bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toluene Toxicity: A Case Report of Transdermal Exposure Causing Hypokalemic Paralysis
Authors: Tran Kelvin MH. , Hinther Kelsey , Bueti Joe , Karpinski Martin , Hingwala Jay 
Published: August 2019

Rationale: Hypokalemia is a common finding. Typically asymptomatic presentations of neuromuscular weakness emerge at levels below 2.5 mmol/L. Causes include gastrointestinal losses, renal losses, or intracellular shift, with gastrointestinal losses and diuretics accounting for the majority. Although the cause is often apparent on clinical assessment, a systematic approach incorporating urine biochemistry can aid in narrowing the differential in obscure cases. Presentation: We describe a case of a previously healthy 27-year-old man who presented with acute ascending paralysis, with an associated severe hypokalemia and metabolic acidosis. There were no apparent causes on clinical assessment. Diagnosis: Based on analysis of urine biochemistry, we concluded that a pathologic kaluresis was present, and given his acidemia and transient pathology, we diagnosed the patient with hypokalemic paralysis secondary to toluene toxicity. Interventions: We provided supportive care and electrolyte repletion for our patient; no specific therapies for toluene were required. Our patient was counseled regarding appropriate protective measures when handling toluene. Outcomes: Complete neurologic recovery and biochemical normalization occurred within 48 hours of presentation with supportive care. He continued to use proper precautions when handling toluene, and experienced no symptom relapse, or further abnormalities on both blood and urine chemistry. Lessons learned: Using this case, we review an algorithmic approach incorporating urine biochemistries to aid in the workup of hypokalemia. We review toluene as a toxicologic entity and highlight its role as a cause of hypokalemia.
Usability evaluation of an eHealth intervention for family carers of individuals affected by psychosis: A mixed-method study
Authors: Sin Jacqueline , Woodham Luke A. , Henderson , Claire , Williams Elen , Sesé Hernández Aurora , Gillard Steve 
Published: August 2019

Background Existing research suggests that eHealth interventions targeting family carers of individuals with long-term illness offer a promising approach to care delivery. In particular, digital psychoeducational interventions with interactive psychosocial support are well-received with high rates of satisfaction and acceptability. However, development of such interventions for psychosis carers is lacking. We developed a multi-component eHealth intervention specifically for carers of individuals affected by psychosis, called COPe-support (Carers fOr People with Psychosis e-support). Objective Using mixed methods to evaluate usability, system heuristics and perceived acceptability, we conducted a usability study to establish the suitability of the intervention prototype for the target user group. Methods Twenty-three carers were recruited to the study and participated in a think-aloud test or a remote online trial of the intervention. Qualitative feedback, post-use System Usability Scale (SUS) scores, and real-world usage data collected from the tests were analysed. These were also supplemented with heuristic evaluation data provided by an independent eLearning technology expert. Results Participants evaluated the intervention content as useful and helpful, and indicated that the system had satisfactory usability with a mean SUS score of 73%, above the usability quality benchmark threshold. Study results identified some minor usability issues, which were corroborated with the eLearning expert’s heuristic evaluation findings. We used these results to refine the COPe-support intervention. Conclusions The usability study with end-users and service providers identified real-life usage and usability issues. The study results helped us refine COPe-support and its delivery strategy before its launch as part of a large-scale clinical trial.
Inflation Dynamics and Monetary Policy in India: A New Keynesian Phillips Curve Perspective
Authors: Salunkhe Bhavesh , Patnaik Anuradha 
Published: August 2019

The present study estimates various specifications of the New Keynesian Phillips Curve (NKPC) models for India over 1996Q2 to 2017Q2 using Consumer Price Index (CPI) and Wholesale Price Index (WPI) inflation, separately. The empirical results suggest that the data support all the specifications of the Phillips curve models based on both the CPI and WPI inflations. However, the backward looking and hybrid models provide robust results for both the inflation indices. While the forward-looking behaviour dominates the CPI inflation trajectory, the backward-looking behaviour greatly influences the trajectory of WPI inflation. Also, a small-to-moderate degree of persistence is evident in both the CPI and WPI inflation. The output gap, which mainly represents the demand side pressures, turns up the major force determining both the CPI and WPI inflations. Besides the output gap, real effective exchange rate (reer), international crude oil price inflation, global non-fuel commodity price inflation and rainfall have a modest impact on the CPI and WPI inflations. JEL Classification: E12, E52, C36, C14
Brain Responses in CFS and TMD to Autonomic Challenges: An Exploratory fMRI Study
Authors: Vuong Q.C. , Allison J.R. , Finkelmeyer A. , Newton J. , Durham J. 
Published: August 2019

Introduction: Dysfunction of the autonomic nervous system (ANS) is seen in chronic fatigue syndrome (CFS) and temporomandibular disorders (TMDs). Both conditions have poorly understood pathophysiology. Several brain structures that play a role in pain and fatigue, such as the insular cortex and basal ganglia, are also implicated in autonomic function. Objectives: ANS dysfunction may point to common neurophysiologic mechanisms underlying the predominant symptoms for CFS and TMD. No studies to date have investigated the combination of both conditions. Thus, our aim was to test whether patients with CFS with or without TMD show differences in brain responses to autonomic challenges. Methods: In this exploratory functional imaging study, patients with CFS who screened positive for TMD (n = 26), patients who screened negative for TMD (n = 16), and age-matched control participants (n = 10) performed the Valsalva maneuver while in a 3-T magnetic resonance imaging scanner. This maneuver is known to activate the ANS. Results: For all 3 groups, whole-brain F test showed increased brain activation during the maneuver in the superior and inferior frontal gyri, the left and right putamen and thalamus, and the insular cortex. Furthermore, group contrasts with small-volume correction showed that patients with CFS who screened positive for TMD showed greater activity in the left insular cortex as compared with patients who screened negative and in the left caudate nucleus as compared with controls. Conclusion: Our results suggest that increased activity in the cortical and subcortical regions observed during autonomic challenges may be modulated by fatigue and pain. ANS dysfunction may be a contributing factor to these findings, and further work is required to tease apart the complex relationship among CFS, TMD, and autonomic functions. Knowledge Transfer Statement: Brain activity related to activation of the autonomic nervous system in patients with chronic fatigue syndrome who screened positive for painful temporomandibular disorder was greater than in patients who screened negative; activity was seen in brain regions associated with autonomic functions and pain. These findings suggest that autonomic dysfunction may play a role in the pathophysiology of both conditions, explain some of the apparent comorbidity between them, and offer avenues to help with treatment.
The effectiveness of semantic intervention for word-finding difficulties in college-aged students (16–19 years) with persistent Language Disorder
Authors: Campbell Lisa , Nicoll Hilary , Ebbels Susan H 
Published: August 2019

Background and aims Little evidence exists for the effectiveness of intervention for older adolescents and young adults with language disorders, particularly for those over 16 years. This study involves college-aged students aged 16–19 years with Language Disorder and Word-Finding Difficulties and investigates whether progress in word finding following 1:1 semantic intervention is greater than progress during a baseline period as measured by a standardised test. Methods Twenty-five college-aged students (20 males and 5 females) with Language Disorder and Word-Finding Difficulties (aged 16;4–18;4 years) participated in a single baseline design study comparing progress on the Test of Adolescent and Adult Word Finding during an intervention period with progress during a baseline period of equal length. Intervention was focused on semantics of different words from those in the Test of Adolescent and Adult Word Finding and was delivered 1:1 by the participants’ usual Speech and Language Therapist, 30 minutes per week, for eight weeks. Results The participants made significant progress in raw score on the Test of Adolescent and Adult Word Finding during both the baseline ( d = 1.4) and intervention ( d = 2.5) periods, but progress during the intervention period was significantly greater than during the baseline period ( d = 1.16). Individual data showed reliable change for five participants during the baseline period and for 20 participants during the intervention period. At the start of the study, all participants had standard scores below 85, but after intervention, 10/25 participants scored above 85. Conclusions Four hours of semantic intervention led to significantly greater gains on a standardised test of word finding than during a baseline period of equal length in 16–19 year olds with Language Disorder and Word-Finding Difficulties. The words in the standardised test had not been included in the intervention, indicating generalised gains. Implications This study shows that intervention (at least for Word-Finding Difficulties) can be effective for this older age group of college-aged students with Language Disorder and therefore the effectiveness of Speech and Language Therapy services for this age group in a wider range of areas of language should also be investigated.
Thrombolytic therapy in older acute ischemic stroke patients with gastrointestinal malignancy or recent bleeding
Authors: Inohara Taku , Liang Li , Kosinski Andrzej S , Smith Eric E , Schwamm Lee H , Hernandez Adrian F , Bhatt Deepak L , Fonarow Gregg C , Peterson Eric D , Xian Ying 
Published: August 2019

Background There are limited data on the safety of intravenous recombinant tissue plasminogen activator (rtPA) for treating acute ischemic stroke in patients with gastrointestinal malignancy or recent gastrointestinal bleeding within 21 days of their index stroke. Aims To evaluate clinical outcomes in patients treated with rtPA for acute ischemic stroke who had gastrointestinal malignancy or recent gastrointestinal bleeding Methods We identified patients who were treated with rtPA for acute ischemic stroke between 2/2009 and 12/2015 from the Get With The Guidelines-Stroke linked to Medicare claims data. Gastrointestinal malignancy and recent gastrointestinal bleeding were defined as any gastrointestinal malignancy hospitalisation within one year prior to acute ischemic stroke and gastrointestinal bleeding hospitalisation within 21 days prior to acute ischemic stroke, respectively. Outcomes of interest included in-hospital mortality and bleeding complications. Results Among 40,396 patients aged 65 years or older treated with rtPA for acute ischemic stroke from 1522 sites (mean age [SD] 81.0 [8.1] years; 41.9% women), 136 (0.3%) had gastrointestinal malignancy ( n = 96) or recent gastrointestinal bleeding ( n = 43). Patients with gastrointestinal malignancy or bleeding had more severe stroke than those without (median NIHSS [interquartile range]: 14.0 [8.0–19.0] vs. 11.0 [6.0–18.0]). The rates of in-hospital mortality and life-threatening systemic haemorrhage were not significantly different between those with and without gastrointestinal malignancy or bleeding (mortality: 10.3% vs. 9.0%, adjusted odds ratio [aOR] 1.01, 95%CI 0.58–1.75; bleeding: 2.3% vs. 1.2%, aOR 1.72, 95%CI 0.58–5.11). Conclusions In this observational cohort, we did not find increased risk of in-hospital mortality and bleeding in rtPA-treated patients with gastrointestinal malignancy or recent gastrointestinal bleeding.
Monoclonal immunoglobulin–mediated kidney disease: What is beyond amyloidosis in real practice?
Authors: Zakharova Elena V , Makarova Tatyana A , Stolyarevich Ekaterina S , Vorobyeva Olga A 
Published: August 2019

Background: Monoclonal immunoglobulin–mediated kidney disease with various patterns of damage may occur in patients with B-cell malignancies and non-malignant monoclonal gammopathies, and the latter are actually merged under the umbrella of monoclonal gammopathy of renal significance. Amyloidosis is the most well-known monoclonal immunoglobulin–related kidney damage. We focused on the rarer conditions and aimed to evaluate the non-amyloid spectrum of monoclonal immunoglobulin–mediated patterns of renal damage in real clinical practice. Methods: A single-center non-interventional retrospective study included 45 patients with pathology-proven non-amyloid monoclonal immunoglobulin–mediated kidney disease, followed during 2002–2018. Disease duration, proteinuria, serum creatinine, need for dialysis at the time of kidney biopsy, clinical diagnosis, and kidney pathology findings were analyzed. Results: No significant differences in the median age, disease duration at the time of biopsy, or main clinical presentation of kidney disease were found between patients with monoclonal gammopathy of renal significance and patients with B-cell malignancies. Pathology patterns like proliferative glomerulonephritis with monoclonal immunoglobulin deposits, membranous nephropathy, C3 glomerulopathy, cryoglobulinemic glomerulonephritis, and combinations of light chain proximal tubulopathy with monoclonal immunoglobulin deposition disease, and of C3 glomerulopathy with light chain proximal tubulopathy were found in monoclonal gammopathy of renal significance setting only. In contrast, light chain proximal tubulopathy alone, anti-glomerular basement glomerulonephritis, and combinations of cast nephropathy with light chain proximal tubulopathy, and cast nephropathy with monoclonal immunoglobulin deposition disease were associated with multiple myeloma only. Monoclonal immunoglobulin deposition disease, intracapillary monoclonal immunoglobulin M deposits, and cast nephropathy alone were seen in both settings. Conclusion: The presence of monoclonal gammopathy in patients with proteinuria and/or impaired kidney function demands kidney biopsy. Neither duration of kidney disease nor its clinical presentation allows differentiating malignant and non-malignant causes of monoclonal immunoglobulin–mediated renal damage. Several pathology patterns, even cast nephropathy, can be found both in cases of monoclonal gammopathy of renal significance and in cases of B-cell malignancies. Dual patterns of damage, including combinations of organized and non-organized deposits, or organized deposits with monoclonal immunoglobulin–induced damage without monoclonal immunoglobulin deposition, constitute up to 9%, mostly in multiple myeloma cases.
Long-term outcome of patients with relapsed/refractory B-cell non-Hodgkin lymphoma treated with blinatumomab
Authors: Dufner Vera , Sayehli Cyrus M. , Chatterjee Manik , Hummel Horst D. , Gelbrich Götz , Bargou Ralf C. , Goebeler Maria-Elisabeth 
Published: August 2019

Abstract
Blinatumomab, the first-in-class CD3/CD19 bispecific T-cell engager antibody construct, has recently been approved for treating patients with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia. However, the clinical proof of concept of blinatumomab efficacy was initially demonstrated in patients with R/R B-cell non-Hodgkin lymphoma (B-NHL) in the MT103-104 phase 1 dose-escalation and expansion trial (NCT00274742), which defined 60 µg/m2 per day as the maximum tolerated dose (MTD). The clinically most relevant adverse effects were neurologic symptoms and cytokine release syndrome. Currently, there are no data on long-term outcomes and toxicity for B-NHL patients receiving blinatumomab treatment, so we performed a single-center, long-term follow-up analysis of 38 patients who participated in the MT103-104 phase 1 trial. We found no evidence for long-term toxicities, especially no blinatumomab-induced neurocognitive impairments. For the entire study population, the median overall survival (OS) was 4.6 years. Remarkably, patients who had received ≥60 µg/m2 per day and responded to blinatumomab achieved a median OS of 7.7 years. Of note, 6 of the surviving patients treated at the MTD have been treatment-free for more than 7 years. In contrast, patients who were treated at dose levels below the MTD had a median OS of only 1.1 years. These results indicate that 60 µg/m2 per day seems to represent the targeted dose level of blinatumomab required for durable remission in R/R B-NHL. Here, we provide the first clinical evidence that blinatumomab lacks long-term toxicity and has the potential to induce sustained remissions in patients with R/R B-NHL.
Subcutaneous C1 inhibitor for prevention of attacks of hereditary angioedema: additional outcomes and subgroup analysis of a placebo-controlled randomized study
Authors: Li H. Henry , Zuraw Bruce , Longhurst Hilary J. , Cicardi Marco , Bork Konrad , Baker James , Lumry William , Bernstein Jonathan , Manning Michael , Levy Donald , Riedl Marc A. , Feuersenger Henrike , Prusty Subhransu , Pragst Ingo , Machnig Thomas , Craig Timothy ,   for the COMPACT Investigators
Published: August 2019

Abstract
Background
Hereditary angioedema (HAE) is a debilitating disorder resulting from C1-esterase inhibitor (C1-INH) deficiency. In the COMPACT phase 3 study the prophylactic use of a subcutaneous C1 inhibitor (C1-INH [SC], HAEGARDA®, CSL Behring) twice weekly significantly reduced the frequency of acute edema attacks. Analysis of treatment effects by subgroups, onset of effect, and other exploratory analysis have not been reported.

Methods
This is a post hoc exploratory analysis on data from the randomized, placebo-controlled COMPACT study. 90 patients with C1-INH-HAE were randomized to 1 of 4 treatment sequences: C1-INH (SC) 40 or 60 IU/kg of body weight twice weekly for 16 weeks, preceded or followed by a placebo period. The pre-specified primary efficacy endpoint was the time-normalized number of HAE attacks, and pre-specified secondary efficacy endpoints were the percentage of patients with a certain treatment response (≥ 50% reduction on C1-INH (SC) versus placebo in the time-normalized number of attacks) and the time-normalized number of use of rescue medication. Pre-specified exploratory endpoints included severity of attacks, alone and combined with rescue medication use. Post hoc analyses included exploration of onset of effect and clinical assessment of patients with < 50% of response.

Results
Subgroup findings by various patient characteristics showed a consistent preventive effect of C1-INH (SC). In a post hoc analysis of attacks, the onset of the preventive effect within the first 2 weeks after treatment initiation in COMPACT showed that 10/43 patients (23%) experienced attacks of any severity with 60 IU/kg versus 34/42 patients (81%) with placebo. The need for rescue medication was tenfold lower with 60 IU/kg (35 treated attacks) versus placebo (358 treated attacks). A qualitative analysis of the 4 patients treated with 60 IU/kg and with < 50% reduction of attacks demonstrated a reduction in severity of attacks, rescue medication use, and symptom days which was considered a clinically meaningful treatment effect.

Conclusions
C1-INH (SC) prophylaxis demonstrated a preventive treatment effect with evidence of benefit within 2 weeks. A consistent treatment effect at recommended C1-INH (SC) dosing was evident in all subgroups of patients with type I/II HAE and by various measures of disease and treatment burden.
Trial registration EU Clinical Trials Register, 2013-000916-10, Registered 10 December 2013, https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-000916-10; ClinicalTrials.gov Register, NCT01912456, Registered 31 July 2013, https://clinicaltrials.gov/ct2/show/NCT01912456.
Phase II Study of Avelumab in Patients With Mismatch Repair Deficient and Mismatch Repair Proficient Recurrent/Persistent Endometrial Cancer
Authors: Konstantinopoulos Panagiotis A. , Luo Weixiu , Liu Joyce F. , Gulhan Doga C. , Krasner Carolyn , Ishizuka Jeffrey J. , Gockley Allison A. , Buss Mary , Growdon Whitfield B. , Crowe Heather , Campos Susana , Lindeman Neal I. , Hill Sarah , Stover Elizabeth , Schumer Susan , Wright Alexi A. , Curtis Jennifer , Quinn Roxanne , Whalen Christin , Gray Kathryn P. , Penson Richard T. , Cannistra Stephen A. , Fleming Gini F. , Matulonis Ursula A. 
Published: August 2019

PURPOSE Despite the tissue-agnostic approval of pembrolizumab in mismatch repair deficient (MMRD) solid tumors, important unanswered questions remain about the role of immune checkpoint blockade in mismatch repair–proficient (MMRP) and –deficient endometrial cancer (EC). METHODS This phase II study evaluated the PD-L1 inhibitor avelumab in two cohorts of patients with EC: (1) MMRD/ POLE (polymerase ε) cohort, as defined by immunohistochemical (IHC) loss of expression of one or more mismatch repair (MMR) proteins and/or documented mutation in the exonuclease domain of POLE; and (2) MMRP cohort with normal IHC expression of all MMR proteins. Coprimary end points were objective response (OR) and progression-free survival at 6 months (PFS6). Avelumab 10 mg/kg intravenously was administered every 2 weeks until progression or unacceptable toxicity. RESULTS Thirty-three patients were enrolled. No patient with POLE-mutated tumor was enrolled in the MMRD cohort, and all MMRP tumors were not POLE-mutated. The MMRP cohort was closed at the first stage because of futility: Only one of 16 patients exhibited both OR and PFS6 responses. The MMRD cohort met the predefined primary end point of four ORs after accrual of only 17 patients; of 15 patients who initiated avelumab, four exhibited OR (one complete response, three partial responses; OR rate, 26.7%; 95% CI, 7.8% to 55.1%) and six (including all four ORs) PFS6 responses (PFS6, 40.0%; 95% CI, 16.3% to 66.7%), four of which are ongoing as of data cutoff date. Responses were observed in the absence of PD-L1 expression. IHC captured all cases of MMRD subsequently determined by polymerase chain reaction or genomically via targeted sequencing. CONCLUSION Avelumab exhibited promising activity in MMRD EC regardless of PD-L1 status. IHC for MMR assessment is a useful tool for patient selection. The activity of avelumab in MMRP/non- POLE–mutated ECs was low.