Direction- and Angle-Assisted Buttonhole Cannulation of Arteriovenous Fistula in Hemodialysis Patients: A Multicenter Randomized Controlled Trial

Rationale & objective: Arteriovenous fistula cannulation with the buttonhole technique is often preferred by patients but has been associated with an increased infection risk. Guidelines disagree on whether it should be abandoned, thus we assessed a technologically simple method to facilitate gentler arteriovenous fistula cannulation with potentially less discomfort and damage to the epithelial lining of the buttonhole tract. Study design: 8-week, prospective, open-label, randomized controlled trial. Setting & participants: Patients with buttonhole tracts receiving hemodialysis at 7 dialysis centers in Norway were randomized to the intervention group (43 patients, 658 cannulations) or control group (40 patients, 611 cannulations). Intervention: Direction and angle of the established buttonhole tract were marked on the forearm skin in the intervention group, whereas the control group had no structured cannulation information system. Outcomes: The primary outcome was successful cannulation, defined as correct placement of both blunt needles at the first attempt without needing to change needles, perform extra perforations, or reposition the needle. The secondary outcomes were patient-reported difficulty of cannulation (verbal rating scale: 1 = very easy, 6 = impossible) and intensity of pain (numeric rating scale: 0 = no pain, 10 = unbearable pain). Results: After a 2-week run-in period, successful cannulation was achieved in 73.9% and 74.8% of the patients in the intervention and control groups, respectively (relative risk [RR], 0.99; 95% CI, 0.87-1.12; P = 0.85). However, the probability of a difficult arterial cannulation (verbal rating scale, 3-6) was significantly lower in the intervention group (RR, 0.69; 95% CI, 0.55-0.85; P = 0.001). There were no improvements for venous cannulations. Furthermore, the probability of a painful cannulation (numeric rating scale, 3-10) was lower in the intervention group (RR, 0.72; 95% CI, 0.51-1.02; P = 0.06). Limitations: Unable to evaluate hard end points such as infections and thrombosis owing to the small sample size. Conclusions: Marking direction and angle of cannulation did not improve cannulation success rates; however, patients more often reported an unproblematic procedure and less pain. Funding: None. Trial registration: ClinicalTrials.gov (NCT01536548).publishedVersio

Hypertensive nephrosclerosis: wider kidney biopsy indications may be needed to improve diagnostics

Background Hypertensive nephrosclerosis is the presumed underlying cause in many end‐stage kidney disease (ESKD) patients, but the diagnosis is disputed and based on clinical criteria with low diagnostic accuracy. Objective To evaluate and improve the diagnostic process for nephrosclerosis patients. Methods We included adults from the population‐based HUNT study (n = 50 552), Norwegian CKD patients referred for kidney biopsy 1988–2012 (n = 7261), and unselected nephrology clinic patients (n = 193) used for matching. Decision tree analysis and ROC curve‐based methods of optimal cut‐offs were used to improve clinical nephrosclerosis criteria. Results Nephrosclerosis prevalence was 2.7% in the general population, and eGFR decline and risk for kidney‐related hospital admissions and ESKD were comparable to patients with diabetic kidney disease. In the biopsy cohort, current clinical criteria had very low sensitivity (0.13) but high specificity (0.94) for biopsy‐verified arterionephrosclerosis. A new optimized diagnostic algorithm based on proteinuria (155 mm Hg) and age (>75 years) only marginally improved diagnostic accuracy (sensitivity 0.19, specificity 0.96). Likewise, there were still false‐positive cases with treatable diagnoses like glomerulonephritis, interstitial nephritis and others (40% of all test positive). Decision curve analysis showed that the new criteria can lead to higher clinical utility, especially for patients considering the potential harms to be close to the potential benefits, while the more risk‐tolerant ones (harm:benefit ratio < 1:4) should consider kidney biopsy. Conclusion Further improvements of the current clinical criteria seem difficult, so risks and benefits of kidney biopsy could be more actively discussed with selected patients to reduce misclassification and direct treatment.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.publishedVersio

Perioperative, short, and long-term mortality related to fixation in primary total hip arthroplasty: a study of 79,557 patients in the Norwegian Arthroplasty Register

Background and purpose — There are reports on perioperative deaths in cemented total hip arthroplasty (THA), and THA revisions are associated with increased mortality. We compared perioperative (intraoperatively or within 3 days of surgery), short-term and long-term mortality after all-cemented, all-uncemented, reverse hybrid (cemented cup and uncemented stem), and hybrid (uncemented cup and cemented stem) THAs. Patients and methods — We studied THA patients in the Norwegian Arthroplasty Register from 2005 to 2018, and performed Kaplan–Meier and Cox survival analyses with time of death as end-point. Mortality was calculated for all patients, and in 3 defined risk groups: high-risk patients (age ≥ 75 years and ASA > 2), intermediate-risk patients (age ≥ 75 years or ASA > 2), low-risk patients (age < 75 years and ASA ≤ 2). We also calculated mortality in patients with THA due to a hip fracture, and in patients with commonly used, contemporary, well-documented THAs. Adjustement was made for age, sex, ASA class, indication, and year of surgery. Results — Among the 79,557 included primary THA patients, 11,693 (15%) died after 5.8 (0–14) years’ follow-up. Perioperative deaths were rare (30/105) and found in all fixation groups. Perioperative mortality after THA was 4/105 in low-risk patients, 34/105 in intermediate-risk patients, and 190/105 in high-risk patients. High-risk patients had 9 (CI 1.3–58) times adjusted risk of perioperative death compared with low-risk patients. All 4 modes of fixation had similar adjusted 3-day, 30-day, 90-day, 3–30 day, 30–90 day, 90-day–10-year, and 10-year mortality risk. Interpretation — Perioperative, short-term, and long-term mortality after primary THA were similar, regardless of fixation type. Perioperative deaths were rare and associated with age and comorbidity, and not type of fixation.publishedVersio

Fixation, sex, and age: highest risk of revision for uncemented stems in elderly women - data from 66,995 primary total hip arthroplasties in the Norwegian Arthroplasty Register

Background and purpose: There is no consensus on best method of fixation in hip arthroplasty. We investigated different modes of fixation in primary total hip arthroplasty (THA) and the influence of age and sex, to assess need for a differentiated approach. Patients and methods: The study was based on data from the Norwegian Arthroplasty Register in the period 2005–2017. Included were all-cemented, all-uncemented, reverse hybrid (uncemented stem and cemented cup), and hybrid (cemented stem and uncemented cup) THA designs that were commonly used, contemporary and well documented, using different causes of revision as endpoints. Results: From the included 66,995 primary THAs, 2,242 (3.3%) were revised. Compared with all-cemented THAs, all-uncemented had a higher risk of revision due to any cause (RR 1.4; CI 1.2–1.6), mainly due to an increased risk of periprosthetic fracture (RR 5.2; CI 3.2–8.5) and dislocation (RR 2.2; CI 1.5–3.0). Women had considerably higher risk of revision due to periprosthetic fracture after all-uncemented THA (RR 12; CI 6–25), compared with cemented. All-uncemented THAs in women of age 55–75 years (RR 1.3; CI 1.0–1.7) and over 75 years of age (RR 1.8; CI 1.2–2.7), and reverse hybrid THAs in women over the age of 75 (RR 1.5; CI 1.1–1.9) had higher risk of revision compared with cemented. Hybrid THAs (RR 1.0; CI 0.9–1.2) and reverse hybrid THAs (RR 1.0; CI 0.7–1.3) had similar risk of revision due to any cause as cemented THAs. Interpretation: Uncemented stems (all-uncemented and reverse hybrid THAs) had increased risk of revision in women over 55 years of age, mainly due to periprosthetic fracture and dislocation, and should probably not be used in THA in these patients.publishedVersio

Risk factors for revision surgery due to dislocation within 1 year after 111,711 primary total hip arthroplasties from 2005 to 2019: a study from the Norwegian Arthroplasty Register

Background and purpose: Dislocation of a hip prosthesis is the 3rd most frequent cause (after loosening and infection) for hip revision in Norway. Recently there has been a shift in surgical practice including preferred head size, surgical approach, articulation, and fixation. We explored factors associated with the risk of revision due to dislocation within 1 year and analyzed the impact of changes in surgical practice. Patients and methods: 111,711 cases of primary total hip arthroplasty (THA) from the Norwegian Arthroplasty Register were included (2005-2019) after primary THA with either 28 mm, 32 mm, or 36 mm femoral heads, or dualmobility articulations. A flexible parametric survival model was used to calculate hazard ratios for risk factors. Kaplan-Meier survival rates were calculated. Results: There was an increased risk of revision due to dislocation with 28 mm femoral heads (HR 2.6, 95% CI 2.0-3.3) compared with 32 mm heads. Furthermore, there was a reduced risk of cemented fixation (HR 0.6, CI 0.5-0.8) and reverse hybrid (HR 0.6, CI 0.5-0.8) compared with uncemented. Also, both anterolateral (HR 0.5, CI 0.4-0.7) and lateral (HR 0.6, CI 0.5-0.7) approaches were associated with a reduced risk compared with the posterior approach. The time-period 2010-2014 had the lowest risk of revision due to dislocation. The trend during the study period was towards using larger head sizes, a posterior approach, and uncemented fixation for primary THA. Interpretation: Patients with 28 mm head size, a posterior approach, or uncemented fixation had an increased risk of revision due to dislocation within 1 year after primary THA. The shift from lateral to posterior approach and more uncemented fixation was a plausible explanation for the increased risk of revision due to dislocation observed in the most recent time-period. The increased risk of revision due to dislocation was not fully compensated for by increasing femoral head size from 28 to 32 mm.publishedVersio

No difference in risk of revision due to infection between clindamycin and cephalosporins as antibiotic prophylaxis in cemented primary total knee replacements: a report from the Norwegian Arthroplasty Register 2005–2020

Background and purpose: Systemic antibiotic prophylaxis with clindamycin, which is often used in penicillin- or cephalosporin-allergic patients’, has been associated with a higher risk of surgical revision for deep prosthetic joint infection (PJI) than cloxacillin in primary total knee replacement (TKR). We aimed to investigate whether clindamycin increases the risk of surgical revisions due to PJI compared with cephalosporins in primary cemented TKR. Patients and methods: Data from 59,081 TKRs in the Norwegian Arthroplasty Register (NAR) 2005–2020 was included. 2,655 (5%) received clindamycin and 56,426 (95%) received cephalosporins. Cox regression analyses were performed with adjustment for sex, age groups, diagnosis, and ASA score. Survival times were calculated using Kaplan–Meier estimates and compared using Cox regression with revision for PJI as endpoint. The cephalosporins cefalotin and cefazolin were also compared. Results: Of the TKRs included, 1.3% (n = 743) were revised for PJI. 96% (n = 713) had received cephalosporins and 4% (n = 30) clindamycin for perioperative prophylaxis. Comparing cephalosporins (reference) and clindamycin, at 3-month follow-up the adjusted hazard ratio rate (HRR) for PJI was 0.7 (95% confidence interval [CI] 0.4–1.4), at 1 year 0.9 (CI 0.6–1.5), and at 5 years 0.9 (CI 0.6–1.4). Analysis using propensity score matching showed similar results. Furthermore, comparing cefalotin (reference) and cefazolin, HRR was 1.0 (CI 0.8–1.4) at 3 months and 1.0 (CI 0.7–1.3) at 1-year follow-up. Conclusion: We found no difference in risk of revision for PJI when using clindamycin compared with cephalosporins in primary cemented TKRs. It appears safe to continue the use of clindamycin in penicillin- or cephalosporin-allergic patients.publishedVersio

Association of Mild to Moderate Chronic Kidney Disease With Venous Thromboembolism Pooled Analysis of Five Prospective General Population Cohorts

BACKGROUND: Recent findings suggest that chronic kidney disease (CKD) may be associated with increased risk of venous thromboembolism (VTE). Given the high prevalence of mild-to-moderate CKD in the general population, in depth analysis of this association is warranted. METHODS AND RESULTS: We pooled individual participant data from five community-based cohorts from Europe (HUNT2, PREVEND and Tromsø study) and United States (ARIC and CHS study) to assess the association of estimated glomerular filtration rate (eGFR), albuminuria and CKD with objectively verified VTE. To estimate adjusted hazard ratios (HRs) for VTE, categorical and continuous spline models were fit using Cox regression with shared-frailty or random-effect meta-analysis. A total of 1,178 VTE events occurred over 599,453 person-years follow-up. Relative to eGFR 100 mL/min/1.73m(2), HRs for VTE were 1.29 (95%CI, 1.04-1.59) for eGFR 75, 1.31 (1.00-1.71) for 60, 1.82 (1.27-2.60) for 45 and 1.95 (1.26-3.01) for 30 mL/min/1.73m(2). Compared with albumin-creatinine ratio (ACR) of 5.0 mg/g, the HRs for VTE were 1.34 (1.04-1.72) for 30 mg/g, 1.60 (1.08-2.36) for 300 mg/g and 1.92 (1.19-3.09) for 1000 mg/g. There was no interaction between clinical categories of eGFR and ACR (P=0.20). The adjusted HR for CKD defined as eGFR <60 mL/min/1.73m(2) or albuminuria ≥30 mg/g (vs. no CKD) was 1.54 (95%CI, 1.15-2.06). Associations were consistent in subgroups according to age, gender, and comorbidities as well as for unprovoked versus provoked VTE. CONCLUSIONS: Both eGFR and ACR are independently associated with increased risk of VTE in the general population, even across the normal eGFR and ACR ranges

Low infection rates after 34,361 intramedullary nail operations in 55 low- and middle-income countries: Validation of the Surgical Implant Generation Network (SIGN) Online Surgical Database

Background: The Surgical Implant Generation Network (SIGN) supplies intramedullary (IM) nails for the treatment of long bone fractures free of charge to hospitals in low- and middle-income countries (LMICs). Most operations are reported to the SIGN Online Surgical Database (SOSD). Follow-up has been reported to be low, however. We wanted to examine the pattern of follow-up and to assess whether infection rates could be trusted. Patients and methods: The SOSD contained 36,454 IM nail surgeries in 55 LMICs. We excluded humerus and hip fractures, and fractures without a registered surgical approach. This left 34,361 IM nails for analysis. A generalized additive regression model (gam) was used to explore the association between follow-up rates and infection rates. Results: The overall follow-up rate in the SOSD was 18.1% (95% CI: 17.7–18.5) and national follow-up rates ranged from 0% to 74.2%. The overall infection rate was 0.7% (CI: 0.6–0.8) for femoral fractures and 1.2% (CI: 1.0–1.4) for tibial fractures. If only nails with a registered follow-up visit were included (n = 6,224), infection rates were 3.5% (CI: 3.0–4.1) for femoral fractures and 7.3% (CI: 6.2–8.4) for tibial fractures. We found an increase in infection rates with increasing follow-up rates up to a level of 5%. Follow-up above 5% did not result in increased infection rates. Interpretation: Reported infection rates after IM nailing in the SOSD appear to be reliable and could be used for further research. The low infection rates suggest that IM nailing is a safe procedure also in low- and middle-income countries.publishedVersio