scholarly journals Interventions to Increase Leukocyte Testing during Treatment with Dimethyl Fumarate

Author(s):  
Paul A. Heidenreich ◽  
Shoutzu Lin ◽  
Parisa Gholami ◽  
Von R. Moore ◽  
Muriel L. Burk ◽  
...  

Dimethyl fumarate (DMF), a treatment for multiple sclerosis, may cause leukopenia and infection. Accordingly, periodic white blood cell (WBC) monitoring is recommended. We sought to evaluate the US Department of Veteran Affairs’ safety program which provides facilities with a list of patients prescribed DMF therapy without a documented white blood cell count (WBC). We identified 118 sites with patients treated with DMF from 1/1/2016 through 9/30/2016. Each site was asked if any of seven interventions were used to improve WBC monitoring (academic detailing, provider education without academic detailing, electronic clinical reminders, request for provider action plan, draft orders for WBC monitoring, patient mailings, and patient calls). The survey response rate was 78%. For the 92 responding sites (78%) included sites (1115 patients) the mean rate of WBC monitoring was 54%. In multivariate analysis, academic detailing increased the rate by 17% (95% CI 4 to 30%, p = 0.011) and provider education increased the rate by 9% (95% CI 0.6 to 18%, p = 0.037). The WBC monitoring rate increased by 3.8% for each additional intervention used (95% CI 1.2–6.4%, p = 0.005). Interventions focused on the physician, including academic detailing, were associated with improved WBC monitoring for patients at risk for leukopenia from DMF treatment.

2021 ◽  
Author(s):  
Paul Heidenreich ◽  
Anju Sahay ◽  
Shoutzu Lin ◽  
Parisa Gholami ◽  
Mary Goldstein ◽  
...  

Abstract Background: Dimethyl fumarate (DMF), a treatment for multiple sclerosis, may cause leukopenia and infection. Accordingly, periodic white blood cell (WBC) monitoring is recommended. We sought to evaluate the VA Medication Use Evaluation Tracker (MUET) initiative which provides VA facilities with a list of patients prescribed DMF therapy without a documented white blood cell count (WBC).Methods: We identified 118 VA facilities with patients treated with DMF from 1/1/2016 through 9/30/2016. We determined WBC measurements within three months of the first filled prescription. The lead pharmacist at each facility was surveyed asking if any of seven intervention types were used to improve WBC monitoring (academic detailing, provider education without academic detailing, electronic clinical reminders, request for provider action plan, draft orders for WBC monitoring, patient mailings, and patient calls).Results: The facility response rate for the survey was 78% (92 of 118 facilities). For the 92 included facilities (1,115 patients) the mean rate of WBC monitoring was 54%. Use of the at-risk patient lists was noted in 55% (51/92) of facilities. In multivariate analysis, only academic detailing and provider education remained significantly associated with higher WBC monitoring. From a base WBC monitoring rate of 46%, academic detailing increased the rate by 17% (95% CI 4 to 30%, p=0.011) and provider education increased the rate by 9% (95% CI 0.6 to 18%, p=0.037). The WBC monitoring rate increased by 3.8% for each additional intervention used (95% CI 1.2%-6.4%, p=0.005).Conclusions: Interventions focused on the physician, including academic detailing, were associated with improved WBC monitoring for patients at risk for leukopenia from dimethyl fumarate treatment.


2013 ◽  
Vol 04 (S 01) ◽  
pp. S31-S34 ◽  
Author(s):  
Shin Yi Ng ◽  
Ki Jinn Chin ◽  
Tong Kiat Kwek

ABSTRACT Background: Leucopenia has been reported after induction of thiopentone barbiturate therapy for refractory intracranial hypertension. However, the incidence and characterisitics are not well described. Aims: We performed a retrospective review to describe the incidence and characteristics of leucopenia after induction of thiopentone barbiturate therapy. Setting and Design: Our centre is a national referral centre for neurotrauma and surgery in a tertiary medical institution.Materials and Methods: We performed a retrospective review of all patients who received thiopentone barbiturate therapy for refractory intracranial hypertension during an 18 month period from January 2004 to June 2005 in our neurosurgical intensive care unit. Statistical Analysis Used: Statistical analysis was performed using SPSS version 15.0. All data are reported as mean ± standard deviation or median (interquartile range). The Chi square test was used to analyze categorical data and student t test done for comparison of means. For paired data, the paired t?test was used.-test was used. Results: Thirty eight (80.9%) out of 47 patients developed a decrease in white blood cell (WBC) count after induction of thiopentone barbiturate coma. The mean decrease in WBC from baseline to the nadir was 6.4 × 10 9 /L (P <lt; 0.001) and occurred 57 (3-147) h after induction. The mean nadir WBC was 8.6 < 3.6 × 10 9 /L. Three (6.4%) patients were leucopenic, with a WBC count of 2.8, 3.1, and 3.6 < 10 9 /L. None of them were neutropenic. We did not find an association between decrease in WBC count and clinical diagnosis of infection. We did not find any association between possible risk factors such as admission GCS, maximum ICP prior to induction of barbiturate coma, APACHE II score, total duration and dose of thiopentone given, and decrease in WBC count. Conclusions: Decrease in WBC count is common, while development of leucopenia is rare after thiopentone barbiturate coma. Regular monitoring of WBC counts is recommended.


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4743-4743
Author(s):  
Nahal Rose Lalefar ◽  
Ward Hagar

Abstract Introduction: Therapeutic red blood cell exchange (RBCX) is a process by which diseased red cells are replaced by healthy donor red blood cells. In patients with sickle cell disease, RBCX has been used to treat acute stroke, severe acute chest syndrome, multiorgan failure, priapism and splenic sequestration. It is also being used more commonly in the prevention of vaso-occlusive pain crises and for stroke prophylaxis for patients considered to be at high risk of stroke based on abnormal transcranial Doppler flow rates. In May 2014, we transitioned from the COBE Spectra apheresis system (Terumo BCT) to the next-generation Spectra Optia apheresis system (Terumo BCT) for all red cell exchange transfusions performed on our patients with sickle cell disease. A previous small study (n = 33 RBCX transfusions) compared the two instruments (Caridian BCT) and showed no difference between exchange volumes, processing time, pre and post-exchange hematocrit and HbS levels (Perseghin et al. Transfusion and Apheresis Science, 2013). However, other clinical parameters such as changes in white blood cell count and platelet counts were not examined. In order to determine if there were any differences in hematologic parameters between the 2 apheresis instruments, we measured the differences between pre and post-exchange HbS levels, white blood cell count (WBC), hematocrit (Hct), and platelet counts for all of our adult patients who underwent RBCX transfusions on both instruments. Methods: This was a single institution, retrospective chart review of all adult patients with sickle cell disease (HbSS n=17, HbS/β0 thalassemia n = 1, HbSC n =1) who underwent routine, monthly RBCX at Children's Hospital and Research Center Oakland between November 2013 and February 2015. Indications for RBCX included a risk of stroke or a history of stroke, acute chest syndrome, or renal failure. All patients received RBCX transfusions on the COBE Spectra prior to May 2014 and were then transitioned to Spectra Optia in May 2014. Pre and post-exchange transfusion HbS levels, WBC, Hct, and platelet counts were measured for each procedure. All exchange transfusions were non-emergent and well tolerated. Statistical analyses using the student's t test and rank sum test were performed with Stata 14.0 software (College Station, Texas). Results: A total of 19 adult patients (mean average age 25 years old) underwent 153 red blood cell exchange transfusions (Spectra Optia n =87, COBE Spectra n = 66). There was a small increase in mean hematocrit percentage for both instruments (28.33 + 4.3 % to 29 + 3.06 % and 28.16 + 4.29% to 29.2 + 3.04% on the Spectra Optia and COBE Spectra, respectively). All other post-RBCX parameters decreased. The mean changes are shown in Table I. The HbS percent decreased from a combined mean of 39.86 + 12.11 % to 20.26 + 8.43 % for both instruments. The WBC decreased from a combined mean of 12.72 + 3.13 x 1000/ mm3 to 8.67 + 2.15 x 1000/ mm3. The platelet count decreased from a combined mean of 368.82 + 125.75 x 1000/ mm3 to 191.01 + 62.78 x 1000/ mm3. The mean parameter values for each patient correlated with the mean changes for each instrument based on statistical analysis using both the student's t test and rank sum test. Conclusions: The starting hematologic values were similar between the two instruments. There was no statistical difference between the raw pre and post-RBCX HbS, Hct, WBC, or platelet values or the mean changes in these parameters between the COBE Spectra and Spectra Optia instruments. There was also no statistical difference in the mean changes between the pre and post RBCX hematologic parameters amongst the 19 patients. Both instruments allowed for effective reduction in HbS percentage with comparable decreases in WBC and platelet counts while maintaining adequate hematocrit values for all 19 adult patients with sickle cell disease. Table 1. Mean changes between Pre-RBCX and Post-RBCX. Instrument Change in % HbS Change in WBC x1000/mm3 Change in % Hct Change in platelet count x1000/mm3 Spectra Optia N 84 87 87 85 Mean -20.28 -4.01 0.67 -172.44 SD 7.02 2.55 2.86 76.98 COBE Spectra N 66 66 66 66 Mean -19.18 -4.12 1.09 -178.02 SD 7.89 2.26 2.57 81.02 p-value 0.37 0.78 0.34 0.67 There are 3 missing values for HbS and 2 missing values for platelet count for Spectra Optia. SD = standard deviation, WBC = white blood cell count, Hct = hematocrit Disclosures No relevant conflicts of interest to declare.


2018 ◽  
Vol 24 (1) ◽  
pp. 37
Author(s):  
Hale Goksever Celik ◽  
Engin Celik ◽  
Selin Dikmen ◽  
Merve Konal ◽  
Ali Gedikbasi

<p><strong>Objective:</strong> The present study aimed to define characteristics of the patients who were readmitted with the diagnosis of surgical site infections after gynecologic or obstetric procedures and management of these patients. We also reviewed the literature in this context.</p><p><strong>Study design:</strong> We examined 120 patients with surgical site infections that had been hospitalized and managed medically and/or surgically between April 2014 and April 2015. Characteristics of the patients were recorded and analyzed.</p><p><strong>Results:</strong> The mean age of the patients was 33.4±11.8 years. The patients were readmitted for surgical site infections on the mean of 9.6±5.4 days after the first operation. The most frequent procedures resulted with SSI were cesarean delivery, abdominal hysterectomy and vaginal birth. When patients were compared according to these procedures, there were statistically significant differences regarding age, gravida, parity, preoperative white blood cell count, postoperative white blood cell count and antibiotics usage.</p><p><strong>Conclusion:</strong> Combining evidence-based surgical site infections prevention practices and clinician and patient cooperation will result in reduction in surgical site infections incidence following obstetric and gynecologic procedures. Because of economic burden and threat to the physical and psychological health of the patients, these modifiable risks should be recognized and surgical site infections should be minimized. After surgical site infections occurred, diagnosis and proper management with antibiotics and wound care with debridement and secondary suturing is important.</p>


Perfusion ◽  
1994 ◽  
Vol 9 (1) ◽  
pp. 35-40 ◽  
Author(s):  
Per Bergman ◽  
Ali Belboul ◽  
Lars Göran Friberg ◽  
Najib Al-Khaja ◽  
Gösta Mellgren ◽  
...  

Preserving the rheological properties of whole blood cells is vital for their smooth passage in the capillaries without causing blockage and disturbances in the microcirculation. To evaluate the effect of mechanical trauma on the rheology of white blood cells during prolonged perfusion with membrane oxygenation (PPMO), 16 in vitro experiments were conducted for 72 hours. The St George Carrimed Filtrometer was used to estimate the plasma white cell filtration rates (P-WFR). Also an in vitro estimation of the ability of individual cells to pass through capillaries, the white blood cell clogging rate (WBC-CR), the number of clogging particles (WBC-CP), the total white blood cell count (T-WBC) and two in vitro estimations to assess the effect of aggregates and stiff cells in blocking the microcirculation were performed. The traumatized white cells reduced their mean P-WFR by 37% ± 9, 72% ± 2 and 76% ± 2 at 24, 48 and 72 hours respectively (p < 0.001). The mean WBC-CR was increased to 15.2 ± 1.5, 32.6 ± 2.2 and 40.3 ± 8.3 x 102%/ml at 24, 48 and 72 hours respectively (p < 0.001). The mean WBC-CP was increased to 6.6 ± 1.5, 9.7 ± 1.2 and 13.9 ± 2.1 x 106/ml at 24 hours (p < 0.05), 48 and 72 hours respectively (p < 0.001). The T-WBC was decreased to 55% ± 0.3, 23% ± 0.2 and 14% ± 0.1 at 24,48 and 72 hours respectively (p < 0.001). This study showed a serious loss in white cell rheology during PPMO, which may contribute to the plugging effect of the microvessels in clinical use and may explain the organ dysfunction seen during ECMO on the basis of inadequate tissue oxygenation and nutrition due to areas of reduced perfusion, which results in increased frequency of morbidity.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3148-3148
Author(s):  
Gregory A. Abel ◽  
J. Taylor Hays ◽  
Paul Decker ◽  
Gary Croghan ◽  
David J. Kuter ◽  
...  

Abstract BACKGROUND: Previous work has demonstrated that smokers have higher white blood cell counts than nonsmokers, but the effect of biochemically-confirmed smoking cessation on peripheral leukocyte counts has not been demonstrated in a large prospective study. METHODS: Subjects were healthy smokers enrolled in a trial of sustained-release bupropion for relapse prevention after smoking cessation. White blood cell (WBC) counts and absolute neutrophil counts (ANC) were measured at baseline, week 7 and week 52. Smoking status was assessed at weeks 7 and 52 by self-report and biochemically confirmed with expired air carbon monoxide levels. Multivariate analyses compared changes in WBC count and ANC between smokers who did and did not stop smoking, adjusting for treatment group, age, sex, and body mass index. RESULTS: Of 784 smokers enrolled, 461 had biochemically-confirmed tobacco abstinence after 7 weeks of bupropion; 429 were randomly assigned to receive continued bupropion or placebo until week 52. At baseline, the mean WBC count was 8.4 x 109/L (SD ±2.3) and the mean ANC was 5.3 x 109/L (SD ±1.9). The baseline WBC count and ANC were higher in smokers with greater tobacco exposure, measured by daily cigarette consumption and serum cotinine level. Between baseline and week 7, there was a significantly larger decrease in WBC count in continuously abstinent subjects compared with continuing smokers (adjusted p =.031). At 52 weeks, biochemically-confirmed continuously abstinent subjects, as compared with continuing smokers, had a greater decline from baseline in WBC count (1.2 x 109/L versus 0.1 x 109/L, p&lt;0.001) and ANC (0.1 x 109/L versus 0.2 x 109/L, p&lt;0.001). CONCLUSION: The WBC count and ANC of healthy smokers increase with increasing tobacco exposure. Biochemically-confirmed tobacco abstinence leads to a rapid and sustained decrease in WBC count and ANC, possibly reflecting a decrease in an underlying state of tobacco-induced inflammation.


2019 ◽  
Vol 4 (2) ◽  
pp. 99-110
Author(s):  
Simeon O. Ayoola ◽  
Loveth N. Omoile

Aquaculture industry is facing challenges of the high cost of fish feed, and therefore it is very crucial to explore the alternative raw materials for feed formulation at the lowest cost. Therefore, the objective of the present study was to evaluate the effect of Plukenetia conophora shells on the growth, haematological and biochemical parameters, and its genotoxicity on African catfish Clarias gariepinus juveniles. Five experimental diets were formulated having three replicates at 0% (0WS), 25% (25WS), 50% (50WS), 75% (75WS) and 100% (100WS) inclusion of walnut shell respectively. The fishes were fed on experimental diet two time a day for 12 weeks. The results showed that the fish in tank 25WS had the best weight gain with the mean of 33.5±5.8 g and the least was recorded in tank 100WS. The specific growth rate was highest in-tank 75WS with the mean value of 0.46±0.05 g was recorded. The highest feed intake was found in fish fed with 25% inclusion of P. conophora.  The fish fed with P. conophorashowed increased values of haemoglobin, (12.05±1.63g/dL), Red blood cell, (2.785±0.28µL) and White blood cell, (11.25±4.59µL) compared with control diet values of fish fed of  Red blood cell, (1.81±1.54µL) and White blood cell, (5.15±6.57µL). There was a reduction in the haematological value of the fish fed with control feed having Haemoglobin, (10.75±8.13g/dL). The genotoxicity test that was carried out showed that the highest counts of micronucleus were in tank 75WS. The Duncan Multiple Range Test (DMRT) shows a significant difference (p0.05) in the growth performance of the fish. It is concluded that inclusion of 50% P. conophora shells in the feed of C. gariepinus gave no negative impact on the health status  and growth performance of the fish.  Keywords: Toxicity test, Growth indices, Plukenetia conophora, Clarias gariepinus  


2014 ◽  
Vol 13 (2) ◽  
pp. 189-191 ◽  
Author(s):  
A. Leland Albright ◽  
Susan S. Ferson ◽  
Humphrey Okechi

Object The authors undertook this study to determine white blood cell (WBC) counts in CSF obtained from lateral ventricles and myelomeningoceles (MMCs) in infants in a developing country at the time of their initial presentation for medical evaluation. Methods CSF was aspirated from the lateral ventricles and from MMC sacs of 100 consecutive infants at Kijabe Hospital, Kijabe, Kenya. Peripheral blood WBC counts and CSF WBC counts were determined in the laboratory. CSF with WBC counts of 5 cells/mm3 or greater was cultured. Results The mean WBC count in ventricular CSF was 16 cells/mm3, with a median and mode of 0 cells/mm3. The mean WBC count of CSF in MMC sacs was 141 cells/mm3 (median 15 cells/mm3). No child had both a positive culture from ventricular CSF and a negative culture from MMC CSF. There was no correlation between age at presentation and WBC counts in the MMCs. Infants younger than 8 days old were as likely to have high WBC counts in CSF from their MMC sacs as were older children; 7 of 12 infants with 500 WBCs or more in CSF from their MMCs were younger than 8 days old. Only 5 of 58 CSF specimens from MMC sacs with 5 or more WBCs/mm3 had positive bacterial cultures, which may be a reflection of CSF specimen processing rather than of true culture negativity. Conclusions CSF from ventricular fluid of infants presenting with MMCs infrequently has high WBC counts, so infrequently that it does not need to be evaluated routinely. CSF in MMC sacs often has high WBC counts that suggest the presence of bacterial infection. In developing countries where culture reliability is questionable, intravenous administration of antibiotics before MMC closure for infants with high MMC WBC counts may diminish postoperative meningitis/ventriculitis.


2016 ◽  
Vol 35 (2) ◽  
pp. 5
Author(s):  
Darinnat Buathong ◽  
Jarin Buakaew ◽  
Chutarat Nukfon

Objective: The purpose of this study is to assess the quality of platelet concentrates on storage days 1 and 5 prepared by platelet rich plasma-platelet concentrate (PRP-PC) and buffy coat poor-platelet concentrate (BC-PC) methods comparing to the American Association of Blood Banks (AABB) recommendations.Material and Method: Totally of 120 platelet concentrates (PC) units on storage days 1 and 5 (60 of PRP-PC triple blood bag and 60 of BC-PC quadruple AS-5 blood bag) were separated from whole blood donations at Songklanagarind Hospital. The prepared PC were assessed with 5 parameters such as volume, platelet count, white blood cell count per unit, pH, swirling phenomenon score and hypotonic shock response. The independent t-tests, paired Student’s t-tests and SPSS program were utilized in statistical analysis step.Results: The mean±standard deviation (S.D.) of each parameter were as follow : (1) Volume of PRP-PC and BC-PC met the standard (40-70 ml). (2) All of the platelet concentrates met the standard (≥ 5.5x1010/unit). The mean±S.D.: PRP-PC and BC-PC (day 1) were 6.820±1.480 x1010 and 7.010±1.300 x1010/unit (p-value=0.260), while PRP-PC and BC-PC (day 5) were 6.620±1.160x1010 and 6.720± 1.150x1010/unit (p-value=0.040). (3) The white blood cell in platelet concentrates met the standard (<0.2x1010/unit). The mean±S.D.: PRP-PC and BC-PC (day 1) were 0.030±0.017 x1010and 0.026±0.019x1010/unit (p-value=0.040), while PRP-PC and BC-PC (day 5) were0.033±0.013x1010 and 0.027±0.019x1010/unit (p-value= 0.580). (4) The pH of all units (PRP-PC and BC-PC) met the standard (≥6.2). The mean±S.D.: PRP-PC and BC-PC (day 1) were 7.430±0.330 and 7.750±0.160 (p-value=0.006), while PRP-PC and BC-PC (day 5) were 7.590±0.350 and 7.620±0.280 (p-value=0.710). The swirling phenomenon score and hypotonic shock response were the same as standard AABB and were not statistically difference.Conclusion: The quality of PRP-PC and BC-PC after storing on days 1 and 5 as follow (1) Volume of PRP-PC and BC-PC met the standard. (2) The platelet count per unit of PRP-PC and BC-PC (day 1), PRP-PC and BC-PC (day 5) were not statistically difference. (3) The white blood cell count per unit of PRP-PC and BC-PC (day 1) were statistically difference, while PRP-PC and BC-PC (day 5) were not statistically difference. (4) The pH of PRP-PC and BC-PC (day 1) were statistically difference, while PRP-PC and BC-PC (day 5) were not statistically difference. The swirling phenomenon score and hypotonic shock response of PRP-PC and BC-PC were not statistically difference. Platelet concentrates of both method storing on days 1 and 5 fulfilled the quality guideline of AABB.


2013 ◽  
Author(s):  
Μαρία Καπαρού

Introduction: Acute lymphoblastic leukemia (ALL) accounts for nearly 1/3 of all pediatric malignancies and 75% of all childhood leukemias. The annual incidence of ALL has been estimated to 30 cases per million, with a peak incidence in children aged two to five years. Progress in the diagnosis with novel molecular techniques, risk classification, and treatment strategy in ALL has led to cure rates that now exceed 80%. However, a significant proportion (20%) of patients fails to respond to therapy, and treatment failure can occur even in patients with favorable prognostic features. It has been suggested that leukemia is characterized by impaired balance between proliferation of blood cells and their capacity to undergo apoptosis. The aim of this study was to assess the expression of the apoptosis-related genes bcl-2 and bax in childhood ALL, both at the time of diagnosis and at remission achieved post induction treatment. In addition, we measured the levels of the apoptotic receptors Fas, FasLigand, and their co-expression on patients’ leukemic cells. To explore the prognostic significance of apoptosis-related genes in childhood ALL, we examined associations between expression levels and established clinical and cytogenetic disease parameters.Materials-Methods: The study included 26 children (eighteen boys, eight girls) with newly diagnosed ALL (twenty-three B-ALL, three T-ALL). The mean age was 7.1 ± 1.2 years, the mean white blood cell count was 27.5 ± 10.6 K/μL and the mean hemoglobin was 9.1 ± 0.6 g/dL. All patients were diagnosed, treated and followed at the Department of Pediatric Hematology-Oncology, University Hospital of Heraklion - Crete, and they received chemotherapy according to the ALL BFM 2000 protocol. There were 34 age-matched children who served as controls (20 children with benign blood diseases -12 with Idiopathic Thrombocytopenic Purpura, 8 with Autoimmune Neutropenias- and 14 children with solid tumors without bone marrow infiltration). Bone marrow specimens were obtained from all children, under informed consent signed by the parents/guardians. Cytogenetic abnormalities were examined with conventional karyotype and FISH. Disease remission following induction therapy was assessed by bone marrow microscopic evaluation and flow cytometry. Measurement of bcl-2 and bax mRNA was performed by quantitative real-time PCR, and membrane expression of Fas and Fas-L was assessed by flow cytometry in bone marrow mononuclear cells, both at diagnosis and at remission following induction chemotherapy.Results: At diagnosis, increased level of the apoptotic bax/bcl-2 ratio was observed in children older than 10 years and with higher white blood cell count. DNA index <1,16 was associated with increased bax/bcl-2 both at diagnosis and at remission, and the del(9p) abnormality with increased bax/bcl-2 at remission. Expression of the apoptotic receptor Fas was significantly higher at remission compared to diagnosis, which might reflect enhanced sensitivity of the leukemic clone to apoptosis and response to treatment. Conclusions: In conclusion, our study highlights the association between the apoptotic bax/bcl-2 ratio with high-risk features in children with ALL, such as older age, white blood cell count, the del(9p) abnormality and DNA index <1.16. The increase in Fas expression once remission has been achieved after induction treatment, could represent a prognostic factor of favorable response to chemotherapy and deserves further investigation. Delineation of the role of apoptosis in pathogenesis and prognosis of pediatric ALL should enable the design of novel targeted therapies.


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