Erik Bülow

A Diagnostic Algorithm to Identify Paired Tumors with Clonal Origin

Despite practical implications we still lack standardized methods for clonality testing of tumor pairs. Each tumor is characterized by a set of chromosomal abnormalities, nonrandom changes preferentially involving specific chromosomes and chromosomal regions. Although tumors accumulate chromosomal abnormalities during their development, the majority of these alterations is specific and characteristic for each individual tumor is not exhibited at the population level. Assumingly, secondary tumors that develop from disseminated cells from the primary tumor inherit not only chromosomal changes specific for the cancerous process but also random chromosomal changes that accumulate during tumor development. Based on this assumption, we adopted an intuitive index for genomic similarities of paired tumors, which ranges between zero (completely different genomic profiles) and one (identical genomic profiles). To test the assumption that two tumors have clonal origins if they share a higher degree of genomic similarity than two randomly paired tumors, we built a permutation‐based null‐hypothesis procedure. The procedure is demonstrated using two publicly available data sets. The article highlights the complexities of clonality testing and aims to offer an easy to follow blueprint that will allow researchers to test genomic similarities of paired tumors, with the proposed index or any other index that fits their need.

Trends in hip replacements between 1999 and 2012 in Sweden

National Registers document changes in the circumstance, practice, and outcome of surgery with the passage of time. In the context of total hip replacement (THR), registers can help elucidate the relevant factors that affect the clinical outcome. We evaluated the evolution of factors related to patient, surgical procedure, socio‐economy, and various outcome parameters after merging databases of the Swedish Hip Arthroplasty Register, Statistics Sweden and the National Board of Health and Welfare. Data on 193,253 THRs (164,113 patients) operated between 1999 and 2012 were merged. We studied the evolution of surgical volume, patient demographics, socio‐economic factors, surgical factors, length‐of‐stay, mortality rate, adverse events, re‐operation and revision rates, and Patient Reported Outcome Measures (PROMs). Throughout this time period the majority of patients were operated on with a diagnosis of primary osteoarthritis. Comorbidity indices increased each year observed. The share of all‐cemented implants has dropped from 92% to 68%. More than 88% of the bearings were metal‐on‐polyethylene. Length‐of‐stay decreased by 50%. There was a reduction in 30‐ and 90‐day mortality. Re‐operation and revision rates at 2 years are decreasing. The post‐operative PROMs improved despite the observation of worse pre‐operative pain scores getting over time. The demographics of patients receiving a THR, their comorbidities, and their primary diagnosis are changing. Notwithstanding these changes, outcomes like mortality, re‐operations, revisions, and PROMs have improved. The practice of hip arthroplasty has evolved, even in a country such as Sweden that is considered to be conservative with regard taking on new surgical practices.

Comorbidity does not predict long-term mortality after total hip arthroplasty

Background and purpose — In-hospital death following total hip arthroplasty (THA) is related to comorbidity. The long-term effect of comorbidity on all-cause mortality is, however, unknown for this group of patients and it was investigated in this study. Patients and methods — We used data from the Swedish Hip Arthroplasty Register, linked to the National Patient Register from the National Board of Health and Welfare, for patients operated on with THA in 1999–2012. We identified 120,836 THAs that could be included in the study. We evaluated the predictive power of the Charlson and Elixhauser comorbidity indices on mortality, using concordance indices calculated after 5, 8, and 14 years after THA. Results — All comorbidity indices performed poorly as predictors, in fact worse than a base model with age and sex only. Elixhauser was, however, the least bad choice and it predicted mortality with concordance indices 0.59, 0.58, and 0.56 for 5, 8, and 14 years after THA. Interpretation — Comorbidity indices are poor predictors of long-term mortality after THA.

Patients with a previous total hip replacement experience less reduction of back pain following lumbar back surgery: TOTAL HIP REPLACEMENT PRIOR TO LUMBAR SPINE SURGERY

The coexistence of degenerative disorders from the hip joint and the lumbar spine, known as “the hip‐spine syndrome,” is a common encounter in clinical practice. These degenerative conditions may cause similar symptoms which often entail diagnostic challenges in determining the origin of pain. Lumbar back surgery (LBS) with fusion and/or decompression, and total hip replacement (THR) are both often successful interventions. However, the knowledge is limited about the post‐operative patient‐reported outcome (PRO) following LBS in the presence of a prior THR. The aims of this study were to compare 1‐year post‐operative patient‐reported outcome measures (PROMs) following lumbar back surgery (LBS) in patients with and without a prior total hip replacement (THR). Data from Swespine and the Swedish Hip Arthroplasty Register were linked in order to identify the study group of patients with THR prior to LBS. The study group (n = 220) and a matched control group (n = 220) with isolated LBS was defined by using a step‐wise selection process. Linear‐ and logistic regression analyses adjusted for age, sex and pre‐operative PROMs demonstrated that THR prior to LBS was associated with worse back‐pain (VAS) at 1‐year follow‐up (B = 5.3, 95%CI: 0.3;10.3). However, previous THR did not influence the EQ‐5D index (B = 0.01, 95%CI: −0.05;0.06), EQ VAS (B = −3.0, 95%CI: −6.9;1.0), leg pain (B = 1.5, 95%CI: −4.0;7.0), Oswestry Disability Index (B = 2.6, 95%CI: −0.5;5.6) or satisfaction (OR = 1.1, 97.5%CI 0.7;1.6). This knowledge is important to communicate prior to LBS in order to set proper expectations on surgical outcomes.

Risk of further surgery on the same or opposite side and mortality after primary total hip arthroplasty: A multi-state analysis of 133,654 patients from the Swedish Hip Arthroplasty Register

Background and purpose — The hip-related timeline of patients following a total hip arthroplasty (THA) can vary. Ideally patients will live their life without need for further surgery; however, some will undergo replacement on the contralateral hip and/or reoperations. We analyzed the probability of mortality and further hip-related surgery on the same or contralateral hip. Patients and methods — We performed a multi-state survival analysis on a prospectively followed cohort of 133,654 Swedish patients undergoing an elective THA between 1999 and 2012. The study used longitudinally collected information from the Swedish Hip Arthroplasty Register and administrative databases. The analysis considered the patients’ sex, age, prosthesis type, surgical approach, diagnosis, comorbidities, education, and civil status. Results — During the study period patients were twice as likely to have their contralateral hip replaced than to die. However, with passing time, probabilities converged and for a patient who only had 1 non-revised THA at 10 years, there was an equal chance of receiving a second THA and dying (24%). It was 8 times more likely that the second hip would become operated with a primary THA than that the first hip would be revised. Multivariable regression analysis reinforced the influence of age at operation, sex, diagnosis, comorbidity, and socioeconomic status influencing state transition. Interpretation — Multi-state analysis can provide a comprehensive model of further states and transition probabilities after an elective THA. Information regarding the lifetime risk for bilateral surgery, revision, and death can be of value when discussing the future possible outcomes with patients, in healthcare planning, and for the healthcare economy.

No increase in readmissions or adverse events after implementation of fast-track program in total hip and knee replacement at 8 Swedish hospitals: An observational before-and-after study of 14,148 total joint replacements 2011–2015

Background and purpose — Fast-track care programs in elective total hip and knee replacement (THR/TKR) have been introduced in several countries during the last decade resulting in a significant reduction of hospital stay without any rise in readmissions or early adverse events (AE). We evaluated the risk of readmissions and AE within 30 and 90 days after surgery when a fast-track program was introduced in routine care of joint replacement at 8 Swedish hospitals. Patients and methods — Fast-track care programs were introduced at 8 public hospitals in Västra Götaland region from 2012 to 2014. We obtained data from the Swedish Hip and Knee Arthroplasty Registers for patients operated with THR and TKR in 2011–2015. All readmissions and new contacts with the health care system within 3 months with a possible connection to the surgical intervention were requested from the regional patient register. We compared patients operated before and after the introduction of the fast-track program. Results — Implementation of the fast-track program resulted in a decrease in median hospital length of stay (LOS) from 5 to 3 days in both THR and TKR. The total readmission rate <90 days for THR was 7.2% with fast-track compared with 6.7% in the previous program, and for TKR 8.4% in both groups. Almost half of the readmissions occurred without any AE identified. There was no statistically significant difference concerning readmissions or AE when comparing the programs. Interpretation — Implementation of a fast-track care program in routine care of elective hip and knee replacement is effective in reducing hospital stay without increasing the risk of readmissions or adverse events within 90 days after surgery.