Does-dual mobility still offer improved stability in smaller cup sizes? A computer modelling comparison of stability with 22-mm versus 28-mm inner heads in dual-mobility versus single-bearing constructs.

PURPOSE: Dislocation remains 1 of the leading causes of revision after primary total hip arthroplasty (THA) and there is clear evidence the dual-mobility (DM) is used more frequently to minimise this. But in smaller cups, whether the use of DM with smaller 22-mm heads imparts any increased stability compared to standard bearing is unknown; especially when those smaller cups now allow for large single-bearing (SB) heads. METHODS: 3 primary cup sizes (48 mm, 50 mm, 52 mm) were chosen a priori for modelling. Head sizes trialled for the standard bearing (SB) constructs group were 28-0 mm, 32-0 mm and 36-0 mm against neutral polyethylene liners. In the modular sub-hemispheric DM constructs the inner head sizes for the DM constructs were altered where appropriate (22-0 mm vs. 28-0 mm). Cup position, stem offset, and stem size were standardised. RESULTS: Both DM constructs outperformed all SB constructs because of a statistically significant jump distance increase (p < 0.001). However, there was no difference in range of motion (ROM) or jump distances between the 22-mm and 28-mm DM inner heads.The ROM angle before impingement between the DM (with 22-mm or 28-mm heads) and SB (with different head sizes where appropriate) showed no statistically significant difference. However, DM constructs presented significantly larger jump distances than SB constructs for both provocative dislocation tests across all 3 cup sizes.Of interest, for 50-mm and 52-mm cup sizes (for which this particular DM construct design can accommodate both 22-mm and 28-mm inner heads), there were no differences in ROM or jump distance between 22-mm versus 28-mm inner heads. CONCLUSIONS: In this computer-modelling study, DM constructs are advantageous over SB constructs for improving jump distances in clinically provocative positions, but not range of motion angles. Inner head diameter of DM has no effect on stability.

Using implementation science to promote the use of the fascia iliaca blocks in hip fracture care.

PURPOSE: There is variable and suboptimal use of fascia iliaca compartment nerve blocks (FICBs) in hip fracture care. Our objective was to use an evidence-based and theory-informed implementation science approach to analyze barriers and facilitators to timely administration of FICB and select evidence-based interventions to enhance uptake. METHODS: We conducted a qualitative study at a single centre using semistructured interviews and site observations. We interviewed 35 stakeholders including health care providers, managers, patients, and caregivers. We mapped barriers and facilitators to the Theoretical Domains Framework (TDF) and Consolidated Framework for Implementation Research (CFIR). We compared the rate and timeliness of FICB administration before and after evidence-based implementation strategies were applied. RESULTS: The study identified 18 barriers and 11 facilitators within seven themes of influences of FICB use: interpersonal relationships between health care professionals; clinician knowledge and skills related to FICB; roles, responsibilities, and processes for delivering FICB; perceptions on using FICB for pain; patient and caregiver perceptions on using FICB for pain; communication of hip fracture care between departments; and resources for delivering FICBs. We mapped the behaviour change domains to eight implementation strategies: restructure the environment, create and distribute educational materials, prepare patients to be active participants, perform audits and give feedback, use local opinion leaders, use champions, train staff on FICB procedures, and mandate change. We observed an increase in the rates of FICBs administered (48% vs 65%) and a decrease in the median time to administration (1.63 vs 0.81 days). CONCLUSION: Our study explains why FICBs are underused and shows that the TDF and CFIR provide a framework to identify barriers and facilitators to FICB implementation. The mapped implementation strategies can guide institutions to improve use of FICB in hip fracture care.

RéSUMé: OBJECTIF: Il existe une utilisation variable et sous-optimale des blocs nerveux du compartiment fascia iliaca (FICB) dans les soins des fractures de la hanche. Notre objectif était d'utiliser une approche scientifique de la mise en œuvre fondée sur des données probantes et sur la théorie pour analyser les obstacles et les facilitateurs à l'administration opportune d'un FICB et pour sélectionner des interventions fondées sur des données probantes pour améliorer l'adoption de cette technique. MéTHODE: Nous avons mené une étude qualitative dans un seul centre à l'aide d'entrevues semi-structurées et d'observations sur place. Nous avons interviewé 35 intervenant·es, y compris des prestataires de soins de santé, des gestionnaires, des patient·es et des soignant·es. Nous avons cartographié les obstacles et les facilitateurs du cadre des domaines théoriques (Theoretical Domains Framework, TDF) et du cadre consolidé pour la recherche sur la mise en œuvre (Consolidated Framework for Implementation Research, CFIR). Nous avons comparé le taux et la rapidité d'administration d'un FICB avant et après l'application des stratégies de mise en œuvre fondées sur des données probantes. RéSULTATS: L'étude a identifié 18 obstacles et 11 facilitateurs dans sept thèmes d'influence de l'utilisation du FICB : les relations interpersonnelles entre les professionnel·les de la santé; les connaissances et les compétences des clinicien·nes liées au FICB; les rôles, responsabilités et processus d'exécution des FICB; les perceptions de l'utilisation des FICB pour soulager la douleur; les perceptions des patient·es et des soignant·es concernant l'utilisation de FICB pour soulager la douleur; la communication des soins des fractures de la hanche entre les services; et les ressources nécessaires à l'exécution des FICB. Nous avons mis en correspondance les domaines de changement de comportement avec huit stratégies de mise en œuvre : restructurer l'environnement, créer et distribuer du matériel éducatif, préparer les patient·es à participer activement, effectuer des audits et donner de la rétroaction, faire appel à des leaders d'opinion locales et locaux, utiliser des champion·nes, former le personnel sur les interventions de FICB et forcer au changement. Nous avons observé une augmentation des taux de FICB administrés (48% vs 65%) et une diminution du délai médian d'administration (1,63 vs 0,81 jour). CONCLUSION: Notre étude explique pourquoi les FICB sont sous-utilisés et montre que le TDF et le CFIR fournissent un cadre pour identifier les obstacles et les facilitateurs à la mise en œuvre des FICB. Les stratégies de mise en œuvre cartographiées peuvent aider les établissements à améliorer l'utilisation des FICB dans le traitement des fractures de la hanche.

Converting hip and knee arthroplasty cases to same-day surgery due to COVID-19.

AIMS: In 2020, the COVID-19 pandemic meant that proceeding with elective surgery was restricted to minimize exposure on wards. In order to maintain throughput of elective cases, our hospital (St Michaels Hospital, Toronto, Canada) was forced to convert as many cases as possible to same-day procedures rather than overnight admission. In this retrospective analysis, we review the cases performed as same-day arthroplasty surgeries compared to the same period in the previous 12 months. METHODS: We conducted a retrospective analysis of patients undergoing total hip and knee arthroplasties over a three-month period between October and December in 2019, and again in 2020, in the middle of the COVID-19 pandemic. Patient demographics, number of outpatient primary arthroplasty cases, length of stay for admissions, 30-day readmission, and complications were collated. RESULTS: In total, 428 patient charts were reviewed for October to December of 2019 (n = 195) and 2020 (n = 233). Of those, total hip arthroplasties (THAs) comprised 60% and 58.8% for 2019 and 2020, respectively. Demographic data was comparable with no statistical difference for age, sex, contralateral joint arthroplasty, or BMI. American Society of Anesthesiologists grade I was more highly prevalent in the 2020 cohort (5.1-times increase; n = 13 vs n = 1). Degenerative disc disease and fibromyalgia were less significantly prevalent in the 2020 cohort. There was a significant increase in same day discharges for non-direct anterior approach THAs (two-times increase) and total knee arthroplasty (ten-times increase), with a reciprocal decrease in next day discharges. There were significantly fewer reported superficial wound infections in 2020 (5.6% vs 1.7%) and no significant differences in readmissions or emergency department visits (3.1% vs 3.0%). CONCLUSION: The COVID-19 pandemic meant that hospitals and patients were hopeful to minimize the exposure to the wards, and minimize strain on the already taxed inpatient beds. With few positives during the COVID-19 crisis, the pandemic was the catalyst to speed up the outpatient arthroplasty programme that has resulted in our institution being more efficient, and with no increase in readmissions or early complications. Cite this article: Bone Jt Open 2021;2(7):545-551.

Ebola Virus Disease Preparedness Assessment and Risk Mapping in Uganda, August-September 2018.

Uganda's proximity to the tenth Ebola virus disease (EVD) outbreak in the Democratic Republic of the Congo (DRC) presents a high risk of cross-border EVD transmission. Uganda conducted preparedness and risk-mapping activities to strengthen capacity to prevent EVD importation and spread from cross-border transmission. We adapted the World Health Organization (WHO) EVD Consolidated Preparedness Checklist to assess preparedness in 11 International Health Regulations domains at the district level, health facilities, and points of entry; the US Centers for Disease Control and Prevention (CDC) Border Health Capacity Discussion Guide to describe public health capacity; and the CDC Population Connectivity Across Borders tool kit to characterize movement and connectivity patterns. We identified 40 ground crossings (13 official, 27 unofficial), 80 health facilities, and more than 500 locations in 12 high-risk districts along the DRC border with increased connectivity to the EVD epicenter. The team also identified routes and congregation hubs, including origins and destinations for cross-border travelers to specified locations. Ten of the 12 districts scored less than 50% on the preparedness assessment. Using these results, Uganda developed a national EVD preparedness and response plan, including tailored interventions to enhance EVD surveillance, laboratory capacity, healthcare professional capacity, provision of supplies to priority locations, building treatment units in strategic locations, and enhancing EVD risk communication. We identified priority interventions to address risk of EVD importation and spread into Uganda. Lessons learned from this process will inform strategies to strengthen public health emergency systems in their response to public health events in similar settings.

Population Movement Patterns Among the Democratic Republic of the Congo, Rwanda, and Uganda During an Outbreak of Ebola Virus Disease: Results from Community Engagement in Two Districts - Uganda, March 2019.

Tailoring communicable disease preparedness and response strategies to unique population movement patterns between an outbreak area and neighboring countries can help limit the international spread of disease. Global recognition of the value of addressing community connectivity in preparedness and response, through field work and visualizing the identified movement patterns, is reflected in the World Health Organization's declaration on July 17, 2019, that the 10th Ebola virus disease (Ebola) outbreak in the Democratic Republic of the Congo (DRC) was a Public Health Emergency of International Concern (1). In March 2019, the Infectious Diseases Institute (IDI), Uganda, in collaboration with the Ministry of Health (MOH) Uganda and CDC, had previously identified areas at increased risk for Ebola importation by facilitating community engagement with participatory mapping to characterize cross-border population connectivity patterns. Multisectoral participants identified 31 locations and associated movement pathways with high levels of connectivity to the Ebola outbreak areas. They described a major shift in the movement pattern between Goma (DRC) and Kisoro (Uganda), mainly through Rwanda, when Rwanda closed the Cyanika ground crossing with Uganda. This closure led some travelers to use a potentially less secure route within DRC. District and national leadership used these results to bolster preparedness at identified points of entry and health care facilities and prioritized locations at high risk further into Uganda, especially markets and transportation hubs, for enhanced preparedness. Strategies to forecast, identify, and rapidly respond to the international spread of disease require adapting to complex, dynamic, multisectoral cross-border population movement, which can be influenced by border control and public health measures of neighboring countries.

Outcomes of Acetabular Reconstructions for the Management of Chronic Pelvic Discontinuity: A Systematic Review.

BACKGROUND: A number of articles have been published reporting on the clinical outcomes of various acetabular reconstructions for the management of chronic pelvic discontinuity (PD). However, no systematic review of the literature has been published to date comparing the outcome and complications of different approaches to reconstruction. METHODS: The US National Library of Medicine (PubMed/MEDLINE) and EMBASE were queried for publications from January 1980 to January 2019 using keywords pertinent to total hip arthroplasty, PD, acetabular dissociation, clinical or functional outcomes, and revision total hip arthroplasty or postoperative complications. RESULTS: Overall, 18 articles were included in this analysis (569 cases with chronic PD). The overall survival rate of the acetabular components used for the treatment of chronic PD was 84.7% (482 of 569 cases) at mid-term follow-up, whereas the most common reasons for revision were aseptic loosening (54 of 569 hips; 9.5%), dislocations (45 of 569 hips; 7.9%), periprosthetic joint infection (30 of 569 hips; 5.3%), and periprosthetic fractures (11 of 569 hips; 1.9%). Both pelvic distraction technique (combined with highly porous shells) and custom triflanges resulted in less than 5% failure rates (96.2% and 95.8%, respectively) at final follow-up. Also, highly effective in the treatment of PD were cup-cages and highly porous shells with and/or without augments with 92% survivorship free of revision for aseptic loosening for both reconstruction methods. Inferior outcomes were reported for conventional cementless shells combined with acetabular plates (72.7%) as well as ilioischial cages and reconstruction rings (66.7% and 60.6% survivorship, respectively). CONCLUSION: The current literature contains moderate quality evidence in support of the use of custom triflange implants and pelvic distraction techniques for the treatment of chronic PD, with a less than 5% all-cause revision rate and low complication rates at mean mid-term follow-up. Cup-cages and highly porous shells with or without augments could also be considered for the treatment of PD because both resulted in greater than 90% survival rates. Finally, there is still no consensus regarding the impact of different types of acetabular reconstruction methods on optimizing the healing potential of PD, and further studies are required in this area to better understand the influence of PD healing on construct survivorship and functional outcomes with each reconstruction method.

Temporal Trends and Predictors of Thirty-Day Readmissions and Emergency Department Visits Following Total Knee Arthroplasty in Ontario Between 2003 and 2016.

BACKGROUND: Total knee arthroplasty (TKA) is the second most common surgery performed in Canada. Understanding and improving quality metrics associated with such high-volume procedures is of utmost importance to maximize value within the healthcare system, which is a balance between cost and quality. Although rates and predictors of hospital readmission and emergency department (ED) visits following TKA have previously been described in privatized healthcare settings, few studies have evaluated trends in length of stay (LOS), hospital readmissions, and ED visits following TKA in a universal single-payer system. METHODS: Using data from a provincially held and validated registry, the Institute for Clinical and Evaluative Sciences, we undertook a review of all 205,152 TKAs performed in the province of Ontario, Canada, between 2003 and 2016. We determined temporal trends in utilization, LOS, readmissions, and ED visits and evaluated patient and provider predictors of hospital readmissions and ED visits using multivariate logistic regression modeling. We also grouped and described the most common reasons for readmission and ED visits based on the available International Classification of Diseases, Ninth Revision and Tenth Revision coding information. RESULTS: LOS decreased significantly over the study period (P < .0001), from a median of 5 days (10th percentile 3 days, 90th percentile 8 days) in 2003 to a median of 3 days (10th percentile 2 days, 90th percentile 4 days) in 2016. All-cause 30-day readmissions did not change significantly over the study period, but the rate of ED visits increased significantly over time. Predictors of 30-day readmission following TKA included older age, male gender, lower income quartile, not having a postoperative visit with a primary care physician (PCP), increased comorbidities, longer LOS, urgent or revision surgery, admission to a teaching hospital, and discharge to an inpatient rehabilitation facility. Variables that predicted increased odds of an ED visit included older age, male gender, lower income quartile, not having a postop visit with a PCP, increasing comorbidities, year of surgery, longer LOS, and revision surgery. Admission to a teaching hospital and discharge to an inpatient rehabilitation facility showed a trend toward increased odds of an ED visit. CONCLUSIONS: We identified a significant increase in ED visits following TKA in Ontario between 2003 and 2016, with no corresponding increase in hospital readmissions despite a significant temporal trend toward shorter LOS. Predictors of ED visits and readmissions were similar, including male gender, lower income, higher comorbidities, and lacking a PCP visit postoperatively. Increased rates of ED visits following TKA in Ontario represent a quality problem, as they are associated with increased cost to the public healthcare system without any substantial benefit. Interventions aimed at redirecting patients from the ED for minor postoperative concerns should be investigated, as this is likely to improve care by reducing costs, improving efficiency, and enhancing patient experience.

The Development of a Standardized Pathway for Outpatient Ambulatory Fracture Surgery: To Admit or Not to Admit.

BACKGROUND: Increased scrutiny of health-care costs and inpatient length of stay has resulted in many orthopaedic procedures transitioning to outpatient settings. Recent studies have supported the safety and efficiency of outpatient fracture procedures. The aim of the present study was to reduce unnecessary inpatient hospitalizations for healthy patients awaiting surgical treatment of a fracture by 80% by June 30, 2017, with a focus on timely, efficient, and patient-centered care. METHODS: The study design was a time series using statistical process control methodology. Baseline data from October 2014 to June 2016 were compared with the intervention period from July 2016 to December 2018. The Model for Improvement was used as the framework for developing and implementing interventions. The main interventions were a policy change to allow booking of outpatient urgent-room cases, education for patients and nurses, and the development of a standardized outpatient pathway. RESULTS: One hundred and eighty-seven patients during the pre-intervention period and 308 patients during the intervention period were eligible for the ambulatory pathway. The percentage of patients managed as outpatients increased from 1.6% pre-intervention to 89.1% post-intervention. The length of stay was reduced from 2.8 to 0.2 days, a decrease of 94.0%. Patient satisfaction remained high, and there were no safety concerns while patients waited at home for the surgical procedure. CONCLUSIONS: The outpatient fracture pathway vastly improved the efficiency and timeliness of care and reduced health-care costs. A patient-centered culture and support from hospital administration were integral in producing sustainable improvement. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Quality improvement in pediatric urology-a historical perspective on street pumps, puerperal fever, surgical infection, and contemporary methodology.

Quality improvement and patient safety (QIPS) can trace its origin back to the court of Hammurabi (circa 1700BC). However, it did not begin its evolution into its present methodology until the mid-19th century. It was through the application of quantitative parameters around the time of World War I that the field of QIPS has matured and gained a significant presence in the practice of medicine. Herein, the authors present a historical overview of this increasingly important field and correlate the current pediatric urology literature that has arisen from it. Because QIPS research is likely to contribute to efficient, streamlined health care through rapid changes to routine clinical practices, it would behoove pediatric urologists to familiarize themselves with its history and fundamental concepts.

The Predictive Value of the Clinical Frailty Scale on Discharge Destination and Complications in Older Hip Fracture Patients.

OBJECTIVES: To determine whether the Clinical Frailty Scale (CFS), a validated frailty tool, was associated with discharge destination. Secondary objectives were to determine whether the CFS was associated with in-hospital complications and length of stay. DESIGN: This is a 5-year retrospective cohort study. SETTING: The study took place at an academic Level 1 trauma center. PATIENTS/PARTICIPANTS: All patients 65 years of age and older admitted with an isolated hip fracture were included (N = 423). INTERVENTION: Preadmission CFS was determined as part of routine clinical care prospectively and abstracted from the chart. MAIN OUTCOME MEASUREMENTS: We collected demographic and process data associated with adverse outcomes (age, sex, time to surgery, and mode of anesthesia) and used multivariable logistic regression to determine the association between CFS with discharge destination, in-hospital complications, and length of stay. RESULTS: Preadmission frailty was independently associated with adverse discharge destination (adjusted odds ratio 23.0; 95% confidence interval, 3.0-173.5) and in-hospital complications (adjusted odds ratio 4.8; 95% confidence interval, 2.1-10.8) in greater magnitude than traditional risk factors such as age, male sex, time to surgery, and mode of anesthesia. There was a dose-response relationship between increasing frailty and length of stay (P < 0.001). CONCLUSIONS: Preadmission frailty as quantified by the CFS is associated with discharge destination, in-hospital complications, and length of stay. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

A rationale for universal tranexamic acid in major joint arthroplasty: overall efficacy and impact of risk factors for transfusion.

BACKGROUND: Tranexamic acid (TXA) therapy is effective in reducing postoperative red blood cell (RBC) transfusion in total joint arthroplasty (TJA), yet uncertainty persists regarding comparative efficacy and safety among specific patient subgroups. We assessed the impact of a universal TXA protocol on RBC transfusion, postoperative hemoglobin (Hb), and adverse outcomes to determine whether TXA is safe and effective in TJA, both overall and in clinically relevant subgroups. STUDY DESIGN AND METHODS: A retrospective observational study was performed on patients undergoing TJA at our institution spanning 1 year before and after the implementation of a universal protocol to administer intravenous (IV) TXA. The primary outcome was percentage of patients transfused, and secondary outcomes were perioperative Hb and occurrence of adverse events (death, myocardial infarction, stroke, seizure, pulmonary embolism, deep vein thrombosis, and acute kidney injury ). Outcomes were compared in pre- and post-protocol groups with χ2 analysis. Logistic regression compared risk of transfusion in pre- and post-protocol subgroups of patients with differing risk for transfusion (anemia, body mass index [BMI], and sex). RESULTS: No differences were found in baseline patient characteristics across pre- and post-protocol groups (n = 1084 and 912, respectively). TXA use increased from 32.3% to 92.2% while transfusion rates decreased from 10.3% to 4.8% (p < 0.001). Postoperative Day 3 Hb increased from 95.8 to 101.4 g/L (p < 0.001). Logistic regression demonstrated reduced transfusion in post-protocol subgroups regardless of sex, anemia, or BMI (p < 0.001). No increase in adverse events was observed (p = 0.8451). CONCLUSIONS: Universal TXA was associated with a reduction of RBC transfusion, overall and in clinically relevant subgroups, strengthening the rationale for universal therapy.

Building the blocks of executive functioning: differentiating early developing processes contributing to executive functioning skills.

The neural processes that underlie executive function begin to develop in infancy. However, it is unclear how the behavior manifested by these processes are related or if they can be differentiated early in development. This study seeks to examine early emerging executive functioning skills in monkeys (Macaca fascicularis) by using an error analysis approach where traditional measures of the tasks, as well as identification of major error patterns are related. Results show that during the infancy and early juvenile period, two processes that help support set-maintenance could be differentiated: modulation of responses to novelty and persistence despite negative feedback. The results suggest that these two aspects of set-maintenance were largely independent. Modulation of responses to novelty was most prominent in the infancy and early juvenile period. The ability to persist with a response set despite negative feedback emerged in the early juvenile period and was related to task performance until the end of the study.

Variants in the estrogen receptor alpha gene and its mRNA contribute to risk for schizophrenia.

Estrogen modifies human emotion and cognition and impacts symptoms of schizophrenia. We hypothesized that the variation in the estrogen receptor alpha (ESR1) gene and cortical ESR1 mRNA is associated with schizophrenia. In a small case-control genetic association analysis of postmortem brain tissue, genotype CC (rs2234693) and haplotypes containing the C allele of a single-nucleotide polymorphism (SNP) in intron1 (PvuII) were more frequent in African American schizophrenics (P = 0.01-0.001). In a follow-up family-based association analysis, we found overtransmission of PvuII allele C and a PvuII C-containing haplotype (P = 0.01-0.03) to African American and Caucasian patients with schizophrenia. Schizophrenics with the 'at risk' PvuII genotype had lower ESR1 mRNA levels in the frontal cortex. Eighteen ESR1 splice variants and decreased frequencies of the wild-type ESR1 mRNA were detected in schizophrenia. In one patient, a unique ESR1 transcript with a genomic insert encoding a premature stop codon and a truncated ESR1 protein lacking most of the estrogen binding domain was the only transcript detected. Using a luciferase assay, we found that mRNA encoding a truncated ESR1 significantly attenuates gene expression at estrogen-response elements demonstrating a dominant negative function. An intron 6 SNP [rs2273207(G)] was associated with an ESR1 splice variant missing exon seven. The T allele of another intron 6 SNP was part of a 3' haplotype less common in schizophrenia [rs2273206(T), rs2273207(G), rs2228480(G)]. Thus, the variation in the ESR1 gene is associated with schizophrenia and the mechanism of this association may involve alternative gene regulation and transcript processing.

Dynamic changes in clinical features and cytokine/chemokine responses in SARS patients treated with interferon alfacon-1 plus corticosteroids.

Severe acute respiratory syndrome (SARS), caused by a novel coronavirus, emerged in early 2003 as a major international health crisis. We report on serum cytokine levels, viral load and clinical parameters over the course of the disease in a cohort of nine adult SARS patients treated with steroids and interferon alfacon-1 at North York General Hospital in Toronto, Ontario. Considerable variation among SARS patients with respect to circulating viral load and patterns of SARS-CoV-evoked cytokine responses was recorded. No single cytokine profile was observed in all patients, yet serum concentrations of interferon (IFN)-gamma, interleukin (IL)-10, CXCL10, CCL5 and CXCL8 were found to be elevated above normal levels during the course of the disease in all patients. Expression levels for IL-10, IFN-gamma and CXCL10 consistently peaked within 4 days of peak viral load. IL-12p70, IL-4 and tumour necrosis factor-alpha concentrations were consistently highest within 5 days of peak viral load. These results suggest that elevated levels of inflammatory cytokines are sensitive correlates of disease severity, including lung abnormalities and viral load in serum, and may provide a tool for monitoring disease progression in affected individuals.