OBJECTIVE: The purpose of this study was to describe the current practice trends for managing symptomatic cartilage lesions of the knee with microfracture among ICRS (International Cartilage Regeneration & Joint Repair Society) members. DESIGN: A 42-item electronic questionnaire was sent to all ICRS members, which explored indications, surgical technique, postoperative management, and outcomes of the microfracture procedure for the treatment of symptomatic, full thickness chondral and osteochondral defects of the knee. Responses were compared between surgeons from different regions and years of practice. RESULTS: A total of 385 surgeons answered the questionnaire. There was a significant difference noted in the use of microfracture among surgeons by region (P < 0.001). There was no association between the number of years in practice and the self-reported proportion of microfracture cases performed (P = 0.37). Fifty-eight subjects (15%) indicated that they do not perform microfracture at all. Regarding indication for surgery, 56% of surgeons would limit their indication of microfracture to lesions measuring 2 cm2 or less. Half of the surgeons reported no upper age or body mass index limit. Regarding surgical technique, 90% of surgeons would recommend a formal debridement of the calcified layer and 91% believe it is important to create stable vertical walls. Overall, 47% of surgeons use biologic augmentation, with no significant difference between regions (P = 0.35) or years of practice (P = 0.67). Rehabilitation protocols varied widely among surgeons. CONCLUSIONS: Indications, operative technique, and rehabilitation protocols utilized for patients undergoing microfracture procedures vary widely among ICRS members. Regional differences and resources likely contribute to these practice pattern variations.

Experimental data and computational models suggest that blockade of muscarinic cholinergic receptors impairs paired-associate learning and increases proactive interference (E. DeRosa & M. E. Hasselmo, 2000; M. E. Hasselmo & J. M. Bower, 1993). The results presented here provide evidence in humans supporting these hypotheses. Young healthy subjects first learned baseline word pairs (A-B) and, after a delay, learned additional overlapping (A-C) and nonoverlapping (D-E) word pairs. As predicted, when compared with subjects who received the active placebo glycopyrrolate (4 microg/kg) and subjects who were not injected, those who received scopolamine (8 microg/kg) showed (a) overall impairment in new word paired-associate learning, but no impairment in cued recall of previously learned associates; and (b) greater impairment in learning overlapping (A-C) compared with nonoverlapping (D-E) paired associates.

Objective

The aim of this study was to evaluate levels of consensus in rehabilitation practices following MACI (autologous cultured chondrocytes on porcine collagen membrane) treatment based on the experience of an expert panel of U.S. orthopedic surgeons.

Design

A list of 24 questions was devised based on the current MACI rehabilitation protocol, literature review, and discussion with orthopedic surgeons. Known areas of variability were used to establish 4 consensus domains, stratified on lesion location (tibiofemoral [TF] or patellofemoral [PF]), including weightbearing (WB), range of motion (ROM), return to work/daily activities of living, and return to sports. A 3-step Delphi technique was used to establish consensus.

Results

Consensus (>75% agreement) was achieved on all 4 consensus domains. Time to full WB was agreed as immediate (with bracing) for PF patients (dependent on concomitant procedures), and 7 to 9 weeks in TF patients. A progression for ROM was agreed that allowed patients to reach 90° by week 4, with subsequent progression as tolerated. The panel estimated that the time to full ROM would be 7 to 9 weeks on average. A range of time was established for release to activities of daily living, work, and sports, dependent on lesion and patient characteristics.

Conclusions

Good consensus was established among a panel of U.S. surgeons for rehabilitation practices following MACI treatment of knee cartilage lesions. The consensus of experts can aid surgeons and patients in the expectations and rehabilitation process as MACI surgery becomes more prevalent in the United States.

Herein we present major updates to the National NeuroAIDS Tissue Consortium (NNTC) database. The NNTC's ongoing multisite clinical research study was established to facilitate access to ante-mortem and post-mortem data, tissues and biofluids for the neurohuman immunodeficiency virus (HIV) research community. Recently, the NNTC has expanded to include data from the central nervous system HIV Antiretroviral Therapy Effects Research (CHARTER) study. The data and biospecimens from CHARTER and NNTC cohorts are available to qualified researchers upon request. Data generated by requestors using NNTC biospecimens and tissues are returned to the NNTC upon the conclusion of requestors' work, and this external, experimental data are annotated and curated in the publically accessible NNTC database, thereby extending the utility of each case. A flexible and extensible database ontology allows the integration of disparate data sets, including external experimental data, clinical neuropsychological and neuromedical testing data, tissue pathology and neuroimaging data.

Background

Cognitive dysfunction in human immunodeficiency virus (HIV) has decreased, but milder forms of HIV-associated neurocognitive disorders (HAND) persist along with motor dysfunction. The HIV Motor Scale (HMS) is a validated tool that captures motor abnormalities on routine neurologic examination and which is associated with cognitive impairment in HIV. In this study, we applied a modified HMS (MHMS) to a nationwide cohort of people with longstanding HIV to characterize and understand the factors contributing to motor dysfunction.

Methods

The National NeuroAIDS Tissue Consortium is a nationwide longitudinal cohort study. Participants undergo regular assessments including neurological examination, neuropsychological testing, and immunovirologic data collection. Data from examinations were used to calculate the MHMS score, which was then correlated with history of AIDS-related central nervous system (CNS) disorders (ARCD; eg, prior CNS opportunistic infection), cerebrovascular disease (CVD), and HAND.

Results

Sixty-nine percent of participants showed an abnormality on the MHMS, with 27% classified as severe. Results did not vary based on demographic or immunologic variables. The most common abnormalities seen were gait (54%), followed by coordination (39%) and strength (25%), and these commonly co-occurred. CVD (P = .02), history of ARCD (P = .001), and HAND (P = .001) were all associated with higher (ie, worse) HMS in univariate analyses; CVD and ARCD persisted in multivariate analyses. CVD was also marginally associated with symptomatic HAND.

Conclusions

Complex motor dysfunction remains common in HIV and is associated with CVD, ARCD, and to a lesser extent, HAND. Future studies are needed to understand the longitudinal trajectory of HIV-associated motor dysfunction, its neural substrates, and impact on quality of life.

Objectives

Multimorbidity and frailty are consequences of aging with HIV, yet not everyone with medical disease is frail. Our objective was to identify factors associated with frailty in a multimorbid HIV-infected cohort.

Design

Analysis of a prospective, observational, longitudinal cohort.

Methods

Three hundred and thirty-two participants in the medically advanced National NeuroAIDS Tissue Consortium (NNTC) study were categorized as frail, prefrail, or robust with the Fried Frailty Index. A series of logistic regression analyses (first univariate, then multivariable) were conducted to determine whether medical comorbidities, immunologic and virologic parameters, and/or neuropsychiatric variables predicted increased odds of frailty.

Results

The mean number of medical comorbidities per participant was 2.7, mean CD4 T-cell count was 530 cells/μl, and 77% had undetectable HIV RNA in blood. Twenty-two percent were frail, 55% prefrail, and 23% robust. Significant predictors of frailty in multivariable analysis were cognitive diagnosis rendered by Frascati criteria, depressive symptoms, diabetes mellitus, chronic obstructive pulmonary disease (COPD), and sex. Men were less likely to be frail than women. Higher odds of frailty were seen with: symptomatic, but not asymptomatic, cognitive impairment (compared with cognitive normals); more depressive symptoms; diabetes mellitus; and COPD.

Conclusion

Neuropsychiatric illness increased odds of being frail on a predominantly physical/motoric measure, but only when symptomatic. Lack of association with asymptomatic impairment may reflect the importance of functional limitation to frailty, or possibly a unique resilience phenotype. Understanding why sex and symptomatic neuropsychiatric illness are associated with frailty will be important in managing HIV-associated morbidity in aging populations.

OBJECTIVES:Multi-morbidity and frailty are consequences of aging with HIV, yet not everyone with medical disease is frail. Our objective was to identify factors associated with frailty in a multi-morbid HIV-infected cohort. DESIGN:Analysis of a prospective, observational, longitudinal cohort. METHODS:Three hundred thirty two participants in the medically advanced NNTC were categorized as frail, pre-frail, or robust with the Fried Frailty Index. A series of logistic regression analyses (first univariate, then multivariable) were conducted to determine whether medical comorbidities, immunologic and virologic parameters, and/or neuropsychiatric variables predicted increased odds of frailty. RESULTS:The mean number of medical comorbidities per participant was 2.7, mean CD4 T-cell count was 530 cells/mm3, and 77% had undetectable HIV RNA in blood. Twenty two percent were frail, 55% pre-frail, and 23% robust. Significant predictors of frailty in multivariable analysis were: cognitive diagnosis rendered by Frascati criteria, depressive symptoms, diabetes mellitus (DM), chronic obstructive pulmonary disease (COPD), and sex. Men were less likely to be frail than women. Higher odds of frailty were seen with: symptomatic, but not asymptomatic, cognitive impairment (compared to cognitive normals); more depressive symptoms; DM; and COPD. CONCLUSIONS:Neuropsychiatric illness increased odds of being frail on a predominantly physical/motoric measure, but only when symptomatic. Lack of association with asymptomatic impairment may reflect the importance of functional limitation to frailty, or possibly a unique resilience phenotype. Understanding why sex and symptomatic neuropsychiatric illness are associated with frailty will be important in managing HIV-associated morbidity in aging populations.

Objective

Replicating HIV-1 in the brain is present in HIV encephalitis (HIVE) and microglial nodule encephalitis (MGNE) and is putatively linked with HIV-associated neurocognitive disorders (HAND). A cliniconeurovirological correlation was conducted to elucidate the relationship between brain viral load and clinical phenotype. SUBJECTS AND ASSAYS: HIV gag/pol RNA and DNA copies were quantified with reverse transcriptase-polymerase chain reaction or polymerase chain reaction in 148 HAART-era brain specimens. Comparison with HAND, HIVE, and MGNE and correlation with neuropsychological (NP) test scores were done using one-way ANOVA with Tukey-Kramer and Spearman tests, respectively.

Results

Brain HIV RNA was higher in subjects with HAND plus HIVE versus without HAND (delta = 2.48 log10 units, n = 27 versus 36, P < 0.001). In HAND without HIVE or MGNE, brain HIV RNA was not significantly different versus without HAND (P = 0.314). Worse NP scores correlated significantly with higher HIV RNA and interferon responses in brain specimens (P < 0.001) but not with HIV RNA levels in premortem blood plasma (n = 114) or cerebrospinal fluid (n = 104). In subjects with MGNE, brain HIV RNA was slightly higher versus without MGNE (P < 0.01) and much lower versus with HIVE (P < 0.001).

Conclusions

Brain HIV RNA and to a lesser extent HIV DNA are correlated with worse NP performance in the 6 months before death. Linkage occurs primarily in patients with HIVE and MGNE, and these patients could obtain added NP improvement by further reducing brain HIV while on HAART. Patients not in those groups are less certain to obtain added NP benefit.

Myelodysplastic neoplasms (MDS) are a collection of hematopoietic disorders with widely variable prognoses and treatment options. Accurate pathologic diagnoses present challenges because of interobserver variability in interpreting morphology and quantifying dysplasia. We compared local clinical site diagnoses with central, adjudicated review from 918 participants enrolled in the ongoing National Heart, Lung, and Blood Institute National MDS Natural History Study, a prospective observational cohort study of participants with suspected MDS or MDS/myeloproliferative neoplasms (MPNs). Locally, 264 (29%) were diagnosed as having MDS, 15 (2%) MDS/MPN overlap, 62 (7%) idiopathic cytopenia of undetermined significance (ICUS), 0 (0%) acute myeloid leukemia (AML) with <30% blasts, and 577 (63%) as other. Approximately one-third of cases were reclassified after central review, with 266 (29%) diagnosed as MDS, 45 (5%) MDS/MPN overlap, 49 (5%) ICUS, 15 (2%) AML with <30%, and 543 (59%) as other. Site miscoding errors accounted for more than half (53%) of the local misdiagnoses, leaving a true misdiagnosis rate of 15% overall, 21% for MDS. Therapies were reported in 37% of patients, including 43% of patients with MDS, 49% of patients with MDS/MPN, and 86% of patients with AML with <30% blasts. Treatment rates were lower (25%) in cases with true discordance in diagnosis compared with those for whom local and central diagnoses agreed (40%), and receipt of inappropriate therapy occurred in 7% of misdiagnosed cases. Discordant diagnoses were frequent, which has implications for the accuracy of study-related and national registries and can lead to inappropriate therapy. This trial was registered at www.clinicaltrials.gov as #NCT05074550.

Purpose

The use of telemedicine (TM) has accelerated in recent years, yet research on the implementation and effectiveness of TM-delivered medication treatment for opioid use disorder (MOUD) has been limited. This study investigated the feasibility of implementing a care coordination model involving MOUD delivered via an external TM provider for the purpose of expanding access to MOUD for patients in rural settings.

Methods

The study tested a care coordination model in 6 rural primary care sites by establishing referral and coordination between the clinic and a TM company for MOUD. The intervention spanned approximately 6 months from July/August 2020 to January 2021, coinciding with the peak of the COVID-19 pandemic. Each clinic tracked patients with OUD in a registry during the intervention period. A pre-/post-intervention design (N = 6) was used to assess the clinic-level outcome as patient-days on MOUD based on patient electronic health records.

Findings

All clinics implemented critical components of the intervention, with an overall TM referral rate of 11.7% among patients in the registry. Five of the 6 sites showed an increase in patient-days on MOUD during the intervention period compared to the 6-month period before the intervention (mean increase per 1,000 patients: 132 days, P = .08, Cohen's d = 0.55). The largest increases occurred in clinics that lacked MOUD capacity or had a greater number of patients initiating MOUD during the intervention period.

Conclusions

To expand access to MOUD in rural settings, the care coordination model is most effective when implemented in clinics that have negligible or limited MOUD capacity.