Wilcoxan Signed Rank Test Research Articles

Effect of pranayama on sympatho-vagal imbalance and cognitive deficit in premenstrual syndrome.

Premenstrual syndrome (PMS) is a prevalent and often neglected condition that affects around 80% of women of reproductive age. In PMS, abnormal fluctuations in gonadal hormones cause altered homeostasis, resulting in sympatho-vagal imbalance and poor cognition. To compare autonomic function parameters and cognitive performance between PMS and control groups, and to study the effect of pranayama on the above parameters in PMS women. It was a randomized control trial. We recruited 40 women of reproductive age who fit the inclusion criteria. They were asked to complete the Premenstrual Syndrome Screening Tool (PSST) questionnaire and were categorized as having PMS (n = 20) or not having PMS (n = 20). All study participants had their baseline CAFT, HRV, BRS, P300, and MOCA values recorded. Following that, participants in the PMS group were divided into two groups of ten at random. For 8 weeks, one group received pranayama training. Following that, all baseline data were recorded again in both the pranayama and no-intervention groups. SPSS version 20 was used to analyze the data. For parametric data, the unpaired t test was used to compare between the PMS and no PMS groups, whereas the Mann-Whitney U test was employed for non-parametric data. To compare the parameters before and after intervention, the Students paired 't' test for parametric data and the Wilcoxan-signed rank test for non-parametric data were used. According to the findings, autonomic function and cognition were considerably affected in the PMS group and improved significantly in the PMS group following pranayama intervention. Pranayama is an effective and safe non-pharmacological method for treating PMS and improving women's quality of life.

Safety of Dapagliflozin in Children with Heart Failure

PurposeDapagliflozin recently received FDA-approval for use in adults with heart failure with reduced ejection fraction to reduce the risk of cardiovascular death and hospitalization for heart failure (HF). This is the first report describing safety and use of dapagliflozin in children with HF.MethodsThis is a single-center, observational, retrospective analysis assessing safety of dapagliflozin when added to a background of guideline-directed medical therapy in 9 pediatric patients (age < 21 years) with HF. Only patients with dapagliflozin at steady-state and with follow-up data were included. Univariate comparisons were made using Wilcoxan signed rank test before and after addition of dapagliflozin.ResultsMedian age was 14.2 years (IQR 11.2-17.7; range 9-18). Of the 9 patients, 6 had dilated cardiomyopathy, 2 had single ventricle physiology, and 1 had diastolic HF. NYHA functional class was as follows: 6 were class II, 2 were class III, and 1 was class IV. Median baseline hemoglobin A1c was 5.5% (IQR 5.3-5.75). Most (78%) were started on dapagliflozin during a HF-related hospitalization. Median starting dose of dapagliflozin was 5 mg once daily (IQR 5-10). Mean follow-up was 30.6 days (SD 21.6). Median dose at follow-up was 10 mg once daily (IQR 7.5-10). Urine glucose was negative at baseline and 1+ to 3+ at follow-up confirming the pharmacodynamic effect of dapagliflozin. Total daily dose of loop diuretic was decreased 50% for 3 patients at follow-up. There were no significant differences in weight, blood pressure, heart rate, ejection fraction, B-type natriuretic peptide, estimated glomerular filtration rate or blood chemistries at follow-up. No adverse events such as urinary tract infections, hypoglycemia, fractures, hypovolemia or renal injury were observed. Dapagliflozin was discontinued in 1 patient due to receipt of a heart transplant.ConclusionDapagliflozin appears to be safe in the short term when added to guideline-directed medical therapy for children with heart failure. Dapagliflozin recently received FDA-approval for use in adults with heart failure with reduced ejection fraction to reduce the risk of cardiovascular death and hospitalization for heart failure (HF). This is the first report describing safety and use of dapagliflozin in children with HF. This is a single-center, observational, retrospective analysis assessing safety of dapagliflozin when added to a background of guideline-directed medical therapy in 9 pediatric patients (age < 21 years) with HF. Only patients with dapagliflozin at steady-state and with follow-up data were included. Univariate comparisons were made using Wilcoxan signed rank test before and after addition of dapagliflozin. Median age was 14.2 years (IQR 11.2-17.7; range 9-18). Of the 9 patients, 6 had dilated cardiomyopathy, 2 had single ventricle physiology, and 1 had diastolic HF. NYHA functional class was as follows: 6 were class II, 2 were class III, and 1 was class IV. Median baseline hemoglobin A1c was 5.5% (IQR 5.3-5.75). Most (78%) were started on dapagliflozin during a HF-related hospitalization. Median starting dose of dapagliflozin was 5 mg once daily (IQR 5-10). Mean follow-up was 30.6 days (SD 21.6). Median dose at follow-up was 10 mg once daily (IQR 7.5-10). Urine glucose was negative at baseline and 1+ to 3+ at follow-up confirming the pharmacodynamic effect of dapagliflozin. Total daily dose of loop diuretic was decreased 50% for 3 patients at follow-up. There were no significant differences in weight, blood pressure, heart rate, ejection fraction, B-type natriuretic peptide, estimated glomerular filtration rate or blood chemistries at follow-up. No adverse events such as urinary tract infections, hypoglycemia, fractures, hypovolemia or renal injury were observed. Dapagliflozin was discontinued in 1 patient due to receipt of a heart transplant. Dapagliflozin appears to be safe in the short term when added to guideline-directed medical therapy for children with heart failure.

Does Belatacept Provide a Safe Renal Sparing Immunosuppression in Lung Transplant Recipients? A Single-Center Experience

PurposeBelatacept reduces calcineurin inhibitor (CNI) nephrotoxicity in kidney transplant recipients. However, its use in lung transplantation is extremely limited and it remains unclear whether it can provide a safe and effective renal sparing immunosuppression in patients with chronic kidney disease.MethodsThis is a prospective cohort study of patients who were started on Belatacept with lower CNI goals post lung transplantation at our institution between 2018 and 2020. Institutional IRB approval was obtained. Patients aged 18 years or older were included and multiorgan recipients were excluded. Continuous data was reported as median and categorical data as proportions. Paired data analyses that include Wilcoxan signed rank test and McNemar's test were performed.Results85 patients satisfied the inclusion and exclusion criteria. Median time to initiation of Belatacept after transplantation was 293 days, interquartile range (IQR) (148-611). The cohort was followed for a median of 311 days IQR (182-465). 28 patients (33%) stopped the infusion with the majority due to infectious complications. There was a median of 1ml increase in GFR (p=0.68). The FEV1 increased a median of 40ml during the same duration (p=0.0034).ConclusionIn this large cohort, Belatacept provided an effective renal sparing immunosuppression. There was no decline in graft function with stabilization of GFR. There was a tendency towards a higher rate of opportunistic infections and cancers; however, this did not achieve statistical significance. Belatacept reduces calcineurin inhibitor (CNI) nephrotoxicity in kidney transplant recipients. However, its use in lung transplantation is extremely limited and it remains unclear whether it can provide a safe and effective renal sparing immunosuppression in patients with chronic kidney disease. This is a prospective cohort study of patients who were started on Belatacept with lower CNI goals post lung transplantation at our institution between 2018 and 2020. Institutional IRB approval was obtained. Patients aged 18 years or older were included and multiorgan recipients were excluded. Continuous data was reported as median and categorical data as proportions. Paired data analyses that include Wilcoxan signed rank test and McNemar's test were performed. 85 patients satisfied the inclusion and exclusion criteria. Median time to initiation of Belatacept after transplantation was 293 days, interquartile range (IQR) (148-611). The cohort was followed for a median of 311 days IQR (182-465). 28 patients (33%) stopped the infusion with the majority due to infectious complications. There was a median of 1ml increase in GFR (p=0.68). The FEV1 increased a median of 40ml during the same duration (p=0.0034). In this large cohort, Belatacept provided an effective renal sparing immunosuppression. There was no decline in graft function with stabilization of GFR. There was a tendency towards a higher rate of opportunistic infections and cancers; however, this did not achieve statistical significance.

Neck circumference as a risk indicator for type 2 diabetes mellitus: a community based cross-sectional study

Background: Diabetes mellitus is a metabolic syndrome due to insulin deficiency, characterized by hyperglycaemia. Indian diabetes risk score (IDRS) is the most commonly used one to determine the risk status. However there is lot of inconvenience and possible errors in measuring the waist circumference to determine the IDRS, hence the study was planned to evaluate if neck circumference could replace waist circumference in determining the diabetes risk.Methods: This cross sectional study was conducted among 300 study participants fulfilling the eligible criteria. Socio-demographic variables, parameters required for determining the IDRS was assessed, in addition, neck circumference (NC) was measured using standard protocol. Another risk score was calculated by replacing waist circumference (WC) with neck circumference and scoring was named as IDRS-NC. Pearson correlation and Wilcoxan sign rank test was done to find out the relationship between WC and NC and also to determine if IDRS-NC could replace IDRS.Results: Out of 300 study population, majority of the participants are in the age group of &lt;35 years 129 (43%) and around 2/3rd of the participants were females. Among the study participants proportion of participants belonging to low risk, medium risk and high risk assessed using IDRS and IDRS-NC was 18.7%, 41%, 40.3% and 31.7%, 38%, 30.3% respectively. There was a strong positive correlation (r=0.837) between the neck circumference and waist circumference. Wilcoxan sign rank test was significant between the 2 scores having a p value of &lt;0.05.Conclusions: In our study there was a positive correlation between neck circumference and waist circumference.

PENGARUH PELATIHAN RESUSITASI JANTUNG PARU TERHADAP KESIAPAN SEKAA TERUNA TERUNI DALAM MEMBERIKAN PERTOLONGAN PADA KASUS KEGAWATDARURATAN HENTI JANTUNG

Emergency may occur anywhere and anytime. Cardiac Arrest is one of the most life-threatening emergency conditions. The CPR action is an important determinant of survival of cardiac arrest survivors. The purpose of this research is to know the effect of CPR training on the readiness to provide STT relief in cardiac emergency cases in Dawan Kaler Village 2018. This research type is pre experimental with pre-post test approach, and using simple random sampling method with 160 respondents. The instrument used is a questionnaire about the readiness to help victims of cardiac arrest. Data analysis used is univariate and bivariate analysis. The result of the research shows that most of the respondents are female (63.8%), most of the respondents are 17-25 years old (95%), most of them are high school (58.1%), most of them are student (80 , 6%), before CPR training for less ready category (32,5%) and category not ready (67,5%), after CPR training, improvement of readiness to help, category ready (63,8%) and ready category ie 36.3%. Statistical test results using Wilcoxan Signed Rank Test obtained p-value 0.000 <alpha (0,05). Conclusion: CPR training can improve the readiness of providing emergency assistance in cases of cardiac arrest. Suggestion: STT works together with related health officers to create a continuous training program so that the future is able to do quick and proper handling to help cases of cardiac arrest emergency ..

THE DIFFERENCE INTEGRATED NEUROMUSCULAR INHIBITION TECHNIQUE WITH DEEP TISSUE MASSAGE AND CONTRACT-RELAX STRETCHING TO IMPROVE RANGE OF MOTION CERVICAL JOINT IN MYOFASCIAL PAIN SYNDROME UPPER TRAPEZIUS MUSCLE AT SMA NEGERI 1 SEMARAPURA

ABSTRACTMyofascial pain syndrome is a collection of sensory, motor, and autonomic symptoms that cause local andreffered pain, limited range of motion and weakness of the affected muscles. The limitations range of motion will beannoying than the daily activities. Interventions that can improve range of motion of cervikal are IntegratedNeuromuscular Inhibition Technique, Deep Tissue Massage and Contract-Relax Stretching. The results show GroupNeuromuscular Inhibition Technique with Wilcoxan Sign Rank Test obtained a mean difference of 13.7 with p = 0.000,while the test results Hypothesis Group Contract-Relax Stretching with Paired Sample T-test showed a mean differenceof 12.1 with p = 0.000. Test the difference between Mann Whitney U-test showed no significant difference between theother group are obtained p = 0.420. These results indicate that there is no difference in increasing range of motion inboth groups.Keywords: Range of motion of cervical, Upper Trapezius Muscle,Myofascial Pain Syndrome, IntegratedNeuromuscular Inhibition Technique, Deep Tissue Massage, Contract-relax Stretching, Goniometer

What is the most appropriate intraoperative baseline parathormone? A prospective cohort study

IntroductionThe time of drawing pre-incision intraoperative parathyroid hormone (ioPTH) is crucial to provide the right baseline for post-excision PTH measurement. The objective of this study was to identify the optimal time and the numbers of baseline PTH samples that best predict excision of all hypercellular parathyroid tissue when compared with 10-min post-excision PTH level. Materials and methodsIn this prospective study, two pre-incision (pre-induction and 10-min post-induction) baseline ioPTH samples along with pre- and post-excision ioPTH were collected and analyzed for 352 parathyroidectomies in 341 patients for sporadic primary hyperparathyroidism at a University hospital. Paired Wilcoxan signed rank test was used to compare the pre-incision ioPTH levels and their percent drop to 10-min post-excision levels. Sensitivity, specificity, predictive values and receiver operating characteristic (ROC) curves were used to compare the predictability of the two pre-incision levels. ResultsThe difference between pre- and post-induction baseline PTH levels was highly significant (p < 0.001). In 4% cases the criterion of post-excision PTH drop of ≥50% was achieved only with the post-induction baseline PTH and not with pre-induction PTH measurement. Using pre-induction baseline, ioPTH had an overall accuracy of 90% whereas ≥50% fall in the post-excision PTH from the post-induction baseline PTH had the accuracy of 94.85%. DiscussionThere was a significant difference between pre- and post-induction PTH levels and Miami criteria was met in 95.45% cases with post-induction baseline. ConclusionsThe optimal time for drawing pre-incision baseline PTH sample is at 10 min post-induction of general anesthesia and positioning of patient.

Improvement in Esophageal Emptying on Timed Barium Esophagram After Peroral Endoscopic Myotomy (POEM) for Achalasia

Introduction: Timed barium esophagram (TBE) is used for objective assessment of esophageal emptying function in achalasia. Improvement in emptying after pneumatic dilation and Heller myotomy for achalasia have been shown to predict long term symptom relief. Peroral endoscopic myotomy (POEM) is an emerging treatment for achalasia combining the efficacy of surgical myotomy with an incisionless endoscopic procedure. Data on objective assessment of esophageal emptying by TBE after POEM is limited. Purpose of this study was to assess the improvement in esophageal emptying by TBE after POEM in patients with achalasia. Methods: Data on consecutive patients who had POEM for achalasia from April 2014 to April 2015 was collected from our Institutional Review Board approved prospective registry. Our patients routinely get TBE and high resolution esophageal manometry (HREM) before and 2 months after POEM. For TBE, patients were instructed to drink up to 230 ml of low density barium sulfate suspension (60% weight/volume) in upright position (volume of barium sulfate suspension ingested is based on patient tolerance). Then radiographs of the esophagus were taken at 1, 2 and 5 minutes with measurement of height and width of the barium column. Patient demographics, pre-and post-POEM symptoms by Eckardt scores and results of HREM and TBE at 2 month follow-up were analyzed. Data are presented as mean + standard deviation, median (P25, P75) or N (%). Differences between pre- and post-POEM were assessed with onesample t-test, non-parametric Wilcoxan signed rank test and test of symmetry. P < 0.05 was considered significant. Results: POEM was performed in 32 patients. Mean age of patients was 56 + 17 years and 56% were males. There was a significant decrease in all parameters of TBE except barium column height at minute 1. There was also significant improvement in Eckardt scores and LES pressures. Table 1 shows paired analysis assessing the changes in TBE, HREM and Eckardt symptom scores in patients who had tests done pre and post POEM at 2 month follow-up.Table 1: Pre vs. Post POEM characteristics in patients with 2-month follow-upConclusion: Esophageal emptying on TBE improves significantly after POEM in patients with achalasia. Similarly Eckardt symptom scores and LES pressures improve after POEM. Based on our TBE findings after POEM, we predict that POEM will provide durable long term symptom relief in patients with achalasia. However, further studies with long term follow-up are needed to confirm this.

“Clinical study of leech application in various medico-surgical conditions”

IntroductionThe study evaluates the effectiveness of medicinal leech (Hirudo medicinalis) therapy in a population of 150 patients having various medico-surgical conditions to treat diseases like varicose veins, varicose ulcers, perianal haematoma, skin diseases (such as eczema, herpes zoster), inflamed or thrombosed piles and other inflammatory conditions including gangrene and traumatic inflammation. MethodsThe assessment score was recorded on various parameters namely – pain, tenderness, swelling, redness, local temperature, stiffness, Kandu (itching), slough, srava, daha (burning sensation), tvakrukshata (dryness of skin), granulation tissue, assessment of base/floor and wound size. Wilcoxan Signed Rank test was used to compare the pre and post leech application score. ResultThe study clearly indicated significant reduction in severity of pain, burning sensation, itching swelling among the patients. The mean pO2 of blood (40.05) sucked by leeches was found to be almost equal to that of venous blood of the patient (34.55). ConclusionLeech sucked venous blood contributes to reduction in severity of symptoms. The study recommends the therapy to be used as a para-surgical therapy in the management of various medico-surgical conditions mentioned above.

Comparative efficacy of oil pulling and chlorhexidine on oral malodor: a randomized controlled trial.

Oral malodor affects a large section of population. Traditional Indian folk remedy, oil pulling not only reduces it but can also bring down the cost of treatment. To compare the efficacy of oil pulling and chlorhexidine in reducing oral malodor and microbes. Three week randomized controlled trial was conducted among 60 students of three hostels of Maharani College of science and arts and commerce and Smt V.H.D.College of Home Science. The hostels were randomized into two intervention groups namely chlorhexidine group, sesame oil and one control (placebo) group. Twenty girls were selected from each hostel based on inclusion and exclusion criteria. Informed consent was obtained. The parameters recorded at the baseline (day 0) and post intervention on day 22 were plaque index (PI), gingival index (GI), objective (ORG1) and subjective (ORG2) organoleptic scores and anaerobic bacterial colony (ABC) count. Intra and inter group comparisons were made using Kruskal Wallis test, Wilcoxan sign rank test, ANOVA and student t-test. There was significant reduction (p<0.05) in the mean scores of all the parameters within sesame oil and chlorhexidine group. Among the groups significant difference was observed in objective and subjective organoleptic scores. Post hoc test showed significant difference (p<0.000) in mean organoleptic scores of sesame oil and placebo and chlorhexidine and placebo group. No significant difference (p<0.05) was observed between sesame oil and chlorhexidine group. Oil pulling with sesame oil is equally efficacious as chlorhexidine in reducing oral malodor and microbes causing it. It should be promoted as a preventive home care therapy.

Breakfast Behaviors and Cognitions among Parents of Preschoolers

The purpose of this research was to investigate change in elementary students’ willingness to try (WTT) fruits and vegetables after participating in the Santa Fe Farmers’ Market Children's Nutrition Program on a class field trip. The WillTry survey was administered to 139 kindergarten, 2nd, 3rd and 4th grade students before and after participation in the program. Data were also collected in Student Notebooks completed during the program. The change in WTT eight fruits and vegetables between the WillTry preand post-test was evaluated using the Wilcoxan Sign Rank test. Responses regarding WTT these eight foods were also compared between the Student Notebook and the WillTry post-test to evaluate any change between responses recorded immediately upon tasting each food and those recorded two days later. In assessing changes between the WillTry pre-and post-test, we observed an overall decrease in willingness to try the eight foods offered. There was a small but statistically insignificant increase in WTT fruits (with the exception of dried apple, which increased significantly), and a significant decrease in WTT vegetables. In comparing the post-test and notebook data we found that in the two days between the intervention and post-test, many students changed their responses. This indicates flexibility in WTT over time, an encouraging finding that offers promise if a child is unwilling to try a food initially. Findings from this study would benefit by further research investigating the effects of a greater number of exposures to each food and varying presentation of the foods in such an intervention.

Abstract P1-13-08: Chemotherapy for Breast Cancer Causes Sustained Alteration In Number and Type of B Lymphocytes

Abstract Introduction: The initial immune toxicities of chemotherapy have been reported but longer-term effects are less clear. In order to ascertain if patients regain immuno-competence after chemotherapy, we studied the time-course and determinants of changes in lymphocytes during and after breast cancer chemotherapy, and the characteristics of repopulating cells. Methods: To determine the long-term effects of chemotherapy on adaptive immunity, detailed immunophenotyping was performed on primary breast cancer patients before and after chemotherapy. Blood samples were collected from 83 patients prior to and at various time points post-chemotherapy. Total B and T lymphocyte number and B cell subpopulations were assessed by flow cytometry. Data was analysed using Wilcoxan Signed Rank Test, Mann Whitney U test or Kruskal-Wallis test (SPSS). Results: Chemotherapy resulted in significant reduction in numbers of circulating CD3+ cells (median 42.7% of pre-chemotherapy levels, p &amp;lt; 0.001), NK cells (45.4%, p &amp;lt; 0.001) and, most strikingly, B cells (5.3%, p &amp;lt; 0.001). G-CSF treatment, given to combat neutropenia, reduced the magnitude of the chemotherapy effect. B cell numbers post-therapy were significantly higher in patients who received G-CSF as compared to those who did not (7.6% versus 2.2%, p &amp;lt; 0.001), as were CD3+ cells (64.5% versus 34.8%, p = 0.001) and NK cells (81.0% versus 24.7%, p &amp;lt; 0.001). B cell recovery was slow, reaching only 31.0% and 40.1% of initial levels by 3 and 6 months post-chemotherapy. Most repopulating B cells were naïve (CD27−) (pre-chemotherapy: 55.0% of total B cells; 3 months post-chemotherapy: 81.3%) with expanded populations of CD38hiCD24hi (pre-chemotherapy: 5.0%; 3 months post-chemotherapy: 20.8%) and CD5+CD1d+ (pre-chemotherapy: 19.0%; 3 months post-chemotherapy: 51.28%). Smoking had potent influences on B cell repopulation: smokers' B cells recovered to only 21.1% and 32.3% of pre-chemotherapy levels at 3 and 6 months as compared to 41.9% and 47.9% in non-smokers (p &amp;lt; 0.001). Smoking also affected subclasses within repopulating B cells, with smokers having a 3-fold greater proportion of switched memory B cells (p &amp;lt; 0.001). There was no statistically significant difference in B cell repopulation between patients who had radiotherapy along with chemotherapy and those who had chemotherapy alone. There was also no statistically significant difference in B cell depletion or recovery between different age groups, initial tumour size or grade of tumour. Conclusions: These results confirm that B cells are especially vulnerable to chemotherapy toxicity. Detailed phenotyping of B cells revealed that chemotherapy has a profound effect on B cell subpopulations. The significance of this on host immunity is under investigation. We have additionally identified two factors responsible for delayed B cell repopulation, which highlight the need for lymphocyte assessments to be performed during and after chemotherapy. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-13-08.

Effect of standard anthracycline based neoadjuvant chemotherapy on circulating levels of serum IL-6 in patients of locally advanced carcinoma breast – A prospective study

BackgroundElevated IL-6 levels have been associated with advanced stage of breast cancer and metastasis-related morbidity. The present prospective study was carried out to assess the effect of neoadjuvant chemotherapy on circulating levels of serum IL-6 in patients of locally advanced carcinoma breast. MaterialsAll locally advanced carcinoma breast cases presenting to the surgery out patient's department were included in the study excluding pregnant or lactating females and those patients who were unfit for anthracycline based chemotherapy. A total of 30 cases were included. The various parameters that were evaluated include detailed clinico-pathological profile and IL-6 levels. Clinical staging using TNM classification was performed in all enrolled patients. This included documenting tumor size (on USG), node status and metastatic workup. First blood sample was collected before start of any treatment. Second blood sample was collected after 3 cycles of chemotherapy. Blood was centrifuged within 30 min and serum kept at −80 °C until analysis for IL-6. IL-6 levels were quantified by ELISA. ResultsMajority of patients presented in stage T3N1M0 (66.66%). The serum level of IL-6 increased as the disease progressed from T3N1M0 to T4dN2M0 (41.4 ± 31.9 pg/ml vs. 164.0 ± 31.1 pg/ml respectively). A progressive reduction in IL-6 levels with subsequent cycles of chemotherapy was observed which was statistically significant (from 72.8 ± 56.0 pg/ml to 47.0 ± 61.9 pg/ml; p value 0.002 wilcoxan signed rank test). ConclusionOur study shows a consistent decline in the IL-6 levels with chemotherapy. Upon ratification of our findings by large population based multi centric studies, we may state with conviction that a single blood test as serum level of IL6 will prove beneficial in assessing the efficacy of chemotherapy.

Active learning by play dough modeling in the medical profession

Learning the nervous system has always been a difficult task for undergraduate students. In particular, the complexity of the system and the condensed time available present a difficult challenge. Regardless of audiovisual aids (blackboard, PowerPoint presentations, ready-made models, or CD-ROMs),

Regular Replacement Therapy as Prophylaxis In Severe Forms of Von Willebrand Disease: Initial Results From the Von Willebrand Disease Prophylaxis Network (VWD PN) Study Group

Abstract 236 The bleeding patterns of severe von Willebrand Disease (VWD), mainly type 3, adversely affect short- and long-term quality of life, and may be life threatening. The index case of VWD, described by Erik von Willebrand in 1926, was a girl who had a history of serious bleeds from mucous membranes and ankles, and died during her fourth menstrual period. There is no doubt that there is a role for long-term prophylaxis with VWF-containing concentrates, but the experience is scarce and restricted to a retrospective follow-up of 37 patients in Sweden, and a few other small cohorts in Europe. All studies have shown favorable results; however, unresolved issues remain, such as to whom prophylaxis should be given, optimal dose and dose interval, and when to start. The von Willebrand Disease Prophylaxis Network (VWD PN) was formed to investigate the role of prophylaxis in clinically severe VWD that is non-responsive to other treatment(s). The VWD International Prophylaxis (VIP) Study, a combination of prospective and retrospective studies, is an initiative of the VWD PN. Using a retrospective study design, the effect of prophylaxis on bleeding frequency was studied among 39 individuals enrolled from 11 centers in Europe and North America. Data were collected from center records, diaries, and bleeding logs. The period of study was one year prior to start of prophylaxis plus at least 6 months following onset of treatment. Subject demographics, VWD type, and primary bleeding indication for prophylaxis were collected. Annualized bleeding rates were calculated for the period prior to onset of prophylaxis, during prophylaxis for the total group, and by primary bleeding indication defined as the most frequent bleeding symptom. In 4 cases, data were not available to identify the primary indication. Differences (after – before) were calculated. The Wilcoxan Signed Rank test of the differences in the medians was used. The median age (range) at onset of prophylaxis was 29 years (2 to 76). Fifty-one percent were female and 49% male. The vast majority were of European descent, 84.6%, with 12.8% and 2.6% reported as Hispanic and of African descent, respectively. Type 3 VWD accounted for the largest number: 24 (61.5%). Two subjects (5.1%) were type 1, 7 (18.0%) type 2A, 5 (12.8%) type 2B, and 1 (2.6%) type 2M. The usual number of infusions of VWF during prophylaxis was 2 to 3 times per week, with a median usual dose of 45 U VWF:RCo per kg per infusion. The median (range) number of bleeding episodes per year prior to the onset of prophylaxis was 12 (2 – 54), compared to a median (range) of 4 (0 – 24) during prophylaxis, p&lt;0.0001. Changes in bleeding for the total group, as well as the most common primary indications for prophylaxis, are shown in the figure. In 7 cases (not included in the figure) the bleeding pattern was mixed with no primary indication (N=3), or the primary indications occurred with low frequency (N=4). Annualized bleeding rates were lower during prophylaxis for all primary indications, and significantly so (p&lt;0.05) for joint bleeding, epistaxis and GI bleeding. When we examined the effect of prophylaxis by age for subjects &lt;18, and those ≥18, we found that it was similar in both groups. The median number of bleeds per year during prophylaxis was significantly lower, p=0.001 and p&lt;0.0001 respectively, compared to the number prior to prophylaxis. While the primary indications of epistaxis and joint bleeding occurred with similar frequency in both age groups, GI bleeding and menorrhagia were not reported as the primary bleeding indication for prophylaxis for anyone &lt;18. We conclude from this international, multi-center cohort that prophylactic treatment of VWD is efficacious. A network-initiated prospective study is underway, the objectives of which are to provide guidelines for dosing, and address issues of cost-effectiveness and quality of life. Disclosures: Berntorp: CSL Behring: Honoraria, Research Funding. Abshire:CSL Behring: Honoraria, Research Funding. Federici:CSL Behring: Honoraria, Research Funding.

123: Ondansetron Is Safe and Effective In the Out-of-Hospital Treatment of Undifferentiated Nausea and Vomiting by Paramedics

123: Ondansetron Is Safe and Effective In the Out-of-Hospital Treatment of Undifferentiated Nausea and Vomiting by Paramedics

Retargeting of Activated T Cells (ATC) with Gemtuzumab (anti-CD33) Ozogamicin x Anti-CD3 Bispecific Antibody (CD33-OBi) Enhances Cytotoxicity Directed at K562.

Abstract 4094Poster Board III-1029 BackgroundCD33 is expressed in about 90% of blasts in acute myeloid leukemia but the response rate of gemtuzumab ozogamicin (GO) is about 30%. GO is anti-CD33 hP67.6 linked to calicheamicin. The mechanism of resistance of blasts to GO is not clearly understood. Our previous studies show the anti-CD3 activated T cells (ATC) can be redirected with bispecific antibodies (BiAb) to Her2/neu, CD20, and EGFR. We produced CD33-OBi by chemically heteroconjugating GO with OKT3 (anti-CD3). We determined whether ATC armed with CD33-OBi can enhance the killing of a low expressing GO-resistant cell line K562. MethodsATC were produced by stimulating peripheral blood mononuclear cells (PBMC) with anti-CD3 in the presence of IL-2. K562 cell line, expressing 67% CD33 expression was used as a target given the relative resistance of this cell line to GO. Daudi cell line expressing no CD33 was used as control. Cytotoxicity to K562 and Daudi cell lines was performed using 51Cr labeled cells as targets with different concentrations of GO alone, CD33-OBi, ATC alone and CD33-OBi armed ATC. Armed ATC were washed free of arming BiAb unless otherwise indicated. Various arming doses of the CD33-OBi for ATC were also tested, ADCC with CD33-OBi utilizing fresh PBMC were tested. ADCC with GO was not tested as the mechanism of action for GO is through internalization and DNA damage from the cleaved calicheamicin. ResultsIn antibody doses of 5, 50, 500, and 5000 ng/ml of GO or CD33-OBi alone, specific cytotoxicity was 5,7,14, and 14% for GO and was essentially null at all concentrations for CD33-OBi. At arming doses of 0.5, 5, 50 and 500 ng of CD33-OBi/106 ATC, the plateau of mean specific cytotoxicity directed at K562 cells was 38%, achieved between arming doses of 50 and 500 ng/106ATC at an effector to target ratio (E/T) of 25:1. Daudi CD33-negative control cells were not lysed by either GO or CD33-OBi alone. Subsequently, ATC from 3 normal donors (n=3) armed with CD33-OBi with 50 ng/106 cells at E/T of 25:1, 12.5:1, 6.25:1 and 3.125:1 showed % mean [±SEM] specific cytotoxicity of 34.3[±3.2], 28.5[±3.2], 22[±2.8] and 16.2[±2.1]%, respectively to K562. On the other hand, ATC alone at similar E/T showed % mean specific cytotoxicity of 25[±4.6], 16.3[±3.6], 10.3[±2.4] and 5.3[±1.3].There were significant differences between CD33-OBi-ATC and ATC with p values (Wilcoxan signed rank test) at E/T of 25:1, 12.5:1, 6.25:1 and 3.125:1 that were 0.043, 0.033, 0.014 and 0.012, respectively. There was no specific cytotoxicity directed at Daudi cells under similar conditions. ADCC was performed with CD33-OBi added to co-culture of PBMC and labeled K562 and Daudi cells for 24 hrs which showed background specific cytotoxicity. ConclusionsATC armed with CD33-OBi at 50 ng/106 cells showed enhanced cytotoxicity directed at K562 cells which historically is relatively resistant to GO. The unarmed ATC have been shown to have non MHC restricted cytotoxicity and arming them with the CD33-OBi retargets and enhances the cytotoxicity of ATC to targets that express CD33. Given that patients with CD33 positive blasts may contain a population of CD33 positive leukemia stem cells, this approach may provide a non-toxic strategy to target leukemia stem cells. Testing additional GO susceptible and resistant cell lines under conditions in combination with chemotherapy or hematopoietic stem cell transplant may provide proof of principle for developing this approach. [Display omitted] Disclosures:Lum:Transtarget Corporation: Founder.

Mechanical Injury and Cytokines Cause Loss of Cartilage Integrity and Upregulate Proteins Associated with Catabolism, Immunity, Inflammation, and Repair

The objectives of this study were to perform a quantitative comparison of proteins released from cartilage explants in response to treatment with IL-1beta, TNF-alpha, or mechanical compression injury in vitro and to interpret this release in the context of anabolic-catabolic shifts known to occur in cartilage in response to these insults in vitro and their implications in vivo. Bovine calf cartilage explants from 6-12 animals were subjected to injurious compression, TNF-alpha (100 ng/ml), IL-1beta (10 ng/ml), or no treatment and cultured for 5 days in equal volumes of medium. The pooled medium from each of these four conditions was labeled with one of four iTRAQ labels and subjected to nano-2D-LC/MS/MS on a quadrupole time-of-flight instrument. Data were analysed by ProQuant for peptide identification and quantitation. k-means clustering and biological pathways analysis were used to identify proteins that may correlate with known cartilage phenotypic responses to such treatments. IL-1beta and TNF-alpha treatment caused a decrease in the synthesis of collagen subunits (p < 0.05) as well as increased release of aggrecan G2 and G3 domains to the medium (p < 0.05). MMP-1, MMP-3, MMP-9, and MMP-13 were significantly increased by all treatments compared with untreated samples (p < 0.10). Increased release of proteins involved in innate immunity and immune cell recruitment were noted following IL-1beta and TNF-alpha treatment, whereas increased release of intracellular proteins was seen most dramatically with mechanical compression injury. Proteins involved in insulin-like growth factor and TGF-beta superfamily pathway modulation showed changes in pro-anabolic pathways that may represent early repair signals. At the systems level, two principal components were sufficient to describe 97% of the covariance in the data. A strong correlation was noted between the proteins released in response to IL-1beta and TNF-alpha; in contrast, mechanical injury resulted in both similarities and unique differences in the groups of proteins released compared with cytokine treatment.

The effects of a brief relaxation program on heart rate variability in cancer patients

e20713 Background: Objectives were: (1) To characterize the physiologic changes of the autonomic nervous system, demonstrated by heart rate variability (HRV) high frequency (HF) spectral analysis, before and after a 15 minute, one-time, guided relaxation program for cancer patients. (2) To assess whether changes of HRV correlate with subjective feeling for anxiety, based on the Edmonton Symptom Assessment Scale (ESAS), and the summed ESAS score. Methods: 20 patients with any cancer diagnosis and normal cognition were recruited for the study. The ECG electrodes were attached and a 5-minute period of heart rate variability was recorded (HRVbefore) after 15 minutes of supine resting. The patient then began the brief relaxation program via recorded audio. Another 5 minute period of HRV was then recorded (HRVafter). The ESAS was completed before and immediately after the relaxation program. Parasympathetic activity assessed by heart rate variability, as measured by high frequency spectral analysis, was the primary outcome measure. The differences between the pre and post values of low and high frequency HRV, of the ESAS anxiety score, and of the summed ESAS score were compared using a Wilcoxan signed rank test. Results: No statistically significant differences were found in HF HRV power between the pre and post relaxation program. However, the summed ESAS scores were significantly lower after the relaxation program (p &lt;0.001). There was also a trend of decrease in the ESAS anxiety score (p = 0.086). There was no correlation between the change in HRV HF and change in the ESAS anxiety score. Conclusions: A brief guided relaxation program can significantly improve symptoms as measured by ESAS, but not HF HRV power. No significant financial relationships to disclose.

Dual phase qualitative and quantitative 99mTc-MIBI scintimammography for predicting response to neoadjuvant chemotherapy in breast cancer.

To determine the role of dual phase 99mTc-MIBI scintimammography in predicting chemotherapeutic response in breast cancer. Cross-sectional study. Karachi Institute of Radiology and Nuclear Medicine (KIRAN), from September 2004 to March 2005. Female patients with locally advanced breast cancer being planned for the anthracycline-based neoadjuvant chemotherapy were included in this study. All subjects received a 740 MBq bolus intravenous injection of 99mTc-MIBI. Ten minutes and 3 hours post-injection planar images were obtained in prone, lateral and supine positions using double head gamma camera. MIBI washout was scored as follows: >30% as a positive prognostic test (predicting a poor response to chemotherapy) and <30% as negative prognostic test (predicting a good response to chemotherapy). Qualitative analysis of MIBI scans was also performed and categorized as visual wash-out or no visual washout as apparent on the early and delayed images. The criterion for the good and bad response was the reduction of >50% and <50% in the tumour burden respectively. Accuracy analysis, Chi-square test and Wilcoxan sign rank test were applied. There were 32 females (mean age: 46.3 years; median age 46 years; age range 33-65 years). Quantitative dual phase 99mTc-MIBI scintimammography was found to be a good predictor of chemotherapeutic response in breast cancer. These were true positive in 8 patients and true negative in 19 patients with sensitivity (Sens.) 72%, specificity (Spec.) 90%, Positive Predictive Value (PPV) 80%, Negative Predictive Value (NPV) 86.5%, p <0.03. Receiver Operating Characteristics (ROC) curve analysis demonstrates 30% as a cut-off value for the wash-out in quantitative dual phase MIBI for the prediction of the chemotherapeutic response. In comparison, qualitative scintimammography had Sens. 82%, Spec. 53%, PPV 29%, NPV 93% and p <0.38. Statistical difference was found between early and delayed uptake ratios in the responders and non-responders. Quantitative dual phase 99mTc-MIBI scintimammography is a simple, reliable, non-invasive and effective tool for predicting the response to neoadjuvant chemotherapy. Furthermore, quantitative assessment is more precise than qualitative (visual wash-out) approach.