Introduction:
Since the emergence of community-acquired methicillin-resistant S. aureus (MRSA), severe manifestations of infection are encountered more frequently. Venous thrombosis (VT) has been previously reported in children with S. aureus infections. This study reviews our institutional experience and outcomes of children with VT and staphylococcal infections.
Methods:
A retrospective analysis of 15 pediatric patients (≤ 18 years) treated for VT and staphylococcal infections at Children’s Memorial Hermann Hospital between January 1, 2010 and December 31, 2014 was performed.
Results:
Fifteen patients were included (10 males, 5 females) with a median age at diagnosis of 8 years (range 2 mo-17yrs). Underlying infections included: osteomyelitis (n=7), soft tissue infection (n=3), aortitis (n=1), meningitis (n=1), septic arthritis (n=1), central line infection (n=1), septicemia (n=1). Primary presentation included: swelling (n=12), pain (n=11), tenderness (n= 8), and color changes (n=3). One patient had prior history of VT. Family history was positive for VT in one patient. Isolated organisms included: MRSA (n=9), MSSA (n=3), polymicrobial (n=2), and Staphylococcus non- aureus (n=1). Eight patients had central venous catheters (CVC) and 5 of them had thrombosis at the CVC site. VT sites identified by Doppler US (DUS) included: upper extremity (n= 5), lower extremity (n= 8), and neck (n=2). All thrombophilia work up was negative. The median D-dimer at diagnosis was 3 ug/ml (range: 0.31- 6.54 ug/ml). Median time elapsed between infection and VT diagnosis was 5.5 days (range: 0-35 days). All patients received anticoagulation using LMWH (1mg/kg/dose) except one who had superficial thrombophlebitis and was managed conservatively. Median time to achieve therapeutic anti- factor Xa level was 2.5 days (range 1- 6 days). Median duration of anticoagulation was 3 months. Three out of 13 patients (23%) had resolution of thrombosis within one week of anticoagulation. Four other patients had thrombus resolution by DUS at 3-6 months. Five patients did not have DUS at 3-6 months. None of the 15 patients required hospital re- admission for bleeding or thrombotic complications.
Discussion:
Staphylococcal infections may increase the risk of VT in children. Nine out of 15 patients (60%) with VT had a documented MRSA infection, which appears to confer an even higher risk for development of VT. Over half of the patients responded favorably to anticoagulation with resolution of VT within 6 months.
Conclusions:
A high index of suspicion for VT is warranted in children with Staphyloccoccal infections (particularly MRSA) to promptly diagnose and treat. This approach may improve outcomes and minimize complications including septic emboli and post-thrombotic syndrome. Prophylactic anticoagulation in presence of MRSA infection could be considered in future studies.
Keywords: Children, staphylococcal infection, venous thrombosis
Objective:
Hemophilia is marked by frequent joint bleeding, resulting in acute and chronic pain and functional impairment. Surveys in US adults with hemophilia demonstrate suboptimal pain management and quality of life (QoL). The objective of P-FiQ was to methodologically assess QoL parameters, including functional impairment and pain, and pain management strategies.
Methods:
Adult men with mild-severe hemophilia with a history of joint pain and/or bleeding completed a hemophilia/pain history and various patient-reported outcome assessments (completed twice in “retest” population of initially enrolled patients).
Summary:
Of 164 adults with hemophilia (median age 34) in the “retest” population, more had hemophilia A (74%) than B (26%); 6% had inhibitors. Most had some college-or-above education (63%), 81% were employed, 61% were overweight/obese, and 61% self-reported arthritis/bone/joint problems. Current patient-reported treatment regimens were prophylaxis (42%), on-demand (39%), or mostly on-demand (19%; 25/31 using infusions ahead of activity). One-third (32.9%) reported unrestricted school/work/recreational activities in the prior 6 months; 6.2% reported needing assistance for school/work/self-care, or did not participate in recreational activities because of pain, loss of motion, and weakness. Some patients (31.3%) reported using a cane/crutches/walker (3.8% always) and 7.6% a wheelchair (1.3% always), and 47.0% reported a history of joint surgery (41 knee, 37 ankle, 29 elbow). Patients reported losing an average of 3.7 and 1.8 school/work days in the previous 6 months due to lower and upper extremity problems, respectively. Patients reported that during the prior 6 months they had experienced acute pain only (24%), chronic pain only (33%), or both (29%); 15% reported no pain. Acute pain was most frequently described as sharp (77%), aching (66%), shooting (57%), and throbbing (55%), and chronic pain as aching (74%), nagging (49%), throbbing (44%), and sharp (40%). Most common analgesics in the past 6 months for acute/chronic pain were acetaminophen (69%/58%), NSAIDs (40%/52%), hydrocodone-acetaminophen (29%/33%), oxycodone (12%/11%), and oxycodone- acetaminophen (9%/8%). Most common nonanalgesic treatment strategies reported for acute/chronic pain in the past 6 months were ice (73%/37%), rest (48%/34%), factor or bypassing agent (48%/24%), elevation (34%/28%), relaxation (31%/23%), compression (27%/21%), and heat (25%/15%); other reported strategies include medical marijuana (17%/9%), physical therapy (12%/9%), prayer (11%/8%), faith (9%/8%), alcohol (8%/7%), aquatherapy (5%/6%), illicit drugs (4%/2%), acupuncture (2%/1%), hypnosis (2%/1%), and biofeedback (1%/1%).
Conclusions:
Initial data corroborate the high prevalence of pain and functional disability in adults with hemophilia and highlight opportunities to address clinical assessment, patient dialogue, and management strategies to improve outcomes.
Objective:
The ongoing rFIXFc extension study, B-YOND (clinicaltrials.gov #NCT01425723), evaluates the long-term safety and efficacy of rFIXFc for the treatment of severe hemophilia B. Here we report interim safety and efficacy data for adults and adolescents enrolled in B- YOND.
Methods:
Upon completing B-LONG, eligible subjects could enroll in one of 4 treatment groups in B-YOND: weekly prophylaxis (20 to 100 IU/kg every 7 days), individualized prophylaxis (100 IU/kg every 8 to 16 days, or twice monthly), modified prophylaxis (a prophylaxis regimen different from weekly or individualized prophylaxis), or episodic treatment. Subjects could change treatment groups at any point in the study. The primary endpoint was development of inhibitors. Secondary outcomes included annualized bleeding rate (ABR) and rFIXFc exposure days (EDs).
Summary:
93/115 subjects (80.9%) who completed B-LONG enrolled in B-YOND. As of the interim data cut (17 October 2014), 18 subjects had completed, 7 had discontinued, and 68 remained on study (median time on study, 119.9 weeks). From the start of B-LONG to the B- YOND interim data cut, the median time on rFIXFc was 171.6 weeks and 68 subjects (73%) had ≥100 cumulative rFIXFc EDs. 29/90 subjects (32%) from Arms 1-3 of B-LONG changed treatment groups at the start of or during B-YOND, including 9/19 subjects who changed from episodic to prophylactic treatment (1 subject changed back to episodic treatment before the interim data cut). In the weekly prophylaxis group, the median (IQR) average weekly prophylactic dose was 49.5 (21.0, 105.6) IU/kg. The median (IQR) average dosing intervals in the individualized and modified prophylaxis groups were 13.7 (10.1, 14.0) days and 6.9 (4.9, 7.0) days, respectively (a reduction in annual infusions of ~75% and ~50%, respectively, compared with twice-weekly administration of a standard half-life FIX product). As of the B- YOND interim data cut, no inhibitors were observed, and there were no reports of anaphylaxis or serious hypersensitivity reactions associated with rFIXFc, and no thrombotic events. Adverse events were generally typical of the hemophilia B population; no subject discontinued due to an adverse event. Median ABRs were low with rFIXFc prophylaxis (Table). 97.2% of bleeding episodes were controlled with 1 or 2 infusions.
Conclusions:
Interim data from B- YOND confirm the long-term safety of rFIXFc and the maintenance of a low ABR with prophylactic dosing every 1 to 2 weeks.
Pediatric pain, especially in the hemophilia population, is under-recognized and under-treated. Barriers to adequate treatment include lack of knowledge, variability of practice, and outmoded beliefs. All of these factors lead to a culture of slow to no change in practice patterns. Health care providers need current, state-ofthe- art education and tools to assist them in developing the skills required to assess and manage pain in children. Children are often given minimal or no analgesia for procedures that would be treated aggressively in adults. Although more is now known about pain management in children, this knowledge has not been widely or effectively translated into routine pediatric clinical practice, including the practice of most HTCs. In the bleeding disorders community, especially for those with hemophilia, children begin to experience frequent pokes secondary to frequent factor infusions and blood draws at an early age. Depending on the severity of their disorder, they may experience a poke daily or more frequently. This gives rise to anxiety for the child as well as their parents and other family members. Anticipatory anxiety is not uncommon in this setting. The child and their family often feel as though they have no control over the situation. A distraction box is filled with tools for providers to implement during any procedure involving children. The simple act of distraction (in whatever form) can significantly decrease pain and anxiety for both the child as well as their parent. This box offers multiple methods of distraction and informational videos on techniques. The focus of the Poke Plan is to give control over a painful or anxiety provoking situation back to the parent/child. The simple wallet card quickly educates any provider on how the child best handles the discomfort and anxiety associated with a poke/needlestick. Filling out the card educates the parents on distraction techniques that may be helpful for their child in painful and anxiety provoking situations. To date there have not been any studies done in this population. However centers in Michigan using similar Poke Plans in the general pediatric population include but not necessarily limited too are: Sparrow Hospital in Lansing Michigan, Munson Medical Center in Traverse City, Michigan as well as the University of Michigan Children and Women’s Hospital in Ann Arbor, Michigan.
Objective:
This poster outlines evaluation of an educational family board game, “Don’t Push Your Luck!” designed to inspire discussion about hemophilia, and help school-age children learn about decision-making. Since children with hemophilia have a life-long disorder, this game provides a resource to help them learn how to make decisions for transitions to self- care.
Methods:
This game was developed based on recommendations by school-age children from previous research on partnership roles in hemophilia care. In the game, each player takes on the role of a child with hemophilia, exploring choices and consequences in everyday experiences. A multi-site, mixed method research project was coordinated by Mount Royal University, with sub-sites in Canada and United States. In phase I, the board game prototype and questionnaires from boys (n=3) and parents (n=5) living with hemophilia and boys (n=3) and parents (n=5) living with cystic fibrosis was refined. In phase II, we evaluated the revised version of the board game with children who were living with hemophilia and their household family members over age 8 years. The primary objective was to explore how playing an educational board game affected school age children’s engagement in decision-making for self-care. Children and parent perspectives were compared in the way the board game affects engagement in decision-making for children’s hemophilia self-care. Recommendations for future board game development were solicited. Purposive sampling was used to recruit household family members (n=50), including at least one parent/guardian (n= 22) and children aged 8-12 years living with hemophilia (n= 16). Two researchers visited homes to play the game, interview families, observe their responses to the game, and provide pre and post-game questionnaires on decision-making and Haemo-Quol Index© quality of life, and post-game enjoyment. Audio recordings and field notes were documented to record participant observation. Questionnaire items on decision making, quality of life observations, and game enjoyment were analyzed using descriptive statistics. Qualitative analysis of written, verbal and observed behaviours was summarized in thematic categories provided further evaluation of the board game intervention.
Summary:
Comparisons between children and adults were analyzed. Findings indicate that this game is an enjoyable and effective resource for school-age families to engage in discussions relevant to hemophilia self-care skills and decision-making.
Conclusion:
This board game is an interactive, developmentally appropriate resource for families with school-age children who are living with hemophilia to facilitate engagement and conversation about everyday life experiences in preparation for their transition to adult self- care.
This project was generously funded by an unrestricted grant from Bayer Healthcare.
Objective:
Patient-centered medical home (PCMH), a team-based model of practice involving patients, families, providers and care team members, focuses on high quality, efficient, and patient-centered care. The purpose of this project was to implement appropriate elements of the PCMH model in the care delivered by the Intermountain Hemophilia and Thrombosis Center (IHTC).
Methods:
The IHTC, as a medical home neighbor, participated in a 3 1⁄2 year (5/2011- 11/2014) Children’s Health Improvement Collaborative Medical Home Demonstration (MHD) that involved 3 specialty and 9 primary care practices in Utah. IHTC focused on both MHD- wide and practice-specific quality improvement (QI) goals. Our QI team included the IHTC core multidisciplinary team and a parent partner and medical home coordinator (MHC) who were funded by the MHD. The MHD led four sequential, 8-12 month projects: “Improving Collaboration Among Pediatric Generalists and Specialists,” “Implementing Care and Self- Care Plans for Children with Chronic Conditions,” “Improving Healthcare Transitions for Children with Special Health Care Needs,” and “Sustainability.” Practice-specific projects targeted goals established via a needs assessment and parent partner input. Plan-Do-Study- Act (PDSA) cycles were facilitated by the MHC and a practice coach from the MHD. Continuing education and peer support were provided via learning sessions, webinars, and ongoing mentorship.
Summary:
IHTC met all MHD-wide and practice-specific goals. Selected MHD-wide improvements included: completion of the patient history prior to new consultation (improved from ~15% to 95%); patient self-care plans (0% to 97%); and youth with an up-to-date transition tool (0% to 100%). To address “sustainability,” IHTC will continue using QI, implementing the PCMH model, and will maintain the MHC as a member of the care team. Practice-specific strategies resulted in improved efficiency and family-centered approach to the annual comprehensive clinic visit (31⁄2 hour visit decreased to 2 hours with reduced redundancy), reduced no-show/cancellations (~33% to 10%), established means for continuous individual patient/family feedback, and a formalized IHTC-specific emergency preparedness plan (currently in progress).
Conclusions:
Via participation in the MHD, the IHTC learned that QI is both realistic and rewarding. Essential components for ongoing improvement include: specific, defined and measurable goals; a QI leader; parent/consumer input; and participation by all clinical team members. The PCMH model provides a framework for meaningful change for patients, families, and clinical practice.
Acknowledgments:
Funded in part by a CHIPRA Quality Demonstrations grant: CFDA 93.767 from the U.S. Department of Health and Human Services, Centers for Medicare & Medicaid Services.
Introduction:
Extended half-life factor VIII (FVIII) products currently in development require a careful evaluation of dosing options given that the pharmacokinetics of weekly FVIII levels , including FVIII peak and trough levels, have been shown to play a role in bleeding occurrence.
Methods:
Pharmacokinetic (PK) modeling was conducted using published literature and clinical trial data. Published population PK models for recombinant full length DNA, plasma and albumin free FVIII (octocog alfa, rAHF-PFM) and recombinant B-domain-deleted FVIII Fc fusion product (efraloctocog alfa, rFVIIIFc) were used. All calculations were performed assuming linear pharmacokinetics. Dosing frequencies assessed were every 2 days with rAHF-PFM and every 3, 4, 5 or 7 days with rFVIIIFc. Dosages assessed were 30 IU/kg of rAHF-PFM and 30, 40, 50 or 65 IU/kg of rFVIIIFc. Results were generated for a hypothetical patient aged 30 years, with 70 kg body weight, exhibiting a VWF level of 118 IU/dL and a hematocrit of 45%. Time spent below 1% and 3% per week and time spent above 10% and 20% per week were assessed and compared for each scenario.
Summary:
Compared to 30 IU/kg of rAHF-PFM dosed every other day, a patient on rFVIIIFc would spend more time per week below 1% FVIII level when dosed every 5th day up to 50 IU/kg and when dosed every 7th day at any dose within the range tested. Moreover, even when increasing the dosing frequency to 30 IU/kg of rFVIIIFc every 3rd day, or when dosing rFVIIIFc up to 65 IU/Kg every 4th, 5th and 7th day the patient’s plasma FVIII level will drop below 3%. When looking at time per week spent above higher FVIII levels, the model patient would spend more time above 10% when dosed with rAHF-PFM at 30 IU/kg every second day as compared to rFVIIIFc dosed every 3 days at 30IU/kg, and every 4, 5 and 7 days at any dose within the range tested (≤65 IU/kg). Likewise, this patient will also spend more time above 20% with rAHF-PFM every other day than with rFVIIIFc dosed every 4 days at 40 IU/kg and every 5 days at 50 IU/kg and every 7 days at 65 IU/Kg.
Conclusion:
These data indicate that choice and optimal dosing of FVIII products require a better understanding of individual pharmacokinetics in order to avoid that patients would spend extended time at levels insufficient to protect them from bleeding, particularly subjects with a more active lifestyle.
Introduction and Objective:
Prospective clinical trials have demonstrated the efficacy of prophylaxis in reducing bleeding episodes in hemophilia A and B patients and those with inhibitors. However, data, predominantly from observational studies, have suggested more equivocal effects on health-related quality of life (HRQoL) [Buchbinder 2013]. The present review examined the impact of prophylaxis on HRQoL as measured during prospective trials.
Methods:
We conducted a systematic literature review of prospective studies evaluating the efficacy of prophylaxis in hemophilia using factor VIII, factor IX, or bypassing agents. Applying the inclusion criteria, we selected studies which evaluated HRQoL via validated instruments and summarized key data.
Results:
A total of 12 studies (hemophilia A [n=7]; hemophilia B [n=2]; inhibitors [n=3]) met all inclusion criteria and were reviewed. Of these studies, the investigational products were Advate (n=2), Kogenate (n=2), NovoEight (n=2), Eloctate (n=1), Rixubis (n=1), Aprolix (n=1), Feiba (n=2), and NovoSeven (n=1). HRQoL was assessed using one or a combination of the following instruments: SF-36 (n=3), EQ-5D (n=5), Haemo-QoL (n=2), Haem-A-QoL (n=3), Haemo-QOL-A (n=2) and general pain VAS (n=1). Seven of the 12 studies reported significant improvement in ≥1 HRQoL measure following prophylaxis. Advate, Rixubis and Feiba prophylaxis (among good responders with ≥ 50% bleed reduction) demonstrated statistically significant and clinically meaningful improvement in the physical component and certain domain(s) scores of the SF-36 (Valentino 2012; Windyga 2013; Gringeri 2013). Additionally, prophylaxis with Feiba showed clinically meaningful and/or statistically significant improvements in HRQoL (EQ-5D, Haemo-A-QoL), general health status (EQ-VAS) and general pain scores (VAS) (Antunes 2014; Stasyshyn 2014). Although, a previous Kogenate study indicated non-significant change in HRQoL measures (Collins 2003), recently published results from the SPINART trial demonstrated statistically significant and clinically meaningful improvement in several domains of the Haemo-QoL-A (Hong 2014). Prophylaxis with Eloctate and Alprolix resulted in non-significant change in the HRQoL measures used in their respective trials (Wyrwich 2013). Statistical and clinical significance were not reported for prophylaxis treatment with NovoEight (Santagostino 2014). Prophylaxis with NovoSeven showed a non-significant trend towards improvement in all dimensions of the EQ-5D but statistical improvement in general health status (EQ-VAS) (Hoots 2008).
Conclusion:
Results from Advate, Kogenate, Rixubis and Feiba trials offer robust evidence of clinically and statistically significant improvement in HRQoL in hemophilia patients treated with prophylaxis.
