Depression and anxiety in persons with Von Willebrand disease.

OBJECTIVE: We assessed sociodemographic and clinical characteristics associated with depression and anxiety in individuals with Von Willebrand disease (VWD) aged ≥12 years. METHODS: The study collected data on patients' sociodemographic, joint problems and health-related quality of life (HRQoL) using EQ-5D-3L, 8-item patient health questionnaire for depression and 7-item Generalized Anxiety Disorder Questionnaire from participants in seven geographically diverse US haemophilia treatment centres. RESULTS: Analyses included 77 participants. The rates of depression and anxiety were 63.6% and 58.3%, respectively. Persons with low VWF displayed higher rates of depression (86.7%) or anxiety (69.2%) compared to those with VWD (58.1%, p = .04 for depression, and 55.9%, p = .38 for anxiety). Logistic regression analyses demonstrated that having joint problems (odds ratio [OR] = 6.3, confidence interval [CI] = 2.0-20.1) was the most important variable associated with depression, followed by being single, divorced, widowed, or separated in adult participants or parents of participants age < 18 years (OR = 7.0, CI = 1.7-29.0. The most important variable associated with anxiety was being single or lacking a partner (OR = 10.8, CI = 2.5-47.5), followed by age 12-17 years old (OR = 6.7, CI = 1.6-26.9), or having worse health compared to 3-months ago (OR = 12.3, CI = 1.3-116.2). Mean covariates adjusted EQ visual analogue scale score was significantly lower among persons with depression (68.77 ± 3.15 vs. 77.58 ± 4.24, p = .03) than those without depression. CONCLUSIONS: Our study revealed concerning levels of depression and anxiety in this VWD sample. Lack of social support was determined an important factor associated with depression and anxiety in this sample. Mental health screening is critical in VWD clinical evaluation and care.

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.

Trends in dedicated care for females with bleeding disorders within U.S. hemophilia treatment centers.

Graphical representation of increasing percentage of female patients seen at HTCs, percentage of females by diagnosis, number of clinics in existence, and absolute number of female patients seen over a 10-year period (top left then clockwise).

Outcome measures reported for the management of proximal humeral fractures: a systematic review.

BACKGROUND: The American Shoulder and Elbow Surgeons multicenter taskforce studying proximal humerus fractures reached no consensus on which outcome measures to include in future studies, and currently no gold standard exists. Knowledge of commonly used outcome measures will allow standardization, enabling more consistent proximal humerus fracture treatment comparison. This study identifies the most commonly reported outcome measures for proximal humerus fracture management in recent literature. METHODS: A systematic review identified all English-language articles assessing proximal humerus fractures from 2008 to 2018 using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Review articles, meta-analyses, revision surgery, chronic injuries, studies with <15 patients, studies with <12 month follow-up, anatomic/biomechanical studies, and technique articles were excluded. Included studies were assessed for patient demographics and outcome scores, patient satisfaction, complications, range of motion, and strength. RESULTS: Of 655 articles, 74 met inclusion criteria. The number of proximal humerus fractures averaged 74.2 per study (mean patient age, 65.6 years). Mean follow-up was 30.7 months. Neer type 1, 2, 3, and 4 fractures were included in 8%, 51%, 81%, and 88% of studies, respectively. Twenty-two patient-reported outcome instruments were used including the Constant-Murley score (65%), Disabilities of the Arm, Shoulder, and Hand score (31%), visual analog scale pain (27%), and American Shoulder and Elbow Surgeons score (18%). An average of 2.2 measures per study were reported. CONCLUSION: Considerable variability exists in the use of outcome measures across the proximal humerus fracture literature, making treatment comparison challenging. We recommend that future literature on proximal humerus fractures use at least 3 outcomes measures and 1 general health score until the optimal scores are determined.

Aiming to Improve Readmissions Through InteGrated Hospital Transitions (AIRTIGHT): a Pragmatic Randomized Controlled Trial.

BACKGROUND: Despite years of intense focus, inpatient and observation readmission rates remain high and largely unchanged. Hospitals have little, robust evidence to guide the selection of interventions effective at reducing 30-day readmissions in real-world settings. OBJECTIVE: To evaluate if implementation of recent recommendations for hospital transition programs is effective at reducing 30-day readmissions in a population discharged to home and at high-risk for readmission. DESIGN: A non-blinded, pragmatic randomized controlled trial ( Clinicaltrials.gov : NCT02763202) conducted at two hospitals in Charlotte, North Carolina. PATIENTS: A total of 1876 adult patients, under the care of a hospitalist, and at high risk for readmissions. INTERVENTION: Random allocation to a Transition Services (TS) program (n = 935) that bridges inpatient, outpatient, and home settings, providing patients virtual and in-person access to a dedicated multidisciplinary team for 30-days, or usual care (n = 941). MAIN MEASURE: Thirty-day, unplanned, inpatient, or observation readmission rate. KEY RESULTS: The 30-day readmission rate was 15.2% in the TS group and 16.3% in the usual care group (RR 0.93; 95% [CI, 0.76 to 1.15]; P = 0.52). There were no significant differences in readmissions at 60 and 90 days or in 30-day Emergency Department visit rates. Patients, who were referred to TS and readmitted, had less Intensive Care Unit admissions 15.5% vs. 26.8% (RR 0.74; 95% [CI, 0.59 to 0.93]; P = 0.02). CONCLUSIONS: An intervention inclusive of contemporary recommendations does not reduce a high-risk population's 30-day readmission rate. The high crossover to usual care (74.8%) reflects the challenge of non-participation that is ubiquitous in the real-world implementation of population health interventions. TRIAL REGISTRY: ClinicalTrials.gov ; registration ID number: NCT02763202, URL: https://clinicaltrials.gov/ct2/show/NCT02763202.

Association of infections and venous thromboembolism in hospitalized children with nephrotic syndrome.

BACKGROUND: Nephrotic syndrome (NS) results in hypercoagulability and increased risk of infection. Furthermore, infection increases the risk of venous thromboembolism (VTE). Our objective was to determine the prevalence of infection, VTE, and the associated outcomes among a cohort of hospitalized children with NS. METHODS: All children with NS admitted to 17 pediatric hospitals across North America from 2010 to 2012 were included. Prevalence of infection and VTE was determined. Wilcoxon rank-sum and logistic regression were performed. RESULTS: Seven-hundred thirty hospitalizations occurred among 370 children with NS. One-hundred forty-eight children (40%) had ≥ 1 infection (211 episodes) and 11 (3%) had VTE. Those with VTE had infection more frequently (p = 0.046) and were younger at NS diagnosis (3.0 vs. 4.0 years; p = 0.008). The most common infectious pathogen identified was Streptococcus pneumoniae. The median hospital length of stay for those with infection [10 vs 5 days (p < 0.0001)] or VTE [22 vs 6 days (p < 0.0001)] was longer than those without either complication. Of those with infection, 13% had an intensive care unit (ICU) stay compared with 3.3% of those without infection. Median ICU stay was 4 days in those with VTE compared to 0 days in those without (p < 0.001). By logistic regression, only the number of ICU days was associated with VTE (OR 1.074, 95% CI 1.013-1.138). CONCLUSIONS: Hospitalized children with NS have high rates of infection. Presence of VTE was associated with infection. Both were associated with longer hospitalizations and ICU stays.

Distal triceps transosseous cruciate versus suture anchor repair using equal constructs: a biomechanical comparison.

BACKGROUND/HYPOTHESIS: Suture anchor-based repair has been advocated for repair of distal triceps avulsion, but previous models have used an unequal number of sutures across the repair site. We hypothesized that there would be no difference in triceps tendon displacement between gold standard repair with transosseous cruciate bone tunnels and suture anchor repair with an equal number of sutures in the constructs. METHODS: The triceps tendon footprint was measured in 20 cadaveric elbows (10 matched pairs), and a distal triceps tendon rupture was created. The specimens in each pair were randomly assigned to transosseous cruciate repair or knotless, double-row, anatomic footprint, suture anchor repair. Specimens underwent cyclic loading to 1500 cycles and then load to failure. Footprint uncoverage was measured at 1500 cycles. Data for medial and lateral triceps tendon displacement, footprint uncoverage, and failure load were obtained. RESULTS: Triceps displacement did not differ significantly between the transosseous cruciate and the suture anchor repair group at 1500 cycles on the medial (3.6 ± 0.9 mm vs. 4.3 ± 1.6 mm [mean ± standard deviation], respectively; P = .27) and lateral side (3.1 ± 1.2 mm vs. 2.0 ± 1.2 mm, respectively; P = .06). No other differences were found between the constructs. DISCUSSION/CONCLUSION: Transosseous cruciate distal triceps repair and knotless double-row suture anchor repair using constructs with an equal number of sutures showed no significant difference in tendon displacement at 1500 loading cycles. These findings suggest that the biomechanical strength of an all-suture construct is not different from that of suture anchors for repair of distal triceps avulsions.

Influence of Body Mass Index on Clinical Outcomes in Reverse Total Shoulder Arthroplasty.

The purpose of this study was to compare reverse total shoulder arthroplasty (RTSA) outcomes in normal weight, overweight, and obese patients. A RTSA outcomes registry was reviewed for rotator cuff-deficient patients with a minimum 2-year follow-up. Fractures, rheumatoid arthritis, and revisions were excluded. Based on World Health Organization body mass index (BMI) classification, there were 29 normal weight, 50 overweight, and 51 obese patients. All groups demonstrated significant improvements from preoperative to most recent follow-up in function scores, pain, and forward elevation. Obese and overweight groups had significantly worse preoperative rotation than the normal weight group. Postoperatively, there was no significant difference in absolute values or degree of improvement of rotation between groups. There was no significant difference in the incidence of radiographic or clinical complications between groups. Results of this study suggest that BMI has little influence on outcomes or risk of complication following RTSA. Longer-term studies are needed to determine if these results are maintained. (Journal of Surgical Orthopaedic Advances.

Lost at Sea in Search of a Diagnosis: A Case of Unexplained Bleeding.

Scurvy results from a dietary deficiency of vitamin C (ascorbic acid) and is rarely thought of in modern day medicine. It now almost always occurs in pediatric patients with behavioral diagnoses, nutritionally restricted diets, and food allergies. Symptoms of scurvy include ecchymoses, bleeding gums, and arthralgias. Here, we present a 17-year-old male with autism spectrum disorder and a diet severely deficient in ascorbic acid due to textural aversion and food preferences. He presented with recurrent arthritis, hemarthrosis, bruising, and anemia. His vitamin C level was low, and his symptoms improved promptly after treatment with ascorbic acid.

Unusual macrocyclic lactone sex pheromone of Parcoblatta lata, a primary food source of the endangered red-cockaded woodpecker.

Wood cockroaches in the genus Parcoblatta, comprising 12 species endemic to North America, are highly abundant in southeastern pine forests and represent an important prey of the endangered red-cockaded woodpecker, Picoides borealis. The broad wood cockroach, Parcoblatta lata, is among the largest and most abundant of the wood cockroaches, constituting >50% of the biomass of the woodpecker's diet. Because reproduction in red-cockaded woodpeckers is affected dramatically by seasonal and spatial changes in arthropod availability, monitoring P. lata populations could serve as a useful index of habitat suitability for woodpecker conservation and forest management efforts. Female P. lata emit a volatile, long-distance sex pheromone, which, once identified and synthesized, could be deployed for monitoring cockroach populations. We describe here the identification, synthesis, and confirmation of the chemical structure of this pheromone as (4Z,11Z)-oxacyclotrideca-4,11-dien-2-one [= (3Z,10Z)-dodecadienolide; herein referred to as "parcoblattalactone"]. This macrocyclic lactone is a previously unidentified natural product and a previously unknown pheromonal structure for cockroaches, highlighting the great chemical diversity that characterizes olfactory communication in cockroaches: Each long-range sex pheromone identified to date from different genera belongs to a different chemical class. Parcoblattalactone was biologically active in electrophysiological assays and attracted not only P. lata but also several other Parcoblatta species in pine forests, underscoring its utility in monitoring several endemic wood cockroach species in red-cockaded woodpecker habitats.

Wear rates of retentive versus nonretentive reverse total shoulder arthroplasty liners in an in vitro wear simulation.

BACKGROUND: Although short-term outcomes of reverse total shoulder arthroplasty (rTSA) remain promising, the most commonly cited complication remains prosthetic instability. A retentive rTSA liner is commonly used to increase system constraint; however, no studies have evaluated the rate of polyethylene wear. Our hypothesis was that more constrained retentive liners would have higher wear rates than nonretentive liners. METHODS: Six nonretentive and six retentive rTSA non-cross-linked polyethylene liners were subjected to 4.5 million cycles of alternating cycles of abduction-adduction and flexion-extension motion loading profiles. The rTSA liners were assessed for gravimetric wear loss, 3-dimensional volumetric loss by novel micro-computed tomography analysis, and particulate wear debris analysis. RESULTS: Volumetric wear rates were significant at 7 specific time points (1.0, 2.0, 2.5, 3.25, 3.75, 4.0, and 4.5 million cycles) throughout testing between nonretentive and retentive liners; however, overall mean volumetric wear rate was not statistically significant (P = .076). Total volume loss between liner test groups was found to be significant starting after 3.5 million cycles of testing. Maximum and mean surface deviations were found to be larger for retentive liners vs. nonretentive liners by micro-computed tomography analysis across the entire articulation surface. DISCUSSION AND CONCLUSION: Retentive liners undergo significantly greater volume loss and greater surface deviation compared with nonretentive liners, most notably at later time points representing extended implantation times. Additional stability afforded by retentive liners should be balanced against the potential for increased wear and potential for subsequent polyethylene wear-induced aseptic loosening.

Anti-inhibitor coagulant complex prophylaxis in hemophilia with inhibitors.

BACKGROUND: Patients with severe hemophilia A and factor VIII inhibitors are at increased risk for serious bleeding complications and progression to end-stage joint disease. Effective strategies to prevent bleeding in such patients have not yet been established. METHODS: We enrolled patients with hemophilia A who were older than 2 years of age, had high-titer inhibitors, and used concentrates known as bypassing agents for bleeding in a prospective, randomized, crossover study comparing 6 months of anti-inhibitor coagulant complex (AICC), infused prophylactically at a target dose of 85 U per kilogram of body weight (±15%) on 3 nonconsecutive days per week, with 6 months of on-demand therapy (AICC at a target dose of 85 U per kilogram [±15%] used for bleeding episodes). The two treatment periods were separated by a 3-month washout period, during which patients received on-demand therapy for bleeding. The primary outcome was the number of bleeding episodes during each 6-month treatment period. RESULTS: Thirty-four patients underwent randomization; 26 patients completed both treatment periods and could be evaluated per protocol for the efficacy analysis. As compared with on-demand therapy, prophylaxis was associated with a 62% reduction in all bleeding episodes (P<0.001), a 61% reduction in hemarthroses (P<0.001), and a 72% reduction in target-joint bleeding (≥3 hemarthroses in a single joint during a 6-month treatment period) (P<0.001). Thirty-three randomly assigned patients received at least one infusion of the study drug and were evaluated for safety. One patient had an allergic reaction to the study drug. CONCLUSIONS: AICC prophylaxis at the dosage evaluated significantly and safely decreased the frequency of joint and other bleeding events in patients with severe hemophilia A and factor VIII inhibitors. (Funded by Baxter BioScience; Pro-FEIBA ClinicalTrials.gov number, NCT00221195.).

Building the foundation for a community-generated national research blueprint for inherited bleeding disorders: facilitating research through infrastructure, workforce, resources and funding.

BACKGROUND: The National Hemophilia Foundation (NHF) conducted extensive, inclusive community consultations to guide prioritization of research in coming decades in alignment with its mission to find cures and address and prevent complications enabling people and families with blood disorders to thrive. RESEARCH DESIGN AND METHODS: With the American Thrombosis and Hemostasis Network, NHF recruited multidisciplinary expert working groups (WG) to distill the community-identified priorities into concrete research questions and score their feasibility, impact, and risk. WG6 was charged with identifying the infrastructure, workforce development, and funding and resources to facilitate the prioritized research. Community input on conclusions was gathered at the NHF State of the Science Research Summit. RESULTS: WG6 detailed a minimal research capacity infrastructure threshold, and opportunities to enable its attainment, for bleeding disorders centers to participate in prospective, multicenter national registries. They identified challenges and opportunities to recruit, retain, and train the diverse multidisciplinary care and research workforce required into the future. Innovative collaborative approaches to trial design, resource networking, and funding to surmount obstacles facing research in rare disorders were elucidated. CONCLUSIONS: The innovations in infrastructure, workforce development, and resources and funding proposed herein may contribute to facilitating a National Research Blueprint for Inherited Bleeding Disorders.

Research is critical to advancing the diagnosis and care of people with inherited bleeding disorders (PWIBD). This research requires significant infrastructure, including people and resources. Hemophilia treatment centers (HTC) need many different skilled care professionals including doctors, nurses, and other providers; also statisticians, data managers, and other experts to process patients' clinical information into research. Attracting diverse qualified professionals to the clinical and research work requires long-term planning, recruiting individuals in training programs and retaining them as they become experts. Research infrastructure includes physical servers running database software, networks that link them, and the environment in which these components function. US Centers for Disease Control and Prevention (CDC) and American Thrombosis and Hemostasis Network (ATHN) coordinate and fund data collection at HTCs on the health and well-being of thousands of PWIBD into a registry used in research studies.National Hemophilia Foundation (NHF) and ATHN asked our group of health care professionals, technology experts, and lived experience experts (LEE) to identify the infrastructure, workforce, and resources needed to do the research most important to PWIBD. We identified the types of CDC/ATHN studies all HTCs should be able to perform, and the physical and human infrastructure this requires. We prioritized finding the best clinical trial designs to study inherited bleeding disorders, identifying ways to share personnel and tools between HTCs, and innovating how research is governed and funded. Involving LEEs in designing, managing, and carrying out research will be key in conducting research to improve the lives of PWIBD.

Evaluating for Suspected Child Abuse: Conditions That Predispose to Bleeding.

Child abuse might be suspected when children present with cutaneous bruising, intracranial hemorrhage, or other manifestations of bleeding. In these cases, it is necessary to consider medical conditions that predispose to easy bleeding or bruising. When evaluating for the possibility of bleeding disorders and other conditions that predispose to hemorrhage, it is important for pediatricians to consider the child's presenting history, medical history, and physical examination findings before initiating a laboratory investigation. Many medical conditions can predispose to easy bleeding. Before ordering laboratory tests for a disease, it is useful to understand the biochemical basis and clinical presentation of the disorder, condition prevalence, and test characteristics. This technical report reviews the major medical conditions that predispose to bruising or bleeding and should be considered when evaluating for abusive injury.

Practical considerations and consensus opinion for children's hospital-based inpatient hemostasis and thrombosis (HAT) consultative services: Communication from the ISTH SSC Subcommittee on Pediatric/Neonatal Thrombosis and Hemostasis.

Caring for children and adolescents with disorders of hemostasis and thrombosis (HAT) has become more specialized and requires a unique skill set that many providers are not able to obtain in standard pediatric hematology/oncology/bone marrow transplant fellowship training programs. The influx of numerous therapeutic advances and increasing medical complexity has expanded the need for experienced HAT providers and subspecialty collaboration in the inpatient setting due to the nuances in the management of patients with HAT complications and concerns. While there are data highlighting the benefits of an inpatient hemostasis, thrombosis, and anticoagulation management service in adult hospitals, there are limited pediatric data supporting such programs. In this article, we summarize the current practices of various pediatric institutions in the inpatient management of HAT patients and provide a consensus opinion for the development of a pediatric inpatient HAT service at tertiary care referral centers.

Evaluation for Bleeding Disorders in Suspected Child Abuse.

Bruising or bleeding in a child can raise the concern for child abuse. Assessing whether the findings are the result of trauma and/or whether the child has a bleeding disorder is critical. Many bleeding disorders are rare, and not every child with bruising/bleeding that may raise a concern for abuse requires an evaluation for bleeding disorders. However, in some instances, bleeding disorders can present in a manner similar to child abuse. Bleeding disorders cannot be ruled out solely on the basis of patient and family history, no matter how extensive. The history and clinical evaluation can be used to determine the necessity of an evaluation for a possible bleeding disorder, and prevalence and known clinical presentations of individual bleeding disorders can be used to guide the extent of laboratory testing. This clinical report provides guidance to pediatricians and other clinicians regarding the evaluation for bleeding disorders when child abuse is suspected.