Hereditary Thrombotic Thrombocytopenic Purpura.

Hereditary thrombotic thrombocytopenic purpura (hTTP), also known as Upshaw-Schulman syndrome, is a rare genetic disorder caused by mutations in the ADAMTS13 gene that leads to decreased or absent production of the plasma von Willebrand factor (VWF)-cleaving metalloprotease ADAMTS13. The result is circulating ultra-large multimers of VWF that can cause microthrombi, intravascular occlusion and organ damage, especially at times of turbulent circulation. Patients with hTTP may have many overt or clinically silent manifestations, and a high index of suspicion is required for diagnosis. For the treatment of hTTP, the goal is simply replacement of ADAMTS13. The primary treatment is prophylaxis with plasma infusions or plasma-derived factor VIII products, providing sufficient ADAMTS13 to prevent acute episodes. When acute episodes occur, prophylaxis is intensified. Recombinant ADAMTS13, which is near to approval, will immediately be the most effective and also the most convenient treatment. In this review, we discuss the possible clinical manifestations of this rare disease and the relevant differential diagnoses in different age groups. An extensive discussion on prophylaxis and treatment strategies is also presented. Unique real patient cases have been added to highlight critical aspects of hTTP manifestations, diagnosis and treatment.

Long-term follow-up of patients with congenital thrombotic thrombocytopenia purpura receiving a plasma-derived factor VIII (Koate) that contains ADAMTS13.

BACKGROUND: Hereditary thrombotic thrombocytopenia purpura (hTTP) is an ultra-rare disorder resulting from an inherited deficiency of ADAMTS13, a von Willebrand factor (VWF)-cleaving metalloprotease. The plasma-derived factor VIII/VWF Koate (FVIII/VWFKoate ) has been shown to contain ADAMTS13, allowing for its use to treat hTTP at home by the patient/caregiver. AIM: Based on prior demonstration of safe and effective use of FVIII/VWFKoate in eight patients with hTTP, we conducted a retrospective study to gather additional data regarding the use of FVIII/VWFKoate for hTTP. METHODS: This was a multicentre, retrospective, noninterventional chart review of patients who had received FVIII/VWFKoate for the management of hTTP. Data collected included demographics, medical history, relevant family history, past use and tolerability of fresh frozen plasma, and details regarding FVIII/VWFKoate therapy. RESULTS: The cohort included 11 patients (seven males, four females) with hTTP, ranging in age at study entry from 2 to 28 years. The average duration of FVIII/VWFKoate therapy was 4.8 years (range, 0.5-6.5 years). Among nine patients using FVIII/VWFKoate as prophylaxis, the normalized annual rate of breakthrough TTP episodes ranged from 0.2 to 1.1 episodes/year. All nine patients who received FVIII/VWFKoate prophylaxis had thrombocytopenia recorded at baseline, while eight (88.9%) did not have thrombocytopenia after using FVIII/VWFKoate . There was one AE (unspecified) attributed to FVIII/VWFKoate . CONCLUSION: These data suggest that FVIII/VWFKoate is a safe and well-tolerated source of the missing ADAMTS13 enzyme in patients with hTTP, producing a marked reduction in thrombocytopenia prevalence, low frequency of TTP episodes, and with the added benefit of self- or caregiver-administration.

Successful treatment of lupus anticoagulant hypoprothrombinemia syndrome with rituximab.

Lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS) is a rare acquired bleeding disorder secondary to development of antibodies against prothrombin protein, in the presence of antiphospholipid antibodies. We describe the case of a 13-year-old girl who presented with severe menorrhagia and symptomatic anemia. Labs indicated anemia, thrombocytopenia, elevated PT and aPTT, high-titer inhibitor on mixing studies, positive ANA and anti-dsDNA antibodies, along with a triple-positive antiphospholipid antibody panel. Given additional systemic manifestations, systemic lupus erythematosus was diagnosed. High dose steroids and hydroxychloroquine subsequently started. Her clinical course was complicated by femoral deep venous thrombosis and post renal biopsy retroperitoneal hematoma. Further workup revealed low prothrombin level and the diagnosis of lupus anticoagulant hypoprothrombinemia syndrome. In view of suboptimal response to initial immunosuppressive therapy, rituximab was added to her regimen, leading to an improvement in clinical symptoms and resolution of hypoprothrombinemia. She remains recurrence free 5 years from the event.

A Neuro-Informatics Pipeline for Cerebrovascular Disease: Research Registry Development.

BACKGROUND: Although stroke is well recognized as a critical disease, treatment options are often limited. Inpatient stroke encounters carry critical information regarding the mechanisms of stroke and patient outcomes; however, these data are typically formatted to support administrative functions instead of research. To support improvements in the care of patients with stroke, a substantive research data platform is needed. OBJECTIVE: To advance a stroke-oriented learning health care system, we sought to establish a comprehensive research repository of stroke data using the Houston Methodist electronic health record (EHR) system. METHODS: Dedicated processes were developed to import EHR data of patients with primary acute ischemic stroke, intracerebral hemorrhage (ICH), transient ischemic attack, and subarachnoid hemorrhage under a review board-approved protocol. Relevant patients were identified from discharge diagnosis codes and assigned registry patient identification numbers. For identified patients, extract, transform, and load processes imported EHR data of primary cerebrovascular disease admissions and available data from any previous or subsequent admissions. Data were loaded into patient-focused SQL objects to enable cross-sectional and longitudinal analyses. Primary data domains (admission details, comorbidities, laboratory data, medications, imaging data, and discharge characteristics) were loaded into separate relational tables unified by patient and encounter identification numbers. Computed tomography, magnetic resonance, and angiography images were retrieved. Imaging data from patients with ICH were assessed for hemorrhage characteristics and cerebral small vessel disease markers. Patient information needed to interface with other local and national databases was retained. Prospective patient outreach was established, with patients contacted via telephone to assess functional outcomes 30, 90, 180, and 365 days after discharge. Dashboards were constructed to provide investigators with data summaries to support access. RESULTS: The Registry of Neurological Endpoint Assessments among Patients with Ischemic and Hemorrhagic Stroke (REINAH) database was constructed as a series of relational category-specific SQL objects. Encounter summaries and dashboards were constructed to draw from these objects, providing visual data summaries for investigators seeking to build studies based on REINAH data. As of June 2022, the database contains 18,061 total patients, including 1809 (10.02%) with ICH, 13,444 (74.43%) with acute ischemic stroke, 1221 (6.76%) with subarachnoid hemorrhage, and 3165 (17.52%) with transient ischemic attack. Depending on the cohort, imaging data from computed tomography are available for 85.83% (1048/1221) to 98.4% (1780/1809) of patients, with magnetic resonance imaging available for 27.85% (340/1221) to 85.54% (11,500/13,444) of patients. Outcome assessment has successfully contacted 56.1% (240/428) of patients after ICH, with 71.3% (171/240) of responders providing consent for assessment. Responders reported a median modified Rankin Scale score of 3 at 90 days after discharge. CONCLUSIONS: A highly curated and clinically focused research platform for stroke data will establish a foundation for future research that may fundamentally improve poststroke patient care and outcomes.

Does local infiltration analgesia in total joint arthroplasty offer any protection from prosthetic joint infections? An invitro experimental study.

Many local anaesthetic agents are now reported to have anti-microbial properties in various studies, and this ability to inhibit microbial growth is not uniform. As local anaesthetics are commonly infiltrated into the surgical field for perioperative pain management, it is very important to know if this practice offers any protection against surgical site infections. METHODS: In this study, three of the most common prosthetic joint infection-causing organisms, namely, Staphylococcus aureus, Staphylococcus epidermidis and Escherichia coli, were chosen and tested against the commonly used local anaesthetics. The suspension of each organism was inoculated onto three different Mueller-Hinton agar plates and a drop of an undiluted solution of each local anaesthetic agent is inoculated onto one of the three culture plates; vancomycin and gentamicin discs were used as controls. RESULTS: The local anaesthetic agents tested could not inhibit the growth of any of the microorganisms. As there was no inhibition of bacterial growth in the experiment with the above three agents, further experiment with a diluted mixture was not performed. CONCLUSIONS: It can be concluded that local infiltration of anaesthetic agents is less likely to provide any perioperative protection against prosthetic joint infections but may interfere with some diagnostic tests for microbiology.

What explains very poor Yelp reviews of oral and maxillofacial surgeons in private practice?

OBJECTIVE: Websites that maintain online physician ratings, such as Yelp.com, have been growing in popularity throughout the United States. The purpose of this study was to determine which factors increase the risk for very poor reviews (1 out of 5 stars) on Yelp.com for oral and maxillofacial surgeons (OMSs) in private practice. STUDY DESIGN: A retrospective cohort study was conducted using data on OMSs from Yelp.com. Predictor variables included clinician characteristics, practice characteristics, and review characteristics. The primary outcome variable was a very poor review. Logistic regression was used to determine risk factors for a very poor review. RESULTS: The final sample consisted of 3802 reviews. Relative to male clinicians, female clinicians were 2.7 times (P < .01) more likely to receive a very poor review. Clinicians who completed residency during the 1970s were over 4.5 times (P < .01) more likely to receive a very poor review relative to clinicians who completed residency during the 2010s. Relative to clinical reviews, nonclinical reviews were more likely (odds ratio = 2.6, P < .01) to be very poor and clinical and nonclinical reviews were less likely (odds ration = 0.5, P < .01) to be very poor. CONCLUSIONS: Nonclinical reviews were more likely to be very poor relative to clinical reviews. Several clinician factors, including female sex and completing OMS residency during the 1970s, were risk factors for receiving a very poor review.

Eptacog beta efficacy and safety in the treatment and control of bleeding in paediatric subjects (<12 years) with haemophilia A or B with inhibitors.

INTRODUCTION: Eptacog beta is a new recombinant activated human factor VII bypassing agent approved in the United States for the treatment and control of bleeding in patients with haemophilia A or B with inhibitors 12 years of age or older. AIM: To prospectively assess in a phase 3 clinical trial (PERSEPT 2) eptacog beta efficacy and safety for treatment of bleeding in children <12 years of age with haemophilia A or B with inhibitors. METHODS: Using a randomised crossover design, subjects received initial doses of 75 or 225 µg/kg eptacog beta followed by 75 µg/kg dosing at predefined intervals (as determined by clinical response) to treat bleeding episodes (BEs). Treatment success criteria included a haemostasis evaluation of 'excellent' or 'good' without use of additional eptacog beta, alternative haemostatic agent or blood product, and no increase in pain following the first 'excellent' or 'good' assessment. RESULTS: Treatment success proportions in 25 subjects (1-11 years) who experienced 546 mild or moderate BEs were 65% in the 75 µg/kg initial dose regimen (IDR) and 60% in the 225 µg/kg IDR 12 h following initial eptacog beta infusion. By 24 h, the treatment success proportions were 97% for the 75 µg/kg IDR and 98% for the 225 µg/kg IDR. No thrombotic events, allergic reactions, neutralising antibodies or treatment-related adverse events were reported. CONCLUSION: Both 75 and 225 µg/kg eptacog beta IDRs provided safe and effective treatment and control of bleeding in children <12 years of age.

Current practices in pediatric hospital-acquired thromboembolism: Survey of the Children's Hospital Acquired Thrombosis (CHAT) Consortium.

Background: A rise in hospital-acquired venous thromboembolism (HA-VTE) in children has led to increased awareness regarding VTE prophylaxis and risk assessment. Despite no consensus exists regarding these practices in pediatrics. Objective: To describe common practices in VTE prophylaxis, VTE risk assessment models, and anticoagulation dosing strategies in pediatric hospitals that are members of the Children's Hospital Acquired Thrombosis (CHAT) Consortium. Methods: An electronic survey of 44 questions evaluating practices surrounding pediatric HA-VTE risk assessment and prevention was distributed between August 9, 2021, and August 30, 2021, to the primary investigators from the 32 institutions within the CHAT Consortium. Results: The survey response rate was 100% (n = 32). In total, 85% (n = 27) of the institutions assess HA-VTE, but only 63% (n = 20) have formal hospital guidelines. Within the institutions with formal guidelines, 100% (n = 20) include acute systemic inflammation or infection and presence of a central venous catheter (CVC) as risk factors for VTE. Pharmacologic prophylaxis is prescribed at 87% (28) of institutions, with enoxaparin being the most frequent (96%, n = 27). Variability in responses persisted regarding risk factors, risk assessment, thromboprophylaxis, dosing of prophylactic anticoagulation or anticoagulant drug monitoring. A majority of providers were comfortable providing thromboprophylaxis across all age groups. In addition, the global coronavirus disease 2019 increased the providers' use of prophylactic anticoagulation 78% (n = 25). Conclusion: Practices among institutions are variable in regard to use of HA-VTE prophylaxis, risk assessment, or guideline implementation, highlighting the need for further research and a validated risk assessment model through groups like the CHAT Consortium.

Disparities in COVID-19 hospitalizations and mortality among black and Hispanic patients: cross-sectional analysis from the greater Houston metropolitan area.

BACKGROUND: Disparate racial/ethnic burdens of the Coronavirus Disease 2019 (COVID-19) pandemic may be attributable to higher susceptibility to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) or to factors such as differences in hospitalization and care provision. METHODS: In our cross-sectional analysis of lab-confirmed COVID-19 cases from a tertiary, eight-hospital healthcare system across greater Houston, multivariable logistic regression models were fitted to evaluate hospitalization and mortality odds for non-Hispanic Blacks (NHBs) vs. non-Hispanic Whites (NHWs) and Hispanics vs. non-Hispanics. RESULTS: Between March 3rd and July 18th, 2020, 70,496 individuals were tested for SARS-CoV-2; 12,084 (17.1%) tested positive, of whom 3536 (29.3%) were hospitalized. Among positive cases, NHBs and Hispanics were significantly younger than NHWs and Hispanics, respectively (mean age NHBs vs. NHWs: 46.0 vs. 51.7 years; p < 0.001 and Hispanic vs. non-Hispanic: 44.0 vs. 48.7 years; p < 0.001). Despite younger age, NHBs (vs. NHWs) had a higher prevalence of diabetes (25.2% vs. 17.6%; p < 0.001), hypertension (47.7% vs. 43.1%; p < 0.001), and chronic kidney disease (5.0% vs. 3.3%; p = 0.001). Both minority groups resided in lower median income (median income [USD]; NHBs vs. NHWs: 63,489 vs. 75,793; p < 0.001, Hispanic vs. non-Hispanic: 59,104 vs. 68,318; p < 0.001) and higher population density areas (median population density [per square mile]; NHBs vs. NHWs: 3257 vs. 2742; p < 0.001, Hispanic vs. non-Hispanic: 3381 vs. 2884; p < 0.001). In fully adjusted models, NHBs (vs. NHWs) and Hispanics (vs. non-Hispanic) had higher likelihoods of hospitalization, aOR (95% CI): 1.42 (1.24-1.63) and 1.61 (1.46-1.78), respectively. No differences were observed in intensive care unit (ICU) utilization or treatment parameters. Models adjusted for demographics, vital signs, laboratory parameters, hospital complications, and ICU admission vital signs demonstrated non-significantly lower likelihoods of in-hospital mortality among NHBs and Hispanic patients, aOR (95% CI): 0.65 (0.40-1.03) and 0.89 (0.59-1.31), respectively. CONCLUSIONS: Our data did not demonstrate racial and ethnic differences in care provision and hospital outcomes. Higher susceptibility of racial and ethnic minorities to SARS-CoV-2 and subsequent hospitalization may be driven primarily by social determinants.

Transarterial Radioembolization Treatment as a Bridge to Surgical Resection in Pediatric Hepatocellular Carcinoma.

BACKGROUND: Children with unresectable hepatocellular carcinoma (HCC) have a poor prognosis and limited treatment options. Transarterial radioembolization (TARE) using Yttrium-90 (Y90) has emerged as a potential bridge therapy to hepatic resection or transplantation for HCC with very limited studies in children. OBSERVATIONS: Here we present the clinical course of 2 children successfully treated with TARE Y90 for initially unresectable fibrolamellar HCC (FL-HCC) and bridged to partial hemihepatectomy with >1-year overall survival post-TARE. CONCLUSION: Although there have been prior published reports of pediatric patients with HCC being treated with TARE Y90 and some being able to undergo subsequent orthotopic liver transplantation, this is the first report of pediatric HCC patients treated with TARE Y90 as a bridge to nontransplant resections and going on to have >1-year overall survival.

Rapid Response to Drive COVID-19 Research in a Learning Health Care System: Rationale and Design of the Houston Methodist COVID-19 Surveillance and Outcomes Registry (CURATOR).

BACKGROUND: The COVID-19 pandemic has exacerbated the challenges of meaningful health care digitization. The need for rapid yet validated decision-making requires robust data infrastructure. Organizations with a focus on learning health care (LHC) systems tend to adapt better to rapidly evolving data needs. Few studies have demonstrated a successful implementation of data digitization principles in an LHC context across health care systems during the COVID-19 pandemic. OBJECTIVE: We share our experience and provide a framework for assembling and organizing multidisciplinary resources, structuring and regulating research needs, and developing a single source of truth (SSoT) for COVID-19 research by applying fundamental principles of health care digitization, in the context of LHC systems across a complex health care organization. METHODS: Houston Methodist (HM) comprises eight tertiary care hospitals and an expansive primary care network across Greater Houston, Texas. During the early phase of the pandemic, institutional leadership envisioned the need to streamline COVID-19 research and established the retrospective research task force (RRTF). We describe an account of the structure, functioning, and productivity of the RRTF. We further elucidate the technical and structural details of a comprehensive data repository-the HM COVID-19 Surveillance and Outcomes Registry (CURATOR). We particularly highlight how CURATOR conforms to standard health care digitization principles in the LHC context. RESULTS: The HM COVID-19 RRTF comprises expertise in epidemiology, health systems, clinical domains, data sciences, information technology, and research regulation. The RRTF initially convened in March 2020 to prioritize and streamline COVID-19 observational research; to date, it has reviewed over 60 protocols and made recommendations to the institutional review board (IRB). The RRTF also established the charter for CURATOR, which in itself was IRB-approved in April 2020. CURATOR is a relational structured query language database that is directly populated with data from electronic health records, via largely automated extract, transform, and load procedures. The CURATOR design enables longitudinal tracking of COVID-19 cases and controls before and after COVID-19 testing. CURATOR has been set up following the SSoT principle and is harmonized across other COVID-19 data sources. CURATOR eliminates data silos by leveraging unique and disparate big data sources for COVID-19 research and provides a platform to capitalize on institutional investment in cloud computing. It currently hosts deeply phenotyped sociodemographic, clinical, and outcomes data of approximately 200,000 individuals tested for COVID-19. It supports more than 30 IRB-approved protocols across several clinical domains and has generated numerous publications from its core and associated data sources. CONCLUSIONS: A data-driven decision-making strategy is paramount to the success of health care organizations. Investment in cross-disciplinary expertise, health care technology, and leadership commitment are key ingredients to foster an LHC system. Such systems can mitigate the effects of ongoing and future health care catastrophes by providing timely and validated decision support.

Racial and ethnic disparities in SARS-CoV-2 pandemic: analysis of a COVID-19 observational registry for a diverse US metropolitan population.

INTRODUCTION: Data on race and ethnic disparities for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are limited. We analysed sociodemographic factors associated with higher likelihood of SARS-CoV-2 infection and explore mediating pathways for race and ethnic disparities in the SARS-CoV-2 pandemic. METHODS: This is a cross-sectional analysis of the COVID-19 Surveillance and Outcomes Registry, which captures data for a large healthcare system, comprising one central tertiary care hospital, seven large community hospitals and an expansive ambulatory/emergency care network in the Greater Houston area. Nasopharyngeal samples for individuals inclusive of all ages, races, ethnicities and sex were tested for SARS-CoV-2. We analysed sociodemographic (age, sex, race, ethnicity, household income, residence population density) and comorbidity (Charlson Comorbidity Index, hypertension, diabetes, obesity) factors. Multivariable logistic regression models were fitted to provide adjusted OR (aOR) and 95% CI for likelihood of a positive SARS-CoV-2 test. Structural equation modelling (SEM) framework was used to explore three mediation pathways (low income, high population density, high comorbidity burden) for the association between non-Hispanic black (NHB) race, Hispanic ethnicity and SARS-CoV-2 infection. RESULTS: Among 20 228 tested individuals, 1551 (7.7%) tested positive. The overall mean (SD) age was 51.1 (19.0) years, 62% were females, 22% were black and 18% were Hispanic. NHB and Hispanic ethnicity were associated with lower socioeconomic status and higher population density residence. In the fully adjusted model, NHB (vs non-Hispanic white; aOR, 2.23, CI 1.90 to 2.60) and Hispanic ethnicity (vs non-Hispanic; aOR, 1.95, CI 1.72 to 2.20) had a higher likelihood of infection. Older individuals and males were also at higher risk of infection. The SEM framework demonstrated a significant indirect effect of NHB and Hispanic ethnicity on SARS-CoV-2 infection mediated via a pathway including residence in densely populated zip code. CONCLUSIONS: There is strong evidence of race and ethnic disparities in the SARS-CoV-2 pandemic that are potentially mediated through unique social determinants of health.

Non-Hodgkin's Lymphoma of the Anterior Maxilla Mimicking a Chronic Apical Abscess.

Non-Hodgkin lymphomas (NHLs) are malignant neoplasms of the lymphatic system, typically occurring in the fifth through seventh decades of life. Tumors develop from abnormal lymphocyte proliferation and accumulation. Although a majority of NHLs occur in nodal regions, 40% of cases appear in extranodal sites involving the stomach, spleen, Waldeyer's ring, central nervous system, lung, skin, and bone. Extranodal NHL presents a diagnostic challenge because it may mimic endodontic disease when occurring in intraosseous and soft tissue sites. This case report presents misdiagnosis of a diffuse large B-cell lymphoma (DLBCL) of the anterior maxilla in a 72-year-old man with a history of Waldenstrom's macroglobulinemia, where the lesion was thought to be associated with a necrotic pulp and a chronic apical abscess on tooth #7. Clinical findings of a facial sinus tract, a nonresponsive pulp, large periapical radiolucency, and history of trauma were in support of this diagnosis for tooth #7. On encountering vital pulpal tissues during cavity access of tooth #7, a cone-beam computed tomography scan and lesion biopsy were obtained. Through immunohistochemistry and histologic analysis, a diagnosis of DLBCL was made. During evaluation of lesions with suspected endodontic etiology, the clinician should consider all factors of the patient's health history, hereditary risk, and comprehensive clinical testing to attain a differential diagnosis. A nonodontogenic etiology of disease should always be considered unless ruled out otherwise. Atypical presentation or testing may prompt the need for biopsy and interspecialty assessment.

The relationship of self-compassion and hope with quality of life for individuals with bleeding disorders.

INTRODUCTION: Minimal research has been conducted examining the relationship of positive psychology variables with quality of life (QOL) for individuals with bleeding disorders. While many individuals manage their bleeding disorders well, some are at higher risk of developing psychosocial complications due to the daily stressors of managing illness-related symptoms. AIM: The purpose of this study is to better understand the relationships between two positive psychology variables, self-compassion and hope and QOL (overall, psychosocial and physical) among individuals diagnosed with bleeding disorders. METHODS: Participants completed a survey identifying demographic information as well as rating scales of self-compassion, hope and quality of life. We conducted Pearson correlational and standard multiple regression analyses to explore the bivariate and linear relationships between the aforementioned variables in a sample of 86 patients with bleeding disorders between the ages of 15 and 65. RESULTS: Self-compassion and hope were significantly related to QOL. Together, self-compassion and hope were predictive of overall QOL, psychosocial QOL and physical QOL. However, hope was the only individual predictor of all three QOL dimensions. CONCLUSION: Due to the significant relationships found between self-compassion, hope and QOL in this sample, it may be beneficial to incorporate positive psychology factors into the treatment of those diagnosed with bleeding disorders, especially those at higher risk for decreased QOL.

Pharmacokinetic-tailored approach to hemophilia prophylaxis: Medical decision making and outcomes.

BACKGROUND: Clinical application of population pharmacokinetics (popPK) is of increasing interest to patients with hemophilia, providers, and payers. Routine use of popPK profiles in factor replacement prophylaxis decision making has the potential to maintain or improve efficacy and reduce product consumption. AIM: To investigate the feasibility of implementation and longitudinal assessment of pharmacokinetic (PK)-tailored prophylaxis in routine clinical practice for hemophilia A and to describe factors that influence decision making for prescribed hemophilia prophylaxis. METHODS: This longitudinal, multicenter, prospective feasibility study of children and adults with hemophilia A without inhibitors used the Web Accessible Population Pharmacokinetic Service-Hemophilia (WAPPS-Hemo) to generate PK profiles. Assessments over 12 weeks captured data on prescribed prophylaxis, popPK tool use, provider decision making, and patient-reported outcomes. RESULTS: Eighteen participants aged 6 to 39 years enrolled; half used extended half-life concentrates. Patient interest in their PK centered on general curiosity followed by a desire for participation in physical activity and decrease in infusion frequency. Providers used the WAPPS clinical calculator feature to simulate prophylaxis regimens under different dose, infusion, and trough conditions. Most targeted troughs were 1 to 3 IU/dL. The feasibility assessment demonstrated challenges with patient recruitment; however, the majority of participants successfully completed study assessments meeting feasibility targets. CONCLUSION: A larger-scale study powered to evaluate the impact of PK-tailored prophylaxis on clinical and patient-reported outcomes is feasible with study design modifications to support increased recruitment rate. Shared decision making incorporating patient and provider goals is important and facilitated by regimen simulations with the clinical calculator.

Remote arterial vasculitis as a possible complication of Phosphorus-32 Radiosynovectomy.

Patients with hemophilia suffer from repeated episodes of hemarthrosis leading to chronic inflammation and synovitis. Radiosynovectomy is an effective nonsurgical modality that can reduce inflammation, pain, and hemarthrosis in such cases. We describe an adolescent male with severe Hemophilia A, who developed arterial vasculitis and perivasculitis targeting the brachiocephalic, right common carotid, and right subclabvian arteries occurring within few days after difficult Phosphorus-32 radiosynovectomy, possibly as a complication of the procedure. Despite prophylaxis with recombinant FVIII therapy, he developed chronic synovitis and underwent radionuclide synovectomy with P-32 injection to the left ankle and right knee. Five days later, he developed pain in the lower right neck and right upper chest. Computed tomography and magnetic resonance imaging and angiography demonstrated inflammation involving the arteries of the right thoracic inlet. Geiger-Mueller meter indicated increased radioactivity not only in the left ankle and right knee but also in the right upper chest. Detection of radioisotope at the right thoracic inlet corresponding to the area of vasculitis was indicative of likely deposition of the P-32 isotope in an area exposed to maximum cardiac output and increased blood flow, leading to subclavian, carotid, and innominate arteritis with surrounding edema.

Focusing in on use of pharmacokinetic profiles in routine hemophilia care.

BACKGROUND: Emergence of population pharmacokinetic models for prediction of individual pharmacokinetic (PK) profiles facilitates individualization of prescribed prophylactic therapy for patients with hemophilia A and B and may have a favorable impact on clinical outcomes and annual factor utilization. How providers approach the integration and application of these data into routine clinical practice is not clear. OBJECTIVE: To explore the potential application of and barriers to incorporating PK profiles into current hemophilia prophylaxis decision making. METHODS: A facilitated group discussion of hematologists practicing within the federally-supported United States Hemophilia Treatment Center Network was conducted. Separately, a group of parents of patients with severe hemophilia less than 18 years of age participated in a focus group on individualizing prophylactic factor regimens with the use of PK data. RESULTS: Physician participants constructed a conceptual model for factors that determined their selection of hemophilia prophylaxis. These factors clustered in five groupings. When charged with creating a prophylaxis regimen for a specific clinical case including PK data, eight of nine providers generated a unique regimen. Parent focus group supported PK data use as they preferred data driven treatment decisions. CONCLUSIONS: Clinician application of PK data for prophylaxis decision making is heterogeneous. Prospective evaluation of the use of PK-tailored prophylaxis in routine care and its impact on patient outcomes is needed. Parents perceived that, while obtaining blood draws could be challenging, images of factor activity decay informed their decisions about physical activity timing and provided an opportunity for partnership and shared decision making with their provider.

Theater Cost Is £16/Minute So What Are You Doing Just Standing There?

The purpose of this study was to measure the time to perform particular activities in the operating room and calculate the cost per minute to perform each activity. We timed how long it takes to perform 15 individual activities carried out by orthopedic trainees during total hip and knee arthroplasty. We developed an algorithm, and then measured the time taken for the preparation of 20 consecutive patients using it. With the algorithm, overall preparation time was reduced by 25.32% for each hip arthroplasty and by 27.60% (P < .0001) for each knee arthroplasty, saving £84.32 and £93.44 per case, respectively. Coordination between surgeons and theater staff is essential to reduce the time spent performing activities, and this will help improve theater efficiency.