Effects of PK-guided prophylaxis on clinical outcomes and FVIII consumption for patients with moderate to severe Haemophilia A.

INTRODUCTION: In recent years, there has been increased focus on individualizing treatment for persons with hemophilia including pharmacokinetic-guided (PK) dosing. AIMS: In this retrospective study clinical outcomes before and after PK-guided prophylaxis were examined. MATERIALS AND METHODS: Eight Haemophilia Treatment Centres from the United States participated in the study and included 132 patients classified into two cohorts: those undergoing a PK-assessment for product switch (switchers) or to optimize treatment (non-switchers). Subset analyses for the two most common products and patients with dosing per prescription label were included for annual bleeding rates (ABR), mean weekly consumption outcomes, and annualized cost of prophylaxis. RESULTS: The most common products before and after index date were octocog alfa, rurioctocog alfa pegol, and efmoroctocog alfa. Seventy-four (56%) patients were identified as switchers and 58 (44%) patients were classified as non-switchers. The majority of patients (78.0%) experienced either a decrease in ABR post-index or maintained 0 ABR during pre- and post-index time periods, with similar proportions identified in both switchers (77.0%) and non-switchers (79.3%) populations. Non-switchers were identified as having no significant change in cost of therapy, while switchers experienced increased cost of therapy driven by higher price of extended half-life products. Within subset analyses, patients receiving rurioctocog alfa pegol and efmoroctocog alfa had mean ABR under 1 after index date. CONCLUSION: PK-guided prophylaxis has the potential to improve clinical outcomes without increase in cost of therapy for patients maintaining product and can aid in maintaining effective protection against bleeds in those switching product.

Unrelated Hematopoietic Cell Transplantation in a Patient with Combined Immunodeficiency with Granulomatous Disease and Autoimmunity Secondary to RAG Deficiency.

The use of HLA-identical hematopoietic stem cell transplantation (HSCT) demonstrates overall survival rates greater than 75 % for T-B-NK+ severe combined immunodeficiency secondary to pathogenic mutation of recombinase activating genes 1 and 2 (RAG1/2). Limited data exist regarding the use of HSCT in patients with hypomorphic RAG variants marked by greater preservation of RAG activity and associated phenotypes such as granulomatous disease in combination with autoimmunity. We describe a 17-year-old with combined immunodeficiency and immune dysregulation characterized by granulomatous lung disease and autoimmunity secondary to compound heterozygous RAG mutations. A myeloablative reduced toxicity HSCT was completed using an unrelated bone marrow donor. With the increasing cases of immune dysregulation being discovered with hypomorphic RAG variants, the use of HSCT may advance to the forefront of treatment. This case serves to discuss indications of HSCT, approaches to preparative therapy, and the potential complications in this growing cohort of patients with immune dysregulation and RAG deficiency.

A randomized study comparing the use of a pelvic lead shield during trans-radial interventions: Threefold decrease in radiation to the operator but double exposure to the patient.

OBJECTIVES: To determine the efficacy of a 0.5-mm lead apron across the patient's abdomen in addition to standard operator protection for the reduction of scatter radiation on operator and patient radiation exposure BACKGROUND: Cardiac angiography using the radial access compared to the femoral approach is associated with reduced complication rate and improved patient comfort but has significantly increased radiation dose. Improvements in radiation protection are needed METHODS: We randomly assigned 332 patients undergoing coronary angiography to a group with pelvic lead shielding and a group with standard protection. In each procedure, eight digital dosimeters were used to measure operator radiation dose [under the lead apron, outside the thyroid shield, and at the left side of the head], patient dose at the level of the umbilicus [above and beneath the lead apron], and two on the acrylic shielding and one on the image receptor to measure scattered radiation RESULTS: Both groups were similar in BMI, procedures performed, and number of sequences. Usage of lead shielding statistically significantly reduced the radiation dose of the operator at all three sites measured: under lead apron [all in µSv]: 0.53 ± 1.4 vs. 0.17 ± 0.6, on thyroid collar 5.9 ± 7.7 vs. 2.9 ± 3.4, and left side of head 3.3 ± 3.4 vs. 2.1 ± 2.2, P<0.001. However the radiation to the patient was doubled from 15.4 ± 24.1 to 28.9 ± 81.1, P=0.04 CONCLUSIONS: The use of a pelvic lead shield during radial angiography reduced the operator radiation exposure at multiple measurement sites. However there was an increased exposure to the patient. This balance should be further investigated before the widespread adoption of this method. .

Successful treatment of secondary graft failure following unrelated cord blood transplant with hematopoietic growth factors in a pediatric patient with Fanconi anemia.

Graft failure following allogeneic HCT in Fanconi anemia is associated with significant mortality. Retransplantation may be considered; however, the limited toxicity profile of HGFs also makes them an option for the treatment of graft failure. We describe a five-yr-old female diagnosed with Fanconi anemia and marrow failure treated with HCT. The course was complicated by secondary graft failure treated successfully with HGFs including G-CSF, EPO, and romiplostim. The outcome could be related to the intervention, but could also be the natural course of recovery, including recovering from a recent CMV infection treated with ganciclovir. We found the use of HGFs to be an effective and safe alternative to the potential complications as well as morbidity and mortality associated with the use of retransplantation.

Noninvasive Blood Pressure Monitoring via a Flexible and Wearable Piezoresistive Sensor.

In the present global context, continuous blood pressure (BP) monitoring is paramount in addressing the global mortality rates attributed to hypertension. Achieving precise insights into the human cardiovascular system necessitates accurate measurement of BP, and the accuracy depends on the faithful recording of oscillations or pulsations. This task ultimately depends on the caliber of the pressure sensor embedded in the BP device. In this context, we have fabricated a flexible resistive pressure sensor based on reduced graphene oxide (rGO) and a polydimethylsiloxane (PDMS) sponge that is highly flexible and sensitive. The designed device operates effectively with a minimal bias voltage of 500 mV, at which point it showed its maximum relative change in current, reaching approximately 25%. Additionally, the sensing device showed a notable change in resistance values, exhibiting almost 100% change in resistance when subjected to a pressure of 400 mmHg and high sensitivity of 0.27 mmHg-1. After promising outcomes were obtained during static pressure measurement, the sensor was used for BP monitoring in humans. The sensor accurately traced the oscillometric waveform (OMW) for distinct systolic blood pressure (SBP) and diastolic blood pressure (DBP) combinations to cover a range of medical situations, including hypotension, standard or normal, and hypertension. The values of SBP, DBP, and MAP were derived from the sensor's output using the MAA technique, and the errors in these values concerning the simulator and the traditional BP monitor follow the universal AAMI/ESH/ISO protocols. Bland-Altman (B&A) correlation and scatter plots were used to compare the sensor's results and further validate the proposed sensor. The sensor showed the mean and standard deviation error in the SBP, DBP, and MBP of -0.2 ± 5.9, -0.5 ± 7, and -0.9 ± 4.7 mmHg when compared with the noninvasive blood pressure (NIBP) simulator. The pulse rate (PR) was also calculated from the same OMW for the specified value of 80 beats per minute (bpm) given by the simulator and reported a mean PR value of ∼81 bpm, close to the reference value. The findings show that the flexible resistive sensing device can accurately measure BP and replace the existing sensors of BP devices.

Costs and impact of disease in adults with sickle cell disease: a pilot study.

ABSTRACT: We assessed the feasibility to estimate illness burden in adults with SCD, investigated factors associated with health-related quality of life (HRQoL), and estimated societal burden. We recruited 32 participants and collected data on fatigue, HRQoL, and work productivity and activity impairment via patient survey. Health care utilization was abstracted for the 12 months before enrollment using medical chart review. Mean age was 36.7 years; 84.4% of participants had hemoglobin SS or Sßthal0 disease, and 81.3% reported chronic pain (experiencing pain on ≥3 days per week in the past 6 months). Mean EQ-5D-3L visual analogue scale score was 63.4 and the index score was 0.79. The mean fatigue score was 57.9. Higher fatigue score was correlated with lower EQ-5D index score (correlation coefficient r = -0.35; P = .049) and Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me) scores, including pain (r = -0.47; P = .006), sleep (r = -0.38; P = .03), and emotion scores (r = -0.79; P < .0001). The number of hospitalizations was negatively correlated with HRQoL (all P < .05). Patients who reported chronic pain had significantly lower mean ASCQ-Me sleep scores (48.3 vs 57.1; P = .04) and EQ-5D index scores (0.72 vs 0.89; P = .002) than those without chronic pain. Mean estimated annual per person costs were $51 779 (median, $36 366) for total costs, $7619 ($0) for indirect costs (estimated from lost earnings of participants), and $44 160 ($31 873) for medical costs. Fatigue, SCD complications, hospitalization, and chronic pain negatively affected HRQoL. This sample experienced a high economic burden, largely from outpatient doctor visits.

Successful cord blood transplantation in a patient with malignant infantile osteopetrosis and hemophilia.

MIOP is a congenital disorder of osteoclast differentiation or dysfunction. Inadequate bone resorption by osteoclasts results in a spectrum of complications including hypocalcemia, osteosclerosis, marrow failure, extramedullary hematopoiesis, hydrocephalus, visual deficits, and eventual mortality. Early diagnosis and timely HCT is a recommended treatment approach for select patients prior to the development of end-organ damage. A comorbid bleeding disorder presents a unique challenge in the setting of MIOP and cord blood HCT given the additional risk factors for bleeding including delayed engraftment, a high risk of developing sinusoidal obstruction syndrome, and potential need for emergent invasive procedures. To our knowledge, this is the first report of a patient with an autosomal recessive form of MIOP who successfully underwent a cord blood HCT complicated by the presence of mild hemophilia A and HCT-related complications including delayed engraftment, sinusoidal obstruction syndrome, and need for multiple invasive procedures (e.g., ventriculostomy, tracheostomy) without clinically significant bleeding. Given the underlying diagnosis of MIOP and need for HCT, the challenge of mitigating the significant risk of bleeding in a patient with a comorbid bleeding disorder is discussed.

Successful autologous cord blood transplantation in a child with acquired severe aplastic anemia.

Over 400 cases of pediatric SAA occur annually in the United States. A growing number of children with SAA may have had their stem cells harvested through cord blood collection. We describe a nine-yr-old male with SAA treated successfully with an autologous cord blood transplant following immunoablative chemotherapy. With the increasing number of people cryopreserving autologous cord blood, the use of autologous cord blood in the treatment of SAA might be considered as initial therapy. This case serves to discuss approaches to preparative therapy as well as the potential complications in this growing cohort of patients.

Global Emerging HEmophilia Panel (GEHEP): A Multinational Collaboration for Advancing Hemophilia Research and Treatment.

GEHEP, established in 2009, is an independent, multi-institutional, international consortium of early career hematology specialists in the field of hemophilia and other inherited bleeding disorders. The main objective of the group, whose members practice at institutions in North America, Europe, and South Africa, is to advance hemophilia care by providing a forum for mentored collaborative research, developing programs for improving clinical care, and promoting academic career development of junior faculty. GEHEP members collect and document anonymized data on intra- and interinstitutional differences in patient populations, diagnosis, and treatment in the field of hemophilia and other bleeding disorders. To facilitate sharing of aggregated data among GEHEP members, a global protocol was developed and approved by most members' local institutional review board. Current GEHEP research initiatives are varied, encompassing work in pediatric and adult patients. GEHEP members have presented research at international meetings on the initiation of prophylaxis in children, use of immune tolerance induction in adults, and prevalence of acute coronary syndromes in older patients with hemophilia. The main goal of the continuing work of GEHEP is to advance the care of patients with hemophilia worldwide.

Evaluation of blood pressure using a flexible and wearable capacitive pressure sensor.

In recent times, the high demand for flexible and wearable pressure sensors to monitor human health, particularly for patients afflicted with hypertension or high blood pressure (BP), has captured the keen interest of researchers. Capacitance-based flexible sensing devices offer real-time metrics regarding vital physiological parameters of the human body, such as BP and pulse rate (PR), thereby enabling the identification of cardiovascular complications. In this regard, we have developed a capacitive pressure sensor using polydimethylsiloxane (PDMS) and deionized water (DIW) and improved its key parameters by adding baking powder to PDMS-DIW. The sensor demonstrated excellent performance in static pressure measurements with a sensitivity of 0.021 Pa-1, detection limit of 1 Pa, and response time of 100 ms. We further investigated its application in human BP monitoring. The sensor successfully captured the oscillometric waveform (OMW) for all 160 participants and demonstrated excellent performance in accurately measuring BP, meeting all criteria outlined as the universal standard when compared with the reference devices: OMRON BP device and the gold-standard mercury-based sphygmomanometer. Furthermore, the sensor accurately provided the PR and agreed well with the reference BP device. Therefore, the developed BP sensor can be a viable alternative to replace the pressure sensors in existing BP devices.

De Novo Lower Urinary Tract Symptoms in COVID-19 Patients.

Background and objective Since early 2020, the novel coronavirus disease 2019 (COVID-19) has turned into a global healthcare concern. The usual clinical presentation of COVID-19 infection includes myalgia, headache associated with pyrexia, and sore throat. Our study aimed to assess the severity of lower urinary tract symptoms (LUTS) in COVID-19 patients and determine its correlation with the prognosis of the disease. Methods We conducted an observational study in the COVID-19 care unit at a tertiary care teaching center in Rajasthan on patients diagnosed as COVID-19-positive. The overactive bladder (OAB) symptom scoring system for LUTS and the CT scoring system for lung involvement in COVID-19 patients were used to evaluate the sample population. Results While our findings showed a non-significant association between OAB and CT score (p>0.05), correlation analysis revealed that the length of hospital stay was significantly longer and oxygen needs were significantly more frequent with severe LUTS. Conclusions Based on our findings, de novo LUTS, particularly storage symptoms, may be present in COVID-19-positive cases, and the severity of these symptoms may have an impact on the patient's length of stay in the hospital. Hence, doctors and other medical professionals should consider COVID-19-related bladder dysfunctions such as de novo LUTS as part of COVID-19 symptomatology.

Unrelated hematopoietic stem cell transplantation in a patient with congenital dyserythropoietic anemia and iron overload.

CDA is a heterogeneous group of disorders that result in morphologically abnormal erythroid maturation and ineffective erythropoiesis. Curative therapy for CDA focuses on the use of HSCT using fully matched sibling donors. This is the first report of a Type II CDA patient with severe iron overload who was successfully treated with HSCT using a HLA-matched unrelated donor after aggressive chelation therapy. Given the challenges of HSCT in any patient with CDA and severe iron overload, the role of novel approaches to iron chelation and HSCT is discussed.

Inflammatory polyps following successful HLA-matched cord blood transplantation in a patient with X-linked lymphoproliferative syndrome.

Gastrointestinal complications following HSCT are numerous and include a variety of issues resulting in hepatic, biliary, pancreatic, and intestinal compromise. In the context of an underlying state of immune dysregulation, novel complications may arise including autoimmunity. To our knowledge, this is the first report of a patient with XLP who was successfully treated with HSCT using an HLA-matched unrelated cord blood unit that was complicated by the development of inflammatory polyps of the colon. Given the underlying diagnosis of XLP and its associated immune dysregulation, the challenge of understanding unique gastrointestinal manifestations of autoimmunity following HSCT is discussed.

Living Profiles: design of a health media platform for teens with special healthcare needs.

Living Profiles is a health media platform in development that aggregates multiple data flows to help teens with special healthcare needs (SHCN), particularly with regard to self-management and independence. A teen-oriented personal health record (PHR) incorporates typical teen behaviors and attitudes about health and wellness, encompasses how teens perceive and convey quality of life, and aligns with data related to their chronic medical condition. We have conceived a secure personalized user interface called the Quality of Life Timeline, which will assist with the transition from pediatric care to an adult provider through modules that include a mood meter, reminder device, and teleport medicine. With this personalized PHR, teens with SHCN can better understand their condition and its effects on daily activities and life goals and vice versa; additionally, use of this PHR allows for better information sharing and communication between providers and patients. The use of a teen-oriented tool such as Living Profiles can impact teens' overall quality of life and disease self-management, important attributes for a successful transition program.

Cognitive and Functional Outcomes following Inpatient Rehabilitation in Patients with Acquired Brain Injury: A Prospective Follow-up Study.

OBJECTIVES: To study the effects of cognitive retraining and inpatient rehabilitation to study the effects of cognitive retraining and inpatient rehabilitation in patients with acquired brain injury (ABI). DESIGN AND SETTING: This was a prospective follow-up study in a neurological rehabilitation department of quaternary research hospital. PATIENTS AND METHODS: Thirty patients with ABI, mean age 36.43 years (standard deviation [SD] 12.6, range 18-60), mean duration of illness 77.87 days (SD 91.78, range 21-300 days) with cognitive, physical, and motor-sensory deficits underwent inpatient rehabilitation for minimum of 14 sessions over a period of 3 weeks. Nineteen patients (63%) reported in the follow-up of minimum 3 months after discharge. Type of ABI, cognitive status (using Montreal Cognitive assessment scale [MoCA] and cognitive Functional Independence Measure [Cog FIM]®), and functional status (motor FIM®) were noted at admission, discharge, and follow-up and scores were compared. RESULTS: Patients received inpatient rehabilitation addressing cognitive and functional impairments. Baseline MoCA, motor FIM, and Cog FIM scores were 15.27 (SD = 7.2, range 3-30), 31.57 (SD = 15.6, range 12-63), and 23.47 (SD = 9.7, range 5-35), respectively. All the parameters improved significantly at the time of discharge (MoCA = 19.6 ± 7.4 range 3-30, motor FIM® = 61.33 ± 18.7 range 12-89, Cog FIM® =27.23 ± 8.10 range 9-35). Patients were discharged with home-based programs. Nineteen patients reported in follow-up and observed to have maintained cognition on MoCA (18.8 ± 6.8 range 6-27), significantly improved (P < 0.01) on Cog FIM® (28.0 ± 7.7 range 14-35) and motor FIM® =72.89 ± 16.2 range 40-96) as compare to discharge scores. CONCLUSIONS: Cognitive and functional outcomes improve significantly with dedicated and specialized inpatient rehabilitation in ABI patients, which is sustainable over a period.

Reliability of patient-reported outcome instruments in US adults with hemophilia: the Pain, Functional Impairment and Quality of life (P-FiQ) study.

BACKGROUND: Hemophilia is marked by frequent joint bleeding, resulting in pain and functional impairment. OBJECTIVE: This study aimed to assess the reliability of five patient-reported outcome (PRO) instruments in people with hemophilia (PWH) in a non-bleeding state. METHODS: Adult male PWH of any severity and inhibitor status, with a history of joint pain or bleeding, completed a pain history and five PRO instruments (EQ-5D-5L, Brief Pain Inventory v2 [BPI], International Physical Activity Questionnaire [IPAQ], Short Form 36 Health Survey v2 [SF-36v2], and Hemophilia Activities List [HAL]) during their routine comprehensive care visit. Patients were approached to complete the PRO instruments again at the end of their visit while in a similar non-bleeding state. Concordance of individual questionnaire items and correlation between domain scores were assessed using intra-class correlation coefficient (ICC). RESULTS: Participants completing the retest (n=164) had a median age of 33.9 years. Median time for completion of the initial survey with PRO instruments was 36.0 minutes and for the five PRO instruments, median retest time was 21.0 minutes. The majority of participants had hemophilia A (74.4%), were white and non-Hispanic (72.6%), and self-reported arthritis/bone/joint problems (61%). Median/mean test-retest concordance was EQ-5D-5L 80.0%/79.1%, BPI 54.5%/58.9%, IPAQ 100%/100%, SF-36v2 77.8%/76.4%, and HAL 77.4%/75.9%. ICCs for test-retest reliability were EQ-5D-5L index 0.890; BPI - severity 0.950; BPI - interference 0.920; IPAQ total activity 0.940; SF-36v2 overall health 0.910; HAL total score 0.970. CONCLUSION: All five PRO scales showed acceptable test-retest reliability in adult PWH. Therefore, the choice of instrument to be used for research or clinical care should be driven by instrument characteristics other than reliability.