Kaplan-Meier and Cox Regression Are Preferable for the Analysis of Time to Revision of Joint Arthroplasty: Thirty-One Years of Follow-up for Cemented and Uncemented THAs Inserted from 1987 to 2000 in the Norwegian Arthroplasty Register

Background: Previous studies have suggested that the probability function of 1 minus the Kaplan-Meier survivorship overestimates revision rates of implants and that patient death should be included in estimates as a competing risk factor. The present study aims to demonstrate that this line of thinking is incorrect and is a misunderstanding of both the Kaplan-Meier method and competing risks. Methods: This study demonstrated the differences, misunderstandings, and interpretations of classical, competing-risk, and illness-death models with use of data from the Norwegian Arthroplasty Register for 15,734 cemented and 7,867 uncemented total hip arthroplasties (THAs) performed from 1987 to 2000, with fixation as the exposure variable. Results: The mean age was higher for patients who underwent cemented (72 years) versus uncemented THA (53 years); as such, a greater proportion of patients who underwent cemented THA had died during the time of the study (47% compared with 29%). The risk of revision at 20 years was 18% for cemented and 42% for uncemented THAs. The cumulative incidence function at 20 years was 11% for cemented and 36% for uncemented THAs. The prevalence of revision at 20 years was 6% for cemented and 31% for uncemented THAs. Conclusions: Adding death as a competing risk will always attenuate the probability of revision and does not correct for dependency between patient death and THA revision. Adjustment for age and sex almost eliminated differences in risk estimates between the different regression models. In the analysis of time until revision of joint replacements, classical survival analyses are appropriate and should be advocated.publishedVersio

Identifisering av koevolusjon mellom klasse IIa bakterieosin og deres immunitetsprotein

Class IIa bacteriocins are Antimicrobial peptides found in many lactic acid bacteria. Here they serve as a weapon against competing bacteria by causing cell leakage through pore-formation in the membrane. An immunity protein is produced along with the bacteriocins, which confers immunity for the producer, while foreign bacteria remain susceptible. We hypothesise that these two proteins have coevolved. To test this, we have gathered hundreds of bacteriocin and immunity protein sequences through an iterative genome-mining procedure using HMMER3. We then extract two subsets of the results and apply two forms of MirrorTree methods to each set. A technique was devised to investigate which regions of the bacteriocin correlated the highest with the immunity protein by cropping the bacteriocin from either end. Lastly, we perform a PCA on both datasets as an explorative measure. The iterative genome mining procedure revealed 59 class IIa bacteriocin-carrying species after filtering, several of which are new additions to the already known bacteriocin producers. Both the conventional MirrorTree method and the pMirrorTree method showed high levels of coevolution between the sequences, and the set consisting of 16 species in the Streptococcus genus showed a very significant coevolution, while the set consisting of sequences from E. faecium and E. faecalis failed to show significant coevolution through the pMirrortree method. The results from the cropping method indicates that the C-terminal half of the bacteriocins hold more influence on the coevolution than the N-terminal half. Lastly, the PCA showed that the bacteriocin and immunity protein were highly correlated in both sets, and interestingly it showed that the bacteriocin and immunity protein in the Enterococcus set did not follow the same evolutionary pattern as more conserved sequences did. We conclude that the class IIa bacteriocins and immunity proteins are coevolved.Klasse IIa bakteriosiner er antimikrobielle peptider som finnes i mange melkesyrebakterier. De opererer som vpen mot konkurrerende bakterier ved forrsake cellelekkasje gjennom porefor- masjon i membranen. Et immunitetsprotein produseres sammen med bakteriosinene, som gjr produsenten immun mot bakteriosinet, en luksus de fremmede bakteriene ikke fr ta del av. Hypotesen som testes er om bakteriosinet og immunitets proteinet er koevolverte. For teste dette har vi samlet hundrevis av bakteriocin- og immunitetsproteinsekvenser gjennom en iterativ genomscan prosedyre ved bruk av HMMER3. Vi trekker deretter ut to sett med bakteriosiner fra resultatene og bruker to former for MirrorTree-metoder for beregne korrelasjon, og dermed koevolusjon. En teknikk ble utformet for underske hvilke regioner av bakteriosinet som korrel- erte hyest med immunitetsproteinet ved trimme aminosyrer fra hver ende av bacteriosinet. Til slutt utfrer vi en PCA p begge datasettene som et eksplorativt tiltak. Den iterative genomscan prosedyren avslrte 59 klasse IIa bakteriosinbrende arter etter filtrering, hvorav flere er nye treff til de allerede kjente bakteriosinprodusentene. Bde den konvensjonelle MirrorTree-metoden og pMirrorTree-metoden viste hye niver av ko- evolusjon mellom sekvensene, og settet bestende av 16 arter i Streptococcus-slekten viste en meget signifikant koevolusjon, mens settet bestende av sekvenser fra E. faecium og E. faecalis mislyktes med vise signifikant koevolusjon gjennom pMirrortree-metoden. Resultatene fra trimmemetoden indikerer at den C-terminale halvparten av bakteriosinet har strre innflytelse p koevolusjonen enn den N-terminale halvparten. Til slutt viste PCA at bakteriosin- og immunitetsproteinet var sterkt korrelert i begge settene, og spesifikt i Enterococcus-settet viste det at bakteriocin- og immunitetsproteinet ikke fulgte det samme evolusjonre mnsteret som mer konserverte sekvenser gjorde. Vi konkluderer med at klasse IIa bakteriociner og immunitetsproteiner er koevolverte.submittedVersionM-BIA

Promoting cemented fixation of the femoral stem in elderly female hip arthroplasty patients and elderly hip fracture patients: a retrospective cohort study from the Norwegian Arthroplasty Register and the Norwegian Hip Fracture Register

Background and purpose: Uncemented stems increase the risk of revision in elderly patients. In 2018, we initiated a national quality improvement project aiming to increase the proportion of cemented stems in elderly female total hip arthroplasty (THA) and hip fracture hemiarthroplasty (HA) patients. We aimed to evaluate the association of this project on the frequency of cemented stems and the risk of secondary procedures in the targeted population. Methods: 10,815 THAs in female patients ≥ 75 years in the Norwegian Arthroplasty Register and 19,017 HAs in hip fracture patients ≥ 70 years in the Norwegian Hip Fracture Register performed in 2015–2017 and 2019–2021 at all Norwegian hospitals were included in this retrospective cohort study. The quality improvement project was implemented at 19 hospitals (8,443 patients). 1-year revision risk (THAs) and reoperation risk (HAs) were calculated for uncemented and cemented stems by Kaplan–Meier and Cox adjusted hazard rate ratios (aHRRs) with all-cause revision/reoperation as main endpoint. Results: The use of cemented stem fixation in the targeted population increased from 26% to 80% for THAs and from 27% to 91% for HAs. For THAs, the 1-year revision rate decreased from 3.7% in 2015–2017 to 2.1% in 2019–2021 (aHRR 0.7, 95% confidence interval [CI] 0.5–0.9) at the intervention hospitals. For HAs, the reoperation rate decreased from 5.9% in 2015–2017 to 3.3% in 2019–2021 (aHRR 0.6, CI 0.4–0.8) at the intervention hospitals. Conclusion: The quality improvement project resulted in a significant increase in the proportion of cemented stems and reduced risk of secondary procedures for both THAs and HAs

Risk of total hip arthroplasty after elite sport: linking 3304 former world-class athletes with the Norwegian Arthroplasty Register

Objectives: At present, there is no cure for osteoarthritis (OA), but severe hip joint degeneration can require total hip arthroplasty (THA). The literature on OA after elite sport is limited. We hypothesise that elite athletic activity increases the risk of receiving a THA later in life. Methods: We linked a cohort of former Norwegian world-class athletes (1402 females and 1902 males, active 1936–2006) to the Norwegian Arthroplasty Register (THA performed 1987–2020). We used standardised incidence ratio (SIR), one-minus Kaplan-Meier and relative Cox regression (relative HR, RHR), with 95% CIs, and funnel plots at age 75, to assess THA risk for different sport disciplines, joint impact categories of sport disciplines and sex. The risk of THA for the corresponding general Norwegian population was used as reference. Results: We found an overall increased risk for THA for the former elite athletes (SIR 2.11, 95% CI 1.82 to 2.40) at age 75 years, compared with the general population. THA risk at age 75 years was 11.6% for female athletes and 8.3% for male athletes. SIR was 1.90 (95% CI 1.49 to 2.31) for female and 2.28 (95% CI 1.87 to 2.70) for male athletes. Among males, high joint impact sport disciplines were associated with increased risk compared with low-impact sport disciplines (RHR 1.81, 95% CI 1.06 to 3.08, p=0.029). Conclusion: Having been an elite athlete was associated with a doubling of THA risk compared with the general population for both sexes. High joint impact sport disciplines were associated with subsequent THA for male athletes.publishedVersio

Kaplan-Meier and Cox Regression Are Preferable for the Analysis of Time to Revision of Joint Arthroplasty: Thirty-One Years of Follow-up for Cemented and Uncemented THAs Inserted from 1987 to 2000 in the Norwegian Arthroplasty Register

Background: Previous studies have suggested that the probability function of 1 minus the Kaplan-Meier survivorship overestimates revision rates of implants and that patient death should be included in estimates as a competing risk factor. The present study aims to demonstrate that this line of thinking is incorrect and is a misunderstanding of both the Kaplan-Meier method and competing risks. Methods: This study demonstrated the differences, misunderstandings, and interpretations of classical, competing-risk, and illness-death models with use of data from the Norwegian Arthroplasty Register for 15,734 cemented and 7,867 uncemented total hip arthroplasties (THAs) performed from 1987 to 2000, with fixation as the exposure variable. Results: The mean age was higher for patients who underwent cemented (72 years) versus uncemented THA (53 years); as such, a greater proportion of patients who underwent cemented THA had died during the time of the study (47% compared with 29%). The risk of revision at 20 years was 18% for cemented and 42% for uncemented THAs. The cumulative incidence function at 20 years was 11% for cemented and 36% for uncemented THAs. The prevalence of revision at 20 years was 6% for cemented and 31% for uncemented THAs. Conclusions: Adding death as a competing risk will always attenuate the probability of revision and does not correct for dependency between patient death and THA revision. Adjustment for age and sex almost eliminated differences in risk estimates between the different regression models. In the analysis of time until revision of joint replacements, classical survival analyses are appropriate and should be advocated

The Clinical Presentation of Endometriosis and Its Association to Current Surgical Staging

(1) Despite its high prevalence, the diagnostic delay of endometriosis is still estimated to be about 7 years. The objective of the present study is to understand the symptomatology of endometriosis in patients across various countries and to assess whether the severity of symptoms correlates with the diagnosed stage of disease. (2) An international online survey collected self-reported responses from 2964 participants from 59 countries. Finalization of the questionnaire and its distribution was achieved by cooperation with various organizations and centers around the globe. (3) Chronic pain presentation remarkably increased between Stage 1 and 2 (16.2% and 32.2%, respectively). The prevalence of pain only around and during menstruation was negatively correlated to the stage, presenting with 15.4% and 6.9% in Stages 1 and 4, respectively. Atypical presentation of pain was most commonly reported in stage 4 (11.4%). Pain related solely to triggering factors was the most uncommon presentation of pain (3.2%). (4) Characteristics of pain and quality of life tend to differ depending on the reported stage of the endometriosis. Further research may allow a better stage estimation and identification of patients with alarming symptomatic presentation indicative of a progressive stage, even those that are not yet laparoscopically diagnosed