The SARS-CoV-2 Omicron (B.1.1.529) variant has been associated with less severe acute disease, however, concerns remain as to whether long-term complaints persist to a similar extent as for earlier ...variants. Studying 1 323 145 persons aged 18-70 years living in Norway with and without SARS-CoV-2 infection in a prospective cohort study, we found that individuals infected with Omicron had a similar risk of post-covid complaints (fatigue, cough, heart palpitations, shortness of breath and anxiety/depression) as individuals infected with Delta (B.1.617.2), from 14 to up to 126 days after testing positive, both in the acute (14 to 29 days), sub-acute (30 to 89 days) and chronic post-covid (≥90 days) phases. However, at ≥90 days after testing positive, individuals infected with Omicron had a lower risk of having any complaint (43 (95%CI = 14 to 72) fewer per 10,000), as well as a lower risk of musculoskeletal pain (23 (95%CI = 2-43) fewer per 10,000) than individuals infected with Delta. Our findings suggest that the acute and sub-acute burden of post-covid complaints on health services is similar for Omicron and Delta. The chronic burden may be lower for Omicron vs Delta when considering musculoskeletal pain, but not when considering other typical post-covid complaints.
To assess the long-term effects of arthroscopic partial meniscectomy (APM) on the development of radiographic knee osteoarthritis, and on knee symptoms and function, at 5 years follow-up.
...Multicentre, randomised, participant- and outcome assessor-blinded, placebo-surgery controlled trial.
Orthopaedic departments in five public hospitals in Finland.
146 adults, mean age 52 years (range 35-65 years), with knee symptoms consistent with degenerative medial meniscus tear verified by MRI scan and arthroscopically, and no clinical signs of knee osteoarthritis were randomised.
APM or placebo surgery (diagnostic knee arthroscopy).
We used two indices of radiographic knee osteoarthritis (increase in Kellgren and Lawrence grade ≥1, and increase in Osteoarthritis Research Society International (OARSI) atlas radiographic joint space narrowing and osteophyte sum score, respectively), and three validated patient-relevant measures of knee symptoms and function (Western Ontario Meniscal Evaluation Tool (WOMET), Lysholm, and knee pain after exercise using a numerical rating scale).
There was a consistent, slightly greater risk for progression of radiographic knee osteoarthritis in the APM group as compared with the placebo surgery group (adjusted absolute risk difference in increase in Kellgren-Lawrence grade ≥1 of 13%, 95% CI -2% to 28%; adjusted absolute mean difference in OARSI sum score 0.7, 95% CI 0.1 to 1.3). There were no relevant between-group differences in the three patient-reported outcomes: adjusted absolute mean differences (APM vs placebo surgery), -1.7 (95% CI -7.7 to 4.3) in WOMET, -2.1 (95% CI -6.8 to 2.6) in Lysholm knee score, and -0.04 (95% CI -0.81 to 0.72) in knee pain after exercise, respectively. The corresponding adjusted absolute risk difference in the presence of mechanical symptoms was 18% (95% CI 5% to 31%); there were more symptoms reported in the APM group. All other secondary outcomes comparisons were similar.
APM was associated with a slightly increased risk of developing radiographic knee osteoarthritis and no concomitant benefit in patient-relevant outcomes, at 5 years after surgery.
ClinicalTrials.gov (NCT01052233 and NCT00549172).
To estimate the extent that overweight/obesity, smoking, and alcohol are associated with prevalence and longitudinal changes of radiographic hand osteoarthritis (OA).
Participants from the ...Osteoarthritis Initiative (n = 1232) were included, of whom 994 had 4-year followup data. In analyses on incident hand OA, only persons without hand OA at baseline were included (n = 406). Our exposure variables were overweight/obesity body mass index (BMI), waist circumference, smoking (current/former, smoking pack-yrs), and alcohol consumption (drinks/week). Using linear and logistic regression analyses, we analyzed possible associations between baseline exposure variables and radiographic hand OA severity, erosive hand OA, incidence of hand OA, and radiographic changes. Analyses were adjusted for age, sex, and education.
Neither overweight nor obesity were associated with hand OA. Current smoking was associated with less hand OA in cross-sectional analyses, whereas longitudinal analyses suggested higher odds of incident hand OA in current smokers (OR 2.20, 95% CI 1.02-4.77). Moderate alcohol consumption was associated with higher Kellgren-Lawrence sum score at baseline (1-3 drinks: 1.55, 95% CI 0.43-2.67) and increasing sum score during 4-year followup (4-7 drinks: 0.33, 95% CI 0.01-0.64). Moderate alcohol consumption (1-7 drinks/week) was associated with 2-fold higher odds of erosive hand OA, which was statistically significant. Additional adjustment for BMI gave similar strengths of associations.
Overweight/obesity were not associated with hand OA. Contrasting results were observed for smoking and hand OA, suggesting lack of association. Moderate alcohol consumption was associated with hand OA severity, radiographic changes, and erosive hand OA, warranting further investigation.
We studied the prevalence and patterns of typical long COVID complaints in ~ 2.3 million individuals aged 18-70 years with and without confirmed COVID-19 in a Nation-wide population-based prospective ...cohort study in Norway. Our main outcome measures were the period prevalence of single-occurring or different combinations of complaints based on medical records: (1) Pulmonary (dyspnea and/or cough), (2) Neurological (concentration problems, memory loss), and/or (3) General complaints (fatigue). In persons testing positive (n = 75 979), 64 (95% confidence interval: 54 to 73) and 122 (111 to 113) more persons per 10 000 persons had pulmonary complaints 5-6 months after the test compared to 10 000 persons testing negative (n = 1 167 582) or untested (n = 1 084 578), respectively. The corresponding difference in prevalence of general complaints (fatigue) was 181 (168 to 195) and 224 (211 to 238) per 10 000, and of neurological complaints 5 (2 to 8) and 9 (6-13) per 10 000. Overlap between complaints was rare. Long COVID complaints were only slightly more prevalent in persons with than without confirmed COVID-19. Still, long COVID may pose a substantial burden to healthcare systems in the future given the lasting high incidence of symptomatic COVID-19 in both vaccinated and unvaccinated individuals.
Knee arthroscopy is one of the most common surgical procedures worldwide and the number of arthroscopies has substantially increased in the last 30 years. Thus, our aim was to provide updated ...estimates on the risk of complications and compare it with the background risk in the general population.
We identified patients aged 15-84 years with knee arthroscopy in the years 2005-2016 in southern Sweden. We calculated the risk of pyogenic arthritis, venous thromboembolism, and other typical complications within 30 days. As a reference cohort we included the regional population in the corresponding age interval. We estimated the relative and absolute risks of complications compared to the reference cohort using logistic regression adjusted for age, sex, and level of education. We also estimated the proportion of complications in the population explained by knee arthroscopy (population attributable fraction).
We identified 18,735 knee arthroscopy patients (mean age 39 years) and 1,171,084 reference subjects (mean age 46 years). The absolute risk of one or more complications was 1.1% after knee arthroscopy and 0.16% in references. The odds ratio of any complication after knee arthroscopy vs. the reference cohort was 9.4 (95% confidence interval CI 8.1, 10.9) with an absolute risk difference of 1.4% (1.1, 1.6%). The relative risk (95% CI) for pyogenic arthritis was 115 (75, 174), venous thromboembolism 6.8 (5.1, 9.1), and other complications 7.7 (6.3, 9.5). The population attributable fraction for pyogenic arthritis was 5%.
The absolute risks of complications associated with knee arthroscopy remain small at about 1%. Still, 5% of all pyogenic knee arthritis cases in adults are attributable to knee arthroscopy, thus risks with knee arthroscopy should be carefully considered in the choice of treatment.
Background and purpose - Few data are available regarding structural changes present in knees without radiographically evident osteoarthritis (OA). We evaluated the prevalence of findings suggestive ...of knee OA by magnetic resonance imaging (MRI) in middle-aged subjects without radiographic OA with or without OA risk factors.
Patients and methods - 340 subjects from the Osteoarthritis Initiative, aged 45-55 years (51% women) with Kellgren-Lawrence grade 0 in both knees, who had 3T knee MR images were eligible. 294 subjects had risk factors and 46 were without risk factors. MR images were assessed using the MOAKS scoring system.
Results - At least 1 MR-detected feature was found in 96% (283/294) of subjects with risk factors and in 87% (40/46) of those without. Cartilage damage (82%), bone marrow lesions (60%), osteophytes (45%), meniscal body extrusion (32%), and synovitis-effusion (29%) were the most common findings in subjects with risk factors, while cartilage damage (67%), osteophytes (46%), meniscal body extrusion (37%), and bone marrow lesions (35%) were most common in subjects without. The prevalence of any abnormality was higher in subjects with OA risk factors than in subjects without (prevalence ratio adjusted for age and sex 1.3 95% CI 1.1-1.6), so was prevalence of subchondral cysts and bone marrow lesions. MR-detected structural changes were more frequent in patellofemoral joints.
Interpretation - Our findings highlight the great challenge in distinguishing pathological features of early knee OA from what could be considered part of "normal ageing." Bone marrow lesions were more frequently found in subjects with multiple OA risk factors.
To assess the natural history of intrameniscal signal intensity on magnetic resonance (MR) images of the medial compartment.
Both knees of 269 participants (55% women, aged 45-55 years) in the ...Osteoarthritis Initiative without radiographic knee osteoarthritis (OA) and without medial meniscal tear at baseline were studied. One radiologist assessed 3-T MR images from baseline and 24-, 48-, and 72-month follow-up for intrameniscal signal intensity and tears. A complementary log-log model with random effect was used to evaluate the risk of medial meniscal tear, adjusting for age, sex, body mass index, and knee side.
At baseline, linear intrameniscal signal intensity in the medial compartment was present in 140 knees (26%). Once present, regression only in a single knee was observed. In 31 knees (19%) with linear intrameniscal signal intensity at any of the first three time points, the signal intensity progressed to a tear in the same segment, and in a single knee, the tear occurred in an adjacent segment. The corresponding number of tears without prior finding of intrameniscal signal intensities was 11 (3%). In the adjusted model, the hazard ratio for developing medial meniscal tear was 18.2 (95% confidence interval: 8.3, 39.8) if linear intrameniscal signal intensity was present, compared when there was no linear signal intensity. There was only one of 43 knees with injury reported in conjunction with the incident tear.
In middle-aged persons without OA, linear intrameniscal signal intensity on MR images is highly unlikely to resolve and should be considered a risk factor for medial degenerative meniscal tear.
There are multiple options for the treatment of thumb carpometacarpal joint osteoarthritis (CMC1 OA), with evidence for pain relief and improved function. Although simple trapeziectomy has the lowest ...complication risk, tendon suspension of the first metacarpal and interposition is still the most commonly used surgical procedure in patients with CMC1 OA. Although there are several reports of good short-term results after trapeziectomy and tendon suspension-interposition arthroplasty, few studies have evaluated long-term outcomes. This study is one of the largest and longest follow-up evaluations of a cohort of patients with CMC1 OA who were treated with trapeziectomy and suspension-interposition arthroplasty, capturing 96% of the original cohort for evaluation.
(1) After trapeziectomy and tendon suspension surgery, what are the long-term, patient-reported outcomes and clinical measurements (strength and ROM); and in unilateral procedures, how do these parameters compare with those of the contralateral hand that was not operated on? (2) What is the mean subsidence (unloaded trapezial space), and does pinch strength correlate with the amount of subsidence?
From 1998 to 2005, 130 patients underwent trapeziectomy and abductor pollicis longus (APL) suspension-interposition arthroplasty for CMC1 OA at one orthopaedic department. During this period, 15 patients were treated with CMC1 arthrodesis and four were treated with implant arthroplasty, for a total of 149 patients. The surgeons used APL suspensionplasty for most patients, based on age and expected postoperative function; they also employed this procedure to avoid hardware or implant failure issues. The 100 living patients were asked to participate in this retrospective study, 96% (96) of whom were enrolled. The mean age at surgery was 58 ± 7 years. The patients completed a two-item thumb pain scale (modified from the SF-36 body pain scale), a hand pain VAS (average level of pain experienced over the week preceding measurement), and the 11-item QuickDASH. Patient-reported outcomes data were obtained from all 96 patients, and 83% (80) of patients underwent bilateral hand radiography and a physical examination at a mean follow-up of 17 ± 2.4 years. We calculated outcome data for each patient, and in 39 patients with unilateral surgery and intact contralateral CMC1 joint, we compared the operated side with the contralateral side. We compared our outcome data with that from the Swedish National Quality Registry for Hand Surgery (HAKIR), noting comparable outcomes for pain and QuickDASH scores.
At long-term follow-up after trapeziectomy and APL suspension surgery, the mean thumb pain score was 19 ± 26, hand pain VAS score 23 ± 25, and QuickDASH score 26 ± 21. In the patients with unilateral surgery and intact contralateral CMC1 joint, the thumb pain score for the operated side was lower than the contralateral side, specifically 19 ± 25 compared with 29 ± 30 (mean difference -9.8 95% CI -19.5 to -0.2; p = 0.045); hand pain VAS score was 24 ± 23 versus 30 ± 25 (mean difference -6.1 95% CI -15.2 to 3.1; p = 0.19), and the QuickDASH score was 27 ± 19. Grip strength showed no differences between the operated and contralateral sides (mean 16.7 ± 7.3 kg versus 16.6 ± 6.9 kg, mean difference 0.1 95% CI -1.6 to 1.8; p = 0.90), while pinch was different (4.4 ± 1.4 versus 5.0 ± 1.5 kg, mean difference -0.6 95% CI -0.9 to -0.3; p = 0.001). The mean trapezial space was 4.4 ± 2.2 mm, and there was no association between the trapezial space and pinch strength (0.07 kg 95% CI -0.04 to 0.18 per mm of space; p = 0.17).
The finding of comparable pain and function between operated and unoperated sides at long-term follow-up suggests that trapeziectomy and tendon suspension-interposition arthroplasty provides predictable outcomes, and surgeons can use these data to counsel patients that surgery can potentially return them to comparable use. However, as patients often have asymptomatic radiographic OA on the contralateral side, future studies are needed to examine the impact of asymptomatic disease on function.
Level IV, therapeutic study.
Notch signaling is a conserved pathway that converts extracellular receptor-ligand interactions into changes in gene expression via a single transcription factor (CBF1/RBPJ in mammals; Su(H) in ...Drosophila). In humans, RBPJ variants have been linked to Adams-Oliver syndrome (AOS), a rare autosomal dominant disorder characterized by scalp, cranium, and limb defects. Here, we found that a previously described Drosophila Su(H) allele encodes a missense mutation that alters an analogous residue found in an AOS-associated RBPJ variant. Importantly, genetic studies support a model that heterozygous Drosophila with the AOS-like Su(H) allele behave in an opposing manner to heterozygous flies with a Su(H) null allele, due to a dominant activity of sequestering either the Notch co-activator or the antagonistic Hairless co-repressor. Consistent with this model, AOS-like Su(H) and Rbpj variants have decreased DNA binding activity compared to wild type proteins, but these variants do not significantly alter protein binding to the Notch co-activator or the fly and mammalian co-repressors, respectively. Taken together, these data suggest a cofactor sequestration mechanism underlies AOS phenotypes associated with RBPJ variants, whereby the AOS-associated RBPJ allele encodes a protein with compromised DNA binding activity that retains cofactor binding, resulting in Notch target gene dysregulation.
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