Racial and Ethnic Disparities in Outpatient Treatment of COVID-19 - United States, January-July 2022.

In December 2021 and early 2022, four medications received emergency use authorization (EUA) by the Food and Drug Administration for outpatient treatment of mild-to-moderate COVID-19 in patients who are at high risk for progressing to severe disease; these included nirmatrelvir/ritonavir (Paxlovid) and molnupiravir (Lagevrio) (both oral antivirals), expanded use of remdesivir (Veklury; an intraveneous antiviral), and bebtelovimab (a monoclonal antibody [mAb]).* Reports have documented disparities in mAb treatment by race and ethnicity (1) and in oral antiviral treatment by zip code-level social vulnerability (2); however, limited data are available on racial and ethnic disparities in oral antiviral treatment.† Using electronic health record (EHR) data from 692,570 COVID-19 patients aged ≥20 years who sought medical care during January-July 2022, treatment with Paxlovid, Lagevrio, Veklury, and mAbs was assessed by race and ethnicity, overall and among high-risk patient groups. During 2022, the percentage of COVID-19 patients seeking medical care who were treated with Paxlovid increased from 0.6% in January to 20.2% in April and 34.3% in July; the other three medications were used less frequently (0.7%-5.0% in July). During April-July 2022, when Paxlovid use was highest, compared with White patients, Black or African American (Black) patients were prescribed Paxlovid 35.8% less often, multiple or other race patients 24.9% less often, American Indian or Alaska Native and Native Hawaiian or other Pacific Islander (AIAN/NHOPI) patients 23.1% less often, and Asian patients 19.4% less often; Hispanic patients were prescribed Paxlovid 29.9% less often than non-Hispanic patients. Racial and ethnic disparities in Paxlovid treatment were generally somewhat higher among patients at high risk for severe COVID-19, including those aged ≥50 years and those who were immunocompromised. The expansion of programs focused on equitable awareness of and access to outpatient COVID-19 treatments, as well as COVID-19 vaccination, including updated bivalent booster doses, can help protect persons most at risk for severe illness and facilitate equitable health outcomes.

Cardiac Complications After SARS-CoV-2 Infection and mRNA COVID-19 Vaccination - PCORnet, United States, January 2021-January 2022.

Cardiac complications, particularly myocarditis and pericarditis, have been associated with SARS-CoV-2 (the virus that causes COVID-19) infection (1-3) and mRNA COVID-19 vaccination (2-5). Multisystem inflammatory syndrome (MIS) is a rare but serious complication of SARS-CoV-2 infection with frequent cardiac involvement (6). Using electronic health record (EHR) data from 40 U.S. health care systems during January 1, 2021-January 31, 2022, investigators calculated incidences of cardiac outcomes (myocarditis; myocarditis or pericarditis; and myocarditis, pericarditis, or MIS) among persons aged ≥5 years who had SARS-CoV-2 infection, stratified by sex (male or female) and age group (5-11, 12-17, 18-29, and ≥30 years). Incidences of myocarditis and myocarditis or pericarditis were calculated after first, second, unspecified, or any (first, second, or unspecified) dose of mRNA COVID-19 (BNT162b2 [Pfizer-BioNTech] or mRNA-1273 [Moderna]) vaccines, stratified by sex and age group. Risk ratios (RR) were calculated to compare risk for cardiac outcomes after SARS-CoV-2 infection to that after mRNA COVID-19 vaccination. The incidence of cardiac outcomes after mRNA COVID-19 vaccination was highest for males aged 12-17 years after the second vaccine dose; however, within this demographic group, the risk for cardiac outcomes was 1.8-5.6 times as high after SARS-CoV-2 infection than after the second vaccine dose. The risk for cardiac outcomes was likewise significantly higher after SARS-CoV-2 infection than after first, second, or unspecified dose of mRNA COVID-19 vaccination for all other groups by sex and age (RR 2.2-115.2). These findings support continued use of mRNA COVID-19 vaccines among all eligible persons aged ≥5 years.

Prevalence of Select New Symptoms and Conditions Among Persons Aged Younger Than 20 Years and 20 Years or Older at 31 to 150 Days After Testing Positive or Negative for SARS-CoV-2.

Importance: New symptoms and conditions can develop following SARS-CoV-2 infection. Whether they occur more frequently among persons with SARS-CoV-2 infection compared with those without is unclear. Objective: To compare the prevalence of new diagnoses of select symptoms and conditions between 31 and 150 days after testing among persons who tested positive vs negative for SARS-CoV-2. Design, Setting, and Participants: This cohort study analyzed aggregated electronic health record data from 40 health care systems, including 338 024 persons younger than 20 years and 1 790 886 persons aged 20 years or older who were tested for SARS-CoV-2 during March to December 2020 and who had medical encounters between 31 and 150 days after testing. Main Outcomes and Measures: International Statistical Classification of Diseases, Tenth Revision, Clinical Modification codes were used to capture new symptoms and conditions that were recorded 31 to 150 days after a SARS-CoV-2 test but absent in the 18 months to 7 days prior to testing. The prevalence of new symptoms and conditions was compared between persons with positive and negative SARS-CoV-2 tests stratified by age (20 years or older and young than 20 years) and care setting (nonhospitalized, hospitalized, or hospitalized and ventilated). Results: A total of 168 701 persons aged 20 years or older and 26 665 younger than 20 years tested positive for SARS-CoV-2, and 1 622 185 persons aged 20 years or older and 311 359 younger than 20 years tested negative. Shortness of breath was more common among persons with a positive vs negative test result among hospitalized patients (≥20 years: prevalence ratio [PR], 1.89 [99% CI, 1.79-2.01]; <20 years: PR, 1.72 [99% CI, 1.17-2.51]). Shortness of breath was also more common among nonhospitalized patients aged 20 years or older with a positive vs negative test result (PR, 1.09 [99% CI, 1.05-1.13]). Among hospitalized persons aged 20 years or older, the prevalence of new fatigue (PR, 1.35 [99% CI, 1.27-1.44]) and type 2 diabetes (PR, 2.03 [99% CI, 1.87-2.19]) was higher among those with a positive vs a negative test result. Among hospitalized persons younger than 20 years, the prevalence of type 2 diabetes (PR, 2.14 [99% CI, 1.13-4.06]) was higher among those with a positive vs a negative test result; however, the prevalence difference was less than 1%. Conclusions and Relevance: In this cohort study, among persons hospitalized after a positive SARS-CoV-2 test result, diagnoses of certain symptoms and conditions were higher than among those with a negative test result. Health care professionals should be aware of symptoms and conditions that may develop after SARS-CoV-2 infection, particularly among those hospitalized after diagnosis.

Characteristics of new adult users of mepolizumab with asthma in the USA.

BACKGROUND: In the USA, over 25 million people have asthma; 5%-10% of cases are severe. Mepolizumab (Nucala) is an interleukin-5 antagonist monoclonal antibody; it was approved by the FDA in 2015 as add-on maintenance treatment of severe asthma for patients aged ≥12 years with an eosinophilic phenotype. OBJECTIVES: (1) Describe baseline demographic and clinical characteristics of new US adult mepolizumab users 2015-2019, (2) describe asthma medication use in the 12 months preceding initiation of and concomitant with mepolizumab and (3) assess mepolizumab adherence, persistence and discontinuation patterns in 12 months postinitiation. METHODS: We conducted a new-user observational cohort study using data from Aetna, a CVS Health Company, HealthCore (Anthem), Harvard Pilgrim Healthcare, and IBM MarketScan Research Databases. Curated administrative claims data in the FDA Sentinel System common data model format and publicly available Sentinel analytical tools were used to query the databases. We included adults who initiated mepolizumab in 2015-2019 with an asthma diagnosis in the preceding 12 months and no evidence of cystic fibrosis. We examined age, sex, comorbid conditions, asthma medication use and severe asthma exacerbations. RESULTS: We identified 3496 adults (mean age 54.2 years, SD 12.5 years) who initiated mepolizumab. In the 12 months before mepolizumab initiation, 22% had received inhaled corticosteroids, 46% had inhaled corticosteroid/long-acting beta agonists, 72.6% had leukotriene antagonists, 38% had long-acting muscarinic antagonist, 18% had omalizumab,<1% had reslizumab, dupilumab or benralizumab. In the previous 12 months, 70% had a diagnosis of allergic rhinitis, 32% had chronic obstructive pulmonary disease, 17% eosinophilia and 3% eosinophilic granulomatosis with polyangiitis. Further, 56% had an asthma-related ambulatory visit, 73%≥1 course of oral corticosteroids lasting 3-27 days, 10% an asthma-related emergency department visit and 22% an asthma-related hospitalisation. In the 12 months following initiation, the mean proportion of days covered was 70%, and reductions in the average mean dispensings of rescue oral corticosteriods (35%) and omalizumab (61%) were observed. CONCLUSIONS: Adults with asthma treated with mepolizumab had varying levels of healthcare utilisation and we observed evidence of mepolizumab use in patients without severe asthma.

A Gene Therapy Approach to Improve Copper Metabolism and Prevent Liver Damage in a Mouse Model of Wilson Disease.

Wilson disease (WD), an autosomal recessive disease caused by mutations in a copper-transporting P-type ATPase (Atp7b), causes severe liver damage. This disease is currently treated with the lifelong use of copper chelation therapy, which has side effects and does not fix copper metabolism. Here, we thoroughly characterized a mouse model of WD, the toxic milk mouse, and used the model to test a gene therapy approach for treating WD. WD mice accumulated copper in the liver from birth; severe copper accumulation and concurrent liver disease were evident by 2 months of age. Intravenously administering an adeno-associated viral (AAV) 8 vector expressing a codon-optimized version of the human ATP7B transgene into 2-month-old WD mice significantly decreased liver copper levels compared with age-matched, uninjected, WD mice. We also observed a significant dose-dependent decrease in liver disease. Male mice injected with 1011 genome copies of AAV8 vector showed only mild histopathological findings with a complete lack of liver fibrosis. Therefore, we conclude that administering gene therapy at the early stages of disease onset is a promising approach for reducing liver damage and correcting copper metabolism in WD.

Determining the Minimally Effective Dose of a Clinical Candidate AAV Vector in a Mouse Model of Crigler-Najjar Syndrome.

Liver metabolism disorders are attractive targets for gene therapy, because low vector doses can reverse the buildup of toxic metabolites in the blood. Crigler-Najjar syndrome is an inherited disorder of bilirubin metabolism that is caused by the absence of uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) activity. This syndrome is characterized by hyperbilirubinemia and jaundice. Unfortunately, current phototherapy treatment is not effective long term. We intravenously injected phototherapy-rescued adult UGT1 knockout mice with 2.5 × 1010-2.5 × 1013 genome copies (GC)/kg of a clinical candidate vector, AAV8.TBG.hUGT1A1co, to study the treatment of disease compared to vehicle-only control mice. There were no apparent vector-related laboratory or clinical sequelae; the only abnormalities in clinical pathology were elevations in liver transaminases, primarily in male mice at the highest vector dose. Minimal to mild histopathological findings were present in control and vector-administered male mice. At vector doses greater than 2.5 × 1011 GC/kg, we observed a reversal of total bilirubin levels to wild-type levels. Based on a significant reduction in serum total bilirubin levels, we determined the minimally effective dose in this mouse model of Crigler-Najjar syndrome to be 2.5 × 1011 GC/kg.

AAV8 Gene Therapy Rescues the Newborn Phenotype of a Mouse Model of Crigler-Najjar.

Adeno-associated viral (AAV) vectors can target the liver, making them an attractive platform for gene therapy approaches that require the correction of hepatocytes. Crigler-Najjar syndrome is an autosomal recessive disorder of bilirubin metabolism that occurs when the liver's uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) enzyme activity is partially or completely absent. This syndrome is characterized by elevated bilirubin levels in the blood. An AAV8 vector was developed expressing a codon-optimized human version of UGT1A1 from a liver-specific promoter. High doses of the vector rescued neonatal lethality in newborn UGT1 knockout (KO) mice, which serve as a model of Crigler-Najjar syndrome, and significantly increased survival from 5 to 270 days. Newborn UGT1 KO mice treated with AAV had serum total bilirubin levels that were 5.7 times higher than the levels seen in heterozygous and wild-type mice, likely due to dilution of vector genome copies (GC) in the liver resulting from a proliferation of hepatocytes during growth of the animal. The elevation in serum total bilirubin levels in adult UGT1 KO mice depended on the AAV8 vector dose. At doses <1011 GC/mouse, total bilirubin levels returned to those seen in phototherapy-rescued UGT1 KO mice. Mice injected with vector at 1011 or 3 × 1011 GC/mouse had sustained reduced total bilirubin levels throughout the duration of the study. When an AAV8 vector was re-administered in mice with elevated total bilirubin levels, serum total bilirubin levels decreased to wild-type levels (0.1-0.3 mg/dL) in mice that received a vector dose of 3 × 1012 GC/kg. Therefore, a low-level and likely transient decrease in serum total bilirubin during the first days of life is necessary for rescuing the lethal phenotype present in the neonatal UGT1 KO mouse. Furthermore, it was possible to ablate the elevated total bilirubin levels in adult mice by re-administering an AAV8 vector.

Alternative Start Sites Downstream of Non-Sense Mutations Drive Antigen Presentation and Tolerance Induction to C-Terminal Epitopes.

CTL responses to the transgene product remain an active area of concern for the gene therapy field. A patient's underlying genetic mutation may influence the qualitative nature of these potentially destructive T cell responses. Individuals with a mutation that introduces a premature termination codon (PTC) that prevents synthesis of the full-length peptide are considered more likely to mount a transgene-specific T cell response because of a lack of immune tolerance to C-terminal epitopes as a consequence of absent endogenous Ag presentation. In this article, we demonstrate that a human ornithine transcarbamylase gene containing various PTC-inducing non-sense mutations is able to generate and present epitopes downstream of the termination codon. Generation of these epitopes occurs primarily from alternative translation start sites downstream of the stop codon. Furthermore, we show that expression of these genes from adeno-associated virus vectors in C57BL/6 mice is able to induce peripheral tolerance to epitopes downstream of the PTC. These results suggest that, despite the lack of full-length endogenous protein, patients with PTC-inducing non-sense mutations may still present T cell epitopes downstream of the premature termination site that may render the subject tolerant to wild-type transgene products.

The Role of Cartilage Stress in Patellofemoral Pain.

PURPOSE: Elevated cartilage stress has been identified as a potential mechanism for retropatellar pain; however, there are limited data in the literature to support this mechanism. Females are more likely to develop patellofemoral pain than males, yet the causes of this dimorphism are unclear. We used experimental data and computational modeling to determine whether patients with patellofemoral pain had elevated cartilage stress compared with pain-free controls and test the hypothesis that females exhibit greater cartilage stress than males. METHODS: We created finite element models of 24 patients with patellofemoral pain (11 males and 13 females) and 16 pain-free controls (8 males and 8 females) to estimate peak patellar cartilage stress (strain energy density) during a stair climb activity. Simulations took into account cartilage morphology from magnetic resonance imaging, joint posture from weight-bearing magnetic resonance imaging, and muscle forces from an EMG-driven model. RESULTS: We found no difference in peak patellar strain energy density between those with patellofemoral pain (1.9 ± 1.23 J·m(-3)) and control subjects (1.66 ± 0.75 J·m(-3), P = 0.52). Females exhibited greater cartilage stress compared with males (2.2 vs 1.3 J·m(-3), respectively; P = 0.0075), with large quadriceps muscle forces (3.7 body weight in females vs 3.3 body weight in males) and 23% smaller joint contact area (females, 467 ± 59 mm2, vs males, 608 ± 95 mm2). CONCLUSIONS: Patients with patellofemoral pain did not display significantly greater patellar cartilage stress compared with pain-free controls; however, there was a great deal of subject variation. Females exhibited greater peak cartilage stress compared with males, which might explain the greater prevalence of patellofemoral pain in females compared with that in males, but other mechanical and biological factors are clearly involved in this complex pathway to pain.

Biodistribution of AAV8 vectors expressing human low-density lipoprotein receptor in a mouse model of homozygous familial hypercholesterolemia.

Recombinant adeno-associated viral vectors based on serotype 8 (AAV8) transduce liver with superior tropism following intravenous (IV) administration. Previous studies conducted by our lab demonstrated that AAV8-mediated transfer of the human low-density lipoprotein receptor (LDLR) gene driven by a strong liver-specific promoter (thyroxin-binding globulin [TBG]) leads to high level and persistent gene expression in the liver. The approach proved efficacious in reducing plasma cholesterol levels and resulted in the regression of atherosclerotic lesions in a murine model of homozygous familial hypercholesterolemia (hoFH). Prior to advancing this vector, called AAV8.TBG.hLDLR, to the clinic, we set out to investigate vector biodistribution in an hoFH mouse model following IV vector administration to assess the safety profile of this investigational agent. Although AAV genomes were present in all organs at all time points tested (up to 180 days), vector genomes were sequestered mainly in the liver, which contained levels of vector 3 logs higher than that found in other organs. In both sexes, the level of AAV genomes gradually declined and appeared to stabilize 90 days post vector administration in most organs although vector genomes remained high in liver. Vector loads in the circulating blood were high and close to those in liver at the early time point (day 3) but rapidly decreased to a level close to the limit of quantification of the assay. The results of this vector biodistribution study further support a proposed clinical trial to evaluate AAV8 gene therapy for hoFH patients.

Comparison of MRI and ¹8F-NaF PET/CT in patients with patellofemoral pain.

PURPOSE: To determine whether bone metabolic activity corresponds to bone and cartilage damage in patients with patellofemoral pain. MATERIALS AND METHODS: We acquired magnetic resonance imaging (MRI) and (18) F-NaF positron emission tomography (PET) / computed tomography (CT) scans of the knees of 22 subjects. We compared locations of increased tracer uptake on the (18) F-NaF PET images to bone marrow edema and cartilage damage visualized on MRI. RESULTS: We found that increased bone activity on (18) F-NaF PET does not always correspond to structural damage in the bone or cartilage as seen on MRI. CONCLUSION: Our results suggest that (18) F-NaF PET/CT may provide additional information in patellofemoral pain patients compared to MRI.

Patellar tilt correlates with vastus lateralis: vastus medialis activation ratio in maltracking patellofemoral pain patients.

Patellofemoral (PF) pain is a common ailment of the lower extremity. A theorized cause for pain is patellar maltracking due to vasti muscle activation imbalance, represented as large vastus lateralis:vastus medialis (VL:VM) activation ratios. However, evidence relating vasti muscle activation imbalance to patellar maltracking is limited. The purpose of this study was to investigate the relationship between VL:VM activation ratio and patellar tracking measures, patellar tilt and bisect offset, in PF pain subjects and pain-free controls. We evaluated VL:VM activation ratio and VM activation delay relative to VL activation in 39 PF pain subjects and 15 pain-free controls during walking. We classified the PF pain subjects into normal tracking and maltracking groups based on patellar tilt and bisect offset measured from weight-bearing magnetic resonance imaging. Patellar tilt correlated with VL:VM activation ratio only in PF pain subjects classified as maltrackers. This suggests that a clinical intervention targeting vasti muscle activation imbalance may be effective only in PF pain subjects classified as maltrackers.

Patients with patellofemoral pain exhibit elevated bone metabolic activity at the patellofemoral joint.

Patellofemoral pain is characterized by pain behind the kneecap and is often thought to be due to high stress at the patellofemoral joint. While we cannot measure bone stress in vivo, we can visualize bone metabolic activity using (18) F NaF PET/CT, which may be related to bone stress. Our goals were to use (18) F NaF PET/CT to evaluate whether subjects with patellofemoral pain exhibit elevated bone metabolic activity and to determine whether bone metabolic activity correlates with pain intensity. We examined 20 subjects diagnosed with patellofemoral pain. All subjects received an (18) F NaF PET/CT scan of their knees. Uptake of (18) F NaF in the patella and trochlea was quantified by computing the standardized uptake value and normalizing by the background tracer uptake in bone. We detected increased tracer uptake in 85% of the painful knees examined. We found that the painful knees exhibited increased tracer uptake compared to the pain-free knees of four subjects with unilateral pain (P = 0.0006). We also found a correlation between increasing tracer uptake and increasing pain intensity (r(2) = 0.55; P = 0.0005). The implication of these results is that patellofemoral pain may be related to bone metabolic activity at the patellofemoral joint.

New MR imaging methods for metallic implants in the knee: artifact correction and clinical impact.

PURPOSE: To evaluate two magnetic resonance imaging (MRI) techniques, slice encoding for metal artifact correction (SEMAC) and multiacquisition variable-resonance image combination (MAVRIC), for their ability to correct for artifacts in postoperative knees with metal. MATERIALS AND METHODS: A total of 25 knees were imaged in this study. Fourteen total knee replacements (TKRs) in volunteers were scanned with SEMAC, MAVRIC, and 2D fast spin-echo (FSE) to measure artifact extent and implant rotation. The ability of the sequences to measure implant rotation and dimensions was compared in a TKR knee model. Eleven patients with a variety of metallic hardware were imaged with SEMAC and FSE to compare artifact extent and subsequent patient management was recorded. RESULTS: SEMAC and MAVRIC significantly reduced artifact extent compared to FSE (P < 0.0001) and were similar to each other (P = 0.58), allowing accurate measurement of implant dimensions and rotation. The TKRs were properly aligned in the volunteers. Clinical imaging with SEMAC in symptomatic knees significantly reduced artifact (P < 0.05) and showed findings that were on the majority confirmed by subsequent noninvasive or invasive patient studies. CONCLUSION: SEMAC and MAVRIC correct for metal artifact, noninvasively providing high-resolution images with superb bone and soft tissue contrast.

Comparison of quadriceps angle measurements using short-arm and long-arm goniometers: correlation with MRI.

OBJECTIVE: To compare the reliability of quadriceps-angle (Q-angle) measurements performed using a short-arm goniometer and a long-arm goniometer and to assess the accuracy of goniometer-based Q-angle measurements compared with anatomic Q angles derived from magnetic resonance imaging (MRI). DESIGN: An intra- and interobserver reliability study. SETTING: University hospital. PARTICIPANTS: Eighteen healthy subjects with no history of knee pain, trauma, or prior surgery were examined. METHODS: Two physicians, blinded to subject identity, measured Q angles on both knees of all subjects using 2 goniometers: (1) a short-arm goniometer and (2) a long-arm goniometer. Q angles were derived from axial MRIs of the subjects' hip and knees. MAIN OUTCOME MEASUREMENTS: The intra- and interobserver reliabilities of each goniometer were assessed using the intraclass correlation coefficient (ICC). The comparison between clinical and MRI-based Q angles was assessed by using the ICC and a paired t-test. RESULTS: Intra- and interobserver reliabilities of the long-arm goniometer (intraobserver ICC, 0.92; interobserver ICC, 0.88) were better than those of the short-arm goniometer (intraobserver ICC, 0.78; interobserver ICC, 0.56). Although both goniometers measured Q angles that were moderately correlated to the MRI-based measurements (ICC, 0.40), the clinical Q angles were underestimated compared with the MRI-based anatomic Q angles (P < .05). CONCLUSION: The results of this study suggest that, although reproducible Q-angle measurements can be performed using standardized patient positioning and a long-arm goniometer, methods to improve the accuracy of clinical Q-angle measurements are needed.

Differences in patellofemoral kinematics between weight-bearing and non-weight-bearing conditions in patients with patellofemoral pain.

Patellar maltracking is thought to be one source of patellofemoral pain. Measurements of patellar tracking are frequently obtained during non-weight-bearing knee extension; however, pain typically arises during highly loaded activities, such as squatting, stair climbing, and running. It is unclear whether patellofemoral joint kinematics during lightly loaded tasks replicate patellofemoral joint motion during weight-bearing activities. The purpose of this study was to: evaluate differences between upright, weight-bearing and supine, non-weight-bearing joint kinematics in patients with patellofemoral pain; and evaluate whether the kinematics in subjects with maltracking respond differently to weight-bearing than those in nonmaltrackers. We used real-time magnetic resonance imaging to visualize the patellofemoral joint during dynamic knee extension from 30° to 0° of knee flexion during two conditions: upright, weight-bearing and supine, non-weight-bearing. We compared patellofemoral kinematics measured from the images. The patella translated more laterally during the supine task compared to the weight-bearing task for knee flexion angles between 0° and 5° (p = 0.001). The kinematics of the maltrackers responded differently to joint loading than those of the non-maltrackers. In subjects with excessive lateral patellar translation, the patella translated more laterally during upright, weight-bearing knee extension for knee flexion angles between 25° and 30° (p = 0.001). However, in subjects with normal patellar translation, the patella translated more laterally during supine, non-weight-bearing knee extension near full extension (p = 0.001). These results suggest that patellofemoral kinematics measured during supine, unloaded tasks do not accurately represent the joint motion during weight-bearing activities.

Patellar maltracking correlates with vastus medialis activation delay in patellofemoral pain patients.

BACKGROUND: Delayed onset of vastus medialis (VM) activity compared with vastus lateralis activity is a reported cause for patellofemoral pain. The delayed onset of VM activity in patellofemoral pain patients likely causes an imbalance in muscle forces and lateral maltracking of the patella; however, evidence relating VM activation delay to patellar maltracking is sparse. The aim of this study was to investigate the relationship between VM activation delay and patellar maltracking measures in pain-free controls and patellofemoral pain patients. HYPOTHESIS: Patellar tilt and bisect offset, measures of patellar tracking, correlate with VM activation delay in patellofemoral pain patients classified as maltrackers. STUDY DESIGN: Case control study; Level of evidence, 3. METHODS: Vasti muscle activations were recorded in pain-free (n = 15) and patellofemoral pain (n = 40) participants during walking and jogging. All participants were scanned in an open-configuration magnetic resonance scanner in an upright weightbearing position to acquire the position of the patella with respect to the femur. Patellar tilt and bisect offset were measured, and patellofemoral pain participants were classified into normal tracking and maltracking groups. RESULTS: Correlations between VM activation delay and patellar maltracking measures were statistically significant in only the patellofemoral pain participants classified as maltrackers with both abnormal tilt and abnormal bisect offset (R(2) = .89, P < .001, with patellar tilt during walking; R(2) = .75, P = .012, with bisect offset during jogging). There were no differences between the means of activation delays in pain-free and all patellofemoral pain participants during walking (P = .516) or jogging (P = .731). CONCLUSION: There was a relationship between VM activation delay and patellar maltracking in the subgroup of patellofemoral pain participants classified as maltrackers with both abnormal tilt and abnormal bisect offset. CLINICAL RELEVANCE: A clinical intervention such as VM retraining may be effective in only a subset of patellofemoral pain participants-namely, those with excessive tilt and excessive bisect offset measures. The results highlight the importance of appropriate classification of patellofemoral pain patients before selection of a clinical intervention.

Using real-time MRI to quantify altered joint kinematics in subjects with patellofemoral pain and to evaluate the effects of a patellar brace or sleeve on joint motion.

Abnormal patellofemoral joint motion is a possible cause of patellofemoral pain, and patellar braces are thought to alleviate pain by restoring normal joint kinematics. We evaluated whether females with patellofemoral pain exhibit abnormal patellofemoral joint kinematics during dynamic, weight-bearing knee extension and assessed the effects of knee braces on patellofemoral motion. Real-time magnetic resonance (MR) images of the patellofemoral joints of 36 female volunteers (13 pain-free controls, 23 patellofemoral pain) were acquired during weight-bearing knee extension. Pain subjects were also imaged while wearing a patellar-stabilizing brace and a patellar sleeve. We measured axial-plane kinematics from the images. Females with patellofemoral pain exhibited increased lateral translation of the patella for knee flexion angles between 0 degrees and 50 degrees (p = 0.03), and increased lateral tilt for knee flexion angles between 0 degrees and 20 degrees (p = 0.04). The brace and sleeve reduced the lateral translation of the patella; however, the brace reduced lateral displacement more than the sleeve (p = 0.006). The brace reduced patellar tilt near full extension (p = 0.001), while the sleeve had no effect on patellar tilt. Our results indicate that some subjects with patellofemoral pain exhibit abnormal weight-bearing joint kinematics and that braces may be effective in reducing patellar maltracking in these subjects.

Feasibility of using real-time MRI to measure joint kinematics in 1.5T and open-bore 0.5T systems.

PURPOSE: To test the feasibility and accuracy of measuring joint motion with real-time MRI in a 1.5T scanner and in a 0.5T open-bore scanner and to assess the dependence of measurement accuracy on movement speed. MATERIALS AND METHODS: We developed an MRI-compatible motion phantom to evaluate the accuracy of tracking bone positions with real-time MRI for varying movement speeds. The measurement error was determined by comparing phantom positions estimated from real-time MRI to those measured using optical motion capture techniques. To assess the feasibility of measuring in vivo joint motion, we calculated 2D knee joint kinematics during knee extension in six subjects and compared them to previously reported measurements. RESULTS: Measurement accuracy decreased as the phantom's movement speed increased. The measurement accuracy was within 2 mm for velocities up to 217 mm/s in the 1.5T scanner and 38 mm/s in the 0.5T scanner. We measured knee joint kinematics with small intraobserver variation (variance of 0.8 degrees for rotation and 3.6% of patellar width for translation). CONCLUSION: Our results suggest that real-time MRI can be used to measure joint kinematics when 2 mm accuracy is sufficient. They can also be used to prescribe the speed of joint motion necessary to achieve certain measurement accuracy.