bluuebunny/crossref_metadata_2025_split huggingface dataset:
Large differences in neonatal drug use between NICUs are common practice: time for consensus?
Authors: Flint Robert B. , van Beek Floor , Andriessen Peter , Zimmermann Luc J. , Liem Kian D. , Reiss Irwin K.M. , de Groot Ronald , Tibboel Dick , Burger David M. , Simons Sinno H.P. ,   DINO Research group
Published: April 2018

AbstractAimsEvidence for drug use in newborns is sparse, which may cause large differences in drug prescriptions. We aimed to investigate the differences between neonatal intensive care units (NICUs) in the Netherlands in currently prescribed drugs.MethodsThis multicentre study included neonates admitted during 12 months to four different NICUs. Drugs were classified in accordance with the Anatomical Therapeutic Chemical (ATC) classification system and assessed for on/off‐label status in relation to neonatal age. The treatment protocols for four common indications for drug use were compared: pain, intubation, convulsions and hypotension.ResultsA total of 1491 neonates (GA range 23+6–42+2 weeks) were included with a total of 32 182 patient days, 181 different drugs and 10 895 prescriptions of which 23% was off‐label in relation to neonatal age. Overall, anti‐infective drugs were most frequently used with a total of 3161 prescriptions, of which 4% was off‐label in relation to neonatal age. Nervous system drugs included 2500 prescriptions of which 31% was off‐label in relation to neonatal age. Nervous system drugs, blood and blood forming organs, and cardiovascular drugs showed the largest differences between NICUs with ranges of 919–2278, 554–1465, and 238–952 total prescriptions per 1000 patients per ATC class, respectively.ConclusionsWe showed that drug use varies widely in neonatal clinical practice. The drug classes with the highest proportion of off‐label drugs in relation to neonatal age showed the largest differences between NICUs, i.e. cardiovascular and nervous system drugs. Drug research in neonates should receive high priority to guarantee safe and appropriate medicines and optimal treatment.
Pharmacokinetics of efavirenz in patients on antituberculosis treatment in high human immunodeficiency virus and tuberculosis burden countries: A systematic review
Authors: Atwine Daniel , Bonnet Maryline , Taburet Anne‐Marie 
Published: April 2018

AimsEfavirenz (EFV) and rifampicin–isoniazid (RH) are cornerstone drugs in human immunodeficiency virus (HIV)–tuberculosis (TB) coinfection treatment but with complex drug interactions, efficacy and safety challenges. We reviewed recent data on EFV and RH interaction in TB/HIV high‐burden countries.MethodsWe conducted a systematic review of studies conducted in the high TB/HIV‐burden countries between 1990 and 2016 on EFV pharmacokinetics during RH coadministration in coinfected patients. Two reviewers conducted article screening and data collection.ResultsOf 119 records retrieved, 22 were included (two conducted in children), reporting either EFV mid‐dose or pre‐dose concentrations. In 19 studies, median or mean concentrations of RH range between 1000 and 4000 ng ml–1, the so‐called therapeutic range. The proportion of patients with subtherapeutic concentration of RH ranged between 3.1 and 72.2%, in 12 studies including one conducted in children. The proportion of patients with supratherapeutic concentration ranged from 19.6 to 48.0% in six adult studies and one child study. Five of eight studies reported virological suppression >80%. The association between any grade hepatic and central nervous system adverse effects with EFV/RH interaction was demonstrated in two and three studies, respectively. The frequency of the CYP2B6 516G > T polymorphism ranged from 10 to 28% and was associated with higher plasma EFV concentrations, irrespective of ethnicity.ConclusionsAnti‐TB drug coadministration minimally affect the EFV exposure, efficacy and safety among TB‐HIV coinfected African and Asian patients. This supports the current 600 mg EFV dosing when coadministered with anti‐TB drugs.
Proximal hypospadias treated with a transverse preputial island tube: long‐term functional, sexual, and cosmetic outcomes
Authors: Rynja Sybren P. , de Jong Tom P.V.M. , Bosch J.L.H. Ruud , de Kort Laetitia M.O. 
Published: April 2018

ObjectiveTo study long‐term urinary and sexual function, and cosmetic outcomes in adult patients who underwent single‐stage transverse preputial island tube (TPIT) for proximal hypospadias repair in childhood. Long‐term data on outcomes of patients with proximal hypospadias with severe coexisting curvature and insufficient urethral plate are scarce, but are necessary to decide which repair technique is most beneficial.Patients, Subjects and MethodsPatients with proximal hypospadias operated with TPIT (TPIT Group) were compared to patients with distal hypospadias repair (Distal Group) and to a control group of male medical students (Control Group). Participants completed the International Prostate Symptom Score, the International Index of Erectile Function (IIEF‐15), additional non‐validated questions, and performed uroflowmetry. Cosmesis was assessed in the patients with hypospadias using the Pediatric Penile Perception Score (PPPS); stretched penile length was also measured.ResultsOf the 121 eligible patients with hypospadias, 54 with either TPIT or distal hypospadias repairs participated. The TPIT Group comprised 12 patients (median age of 20.0 years) and the Distal Group comprised 42 patients (median age of 19.6 years). The complication rates were similar, at 8 of the 12 patients in the TPIT Group vs 26/42 (62%) in the Distal Group (P = 0.76). Urinary outcomes were similar in the TPIT, Distal, and the Control (comprised of 148 medical students with a median age of 21.0 years) groups. The TPIT Group had a lower maximum urinary flow rate compared to the Control Group, at 24.1 vs 28.6 mL/s (P < 0.05). IIEF‐15 scores were similar in the TPIT, Distal and Control groups, except for ‘Orgasmic Function’ (7.5 vs 10.0 vs 10.0, respectively; P < 0.01). Although the TPIT Group had a smaller penile length compared to the Distal Group (10.1 vs 12.9 cm, P < 0.01), PPPS outcomes were similar.ConclusionIn these TPIT patients, long‐term urinary, sexual and cosmetic outcomes were similar to those in patients with distal hypospadias repairs and controls.
Abdominal Aortic Aneurysms Presenting as Renal Colic
Authors: ECKFORD S. D. , GILLATT D. A. 
Published: April 2018

SummaryIn a 6‐year period, 9 patients were referred by their General Practitioners to the urology unit with a clinical diagnosis of renal colic but were subsequently found to have leaking abdominal aortic aneurysms (AAA). In all cases of loin pain, especially in the elderly patient, the possibility of a leaking abdominal aneurysm must be considered. If no intrinsic urological cause for the pain is found or patterns suggestive of ureteric obstruction are seen on urography, ultrasound examination of the aorta‐iliac vessels should be performed. Magnetic resonance imaging (MRI) and computed tomography (CT) scans may be useful adjuncts to this investigation.
Psychological Aspects of Female Urinary Incontinence in General Practice
Authors: LAGRO-JANSSEN A. L. M. , DEBRUYNE F. M. J. , VAN WEEL C. 
Published: April 2018

SummaryThe aim of this study was to determine whether urge incontinence was associated with a higher prevalence of psychological symptoms than other types of incontinence. The psychological aspects of 110 women presenting with urinary incontinence in general practice were assessed by means of standardised questionnaires and medical history‐taking. The results showed no difference in psychological characteristics between patients with urge incontinence and those with other types of incontinence. These findings were contrary to the conclusions of almost all other studies based on populations selected for specialist care.It was concluded that in general practice the psychological approach to urinary incontinence depends more on the individual needs of the patient than specifically on the type of incontinence.
Does Residual Urine Predispose to Urinary Tract Infection?
Authors: HAMPSON S. J. , NOBLE J. G. , RICKARDS D. , MILROY E. J. G. 
Published: April 2018

SummaryThe relationship between the presence of post‐micturition residual urine and urinary tract infection is unclear. We have performed a retrospective analysis of 342 studies on bladder emptying and compared the incidence of bacterial infection and pyuria in patients with residual urinary volumes of more or less than 100 ml. In patients with a residual volume > 100 ml 49/219 studies showed evidence of pyuria and 28/198 studies of patients whose residual urine was less than 100 ml showed evidence of infection. In cases where the residuals were > 100 m133/123 had evidence of pyuria and 19/109 infection. There was no significant increase in the rate of infection in patients with large residual urinary volumes, suggesting that there is no definite correlation between post‐micturition residues and urinary tract infection.
High Resolution Ultrasonography in the Diagnosis of Simple Intratesticular Cysts
Authors: HÖBARTH K. , KRATZIK CH. 
Published: April 2018

SummarySimple intratesticular cysts are a rare condition. High resolution sonography permits unequivocal sonographic differentiation between intratesticular cysts and neoplastic lesions with a cystic appearance, so that conservative treatment seems justified. Seventeen patients with sonographically diagnosed intraparenchymal testicular cysts were followed up for an average of 29 months. No increase in size or change in echo pattern was found and surgical intervention was therefore not indicated.
Prevalence and measurement of anterior loop of the mandibular canal using CBCT: A cross sectional study
Authors: J Pradeep Christopher , Marimuthu Thenaruvi , C Krithika , Devadoss Poorna , Kumar Santhosh M. 
Published: April 2018

AbstractBackgroundAnterior loop of the mental nerve is a very important anatomic landmark in implant placement and anterior mandibular osteotomies.PurposeTwo‐dimensional imaging techniques are not competent enough to locate and measure the mental nerve loop in majority of the cases. Any injury to this loop results in pain/paresthesia/numbness in the region supplied by the mental nerve. The aim of this study is to analyze the prevalence and measure the length of the loop using cone beam computerized tomography (CBCT) and calculate the average length and prevalence so that a safe margin can be given while placing the implants or the osteotomy cuts in the premolar region.Materials and MethodsA cross‐sectional study was done using CBCT images of 85 patients taken for impaction surgery. The length of the loop was measured in mm using standardized lines drawn along specific anatomic landmarks.ResultsIn our study 11.76% of patients had anterior loop in their mental nerve. Mean length of the mental nerve loop was calculated and found to be 2.79 mm.ConclusionA margin of 4 mm anterior to the mental foramen should be safe to avoid any damage to the mental nerve loop bundle in majority of the cases where the loop is present.
Altered lactate metabolism in Huntington's disease is dependent on GLUT3 expression
Authors: Solís‐Maldonado Macarena , Miró María Paz , Acuña Aníbal I. , Covarrubias‐Pinto Adriana , Loaiza Anitsi , Mayorga Gonzalo , Beltrán Felipe A. , Cepeda Carlos , Levine Michael S. , Concha Ilona I. , Bátiz Luis Federico , Carrasco Mónica A. , Castro Maite A. 
Published: April 2018

SummaryAimsHuntington's disease (HD) is a neurodegenerative disorder characterized by progressive abnormalities in cognitive function, mental state, and motor control. HD is characterized by a failure in brain energy metabolism. It has been proposed that monocarboxylates, such as lactate, support brain activity. During neuronal synaptic activity, ascorbic acid released from glial cells stimulates lactate and inhibits glucose transport. The aim of this study was to evaluate the expression and function of monocarboxylate transporters (MCTs) in two HD models.MethodsUsing immunofluorescence, qPCR, and Western blot analyses, we explored mRNA and protein levels of MCTs in the striatum of R6/2 animals and HdhQ7/111 cells. We also evaluated MCT function in HdhQ7/111 cells using radioactive tracers and the fluorescent lactate sensor Laconic.ResultsWe found no significant differences in the mRNA or protein levels of neuronal MCTs. Functional analyses revealed that neuronal MCT2 had a high catalytic efficiency in HD cells. Ascorbic acid did not stimulate lactate uptake in HD cells. Ascorbic acid was also unable to inhibit glucose transport in HD cells because they exhibit decreased expression of the neuronal glucose transporter GLUT3.ConclusionWe demonstrate that stimulation of lactate uptake by ascorbic acid is a consequence of inhibiting glucose transport. Supporting this, lactate transport stimulation by ascorbic acid in HD cells was completely restored by overexpressing GLUT3. Therefore, alterations in GLUT3 expression could be responsible for inefficient use of lactate in HD neurons, contributing to the metabolic failure observed in HD.
Disrupted striatal neuron inputs and outputs in Huntington's disease
Authors: Reiner Anton , Deng Yun‐Ping 
Published: April 2018

SummaryHuntington's disease (HD) is a hereditary progressive neurodegenerative disorder caused by a CAG repeat expansion in the gene coding for the protein huntingtin, resulting in a pathogenic expansion of the polyglutamine tract in the N‐terminus of this protein. The HD pathology resulting from the mutation is most prominent in the striatal part of the basal ganglia, and progressive differential dysfunction and loss of striatal projection neurons and interneurons account for the progression of motor deficits seen in this disease. The present review summarizes current understanding regarding the progression in striatal neuron dysfunction and loss, based on studies both in human HD victims and in genetic mouse models of HD. We review evidence on early loss of inputs to striatum from cortex and thalamus, which may be the basis of the mild premanifest bradykinesia in HD, as well as on the subsequent loss of indirect pathway striatal projection neurons and their outputs to the external pallidal segment, which appears to be the basis of the chorea seen in early symptomatic HD. Later loss of direct pathway striatal projection neurons and their output to the internal pallidal segment account for the severe akinesia seen late in HD. Loss of parvalbuminergic striatal interneurons may contribute to the late dystonia and rigidity.
Forty‐nine cases of acute lymphoblastic leukaemia/lymphoma in pleural and pericardial effusions: A cytological‐histological correlation
Authors: Li J. , Zhang W. , Wang W. , Jiang Y. , Zhao S. , Liu W. , Li G. , Liu N. , Li Q. , Su X. 
Published: April 2018

IntroductionAcute lymphoblastic leukaemia/lymphoma (ALL/LBL) is an aggressive entity of precursor lymphoid neoplasm and may cause malignant serous effusion (SE). The current study aimed to analyse the characteristics of SE cytology of ALL/LBL including cytomorphology, immunophenotyping, clonality and evaluate the effectiveness of SE cytology as a diagnostic method for ALL/LBL.MethodsSE specimens with final diagnosis of ALL/LBL from 2006 to 2016 were reviewed for clinical data, cytomorphological features and ancillary studies. Cytodiagnoses were compared with histodiagnoses, and the discordant cases were analysed.ResultsA total of 49 specimens including 47 pleural fluids and 2 pericardial fluids from 49 patients were evaluated. Cytomorphology revealed lymphoblasts varied from small size with scant cytoplasm, condensed nuclear chromatin and indistinct nucleoli to large size with dispersed nuclear chromatin and multiple variably prominent nucleoli. Nuclear clefts and hand mirror‐shaped blasts were demonstrated. The positive rates of CD99 and terminal deoxynucleotidyl transferase were 90.9% and 81.6%, respectively. Both monoclonal immunoglobulin (Ig)H and T‐cell receptor‐γ gene rearrangements were demonstrated in 1 of 3 cases. Monoclonal T‐cell receptor‐γ gene rearrangement was found in 10 of 11 cases. Monoclonal IgH and/or Ig? gene rearrangements were revealed in 2 of 3 cases. Cytodiagnoses included 4 ALL/LBL, 3 B‐ALL/LBL and 42 T‐ALL/LBL. Histodiagnoses were available in 24 cases including 2 ALL/LBL, 2 B‐ALL/LBL and 20 T‐ALL/LBL. The concordance rates of cytological‐histological diagnoses were 66.7%, 0% and 95.2% in the three categories, respectively. There were 3 cases with discrepancies of cell lineages.ConclusionsSE cytological evaluation is a reliable and effective method for the diagnosis of ALL/LBL.
Differentiated cervical intraepithelial neoplasia‐associated invasive cervical squamous cell carcinoma as a source of major cytopathological and surgical pathological discrepancy in Papanicolaou smear screening tests
Authors: Mai K. T. 
Published: April 2018

IntroductionDifferentiated cervical intraepithelial neoplasia (dCIN) analogous to differentiated squamous intraepithelial neoplasia of the vulva is characterised by the proliferation of atypical cells limited to the basal/parabasal layers. Exfoliative cytology of dCIN has not been investigated.Methods and ResultsA 46‐year‐old woman, with a history of normal Papanicolaou (Pap) smear up to 2 years prior to the occurrence of postcoital vaginal bleeding had two consecutive Pap smears, which only revealed atypical squamous cells of unknown significance (ASCUS). The subsequent cervical biopsy revealed dCIN. The cone biopsy showed the invasive cervical squamous cell carcinoma (ICC) that developed from the overlying dCIN. Review of 32 consecutive cases of ICC revealed a second case of dCIN‐associated ICC (Group 1) preceded by ASCUS suspicious for high‐grade neoplastic cells. In both cases, the ASCUS were keratinised atypical cells without koilocytosis. In addition, there were another seven cases showing focal dCIN associated with extensive usual CIN (Group 2). In comparison with the remaining 24 cases with usual CIN (Group 3), Group 2 lesions occurred in younger patients (mean ages of 36 ± 3 vs 47 ± 9 years) and were associated with shorter intervals after the last normal Pap smears. Pap smears in Group 2 occasionally consisted only of ASCUS cells.ConclusionsdCIN may occur in the cervix and accounts for a short interval of normal Pap smears and false negative or low‐grade Pap smears in ICC.
Rehydration before wet fixation in conventional body fluid cytology – An 18‐year experience
Authors: Hsu C.‐Y. , Chen T.‐C. , Chang C.‐B. , Liu Y.‐C. , Lin T.‐R. 
Published: April 2018

PurposeIn conventional cytology, preparation of a specimen by wet fixation for Papanicolaou stain is potentially subject to dry effect or cell loss which may make cytologic interpretation difficult or even impossible. We have been routinely making an additional smear for rehydration with normal saline (rehydration method) before wet fixation to overcome the above shortcomings.MethodsWe reviewed malignant pleural effusion and ascites 15 cases each in our cytology laboratory over the past 1 year. Four slides of each specimen were made. Two were air‐dried for Liu's stain (a Romanowsky stain) and the other two were wet‐fixed for Papanicolaou stain. The air‐dried smears were also served as retained cellularity control. One of the two wet‐fixed smears was processed as a control of preservation of nuclear detail whereas the other one stayed air‐dried for 10 minutes and then covered with normal saline (rehydration method) for 80 seconds before wet fixation.ResultsThere was minor cell loss (P = .032). The cells appeared larger with good preservation of nuclear detail (P < .0001 by two‐sided Wilcoxon rank sum test) but no red blood cells retained on the slide after rehydration.ConclusionThe rehydration method can effectively minimise cell loss, enlarge and preserve the cytological features of malignant cells with haemolysis. This method is simple, practical and good for cytological screening for tumour cells and interpretation especially in a bloody smear. We recommend that the rehydration method be part of traditional cytopreparatory work of wet fixation for Papanicolaou stain in conventional body fluid cytology.
Hyperleukocytosis is associated with distinct genetic alterations and is an independent poor‐risk factor in de novo acute myeloid leukemia patients
Authors: Tien Feng‐Ming , Hou Hsin‐An , Tsai Cheng‐Hong , Tang Jih‐Luh , Chen Chien‐Yuan , Kuo Yuan‐Yeh , Li Chi‐Cheng , Lin Chien‐Ting , Yao Ming , Huang Shang‐Yi , Ko Bor‐Sheng , Hsu Szu‐Chun , Wu Shang‐Ju , Tsay Woei , Tseng Mei‐Hsuan , Liu Ming‐Chih , Liu Chia‐Wen , Lin Liang‐In , Chou Wen‐Chien , Tien Hwei‐Fang 
Published: April 2018

AbstractObjectivesAcute myeloid leukemia (AML) with hyperleukocytosis (HL) is intuitively thought as a unique group with dismal prognosis. However, comprehensive studies regarding the genetic landscape and clinical outcome in this group of patients are limited.MethodsA total of 693 newly diagnosed de novo non‐M3 AML patients were consecutively enrolled. We compared relevant mutations in 20 genes between AML patients with or without HL and exposed their prognostic implications.ResultsHyperleukocytosis, defined as initial white blood cell counts above 50 000/μL, occurred in 28.9% of AML patients. HL patients had higher incidences of FLT3‐ITD, NPM1, DNMT3A, CEBPA, and TET2 mutations. Multivariate analysis demonstrated that HL was an independent poor prognostic factor for overall survival and disease‐free survival in total patients, those with intermediate‐risk cytogenetics and normal karyotype irrespective of genetic alterations. Intriguingly, HL predicted poor survival in CEBPA double mutated, NPM1 + /FLT3‐ITD‐ and NPM1‐/FLT3‐ITD‐ patients. Further, HL patients who received allogeneic hematopoietic stem cell transplantation (allo‐HSCT) in first complete remission (CR) had a significantly longer overall survival and disease‐free survival than those without allo‐HSCT.ConclusionsHyperleukocytosis is an independent poor prognostic factor irrespective of cytogenetics and mutation status. Allo‐HSCT in first CR seems to ameliorate the poor prognostic impact of HL.
Credit Ratings and Managerial Voluntary Disclosures
Authors: He Guanming 
Published: April 2018

AbstractThis study investigates whether managers influence credit ratings via voluntary disclosures. I find that firms near a rating change have a higher incidence of a disclosure regarding product and business expansion (PBE) plans. This finding is more evident for firms that are subject to lower proprietary costs of disclosures, which implies that managers do trade off both the benefits and costs of the disclosures. I find no evidence that firms close to a rating change selectively release good news or suppress bad news on PBE. Overall, my results suggest that firms generally exhibit a credible commitment to maintaining disclosure transparency for a desired credit rating.