bluuebunny/crossref_metadata_2025_split huggingface dataset:
Marijuana use and its influence on sperm morphology and motility: identified risk for fertility among Jamaican men
Authors: Carroll K. , Pottinger A. M. , Wynter S. , DaCosta V. 
Published: July 2019

AbstractBackgroundThe growing international movement legislating medical marijuana has brought renewed interest to the role of marijuana smoking on fertility potential. Although studies have identified that sperm quality can be compromised by marijuana use, little focus has been placed specifically on those trying to conceive. In this study, we aimed to clarify the impact of marijuana use in semen quality in men being investigated for assisted reproduction.Materials and methodsWe conducted a cross‐sectional study at a university‐based facility in Jamaica. Routine semen analyses were performed on 229 men ages 23–72 years who were new clients. Logistic regression analyses were performed in order to independently predict quantifiable measures of the impact of marijuana use. The main outcome measures were sperm motility, total motile spermatozoa and morphology.ResultsOverall, 47% of the participants reported marijuana use with 21% of these men reporting recent use. Regression analyses showed that recent use and users of large quantities of marijuana were 2.6 times (aOR = 2.6; 95% CI, 1.0–6.8, p = 0.044) and 4.3 times (aOR = 4.3; 95% CI, 1.1–15.9, p = 0.030) at greater risk of being diagnosed with abnormal motility (asthenozoospermia). Additionally, moderate quantity users were 3.4 times (aOR = 3.4; 95% CI, 1.5–7.9, p = 0.004) more likely to be diagnosed with abnormal morphology (teratozoospermia).Discussion and conclusionRecent use of marijuana as well as moderate to large quantities had an impact on sperm motility and morphology in men being investigated for infertility. We recommend therefore that men undergoing fertility investigations be routinely asked about their recreational use of marijuana and in particular recent and heavy users counselled to stop.
Efficacy and tolerability of sildenafil/l‐arginine combination relative to sildenafil alone in patients with organic erectile dysfunction
Authors: El‐Wakeel L. M. , Fouad F. A. , Saleem M. D. , Saber‐Khalaf M. 
Published: July 2019

AbstractBackgroundErectile dysfunction is defined as inability to achieve or maintain penile erection sufficient for sexual satisfaction. It is a serious problem that increases by age. The physiology of penile erection depends mainly on nitric oxide release.ObjectivesCompare the efficacy and safety of oral sildenafil 50 mg alone or in combination with l‐arginine 3 g/day orally on the treatment of erectile dysfunction.Material and methodsRandomized controlled study with two parallel groups of erectile dysfunction patients; One group received sildenafil 50 mg every other day, while the other group received a combination of sildenafil (every other day)/l‐arginine on a daily base. Efficacy was assessed using International Index of Erectile Function‐5 score at the baseline and after 8 weeks. Side effects were evaluated across the two groups.ResultsThe mean age was 56.3 ± 5 and 56.2 ± 4.4 years in sildenafil and combination groups, respectively. International Index of Erectile Function‐5 score was comparable between the two groups at the baseline (p value 0.44). International Index of Erectile Function‐5 score was improved from 15.3 ± 2.5 at baseline to 19.2 ± 2.3 after treatment, and this was statistically significant with p value <0.0001. The score was slightly better in combination group in which the average International Index of Erectile Function‐5 score was (19.8 ± 2.2) vs. (18.5 ± 2.3) in sildenafil group with p value 0.05. Side effects were more or less the same between the two groups except for gastritis which was more common on combination group.ConclusionAdding l‐arginine to sildenafil demonstrated more efficacy than sildenafil alone for treatment of erectile dysfunction patients.
Intermittent high‐flux albumin dialysis with continuous venovenous hemodialysis for acute‐on‐chronic liver failure and acute kidney injury
Authors: Niewinski Grzegorz , Raszeja‐Wyszomirska Joanna , Hrenczuk Marta , Rozga Agata , Malkowski Piotr , Rozga Jacek 
Published: July 2019

AbstractAcute‐on‐chronic liver failure (ACLF) requiring intensive medical care and associated with acute kidney injury (AKI) has a mortality rate as high as 90% due to the lack of effective therapies. In this study, we assessed the effects of intermittent high‐flux single‐pass albumin dialysis (SPAD) coupled with continuous venovenous hemodialysis (CVVHD) on 28‐day and 90‐day survival and an array of clinical and laboratory parameters in patients with severe ACLF and renal insufficiency. Sixteen patients were studied. The diagnosis of ACLF and AKI was made in accordance with current EASL Clinical Practice Guidelines, including the recommendations of the International Club of Ascites. All patients received SPAD/CVVHD treatments as the blood purification therapy to support liver, kidneys, and other organs. Five patients were transplanted and 11 were not listed for transplantation because of active alcoholism. Data at the initiation of SPAD/CVVHD were compared with early morning data after the termination of the extracorporeal treatment phase. All patients had ACLF and renal insufficiency with 13/16 additionally fulfilling the AKI criteria. A total of 37 SPAD/CVVHD treatments were performed [2.3 ± 1.4]. The baseline MELD‐Na score was 37.6 ± 6.6 and decreased to 33.4 ± 8.7 after SPAD/CVVHD (P < 0.001). In parallel, the CLIF‐C ACLF grade and OF score, estimated at 28‐ and 90‐day mortality, AKI stage, hepatic encephalopathy grade, and liver function tests were lowered (P = 0.001–0.032). The 28‐ and 90‐day survivals were 56.2% overall and 53.8% in AKI. Survival in patients not transplanted (n = 11) was 45.4%. In patients with severe ACLF and AKI, the renal replacement therapy coupled with high‐performance albumin dialysis improved estimated 28‐ and 90‐day survival and several key clinical and laboratory parameters. It is postulated that these results may be further improved with earlier intervention and more SPAD treatments per patient. High‐performance albumin dialysis improves survival and key clinical and laboratory parameters in severe ACLF and AKI.
Increased risk of developing Crohn’s disease or ulcerative colitis in 17 018 patients while under treatment with anti‐TNFα agents, particularly etanercept, for autoimmune diseases other than inflammatory bowel disease
Authors: Korzenik Joshua , Larsen Michael Due , Nielsen Jan , Kjeldsen Jens , Nørgård Bente Mertz 
Published: July 2019

SummaryBackgroundAnti‐TNFα agents have revolutionised management of chronic inflammatory diseases. Paradoxically, these agents might provoke development of de novo autoimmune diseases.AimTo examine whether there is an increased risk of developing Crohn's disease (CD) and ulcerative colitis (UC) while under treatment with anti‐TNFα agents for diseases other than inflammatory bowel disease (IBD)MethodsA nationwide cohort study, based on Danish health registries, of all patients who utilised anti‐TNFα agents for non‐IBD indications. Included were patients, who had diseases for which anti‐TNFα agent is indicated (rheumatoid arthritis, psoriasis/psoriatic arthritis, ankylosing spondylitis, others). The observation period for development of de novo IBD started from 2004. Exposed patients had received at least one dose of anti‐TNFα.ResultsIn total 17 018 individuals with autoimmune diseases were exposed to anti‐TNFα (the vast majority had infliximab, etanercept and adalimumab), and 63 308 individuals were not. Patients treated with etanercept had an increased risk of being diagnosed with CD and UC while under treatment, adjusted hazard ratio 2.0 [95% CI: 1.4‐2.8] and 2.0 [95% CI: 1.5‐2.8], respectively. The corresponding hazards ratios for infliximab were 1.3 [95% CI: 0.8‐2.2] and 1.0 [95% CI:0.6‐1.6], and for adalimumab 1.2 [95% CI: 0.8‐1.8] and 0.6 [95% CI: 0.3‐1.0].ConclusionsPatients treated for autoimmune diseases with anti‐TNFα had an increased risk of being diagnosed with CD or UC while under treatment with etanercept. The nature of this association is uncertain. This finding has relevance to clinical care and insights into common mechanisms of the pathophysiology of these diseases.
Bridging Narratives: Predictors of Jewish American and Arab American Support for a Two‐State Solution to the Israeli–Palestinian Conflict
Authors: Ben Hagai Ella , Zurbriggen Eileen L. 
Published: July 2019

AbstractIn a survey study of Arab and Jewish Americans, we examined which beliefs best predicted support for a two‐state solution. We compared the role of a sense of collective victimhood, dehumanization of the outgroup, a zero‐sum view, and a monolithic narrative on the conflict. In both the Arab American and the Jewish American samples, framing the conflict in terms of a monolithic narrative played the strongest role in predicting rejection of a two‐state solution. On the other hand, when Jewish Americans agreed with the Palestinian narrative, that depicts the Palestinians as indigenous to the land but as dispossessed, they were more likely to support a two‐state solution. Similarly, when Arab Americans agreed with the Israeli narrative, in which Israelis want to live in peace but need to defend themselves, they were more likely to support a two‐state solution. In a second study, we examined if group values and concerns such as commitment to tikkun olam (commitment for justice for other minority groups) and concern with anti‐Semitism mediated between identification as Jewish and acceptance of the Palestinian narrative on the conflict. We found that concern with anti‐Semitism mediated between Jewish identity and rejection of the Palestinian narrative. On the other hand, grounding Jewish identity in values of tikkun olam mediated between Jewish identity and agreement with the Palestinian narrative. This research makes applied contributions by illuminating the key belief associated with support for peace among Arab and Jewish Americans. It also contributes to psychological theory on intergroup reconciliation by operationalizing and measuring the role of acknowledgement of the narrative of the other, group threat, and inclusive victimhood consciousness, in promoting peace.
Superior outcomes (but at higher costs) of non‐operative management with interval appendectomy over immediate surgery in appendicitis with abscess: Results from a large adult population cohort
Authors: Watanabe Ryohei , Otsuji Ayako , Nakamura Yoichi , Higuchi Tadashi , Takahashi Asako , Saito Tomoaki , Enomoto Toshiyuki , Quero Giuseppe , Diana Michele , Dallemagne Bernard , Marescaux Jacques , Saida Yoshihisa , Kusachi Shinya 
Published: July 2019

AbstractIntroductionThe aim of this study was to compare surgical outcomes and hospitalization costs between immediate surgery and non‐operative management followed by interval appendectomy in adults presenting with appendicitis with abscess.MethodsFrom 2003 to 2015, 3316 patients presented with appendicitis, including 101 who presented with appendicular abscess. Between 2003 and 2006, 33 patients with appendicular abscess were managed with emergency operations (emergency group). Non‐operative management followed by interval appendectomy was implemented in 2007 and offered to 68 patients during the study period. Of these patients, 64 patients underwent the procedure (interval group), and 4 patients refused.ResultsNon‐operative management was successful in 76.6% of cases (49/64 patients) in the interval group. Operative time and length of hospital stay were similar between the emergency and interval groups. In the interval group, blood loss, the need for extended resection, and overall postoperative morbidity were significantly lower than in the emergency group (P < 0.01, respectively). Medical costs for surgery in the interval group were lower than in the emergency group ($4512 vs $6888, P = 0.002), but this group's total medical costs were higher ($9591 vs $6888, P < 0.01).ConclusionThe interval strategy is associated with a reduced need for extended resection, lower postoperative morbidity, and a shorter length of hospital stay. However, total medical costs for the interval strategy are higher than those for emergency operations in cases of appendicular abscess in adults.
Dose‐linearity of the pharmacokinetics of an intravenous [14C]midazolam microdose in children
Authors: van Groen Bianca D. , Vaes Wouter H. , Park B. Kevin , Krekels Elke H.J. , van Duijn Esther , Kõrgvee Lenne‐Triin , Maruszak Wioleta , Grynkiewicz Grzegorz , Garner R. Colin , Knibbe Catherijne A.J. , Tibboel Dick , de Wildt Saskia N. , Turner Mark A. 
Published: July 2019

AimsDrug disposition in children may vary from adults due to age‐related variation in drug metabolism. Microdose studies present an innovation to study pharmacokinetics (PK) in paediatrics; however, they should be used only when the PK is dose linear. We aimed to assess dose linearity of a [14C]midazolam microdose, by comparing the PK of an intravenous (IV) microtracer (a microdose given simultaneously with a therapeutic midazolam dose), with the PK of a single isolated microdose.MethodsPreterm to 2‐year‐old infants admitted to the intensive care unit received [14C]midazolam IV as a microtracer or microdose, followed by dense blood sampling up to 36 hours. Plasma concentrations of [14C]midazolam and [14C]1‐hydroxy‐midazolam were determined by accelerator mass spectrometry. Noncompartmental PK analysis was performed and a population PK model was developed.ResultsOf 15 infants (median gestational age 39.4 [range 23.9–41.4] weeks, postnatal age 11.4 [0.6–49.1] weeks), 6 received a microtracer and 9 a microdose of [14C]midazolam (111 Bq kg−1; 37.6 ng kg−1). In a 2‐compartment PK model, bodyweight was the most significant covariate for volume of distribution. There was no statistically significant difference in any PK parameter between the microdose and microtracer, nor in the area under curve ratio [14C]1‐OH‐midazolam/[14C]midazolam, showing the PK of midazolam to be linear within the range of the therapeutic and microdoses.ConclusionOur data support the dose linearity of the PK of an IV [14C]midazolam microdose in children. Hence, a [14C]midazolam microdosing approach may be used as an alternative to a therapeutic dose of midazolam to study developmental changes in hepatic CYP3A activity in young children.
Nonlinear protein binding of phenytoin in clinical practice: Development and validation of a mechanistic prediction model
Authors: ter Heine Rob , Kane Sean P. , Huitema Alwin D.R. , Krasowski Matthew D. , van Maarseveen Erik M. 
Published: July 2019

AimsTo individualize treatment, phenytoin doses are adjusted based on free concentrations, either measured or calculated from total concentrations. As a mechanistic protein binding model may more accurately reflect the protein binding of phenytoin than the empirical Winter–Tozer equation that is routinely used for calculation of free concentrations, we aimed to develop and validate a mechanistic phenytoin protein binding model.MethodsData were extracted from routine clinical practice. A mechanistic drug protein binding model was developed using nonlinear mixed effects modelling in a development dataset. The predictive performance of the mechanistic model was then compared with the performance of the Winter–Tozer equation in 5 external datasets.ResultsWe found that in the clinically relevant concentration range, phenytoin protein binding is not only affected by serum albumin concentrations and presence of severe renal dysfunction, but is also concentration dependent. Furthermore, the developed mechanistic model outperformed the Winter–Tozer equation in 4 out of 5 datasets in predicting free concentrations in various populations.ConclusionsClinicians should be aware that the free fraction changes when phenytoin exposure changes. A mechanistic binding model may facilitate prediction of free phenytoin concentrations from total concentrations, for example for dose individualization in the clinic.
Differentiated need support by teachers: Student‐specific provision of autonomy and structure and relations with student motivation
Authors: Domen Janneke , Hornstra Lisette , Weijers Desirée , van der Veen Ineke , Peetsma Thea 
Published: July 2019

BackgroundAccording to self‐determination theory, teachers can support their students’ engagement in learning by providing autonomy support and structure. Within classes, however, there appears to be great diversity in the extent to which students experience autonomy and structure.AimsThis study aimed to investigate the degree to which teachers’ perceptions of student‐specific autonomy support and structure differ between students in their class and whether differentiated need support predicts students’ motivation.SampleTwenty‐four elementary school teachers and their students (n = 506) participated in this study.MethodTeachers completed a short questionnaire assessing their perceptions of autonomy support and structure for each student. Students completed two questionnaires assessing perceptions of need support and their motivation. Multilevel analyses were conducted.ResultsThe results showed that the within‐classroom variation in both teacher perceptions and student perceptions of need support was considerably larger than the between‐classroom variation. Teacher perceptions of student‐specific autonomy support were positively associated with students’ autonomous motivation and negatively with students’ controlled motivation. However, teacher perceptions of student‐specific structure were positively associated with students’ controlled motivation.ConclusionsThese findings suggest that teachers differentiate in need support. The positive association between teacher perceptions of structure and students’ controlled motivation might suggest that teachers may offer structure in controlling rather than autonomy‐supportive ways. Furthermore, the relations between need support and students’ motivation differed between the class‐level and the within‐class (student) level highlighting the need for disentangling the effects of need‐supportive teaching at different levels and adopting a multilevel approach.
CXCR4 mutation subtypes impact response and survival outcomes in patients with Waldenström macroglobulinaemia treated with ibrutinib
Authors: Castillo Jorge J. , Xu Lian , Gustine Joshua N. , Keezer Andrew , Meid Kirsten , Dubeau Toni E. , Liu Xia , Demos Maria G. , Kofides Amanda , Tsakmaklis Nicholas , Chen Jiaji G. , Munshi Manit , Guerrera Maria L. , Chan Gloria G. , Patterson Christopher J. , Yang Guang , Hunter Zachary R. , Treon Steven P. 
Published: July 2019

SummaryIbrutinib is associated with response rate of 90% and median progression‐free survival (PFS) in excess of 5 years in Waldenström macroglobulinaemia (WM) patients. CXCR4 mutations are detected in 30–40% of patients with WM and associate with lower rates of response and shorter PFS to ibrutinib therapy. Both frameshift (CXCR4FS) and nonsense (CXCR4NS) CXCR4 mutations have been described. The impact of these mutations on outcomes to ibrutinib have not been evaluated in WM patients. We studied consecutive patients with a diagnosis of WM, on ibrutinib therapy, for the presence of CXCR4FS and CXCR4NS mutations and evaluated the differences in response and PFS between groups. Of 180 patients, 68 patients (38%) had CXCR4 mutations; 49 (27%) had CXCR4NS and 19 (11%) had CXCR4FS mutations. In multivariate models, patients with CXCR4NS had lower odds of major response (Odds ratio 0·25, 95% confidence interval [CI] 0·12–0·53; P < 0·001) and worse PFS (Hazard ratio 4·02, 95% CI 1·95–8·26; P < 0·001) than patients without CXCR4 mutations. CXCR4FS was not associated with worse major response or PFS rates than patients without CXCR4 mutations. Our results suggest different response and PFS rates to ibrutinib for WM patients with CXCR4NS and CXCR4FS, and advocate in favour of CXCR4 mutational testing as well as CXCR4‐directed therapy.
The global prevalence of erectile dysfunction: a review
Authors: Kessler Anna , Sollie Sam , Challacombe Ben , Briggs Karen , Van Hemelrijck Mieke 
Published: July 2019

ObjectiveTo evaluate the global prevalence of erectile dysfunction (ED); as well as its association with physiological and pathological ageing by examining the relationship between ED and cardiovascular disease (CVD), benign prostatic hyperplasia (BPH), and dementia. We also aimed to characterise discrepancies caused by the use of different ED screening tools.MethodsThe Excerpta Medica dataBASE (EMBASE) and Medical Literature Analysis and Retrieval System Online (MEDLINE) were searched to find population‐based studies investigating the prevalence of ED and the association between ED and CVD, BPH, and dementia in the general population.ResultsThe global prevalence of ED was 3–76.5%. ED was associated with increasing age. Use of the International Index of Erectile Function (IIEF) and Massachusetts Male Aging Study (MMAS)‐derived questionnaire identified a high prevalence of ED in young men. ED was positively associated with CVD. Men with ED have an increased risk of all‐cause mortality odds ratio (OR) 1.26 (95% confidence interval [CI] 1.01–1.57), as well as CVD mortality OR 1.43 (95% CI 1.00–2.05). Men with ED are 1.33–6.24‐times more likely to have BPH then men without ED, and 1.68‐times more likely to develop dementia than men without ED.ConclusionED screening tools in population‐based studies are a major source of discrepancy. Non‐validated questionnaires may be less sensitive than the IIEF and MMAS‐derived questionnaire. ED constitutes a large burden on society given its high prevalence and impact on quality of life, and is also a risk factor for CVD, dementia, and all‐cause mortality.
Model‐Informed Dosing of Venetoclax in Healthy Subjects: An Exposure−Response Analysis
Authors: Dave Nimita , Gopalakrishnan Sathej , Mensing Sven , Salem Ahmed Hamed 
Published: July 2019

Venetoclax is an approved drug for the treatment of some hematological malignancies. Venetoclax can cause reduction in B‐lymphocyte counts as an on‐target effect. The purpose of this analysis is to quantify the relationship between venetoclax exposure and B‐lymphocyte levels to inform dosing of venetoclax in healthy subjects. Data were pooled from 10 studies in healthy subjects with venetoclax doses ranging from 10 mg to 400 mg and food ranging from fasting to high‐fat meals. Venetoclax pharmacokinetics (PK) was characterized in 203 subjects using a population approach, as implemented in NONMEM version 7.3 (Icon Development Solutions, Ellicott City, MD, USA). A semimechanistic pharmacodynamic (PD) model with a linear drug effect was fit to the B‐lymphocyte data to determine the exposure‐response relationship. The population PK and PD model described the observed data adequately. The 200 and 400 mg doses were shown to reduce the B‐lymphocyte levels by 24% (15–35%) and 38% (25–54%), respectively. B‐lymphocytes recovered to normal levels within an average of 48 (21–64) days and 59 (30–66) days, respectively, with 200 and 400 mg doses. Venetoclax can be safely administered in healthy subjects. The PK‐PD model characterized the relationship between venetoclax exposure and reduction in B‐lymphocytes and will help design future venetoclax studies in healthy subjects.