary outcome measures requires an adjusted significance level (e.g., Bonferroni correction). Prior to the sample size calculation, the minimal clinically important difference of the primary outcome measure has to be assessed in order to reveal a power that is required to achieve clinically important inferences. However, not only the treatment effect, but multiple factors such as the choice of the study population, follow-up duration, outcome measures, and the design of a study will eventually determine the clinical importance of the results.

Design considerations in implant-related randomized trials.

Implant-related research is particularly prone to produce biased results. Despite a common commitment to evidence-based principles (EBM) principles in current literature, a gap remains between the existing available evidence and its actual implementation in orthopaedic clinical practice. Knowledge of basic principles of implant related trial design is a prerequisite for critical appraisal of the value of scientific evidence and thereby the degree of uncertainty. This article discusses how the quality of implant-related randomized controlled trials (RCT) can be affected by the level of expertise, the choice of outcome measures, the allocation procedure, and the method of blinding. Taking these issues into consideration in the design of an implant-related study improves the value of the study, thereby achieving an unbiased assessment of the safety and efficacy of an innovative implant prior to its widespread implementation in daily health care.

Better early functional outcome after short stem total hip arthroplasty? A prospective blinded randomised controlled multicentre trial comparing the Collum Femoris Preserving stem with a Zweymuller straight cementless stem total hip replacement for the treatment of primary osteoarthritis of the hip.

OBJECTIVES: Primary aim was to compare the functional results at 3 months and 2 years between short and conventional cementless stem total hip arthroplasty (THA). Secondary aim was to determine the feasibility of a double-blind implant-related trial. DESIGN: A prospective blinded randomised controlled multicentre trial in patients with osteoarthritis of the hip. All patients, research assistants, clinical assessors, investigators and data analysts were blinded to the type of prosthesis. POPULATION: 150 patients between 18 and 70 years with osteoarthritis of the hip, 75 in the short stem and 75 in the conventional stem group. Mean age: 60 years (SD 7). INTERVENTIONS: the Collum Femoris Preserving short stem versus the Zweymuller Alloclassic conventional stem. MAIN OUTCOME MEASURES: The Dutch version of the Hip Disability and Osteoarthritis Outcome Score (HOOS). Secondary outcomes measures: Harris Hip Score, the Physical Component Scale of the SF12, the Timed Up and Go test, Pain and the EQ-5D. Feasibility outcomes: continued blinding, protocol adherence and follow-up success rate. RESULTS: No significant difference between the two groups. Mean HOOS total score in the short stem group increased 32.7 points from 36.6 (95% CI 32.9 to 40.2) preoperatively to 69.3 (95% CI 66.4 to 72.1) at 3 months follow-up. Mean HOOS total score in the conventional straight stem group increased 36.3 points from 37.1 (95% CI 33.9 to 40.3) preoperatively to 73.4 (95% CI 70.3 to 76.4) at 3 months follow-up. 91.2% of patients remained blinded at 2 years follow-up. Both protocol adherence and follow-up success rate were 98%. CONCLUSIONS: Functional result at 3 months and 2 years after short stem THA is not superior to conventional cementless THA. There were more perioperative and postoperative complications in the short stem group. Direct comparison of two hip implants in a double-blinded randomised controlled trial is feasible. TRIAL REGISTRATION NUMBER: NTR1560.