Adequate Responders Research Articles

A comprehensive evaluation of humoral immune response to second and third SARS-CoV-2 mRNA vaccination in patients with malignant lymphoma.

More information is needed regarding the efficacy of SARS-CoV-2 mRNA vaccines in immunocompromised populations, including patients with malignant lymphoma. This study aimed to evaluate humoral responses to the second and third mRNA vaccine doses in 165 lymphoma patients by retrospective analysis of serum SARS-CoV-2 spike protein antibody (S-IgG) titers. Patients with S-IgG titers ≥ 300, 10-300, and ≤ 10 binding antibody units (BAU)/mL were defined as adequate responders, low responders, and non-responders, respectively. S-IgG titers > 10BAU/mL were considered to indicate seroconversion. After the second dose, 56%, 16%, and 28% of patients were adequate responders, low responders and non-responders, respectively. Multivariate analysis revealed that being an adequate responder after the second dose was associated with receiving the vaccine > 12months after last chemotherapy, total peripheral lymphocyte count of ≥ 1000/µL, estimated glomerular filtration rate of ≥ 50mL/min/1.73m2, and vaccine type (mRNA-1273). After the third dose, patients had significantly higher S-IgG titers and a greater proportion achieved seroconversion. With this third dose, 26% of second-dose non-responders achieved seroconversion and 68% of second-dose low responders became adequate responders. Subsequent SARS-CoV-2 mRNA vaccinations may elicit an immune response in immunocompromised patients who do not initially respond to vaccination.

Desmopressin for bleeding in non‐severe hemophilia A: Suboptimal use in a real‐world setting

BackgroundDesmopressin is an important treatment option in nonsevere hemophilia A because it has several benefits compared with factor (F) concentrates, including no inhibitor risk and much lower costs. Despite these advantages, data are limited on the real‐world use of desmopressin in the treatment of bleeds. ObjectiveTo describe the clinical use of desmopressin in relation to other therapeutic modalities in the treatment of bleeding episodes in patients with nonsevere hemophilia A. MethodsPatients with nonsevere hemophilia A aged 12–55 years were included from the DYNAMO cohort study. Data on the desmopressin test response and treated bleeding events in the period January 2009 to July 2020 were retrospectively collected from medical files. An adequate desmopressin test response was defined based on a peak FVIII level of ≥30 IU/dl. ResultsA total of 248 patients with a median age of 38 years (interquartile range 25–49) were included. An adequate desmopressin test response was documented in 25% and 73% of patients with moderate and mild hemophilia, respectively. In adequate responders, 51% of bleeds were exclusively treated with FVIII concentrates, 24% exclusively with desmopressin, 21% with a combination of both and 4% with other treatments. In 54% of bleeds treated with a single dose of factor concentrates, the expected FVIII level after desmopressin exceeded the level targeted. ConclusionMost bleeds in patients with an adequate response to desmopressin are treated with factor concentrates. These findings may indicate a suboptimal use of desmopressin and that barriers to the use of desmopressin should be explored.

Nonverbal Behavior in Face-to-face Survey Interviews: An Analysis of Interviewer Behavior and Adequate Responding

We examine relationships between interviewers’ nonverbal behaviors and adequate responding in face-to-face survey interviews. We videotaped professional interviewers administering face-to-face survey interviews and coded them for three interviewer nonverbal behaviors: smiling, nodding, and direct gaze. These nonverbal interviewer behaviors were associated with significant increases in the frequency of respondents’ adequate responses. Moreover, the nonverbal behaviors were equally likely to present in standardized and unstandardized utterances. These results suggest that interviewers’ nonverbal behaviors positively correlate with adequate responding without deviating from standardized interview protocols. We discuss implications for survey theory and interviewer training.

Increasing the efficiency of investigation methods for rail transport accidents

Increasing volume and speed of rail traffic bring a rise in strain of both rolling stock and rail track. Identifying causes of rail accidents and developing adequate responding guidelines play a large part in ensuring traffic safety. Another key factor is analyzing and estimating the involvement of various deviations in the locomotive-car-track system parameters in a derailment or other catastrophic events. Increased stress on car and rail track elements has led to higher frequency of failures in operation and shorter mileage between overhauls. This in turn has deteriorated the technical condition of the locomotive-car-track system and affected the ongoing tendency of growing derailments of freight cars in curves and on mountainous terrains. In particular, the data obtained from rail accident investigations has shown a two-fold increase in the number of car derailments in the aforementioned conditions as the outcome of deviations in the locomotive-car-track system parameters between 2012 and 2020. For this reason, ensuring traffic safety is increasingly dependent on computational-and-empirical evaluation and danger classification of different deviations in system parameters, as well as development mathematical models of concerning processes and situations. The issue has been partially resolved due to investigations in causes of defects and accidents in the car-railway system, followed by identification of the most dangerous defects and the development of appropriate recommendations aimed at improving traffic safety. However, this approach does not fully consider the effect of violations of speed limit in combination with other deviations, nor the danger level of various deviations of the locomotive-car-track system’s elements when moving through mountain-pass sections of the track. In particular, the influence of the uncanceled lateral acceleration that occurs when a train moves in such sections (track slope between 8 and 25 ‰), including when coupled with extra track subsidence conditions, speed limit violation and abnormal elevation of the outer rail inside a curve, has not been fully assessed. Finally, the influence of wear of wheel rolling surfaces and ridges when moving through curves and mountain-pass sections has also yet to be fully researched. Therefore, it remains a pressing task to advance the computational-and-empirical approach as well as mathematical models for assessing danger levels of individual failures and their combinations in the locomotive-car-track system, and to develop recommendations for identifying accident causes and improving traffic safety in curves and on mountainous terrains.

Validation of Deep Learning-based Augmentation for Reduced 18F-FDG Dose for PET/MRI in Children and Young Adults with Lymphoma.

To investigate if a deep learning convolutional neural network (CNN) could enable low-dose fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/MRI for correct treatment response assessment of children and young adults with lymphoma. In this secondary analysis of prospectively collected data (ClinicalTrials.gov identifier: NCT01542879), 20 patients with lymphoma (mean age, 16.4 years ± 6.4 [standard deviation]) underwent 18F-FDG PET/MRI between July 2015 and August 2019 at baseline and after induction chemotherapy. Full-dose 18F-FDG PET data (3 MBq/kg) were simulated to lower 18F-FDG doses based on the percentage of coincidence events (representing simulated 75%, 50%, 25%, 12.5%, and 6.25% 18F-FDG dose [hereafter referred to as 75%Sim, 50%Sim, 25%Sim, 12.5%Sim, and 6.25%Sim, respectively]). A U.S. Food and Drug Administration-approved CNN was used to augment input simulated low-dose scans to full-dose scans. For each follow-up scan after induction chemotherapy, the standardized uptake value (SUV) response score was calculated as the maximum SUV (SUVmax) of the tumor normalized to the mean liver SUV; tumor response was classified as adequate or inadequate. Sensitivity and specificity in the detection of correct response status were computed using full-dose PET as the reference standard. With decreasing simulated radiotracer doses, tumor SUVmax increased. A dose below 75%Sim of the full dose led to erroneous upstaging of adequate responders to inadequate responders (43% [six of 14 patients] for 75%Sim; 93% [13 of 14 patients] for 50%Sim; and 100% [14 of 14 patients] below 50%Sim; P < .05 for all). CNN-enhanced low-dose PET/MRI scans at 75%Sim and 50%Sim enabled correct response assessments for all patients. Use of the CNN augmentation for assessing adequate and inadequate responses resulted in identical sensitivities (100%) and specificities (100%) between the assessment of 100% full-dose PET, augmented 75%Sim, and augmented 50%Sim images. CNN enhancement of PET/MRI scans may enable 50% 18F-FDG dose reduction with correct treatment response assessment of children and young adults with lymphoma.Keywords: Pediatrics, PET/MRI, Computer Applications Detection/Diagnosis, Lymphoma, Tumor Response, Whole-Body Imaging, Technology AssessmentClinical trial registration no: NCT01542879 Supplemental material is available for this article. © RSNA, 2021.

Mothers' experiences learning and performing infant massage-A qualitative study.

To explore the experience of learning infant massage among mothers who are having insecurity and stress in their transition to motherhood. Secure attachment is essential for healthy infant development. An interaction with the caregiver, characterised by sensitivity, engagement and adequate responding, is necessary for the development of attachment. However, transition to parenting can be a major challenge and create insecurity and stress for some mothers. This can interfere with mother's attachment and sensitivity to the baby's cues, which in turn can affect the mother-infant interaction. Mothers who struggled postpartum were invited to participate in a group called Mamma Mia, a programme where mothers learn infant massage as targeted measure for improving interaction between the mother and baby. To date, there is limited knowledge how mothers receiving this group programme experience infant massage. A qualitative and explorative approach was used, based on interviews with 12 mothers who had participated in Mamma Mia group facilitated by public health nurses at Well Child Clinics in Norway. We used qualitative content analysis with manifest and latent content to analyse the transcripts. One main theme emerged: "A relief with an opportunity for emotional and physical connection with the baby" and four categories were identified to highlight the mothers' experiences through (a) appreciating the structure, (b) providing self-esteem and self-confidence, (c) connecting with the baby and (d) discovering the baby's presence. Mothers in this study in Norway enjoyed the experience of learning infant massage and felt closer to their babies as a result. Training of health professionals to provide infant massage to mothers in a Mamma Mia group or similar groups can be a low cost and efficient intervention in primary care.

Executive Functions and Response to Intervention: Identification of Students Struggling with Reading Comprehension.

Inadequate responders demonstrate significant risk for learning disabilities. Previous investigations of the cognitive profiles of inadequate and adequate responders have not included measures of executive functions (EF), which have well-documented associations to reading comprehension. We evaluated EF performance on a common factor comprised of shared variance across tasks as well as five separable EF factors in the context of an intensive reading intervention for struggling fourth graders. To determine if EF performance at pretest is associated with subsequent responder status, we compared EF performance of three subgroups of students: inadequate and adequate responders and typical students not at-risk for reading disabilities. Results of discriminant function analyses and linear regression models comparing groups were largely null; EF performance at pretest demonstrated only small associations with responder status. These results suggest that the assessment of EF may have limited value in predicting which individual students will respond to intensive reading interventions.

Abstract TMP18: Heparin Resistance is an Independent Predictor of Poor outcome in Cerebral Venous Sinus Thrombosis

Background and purpose: Unfractionated Heparin (UFH) infusion represents the most commonly used therapy in the acute management of cerebral venous sinus thrombosis (CVST). effectiveness of heparin in reaching therapeutic anti-coagulation levels has not been well studied in this population. Identifying subgroup of patients who will not respond to Heparin may prove useful in studying alternative treatments such as the new oral anticoagulants and endovascular therapy. We aimed to evaluate the initial response to heparin infusion measured by partial thromboplastin time (PTT) and it implication in discharge outcome. Methods: Retrospective review of all consecutive patients at University of Iowa Hospitals and Clinics between 2004-2014 with CVST was conducted. All patients were treated with initial weight based bolus (14units/kg) of UFH followed by infusion. Consecutive PTT values in the first 48hrs of admission were classified as either therapeutic (40-87), supra-therapeutic (&gt;87), or resistant (&lt;40). Then patients were classified as good responders if 80% of PTT values were in the therapeutic range, classified as adequate if 65-79% of PTT values were therapeutic; rest of patients were classified as non-responders. Univariate and multivariate regressions models were performed to assess the association with discharge mRS, the primary outcome. Results: 115 patients met inclusion criteria (76 women), mean age was 42. Mean PTT was 44.8 (SD=18.6; 95%CI of 41.2-48.5) in the first 48 hours. Patients resistant to Heparin (44%) had significantly worse functional outcomes, mRS [95%CI 2.3-3.6], compared to good [41%, 95%CI 1.2-2.3] and adequate responders to Heparin [15%, 95%CI 0.5-2.3] (p=.003). Mean PTT in the first 48 hours predicted discharge mRS, r=-.28,p&lt;.005 and this effect remained significant when age, sex, altered mental status at admission were controlled, p=.001. Conclusion: A significant portion of patients that receive heparin do not reach therapeutic levels within the initial days after hospitalization, and this does not appear to be a consequence of disease burden in our population. Specifying clinical features that predict heparin resistance might help to identify patients that benefit from alternative anticoagulation therapies.

Monitoring of post-vaccination anti-HBs titles vaccine in children and adolescents in the pre-dialysis of chronic kidney disease.

Bacterial or viral diseases are one of the major causes of death in patients with chronic kidney disease (CKD). These patients show a quantitative reduction of levels of antibodies over time. Among the infectious diseases that affect CKD patients, stands out hepatitis B (HB). Immunization and control of antibodies levels against the hepatitis B surface antigen (anti-HBs) are ways to prevent the HB infection in this population. Patients with anti-HBs levels ≥10 IU/ml are considered adequate responders, whereas those with anti-HBs levels ≥ 100 IU/ml are considered excellent responders. To analyze the variation of the anti-HBs levels obtained after vaccination against HB in children and adolescents in the pre-dialysis stage of CKD. A retrospective cohort study on anti-HBs levels of children and adolescents in the pre-dialysis stage of CKD. Correlation between levels of anti-HBs titers and time since the vaccination were estimated. From the total of 116 studied patients most of the studied patients were considered excellent responders, obtaining in the three anti-HBs titers percentages of 70.7%, 62.1% and 54.9% respectively. The anti-HBs titer levels showed a negative correlation with the time since vaccination (Kendall Tau-b = -0.16; p = 0.02). The majority of the studied population was vaccinated by PNI and showed excellent anti-HBs titer levels, even experiencing a progressive reduced response over the time.

Evaluation of Response to Hepatitis B Vaccination in Chronic Hemodialysis Patients.

Background:Hemodialysis (HD) patients are at an increased risk of acquiring hepatitis B virus (HBV) infection. Active HBV immunization in these patients is recommended. A response rate in HD patients is variable but generally lower than healthy individuals.Objective:The aim of this study is to assess the response of HD patients to the HBV vaccine and correlate response and long-term immunity to various clinical and biomedical factors.Patients and Methods:One hundred and one patients, with a mean age 48.7 ± 18.5 years, received 40 μg of HBV vaccine administered intramuscularly in the deltoid region at 0, 1, 2 and 6 months. The patients' responses to the vaccine were determined by measuring hepatitis B surface antibody (HBsAb) 6 weeks after the last injection and monitored thereafter at 3-month intervals.Results:Seventy-one patients (70.3%) mounted a response with HBsAb >10 mIU/ml 6 weeks following the fourth dose of vaccine, and thus were considered considered as adequate responders. Forty-nine (48.5%) patients mounted an excellent response with HBsAb >100 mIU/ml 6 weeks after the fourth dose. Thirty patients (29.7%) were nonresponders. Responders were significantly younger than nonresponders (P = 0.01). Gender, hemoglobin level, serum albumin, ferritin, parathyroid hormone level and hepatitis C virus infection had no effect on the response to the vaccine. Similarly, there was no difference in diabetic state and adequacy of HD between the two groups. Fifty-nine patients (88%) had persistent protective antibodies at 1 year, while eight (12%) lost such protection. Predictors of persistent immunity at 1 year were high HBsAb level at the completion of the vaccination regime and, to a lesser extent, young age.Conclusion:A 70% response rate to HBV vaccine was observed in the cohort of this study. Young age predicts a favorable response to HBV vaccine in HD patients. High (>100 mIU/ml) HBsAb levels achieved at vaccine completion predict persistent immunity at 1 year.

Elevation of Vδ1 T cells in peripheral blood and livers of patients with primary biliary cholangitis.

Primary biliary cholangitis (PBC), hitherto called primary biliary cirrhosis, is a cholestatic liver disease of unclear aetiology with autoimmune features. Accumulating evidence revealed that γδ T cells were involved in the development of autoimmune diseases. As one of γδ T cells subsets, however, the role of Vδ1 T cells in the immunopathogenesis of PBC is poorly understood. We analysed peripheral blood Vδ1 T cells in PBC patients in active stage (ASP, n = 18), adequate responders (AR, n = 10) and inadequate responders (IAR, n = 4) to ursodeoxycholic acid (UDCA) and an age-matched healthy control group (n = 16) by flow cytometric analysis. The ASP group exhibited a significantly higher proportion and absolute number of Vδ1 T cells, which were also observed in immunofluorescence staining of liver biopsy specimens of PBC patients. Moreover, these Vδ1 T cells expressed a series of activation markers and intracellular cytokines, which may contribute to the immunopathogenesis of PBC. Our study will help to clarify the role of Vδ1 T cells in the development of PBC.

Cognitive Attributes, Attention, and Self-Efficacy of Adequate and Inadequate Responders in a Fourth Grade Reading Intervention.

We examined cognitive attributes, attention, and self-efficacy of fourth grade struggling readers who were identified as adequate responders (n = 27), inadequate responders with comprehension only deficits (n = 46), and inadequate responders with comprehension and word reading deficits (n = 52) after receiving a multicomponent reading intervention. We also included typical readers (n = 40). These four groups were compared on measures of nonverbal reasoning, working memory, verbal knowledge, listening comprehension, phonological awareness, and rapid naming as well as on teacher ratings of attention problems and self-reported self-efficacy. The two inadequate responder groups demonstrated difficulties primarily with verbal knowledge and listening comprehension compared to typical readers and adequate responders. Phonological awareness and rapid naming differentiated the two inadequate responder groups. In addition, both inadequate responder groups showed more attention problems and low self-efficacy compared to typical readers.

Circulating sclerostin and estradiol levels are associated with inadequate response to bisphosphonates in postmenopausal women with osteoporosis

IntroductionThe biological mechanisms associated with an inadequate response to treatment with bisphosphonates are not well known. This study investigates the association between circulating levels of sclerostin and estradiol with an inadequate clinical outcome to bisphosphonate therapy in women with postmenopausal osteoporosis. MethodsThis case-control study is based on 120 Spanish women with postmenopausal osteoporosis being treated with oral bisphosphonates. Patients were classified as adequate responders (ARs, n=66, mean age 68.2±8 years) without incident fractures during 5 years of treatment, or inadequate responders (IRs, n=54, mean age 67±9 years), with incident fractures between 1 and 5 years of treatment. Bone mineral density (DXA), structural analysis of the proximal femur and structural/fractal analysis of the distal radius were assessed. Sclerostin concentrations were measured by ELISA and 17β-estradiol levels by radioimmunoassay based on ultrasensitive methods. ResultsIn the ARs group, sclerostin serum levels were significantly lower (p=0.02) and estradiol concentrations significantly higher (p=0.023) than in the IRs group. A logistic regression analysis was performed, including as independent variables in the original model femoral fracture load, 25 hydroxyvitamin D, previus history of fragility fracture, sclerostin and estradiol. Only previous history of fragility fracture (OR 14.04, 95% CI 2.38–82.79, p=0.004) and sclerostin levels (OR 1.11, 95% CI 1.02–1.20, p=0.011), both adjusted by estradiol levels remained associated with IRs. Also, sclerostin concentrations were associated with the index of resistance to compression (IRC) in the fractal analysis of the distal radius, a parameter on bone microstructure. ConclusionsSclerostin and estradiol levels are associated with the response to bisphosphonate therapy in women with postmenopausal osteoporosis.

Cognitive Attributes of Adequate and Inadequate Responders to Reading Intervention in Middle School.

No studies have investigated the cognitive attributes of middle school students who are adequate and inadequate responders to Tier 2 reading intervention. We compared students in Grades 6 and 7 representing groups of adequate responders (n = 77) and inadequate responders who fell below criteria in (a) comprehension (n = 54); (b) fluency (n = 45); and (c) decoding, fluency, and comprehension (DFC; n = 45). These students received measures of phonological awareness, listening comprehension, rapid naming, processing speed, verbal knowledge, and nonverbal reasoning. Multivariate comparisons showed a significant Group-by-Task interaction: the comprehension-impaired group demonstrated primary difficulties with verbal knowledge and listening comprehension, the DFC group with phonological awareness, and the fluency-impaired group with phonological awareness and rapid naming. A series of regression models investigating whether responder status explained unique variation in cognitive skills yielded largely null results consistent with a continuum of severity associated with level of reading impairment, with no evidence for qualitative differences in the cognitive attributes of adequate and inadequate responders.

Assessment of the immune response to hepatitis B virus vaccine as a major factor in the prevention of hepatitis B infection

ObjectiveThe aim of the work was to study the effect of hepatitis B virus (HBV) vaccine as a major factor in the prevention of HBV infection.BackgroundMeasuring the level of hepatitis B surface antibodies in different age groups to determine the time of fading of hepatitis B surface antibodies and whether there is a need for a booster dose or not.Patients and methodsNinety random persons selected among those attending Menoufia Fever Hospital, Menoufia governorate, who were previously vaccinated with HBV vaccine, were classified into three groups.ResultsSignificantly, the seroprotection rate among vaccinated children up to 5 years was 70.0%, with a mean concentration of HBsAb of 139 mIU/ml; of them, 40.0% were over-responders (>100 mIU/ml), 30% were adequate responders (10-100 mIU/ml), and 30.0% were nonresponders.In the second group, the mean concentration of HBsAb was 70 mIU/ml, wherein 43.3% were considered responders; of them, 13.3% were over-responders, 30% were adequate responders, and 56.7% were nonresponders (HBsAb <10 mIU/ml). The HCW of the third group shows that the mean concentration of HBsAb was 639 mIU/ml; 20.0% were adequate responders and 80.0% were over-responders.ConclusionThe HBV vaccine has a major effect on the prophylaxis and the prevention of HBV infection. The HBV vaccine efficacy decreased with increasing age up to 18 years. There was 100% response in healthcare workers 5 years after vaccination.

AGREEMENT AND COVERAGE OF INDICATORS OF RESPONSE TO INTERVENTION: A MULTI-METHOD COMPARISON AND SIMULATION.

Agreement across methods for identifying students as inadequate responders or as learning disabled is often poor. We report (1) an empirical examination of final status (post-intervention benchmarks) and dual-discrepancy growth methods based on growth during the intervention and final status for assessing response to intervention; and (2) a statistical simulation of psychometric issues that may explain low agreement. After a Tier 2 intervention, final status benchmark criteria were used to identify 104 inadequate and 85 adequate responders to intervention, with comparisons of agreement and coverage for these methods and a dual-discrepancy method. Factors affecting agreement were investigated using computer simulation to manipulate reliability, the intercorrelation between measures, cut points, normative samples, and sample size. Identification of inadequate responders based on individual measures showed that single measures tended not to identify many members of the pool of 104 inadequate responders. Poor to fair levels of agreement for identifying inadequate responders were apparent between pairs of measures In the simulation, comparisons across two simulated measures generated indices of agreement (kappa) that were generally low because of multiple psychometric issues inherent in any test. Expecting excellent agreement between two correlated tests with even small amounts of unreliability may not be realistic. Assessing outcomes based on multiple measures, such as level of CBM performance and short norm-referenced assessments of fluency may improve the reliability of diagnostic decisions.

Evaluation of Aspirin and Clopidogrel resistance in patients with Acute Coronary Syndrome by using Adenosine Diposphate Test and Aspirin Test

Objectives: To evaluate Aspirin and Clopidogrel resistance/non-responders in patients with acute coronary syndrome (ACS) by using adenosine diposphate and aspirin tests. Methodology: In the study patients with ACS loaded with 300 mg of clopidogrel and 300 mg aspirin and patients on stable daily dose of 75 mg of clopidogrel (more than 3 days) underwent PCI. Response to clopidogrel and Aspirin was assessed by Adenosine Diphosphate (ADP) Test (20 µmol/L) and Aspirin Test (Acetyl Acid) (ASP) 20 µmol/L, respectively, using the Multiplate Platelet Function Analyzer (Dynabyte Medical, Munich, Germany). Results: Sixty four patients were included in this study out of which 57 were with ACS and 7 scheduled for percutaneous coronary intervention (PCI) electively. The proportion of Aspirin good responders and adequate responders were 76.56% and 18.75%, respectively while adequate response and good response to Clopidogrel accounted for 29.7 and 48.4%, respectively Hyperlipidaemia was only co-morbidity associated with higher AUC ADP value (p: 0.046). Hypertriglyceridaemia and serum calcium were weakly correlated with higher AUC ADP serum calcium r=0.08, triglyceride r=0.12. Patients admitted for scheduled PCI and on stable dose of 75mg clopidogrel exhibited lower AUC ADP value as compared to those admitted with acute coronary syndrome given loading dose of 300mg of Clopidogrel. Post loading dose measurement of anti-platelet therapy among ACS patients using the Multiplate Platelet Function Analyzer showed comparable results with other methods. Conclusions : As determined by Multiplate Platelet Function Analyzer, Aspirin resistance/non-responders in this study in acute coronary syndrome patients accounted for 4.69% while Non-responders in Clopidogrel was 21.9%.

Serum anti-Müllerian hormone and basal serum FSH as predictors of poor ovarian response in assisted conception cycles

The aim of the study was to correlate serum AMH and serum FSH levels with ovarian response to stimulation in IVF–ICSI cycles. This was a prospective observational study conducted in a private assisted conception unit. One hundred and two patients were selected on their first IVF cycle. Basal serum FSH and serum AMH were measured one month before the stimulation cycle. A fixed dose GnRH antagonist protocol was used in all cycles transferring a maximum of three day-3 cleavage stage embryos. We defined poor ovarian response as retrieval of fewer than four mature oocytes in cycles requiring ⩾ 3000 IU of gonadotropins for stimulation or cycle cancellation due to poor response. The correlation between different parameters was expressed as a Spearman’s correlation coefficient. The clinical value of AMH and FSH as predictors of poor ovarian response as well as predictors of pregnancy was evaluated by constructing relevant receiver operator characteristics curves (ROC curves). Of these 102 cycles, 28 fitted our definition of poor response while the remaining 74 cycles all produced an adequate response to stimulation. There was a statistically significant difference between the adequate responders group and poor responders group regarding their mean age (31.5 versus 39.6, p < 0.001), the mean value of AMH (2.84 ng/ml versus 0.9 ng/ml, p < 0.0001) as well as the mean value of basal FSH (7.6 IU/ml versus 9.7 IU/ml, p < 0.0001). Serum AMH level had a positive correlation while serum FSH had a negative correlation with the number of oocytes collected while only serum AMH had a significant positive correlation with the occurrence of pregnancy. ROC curve analysis of our results showed that serum AMH with an optimal cut-off value of 1.2 ng/ml is a reliable predictor of poor ovarian response with an area under the ROC curve of 90.4%. Serum basal FSH with an optimal cut-off value of 8.9 IU/ml was of lower value than AMH as a predictor of poor ovarian response with an area under the ROC curve of 81.9%. However, neither serum AMH nor basal serum FSH was found to able to reliably predict the occurrence of pregnancy with an area under the ROC curve of 59.4% and 58.6% respectively. Our results show that serum AMH level is more reliable than basal serum FSH as a predictor of poor ovarian response to stimulation with a cut-off value of 1.2 ng/ml shown to predict poor ovarian response with a sensitivity of 91.7%.

Open Access Capture of Patients With Gastroesophageal Reflux Disease Using an Online Patient-Reported Outcomes Instrument

BackgroundPersons with gastroesophageal reflux disease (GERD) frequently search online for information about causes and treatment options. The GerdQ self-assessment questionnaire can be used for diagnosis of GERD and follow-up of symptoms.ObjectivesTo assess whether it is feasible (1) to study the prevalence and impact of GERD in persons visiting a GERD information website, and (2) to identify partial responsiveness to proton pump inhibitor (PPI) therapy using the GerdQ.MethodsAll visitors (aged 18–79 years) to a GERD information website between November 2008 and May 2011 were invited to complete the GerdQ online. The GerdQ questionnaire consists of 6 questions (score per question: 0–3). In respondents who did not use PPIs, we used the questionnaire to identify those with GERD (total score ≥8) and assess the influence of these symptoms on their daily life, divided into low (total score <3 on impact questions) and high impact (total score ≥3 on impact questions). In PPI users, we used the GerdQ to quantify partial responsiveness by any report of heartburn, regurgitation, sleep disturbance, or over-the-counter medication use for more than 1 day in the preceding week. We subsequently asked GerdQ respondents scoring ≥8 to complete the disease-specific Quality of Life in Reflux and Dyspepsia (QOLRAD) questionnaire.ResultsA total of 131,286 visitors completed the GerdQ, of whom 80.23% (n = 105,329) did not use a PPI. Of these, we identified 67,379 respondents (63.97%) to have GERD (n = 32,935; 48.88% high impact). We invited 14,028 non-PPI users to complete the QOLRAD questionnaire, of whom 1231 (8.78%) completed the questionnaire. Mean total QOLRAD scores were 5.14 (SEM 0.04) for those with high-impact GERD and 5.77 (SEM 0.04) for those with low-impact GERD (P < .001). In PPI users, 22,826 of 25,957 respondents (87.94%) reported partial responsiveness. We invited 6238 PPI users to complete the QOLRAD questionnaire, of whom 599 (9.60%) completed the disease-specific quality-of-life questionnaire. Mean total QOLRAD scores were 4.62 (SEM 0.05) for partial responders and 5.88 (SEM 0.14) for adequate responders (P < .001).ConclusionsThe GerdQ identified GERD in many website respondents and measured partial responsiveness in the majority of PPI users. Both non-PPI users with GERD and PPI users with partial responsiveness were associated with a decreased health-related quality of life. We have shown the feasibility of GERD patient identification online.

Tu1381 Effects of 26 Weeks of Linaclotide Treatment on Adequate Relief and IBS Severity in Patients With Irritable Bowel Syndrome With Constipation

Introduction There have been few long-term studies evaluating treatments for IBS. Linaclotide (LIN), a 14 amino acid, minimally absorbed, guanylate cyclase C agonist (GCCA), was evaluated in 2 Phase 3 trials in patients (pts) with IBS-C, including a double-blind trial with an extended 26 wk Treatment Period, in which statistically significant improvements in abdominal pain and complete spontaneous bowel movement (CSBM) frequency were sustained for up to 26 wks. In a subsequent analysis of this study, we assessed the effects of 26 wks of LIN treatment on adequate relief and IBS severity and the relationship between long-term improvement in adequate relief with improvements in abdominal pain and CSBM frequency. Methods Adult pts with IBS-C (Rome II criteria) were randomised to LIN 290 μg or placebo (PBO) qd po for 26 wks. Endpoints included daily pt rating of abdominal pain at its worst during the previous 24 h on an 11-point scale (0 = none, 10 = very severe) and CSBM frequency. Pts also rated adequate relief of IBS symptoms (yes/no) and IBS severity (5-point scale: 1 = none, 5 = very severe) weekly. An Adequate Relief Responder was defined as a pt with adequate relief of IBS symptoms for ≥13 of the 26 wks of the Treatment Period. Spearman correlations were performed for Adequate Relief Responders and individual symptom improvement. Results The study included 401 LIN- and 403 PBO-treated pts. With LIN, 49% of pts were Adequate Relief Responders vs 25% of PBO pts (difference 24.1; p Conclusion Significantly more LIN pts vs PBO pts reported adequate relief of IBS symptoms and improvement of IBS severity during 26 wks of treatment. Gains in the % of pts reporting adequate relief correlated strongly with improvements in abdominal pain and CSBM frequency. Supported by Ironwood Pharmaceuticals Inc and by Forest Laboratories Inc. Editing assistance was provided by Complete Medical Communications, funded by Almirall. Disclosure of Interest E. Quigley Speaker bureau with: Danone, Janssen, Procter and Gamble, sanofi-aventis, Shire and Yakult, Conflict with: Advisory boards for Almirall, Ironwood, Janssen, Norgine, Salix and Shire/Movetis, W. Chey Consultant for: Ironwood Pharmaceuticals and Forest Research Institute, B. Lavins Shareholder of: Ironwood Pharmaceuticals, Employee of: Ironwood Pharmaceuticals, M. Baird Shareholder of: Ironwood Pharmaceuticals, Employee of: Ironwood Pharmaceuticals, D. Fitch Shareholder of: Ironwood Pharmaceuticals, Employee of: Ironwood Pharmaceuticals, X. Hao Shareholder of: Ironwood Pharmaceuticals, Employee of: Ironwood Pharmaceuticals, K. Shi Employee of: Forest Laboratories, M. Currie Shareholder of: Ironwood Pharmaceuticals, Employee of: Ironwood Pharmaceuticals, H. Schneier Shareholder of: Forest Laboratories, Employee of: Forest Laboratories, J. Johnston Shareholder of: Ironwood Pharmaceuticals, Employee of: Ironwood Pharmaceuticals