A novel measure to summarize blood transfusion practice during critical illness.

BACKGROUND: Large-scale observational studies have summarized transfusion practice using traditional measures of central tendency (e.g., the mean hemoglobin concentration at the time of transfusion). However, the mean hemoglobin concentration fails to identify specific hemoglobin concentration thresholds that drive practice. In the following brief report, we propose a novel measure of "practice discontinuity" that identifies specific practice-defining hemoglobin thresholds. STUDY DESIGN AND METHODS: We used the PINC AI Database (2016-2022) to identify adult patients admitted to an intensive care unit with at least one hemoglobin concentration measurement. For each day that hemoglobin was measured, we identified whether the patient received a red blood cell transfusion using hospital charge codes. We defined the "practice discontinuity" measure as the hemoglobin concentration at which there was the largest increase in transfusion use going from a higher to an incrementally lower hemoglobin concentration. We also calculated the mean and median pretransfusion hemoglobin concentrations. RESULTS: We identified 1,298,367 patients and 4,905,839 patient-days for inclusion. RBC transfusion occurred in a total of 530,654 (10.8%) patient-days. The overall pre-transfusion mean and median hemoglobin concentrations were 8.4 and 8.0 g/dL, respectively. The practice discontinuity measure identified 7.0 g/dL as the hemoglobin concentration at which transfusion use increased the most, from 46.6% of patient-days at a concentration of 7.0 g/dL to 74.8% of patient-days at a concentration of 6.9 g/dL. DISCUSSION: We propose that future studies of red blood cell transfusion practice consider inclusion of the practice discontinuity measure to more fully summarize clinical practice.

Gait Alterations and Association With Worsening Knee Pain and Physical Function: A Machine Learning Approach With Wearable Sensors in the Multicenter Osteoarthritis Study.

OBJECTIVE: The objective of this study was to identify gait alterations related to worsening knee pain and worsening physical function, using machine learning approaches applied to wearable sensor-derived data from a large observational cohort. METHODS: Participants in the Multicenter Osteoarthritis Study (MOST) completed a 20-m walk test wearing inertial sensors on their lower back and ankles. Parameters describing spatiotemporal features of gait were extracted from these data. We used an ensemble machine learning technique ("super learning") to optimally discriminate between those with and without worsening physical function and, separately, those with and without worsening pain over two years. We then used log-binomial regression to evaluate associations of the top 10 influential variables selected with super learning with each outcome. We also assessed whether the relation of altered gait with worsening function was mediated by changes in pain. RESULTS: Of 2,324 participants, 29% and 24% had worsening knee pain and function over two years, respectively. From the super learner, several gait parameters were found to be influential for worsening pain and for worsening function. After adjusting for confounders, greater gait asymmetry, longer average step length, and lower dominant frequency were associated with worsening pain, and lower cadence was associated with worsening function. Worsening pain partially mediated the association of cadence with function. CONCLUSION: We identified gait alterations associated with worsening knee pain and those associated with worsening physical function. These alterations could be assessed with wearable sensors in clinical settings. Further research should determine whether they might be therapeutic targets to prevent worsening pain and worsening function.

Mediating Effect of Pain Sensitization on the Paradoxical Relation of Taking Opioids to Pain Severity in Knee Osteoarthritis: The Multicenter Osteoarthritis Study.

OBJECTIVE: One of the less understood adverse effects while taking opioids is the paradoxical increase in pain, known as opioid-induced hyperalgesia (OIH). We sought to determine whether pain sensitization mediates the relation of taking an opioid to pain severity in people with knee osteoarthritis (OA). METHODS: We included participants in a National Institutes of Health-funded cohort study of people with or at risk of knee OA. Participants were categorized into opioid and nonopioid analgesic groups at baseline. Western Ontario McMaster Universities OA Index (WOMAC) pain two years later was assessed as the outcome. We used causal mediation analysis to assess the mediating role of pain sensitization, quantified by changes in pressure pain threshold (PPT) at the wrist and patella over two years, on the effect of taking an opioid on WOMAC pain two years later. RESULTS: We included 296 participants who took opioids and 1,070 participants who took nonopioid analgesics. Compared with taking nonopioid analgesics, taking opioids was associated with greater pain two years later. This relation was mediated by 0.05- and 0.08-unit changes in wrist PPT (95% confidence interval [CI] 0.01-0.10) and patellar PPT (95% CI 0.02-0.14), respectively. When we assessed any worsening in WOMAC pain score over two years, taking opioids, compared with taking nonopioid analgesics, had 2% and 5% higher odds of experiencing any worsening pain mediated by changes in wrist PPT (95% CI 0.99-1.04) and patellar PPT (95% CI 1.01-1.09), respectively. CONCLUSION: Pain sensitization had small mediating effects on the paradoxical phenomenon of OIH, suggesting that pain sensitization may not play a major role and/or that PPT is an inadequate tool to assess OIH.

Relation of Intra-Articular Mineralization to Knee Pain in Knee Osteoarthritis: A Longitudinal Analysis in the MOST Study.

OBJECTIVE: Intra-articular (IA) calcium crystal deposition is common in knee osteoarthritis (OA), but of unclear significance. It is possible that low-grade, crystal-related inflammation may contribute to knee pain. We examined the longitudinal relation of computed tomography (CT)-detected IA mineralization to the development of knee pain. METHODS: We used data from the National Institutes of Health-funded longitudinal Multicenter Osteoarthritis Study. Participants had knee radiographs and bilateral knee CTs at baseline, and pain assessments every 8 months for 2 years. CT images were scored using the Boston University Calcium Knee Score. We longitudinally examined the relation of CT-detected IA mineralization to the risk of frequent knee pain (FKP), intermittent or constant knee pain worsening, and pain severity worsening using generalized linear mixed-effects models. RESULTS: We included 2,093 participants (mean age 61 years, 57% women, mean body mass index 28.8 kg/m2 ). Overall, 10.2% of knees had IA mineralization. The presence of any IA mineralization in the cartilage was associated with 2.0 times higher odds of having FKP (95% confidence interval [CI] 1.38-2.78) and 1.86 times more frequent intermittent or constant pain (95% CI 1.20-2.78), with similar results seen for the presence of any IA mineralization in the meniscus or joint capsule. A higher burden of IA mineralization anywhere within the knee was associated with a higher odds of all pain outcomes (odds ratio ranged from 2.14 to 2.21). CONCLUSION: CT-detected IA mineralization was associated with risk of having more frequent, persistent, and worsening knee pain over 2 years. Targeting IA mineralization may have therapeutic potential for pain improvement in knee OA.

Gait, physical activity and tibiofemoral cartilage damage: a longitudinal machine learning analysis in the Multicenter Osteoarthritis Study.

OBJECTIVE: To (1) develop and evaluate a machine learning model incorporating gait and physical activity to predict medial tibiofemoral cartilage worsening over 2 years in individuals without advanced knee osteoarthritis and (2) identify influential predictors in the model and quantify their effect on cartilage worsening. DESIGN: An ensemble machine learning model was developed to predict worsened cartilage MRI Osteoarthritis Knee Score at follow-up from gait, physical activity, clinical and demographic data from the Multicenter Osteoarthritis Study. Model performance was evaluated in repeated cross-validations. The top 10 predictors of the outcome across 100 held-out test sets were identified by a variable importance measure. Their effect on the outcome was quantified by g-computation. RESULTS: Of 947 legs in the analysis, 14% experienced medial cartilage worsening at follow-up. The median (2.5-97.5th percentile) area under the receiver operating characteristic curve across the 100 held-out test sets was 0.73 (0.65-0.79). Baseline cartilage damage, higher Kellgren-Lawrence grade, greater pain during walking, higher lateral ground reaction force impulse, greater time spent lying and lower vertical ground reaction force unloading rate were associated with greater risk of cartilage worsening. Similar results were found for the subset of knees with baseline cartilage damage. CONCLUSIONS: A machine learning approach incorporating gait, physical activity and clinical/demographic features showed good performance for predicting cartilage worsening over 2 years. While identifying potential intervention targets from the model is challenging, lateral ground reaction force impulse, time spent lying and vertical ground reaction force unloading rate should be investigated further as potential early intervention targets to reduce medial tibiofemoral cartilage worsening.

Comparative Effectiveness of Fludrocortisone and Hydrocortisone vs Hydrocortisone Alone Among Patients With Septic Shock.

Importance: Patients with septic shock may benefit from the initiation of corticosteroids. However, the comparative effectiveness of the 2 most studied corticosteroid regimens (hydrocortisone with fludrocortisone vs hydrocortisone alone) is unclear. Objective: To compare the effectiveness of adding fludrocortisone to hydrocortisone vs hydrocortisone alone among patients with septic shock using target trial emulation. Design, Setting, and Participants: This retrospective cohort study from 2016 to 2020 used the enhanced claims-based Premier Healthcare Database, which included approximately 25% of US hospitalizations. Participants were adult patients hospitalized with septic shock and receiving norepinephrine who began hydrocortisone treatment. Data analysis was performed from May 2022 to December 2022. Exposure: Addition of fludrocortisone on the same calendar day that hydrocortisone treatment was initiated vs use of hydrocortisone alone. Main Outcome and Measures: Composite of hospital death or discharge to hospice. Adjusted risk differences were calculated using doubly robust targeted maximum likelihood estimation. Results: Analyses included 88 275 patients, 2280 who began treatment with hydrocortisone-fludrocortisone (median [IQR] age, 64 [54-73] years; 1041 female; 1239 male) and 85 995 (median [IQR] age, 67 [57-76] years; 42 136 female; 43 859 male) who began treatment with hydrocortisone alone. The primary composite outcome of death in hospital or discharge to hospice occurred among 1076 (47.2%) patients treated with hydrocortisone-fludrocortisone vs 43 669 (50.8%) treated with hydrocortisone alone (adjusted absolute risk difference, -3.7%; 95% CI, -4.2% to -3.1%; P < .001). Conclusions and Relevance: In this comparative effectiveness cohort study among adult patients with septic shock who began hydrocortisone treatment, the addition of fludrocortisone was superior to hydrocortisone alone.

Relation of gait measures with mild unilateral knee pain during walking using machine learning.

Gait alterations in those with mild unilateral knee pain during walking may provide clues to modifiable alterations that affect progression of knee pain and osteoarthritis (OA). To examine this, we applied machine learning (ML) approaches to gait data from wearable sensors in a large observational knee OA cohort, the Multicenter Osteoarthritis (MOST) study. Participants completed a 20-m walk test wearing sensors on their trunk and ankles. Parameters describing spatiotemporal features of gait and symmetry, variability and complexity were extracted. We used an ensemble ML technique ("super learning") to identify gait variables in our cross-sectional data associated with the presence/absence of unilateral knee pain. We then used logistic regression to determine the association of selected gait variables with odds of mild knee pain. Of 2066 participants (mean age 63.6 [SD: 10.4] years, 56% female), 21.3% had mild unilateral pain while walking. Gait parameters selected in the ML process as influential included step regularity, sample entropy, gait speed, and amplitude dominant frequency, among others. In adjusted cross-sectional analyses, lower levels of step regularity (i.e., greater gait variability) and lower sample entropy(i.e., lower gait complexity) were associated with increased likelihood of unilateral mild pain while walking [aOR 0.80 (0.64-1.00) and aOR 0.79 (0.66-0.95), respectively].

The Relationship of Pain Reduction With Prevention of Knee Replacement Under Dynamic Intervention Strategies.

OBJECTIVE: Knee replacement (KR) rates are increasing exponentially in the US and straining insurance budgets. This study was undertaken to investigate how many KRs would be prevented at different levels of pain improvement, a major target of osteoarthritis (OA) trials. METHODS: We used data from the Osteoarthritis Initiative (OAI) to emulate a trial of knee pain interventions on KR risk changes. We modeled hypothetical 1-, 2- or 3-unit reductions of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale whenever a person reported a pain score of ≥5 (of 20) in an affected knee at any clinic visit. We used causal inference-based targeted learning to estimate treatment effects for hypothesized pain intervention strategies adjusted for time-dependent confounding. Sensitivity analyses assessed interventions at WOMAC pain scores of ≥4 and ≥7. RESULTS: Of the 9,592 knees studied (n = 4,796 participants; 58.5% female; baseline age 61.2 years), 40.7% experienced WOMAC pain scores of ≥5. The estimated knee-level (reference) risk of a KR, adjusted for loss to follow-up and death, was 6.3% (95% confidence interval 5.0, 7.7%) in the OAI. Reductions of WOMAC pain scores by 1, 2, or 3 units decreased the KR risk from 6.3% to 5.8%, 5.3%, and 4.9%, respectively. Larger reductions in KR risk were achieved when interventions were applied at a WOMAC pain score of ≥4. CONCLUSION: Modest pain reductions from OA interventions would substantially reduce the number of KRs, with greater reductions achieved when pain decreased more and when interventions were introduced at lower pain levels.

Associations of Body Mass Index With Pain and the Mediating Role of Inflammatory Biomarkers in People With Hand Osteoarthritis.

OBJECTIVE: To examine the association of body mass index (BMI) with pain in people with hand osteoarthritis (OA), and explore whether this association, if causal, is mediated by systemic inflammatory biomarkers. METHODS: In 281 Nor-Hand study participants, we estimated associations between BMI and hand pain, as measured by the Australian/Canadian Osteoarthritis Hand Index (AUSCAN; range 0-20) and Numerical Rating Scale (NRS; range 0-10); foot pain, as measured by NRS (range 0-10); knee/hip pain, as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC; range 0-20); painful total body joint count; and pain sensitization. We fit natural-effects models to estimate natural direct and natural indirect effects of BMI on pain through inflammatory biomarkers. RESULTS: Each 5-unit increase in BMI was associated with more severe hand pain (on average increased AUSCAN by 0.64 [95% confidence interval (95% CI) 0.23, 1.08]), foot pain (on average increased NRS by 0.65 [95% CI 0.36, 0.92]), knee/hip pain (on average increased WOMAC by 1.31 [95% CI 0.87, 1.73]), generalized pain, and pain sensitization. Mediation analyses suggested that the effects of BMI on hand pain and painful total body joint count were partially mediated by leptin and high-sensitivity C-reactive protein (hsCRP), respectively. Effect sizes for mediation by leptin were larger for the hands than for the lower extremities, and were statistically significant for the hands only. CONCLUSION: In people with hand OA, higher BMI is associated with greater pain severity in the hands, feet, and knees/hips. Systemic effects of obesity, measured by leptin, may play a larger mediating role for pain in the hands than in the lower extremities. Low-grade inflammation, measured by hsCRP, may contribute to generalized pain in overweight/obese individuals.

Magnetic Resonance Imaging-Defined Osteoarthritis Features and Anterior Knee Pain in Individuals With, or at Risk for, Knee Osteoarthritis: A Multicenter Study on Osteoarthritis.

OBJECTIVE: The lack of strong association between knee osteoarthritis (OA) structural features and pain continues to perplex researchers and clinicians. Evaluating the patellofemoral joint in addition to the tibiofemoral joint alone has contributed to explaining this structure-pain discordance, hence justifying a more comprehensive evaluation of whole-knee OA and pain. The present study, therefore, was undertaken to evaluate the association between patellofemoral and tibiofemoral OA features with localized anterior knee pain (AKP) using 2 study designs. METHODS: Using cross-sectional data from the Multicenter Osteoarthritis Study, our first approach was a within-person, knee-matched design in which we identified participants with unilateral AKP. We then assessed magnetic resonance imaging (MRI)-derived OA features (cartilage damage, bone marrow lesions [BMLs], osteophytes, and inflammation) in both knees and evaluated the association of patellofemoral and tibiofemoral OA features to unilateral AKP. In our second approach, MRIs from 1 knee per person were scored, and we evaluated the association of OA features to AKP in participants with AKP and participants with no frequent knee pain. RESULTS: Using the first approach (n = 71, 66% women, mean ± SD age 69 ± 8 years), lateral patellofemoral osteophytes (odds ratio [OR] 5.0 [95% confidence interval (95% CI) 1.7-14.6]), whole-knee joint effusion-synovitis (OR 4.7 [95% CI 1.3-16.2]), and infrapatellar synovitis (OR 2.8 [95% CI 1.0-7.8]) were associated with AKP. Using the second approach (n = 882, 59% women, mean ± SD age 69 ± 7 years), lateral and medial patellofemoral cartilage damage (prevalence ratio [PR] 2.3 [95% CI 1.3-4.0] and PR 1.9 [95% CI 1.1-3.3], respectively) and lateral patellofemoral BMLs (PR 2.6 [95% CI 1.5-4.7]) were associated with AKP. CONCLUSION: Patellofemoral but not tibiofemoral joint OA features and inflammation were associated with AKP.

The Association of Tumor Necrosis Factor Inhibitor Use With Incident Hypertension in Ankylosing Spondylitis: Data From the PSOAS Cohort.

OBJECTIVE: Individuals with ankylosing spondylitis (AS) have a greater cardiovascular (CV) risk than those in the general population. The effect of tumor necrosis factor inhibitors (TNFis) on CV risk, including on the development of hypertension (HTN), remains unclear, with some data suggesting higher risk. We assessed the association of TNFi use with incident HTN in a longitudinal AS cohort. METHODS: Adults with AS enrolled in a prospective cohort in 2002-2018 were examined every 4-6 months. TNFi use during the preceding 6 months was ascertained at each study visit. We defined HTN by patient-reported HTN, antihypertensive medication use, or, on 2 consecutive visits, systolic blood pressure (BP) ≥ 140 mmHg or diastolic BP ≥ 90 mmHg. We evaluated the association between TNFi use and the development of HTN with marginal structural models, estimated by inverse probability-of-treatment weighting, to account for time-dependent confounders and informative censoring. Potential confounders included age, sex, race, site, nonsteroidal antiinflammatory drug use, and disease activity. RESULTS: We included 630 patients without baseline HTN and with at least 1 year of follow-up. Of these, 72% were male, mean age was 39 ± 13 years, and 43% used TNFi at baseline. On follow-up (median 5 yrs), 129 developed incident HTN and 163 started on TNFi during follow-up. TNFi use was not associated with incident HTN (adjusted HR 1.10, 95% CI 0.83-1.37). CONCLUSION: In our prospective AS cohort, TNFi use was not significantly associated with incident HTN.

Impact of COVID-19 Pandemic on Physical Activity, Pain, Mood, and Sleep in Adults with Knee Osteoarthritis.

Objective: To examine changes in physical activity, sleep, pain and mood in people with knee osteoarthritis (OA) during the ongoing COVID-19 pandemic by leveraging an ongoing randomized clinical trial (RCT). Methods: Participants enrolled in a 12-month parallel two-arm RCT (NCT03064139) interrupted by the COVID-19 pandemic wore an activity monitor (Fitbit Charge 3) and filled out custom weekly surveys rating knee pain, mood, and sleep as part of the study. Data from 30 weeks of the parent study were used for this analysis. Daily step count and sleep duration were extracted from activity monitor data, and participants self-reported knee pain, positive mood, and negative mood via surveys. Metrics were averaged within each participant and then across all participants for pre-pandemic, stay-at-home, and reopening periods, reflecting the phased re-opening in the state of Massachusetts. Results: Data from 28 participants showed small changes with inconclusive clinical significance during the stay-at-home and reopening periods compared to pre-pandemic for all outcomes. Summary statistics suggested substantial variability across participants with some participants showing persistent declines in physical activity during the observation period. Conclusion: Effects of the COVID-19 pandemic on physical activity, sleep, pain, and mood were variable across individuals with OA. Specific reasons for this variability could not be determined. Identifying factors that could affect individuals with knee OA who may exhibit reduced physical activity and/or worse symptoms during major lifestyle changes (such as the ongoing pandemic) is important for providing targeted healthcare services and management advice towards those that could benefit from it the most.

Misclassification Error-Adjusted Prevalence of Injection Drug Use Among Infective Endocarditis Hospitalizations in the United States: A Serial Cross-Sectional Analysis of the 2007-2016 National Inpatient Sample.

Administrative health databases have been used to monitor trends in infective endocarditis hospitalization related to nonprescription injection drug use (IDU) using International Classification of Diseases (ICD) code algorithms. Because no ICD code for IDU exists, drug dependence and hepatitis C virus (HCV) have been used as surrogate measures for IDU, making misclassification error (ME) a threat to the accuracy of existing estimates. In a serial cross-sectional analysis, we compared the unadjusted and ME-adjusted prevalences of IDU among 70,899 unweighted endocarditis hospitalizations in the 2007-2016 National Inpatient Sample. The unadjusted prevalence of IDU was estimated with a drug algorithm, an HCV algorithm, and a combination algorithm (drug and HCV). Bayesian latent class models were used to estimate the median IDU prevalence and 95% Bayesian credible intervals and ICD algorithm sensitivity and specificity. Sex- and age group-stratified IDU prevalences were also estimated. Compared with the misclassification-adjusted prevalence, unadjusted estimates were lower using the drug algorithm and higher using the combination algorithm. The median ME-adjusted IDU prevalence increased from 9.7% (95% Bayesian credible interval (BCI): 6.3, 14.8) in 2008 to 32.5% (95% BCI: 26.5, 38.2) in 2016. Among persons aged 18-34 years, IDU prevalence was higher in females than in males. ME adjustment in ICD-based studies of injection-related endocarditis is recommended.

Association of Quadriceps Adiposity With an Increase in Knee Cartilage, Meniscus, or Bone Marrow Lesions Over Three Years.

OBJECTIVE: To evaluate the association of fatty infiltration of the quadriceps and vastus medialis (VM) with an increase in knee cartilage, meniscus, or bone marrow lesions, using magnetic resonance imaging (MRI) in knee osteoarthritis (OA) over 3 years. METHODS: Participants (n = 69) with and without radiographic knee OA underwent MRI at baseline and 3 years later. Chemical shift-based water/fat MRI was used to quantify the intramuscular fat fraction and the lean anatomical cross-sectional area (ACSA) for the VM and entire quadriceps muscles. MRI images of the knee were analyzed using the semiquantitative modified whole-organ MRI score (mWORMS) grading to assess change in lesions in the articular cartilage, meniscus, and bone marrow. Logistic regression was used to assess whether baseline quadriceps and VM fat fraction and lean ACSA were associated with an increase in mWORMS scores. Odds ratios (ORs) were adjusted for age, sex, and body mass index. RESULTS: Overall, of the 69 subjects, 43 (62%) had an increase in cartilage lesions (26 of 43), meniscus lesions (19 of 43), or bone marrow lesions (22 of 43) scores. The quadriceps (OR 2.13 [95% confidence interval (95% CI) 1.09-4.15]) and VM (OR 2.05 [95% CI 1.25-3.36]) fat fraction were both associated with an increase in cartilage, meniscus, or bone marrow lesion scores over 3 years. The association of quadriceps or VM lean ACSA with the outcomes was not significant. CONCLUSION: These longitudinal findings using quantitative MRI methods for assessment of muscle adiposity highlight the role of quadriceps adiposity, specifically in the VM, in knee OA progression. However, studies in larger cohorts are needed to confirm these findings.

Gradual decline in outpatient antibiotic prescriptions in paediatrics: A data warehouse-based 11-year cohort study.

AIM: To describe trends in antibiotic (AB) prescriptions in children in primary care over 11 years, using a large data warehouse. METHODS: A retrospective cohort study assessed outpatient AB prescriptions 2007-2017, using the Massachusetts Health Disparities Repository. The evolution of paediatric outpatient AB prescriptions was assessed using time-series analyses through annual per cent change (APC) for the population and for children with or without comorbid condition. RESULTS: About 25 000 children were followed in primary care with 31 248 AB prescriptions reported in the data warehouse. The youngest children had more AB prescriptions. Penicillins were prescribed most frequently (46%), then macrolides (28%). One third of children had comorbid conditions, receiving significantly more antibiotics (30.3 vs 21.0 AB/100 child-years, relative risk: 1.43, 95% CI: 1.40, 1.46). Overall AB prescription decreased over the period (APC = -5.34%, 95% CI: -7.10, -3.54), with similar trends for penicillins (APC = -5.49; 95% CI: -8.27, -2.62) and macrolides (APC = -6.46; 95% CI: -8.37, -4.58); antibiotic prescribing declined more in children with comorbid conditions. CONCLUSION: Outpatient AB prescribing decline was gradual and consistent in paediatrics over the period. Prescription differences persisted between age groups, conditions and indication. The availability of routine care data through data warehouse fosters the surveillance automation, providing inexpensive fast tools to design appropriate antimicrobial stewardship.

The Effect of IL-6 Inhibitors on Mortality Among Hospitalized COVID-19 Patients: A Multicenter Study.

BACKGROUND: The effectiveness of interleukin-6 inhibitors (IL-6i) in ameliorating coronavirus disease 2019 (COVID-19) remains uncertain. METHODS: We analyzed data for patients aged ≥18 years admitted with a positive severe acute respiratory syndrome coronavirus 2 polymerase chain reaction test at 4 safety-net hospital systems with diverse populations and high rates of medical comorbidities in 3 US regions. We used inverse probability of treatment weighting via machine learning for confounding adjustment by demographics, comorbidities, and disease severity markers. We estimated the average treatment effect, the odds of IL-6i effect on in-hospital mortality from COVID-19, using a logistic marginal structural model. RESULTS: Of 516 patients, 104 (20.1%) received IL-6i. Estimate of the average treatment effect adjusted for confounders suggested a 37% reduction in odds of in-hospital mortality in those who received IL-6i compared with those who did not, although the confidence interval included the null value of 1 (odds ratio = 0.63; 95% confidence interval, .29-1.38). A sensitivity analysis suggested that potential unmeasured confounding would require a minimum odds ratio of 2.55 to nullify our estimated IL-6i effect size. CONCLUSIONS: Despite low precision, our findings suggested a relatively large effect size of IL-6i in reducing the odds of COVID-19-related in-hospital mortality.

Does cartilage loss cause pain in osteoarthritis and if so, how much?

OBJECTIVES: Although treatment development in osteoarthritis (OA) focuses on chondroprotection, it is unclear how much preventing cartilage loss reduces joint pain. It is also unclear how nociceptive tissues may be involved. METHODS: Using data from the Osteoarthritis Initiative, we quantified the relation between cartilage loss and worsening knee pain after adjusting for bone marrow lesions (BMLs) and synovitis, and examined how much these factors mediated this association. 600 knee MRIs were scored at baseline, 12 months and 24 months for quantitative and semiquantitative measures of OA structural features. We focused on change in medial cartilage thickness using an amount similar to that seen in recent trials. Linear models calculated mean change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score with cartilage loss, adjusted for baseline BMLs, synovitis and covariates. Mediation analysis tested whether change in synovitis or BMLs mediated the cartilage loss-pain association. We carried out a subanalysis for knees with non-zero baseline WOMAC pain scores and another for non-valgus knees. RESULTS: Cartilage thickness loss was significantly associated with a small degree of worsening in pain over 24 months. For example, a loss of 0.1 mm of cartilage thickness over 2 years was associated with a 0.32 increase in WOMAC pain (scale 0-20). The association of cartilage thickness loss with pain was mediated by synovitis change but not by BML change. Subanalysis results were similar. CONCLUSIONS: Cartilage thickness loss is associated with only a small amount of worsening knee pain, an association mediated in part by worsening synovitis. Demonstrating that chondroprotection reduces knee pain will be extremely challenging and is perhaps unachievable.