bluuebunny/crossref_metadata_2025_split huggingface dataset:
High fracture risk after long term oral bisphosphonates and vitamin D
Authors: Schacht E. , Ringe J. D. 
Published: August 2018

Summary
Introduction: Optimal duration of bisphosphonate (BP) therapy has not been defined. A recent FDA publication suggests periodically re-evaluating patients on BP. Those with low risk may discontinue BP after 3–5 years, those still at high risk may benefit from ongoing BP.
Patients and methods: We compared continued BP therapy plus plain vitamin D to BP plus alfacalcidol in patients still at a significantly increased fracture risk after an average of 4.3 years of BP plus plain vitamin D use over two more years. The study was based on retrospective chart analysis and followed 214 patients (167 female, 47 male). Among these 145 continued alendronate (ALN) and 69 risedronate (RIS). In addition, group A (n = 106) received 800 IU/d plain vitamin D plus 1200 mg/d calcium as before, while patients in group B (n = 108) were switched from plain vitamin D to 1 μg/d alfacalcidol plus 500 mg/d calcium. The respective proportions of males and females and patients with ALN or RIS intake did not differ between group A and B. BMD was measured at 0, 12 and 24 months at lumbar spine (LS) and femoral neck (FN) by DXA. Lateral spine morphometry assessed prevalent and incident vertebral fractures. Recorded were the number of falls and fallers 2 years before and during the trial, back pain (VAS 0–10), adverse events (AE) and prevalent and incident non-vertebral fractures. We also conducted subgroup analyses in four groups – female, male, ALN, RIS on all endpoints.
Results: BMD at LS did not change significantly over two years with +1.1 % in group A, but increased significantly with BP plus alfa-calcidol by + 5.5 % (B vs. A p < 0.01). At the FN site the respective changes were +0.6 % and +3.4 % (p < 0.01). The average number of falls per patient-year was reduced by 12 % in A (ns) and by 44 % in B (p < 0.03). There was a significant decrease in average back pain score with BP plus alfa calcidol vs. BP plus plain vitamin D after two years (p < 0.02). The number of patients with new vertebral fractures did not significantly differ between A and B. There were however significantly less non-vertebral fractures with alfacalcidol (p < 0.05). The above was found significant in all subgroups for nearly all endpoints. The number of adverse events (AE) did not differ between groups. No serious AE were observed.
Discussion: The data show that in male and female osteoporosis patients still at risk after 4.3 years on oral BP a continuation of BP plus alfacalcidol is superior to ongoing therapy with BP plus plain vitamin D.
Vollbild eines Morbus Paget im 21. Jahrhundert
Authors: Eisfeldt C. , Brinkmann O. , Lehmann G. , Stolarczyk Y. 
Published: August 2018

ZusammenfassungVorgestellt wird der Fall eines 71-jährigen Patienten, der nach der Diagnose eines Morbus Paget Ende der 1980er-Jahre nicht wieder in osteologischer, ärztlicher Kontrolle war. Nach ca. 30 Jahren erfolgte die Wiedervorstellung mit dem Vollbild eines Morbus Paget im Sinne einer monströsen Säbelscheidentibia. Der Fall soll die noch immer bestehende Relevanz der Erkrankung aufzeigen und das Behandlungskonzept demonstrieren.
Früherkennung und Prävention der Osteoporose bei Männern
Authors: Ringe J. D. , Feustel A. , Weimer R. , Farahmand P. 
Published: August 2018

ZusammenfassungEtwa sechs Prozent der über 50-jährigen Männer sind in Deutschland von Osteoporose betroffen. Obgleich bereits eine breite Palette an Medikamenten zur Behandlung der männlichen Osteoporose zur Verfügung steht, und Männer mit osteoporotischen Frakturen eine deutlich höhere Mortalität als Frauen mit Frakturen haben, werden Männer seltener behandelt. Nach einer Hüftfraktur werden etwa zwei Drittel aller Frauen mit einem osteoporosespezifischen Medikament behandelt, bei Männern ist es aber nur die Hälfte. Bei Männern stehen in 50–60 % der Fälle sekundäre Osteoporosen im Vordergrund, bei postmenopausalen Frauen hingegen nur bei 30 %. Die häufigsten Risikofaktoren bei der männlichen Osteoporose sind Nikotinkonsum, systemische Glukokortikoide, Alkoholkonsum, chronisch obstruktive Atemwegserkrankungen und der Hypogonadismus. Screening hinsichtlich des Vorliegens von Risikofaktoren ist daher bei Männern zur Früh-erkennung der Osteoporose unerlässlich. Im positiven Falle ist eine systematische osteologische Abklärung inklusive Knochendichtemessung, Bildgebung der Wirbelsäule und Labordiagnostik erforderlich. Prävention muss bereits im Kindesund Jugendalter erfolgen durch körperliche Aktivität, eiweiß- und kalziumreiche Ernährung kombiniert mit adäquater Vitamin-D-Versorgung. Bereits bei Diagnosestellung von Erkrankungen, die mit der Entwicklung einer Osteoporose verbunden sein können, ist osteologische Diagnostik erforderlich. Nur so kann der Entwicklung einer Osteoporose frühzeitig begegnet werden.
Eisen-induzierte Osteomalazie
Authors: Burckhardt P. 
Published: August 2018

ZusammenfassungDas Auftreten einer invalidisierenden Osteomalazie bei einem Mann, der wegen intestinalen Angiodysplasien seit Jahren mit intravenösem Eisen behandelt wird, hat an die Rolle des Wachstumsfaktors FGF23 erinnert. FGF23 hemmt, zusammen mit PTH, die renale Phosphat-Rückresorption und führt zu Hypophosphatämie und Osteomalazie, auch weil es zudem die 25OH Vit.D 1-alpha Hydroxylase hemmt, was wiederum zu einem Mangel an 1,25(OH)2-Vitamin D führt. Die Behandlung besteht in Phosphaten und Calcitriol. Mehrere Medikamente und Krankheiten können FGF23 erhöhen: mesenchymale Tumoren, multiples Myelom, M. Hodgkin, antivirale Therapien, hypophosphatämische Osteomalazie, Nierentransplantation, intensive Wiederernährung u. a. So selten die Erhöhung des FGF23 als wesentliche Krankheitsursache auch ist, so leicht ist sie zu diagnostizieren.
Transplantationsosteoporose
Authors: Bergthaler M. , Dimai H. P. , Fahrleitner-Pammer A. 
Published: August 2018

ZusammenfassungDie Transplantation hat sich während der letzten Jahrzehnte zu einer etablierten Therapie terminaler Organerkrankungen entwickelt. Die derzeit verfügbaren immunsuppressiven Therapieschemata, welche neben Steroiden auch Calcineurin Inhibitoren beinhalten, haben zu einem besseren Langzeitüberleben geführt. Spätkomplikationen wie die Transplantationsosteoporose gewinnen dadurch an Bedeutung. Der ausgeprägteste Knochenmasseverlust tritt während der ersten 6-12 Monate nach erfolgreicher Transplantation auf und ist charakterisiert durch eine hohe Frakturinzidenz, welche in Abhängigkeit vom transplantierten Organ bei über 50 % liegt. Diese frühe Phase ist geprägt durch eine Entkoppelung des Knochenstoffwechsels mit einer unterdrückten Knochenformation und gesteigerten Resorption. Bei Langzeitüberlebenden spielen andere Faktoren, wie eine eingeschränkte Nierenfunktion, ein Hypogonadismus und ein sekundärer Hyperparathyreodismus eine Rolle. Therapeutische Ansätze beinhalten eine Prävention schon zum Zeitpunkt der Evaluierung für eine Transplantation sowie unmittelbar im Anschluss an die Transplantation eine unabhängig von der Knochendichte frühestmögliche spezifische Therapie.
Die oligoostotische fibröse Dysplasie mit enchondromartigen Anteilen
Authors: Bühligen U. , Wojan M. , Roth C. , Heyde C.-E. , Roth A. , Schumann E. 
Published: August 2018

ZusammenfassungDie fibröse Dysplasie (FD) ist eine benigne Tumorerkrankung des Knochens, die durch eine postzygotische Mutation im GNAS1-Gen entsteht. Man unterscheidet eine monostotische und polyostotische Form sowie das McCune-Albright-Syndrom. Die FD kann grundsätzlich jeden Knochen betreffen. Besonders problematisch ist die Manifestation am proximalen Femur mit Ausbildung einer sogenannten Hirtenstabdeformität.Wir berichten über einen Patienten mit polyostotischer FD mit Manifestation am proximalen Femur. Es erfolgte die mehrfache operative Behandlung bei sich entwickelnder “Hirtenstabdeformität”. Nach einer mehrdimensionalen Korrekturosteotomie konnte abschließender eine adäquate Gelenkstellung und Beschwerdefreiheit erreicht werden.Es besteht Einigkeit, dass die Hirtenstabdeformität durch eine Korrektur – osteotomie behandelt werden sollte, um die Coxa vara und damit die präarthrotische Deformität zu beseitigen. In der Literatur werden intramedulläre Osteosynthesen favorisiert, da sie dem “weichen Knochen” eine höhere Stabilität bieten. In unserem Fall konnte jedoch durch die zweimalige intra medulläre Nagelung keine Stabilisierung erreicht werden. Erst durch den Verfahrenswechsel mit Korrekturosteotomie konnte ein zufriedenstellender Befund erzielt werden. Der beschriebene Behandlungsverlauf zeigt verschiedene Probleme in der Diagnostik und Therapie der FD. Die histologische Diagnose kann bei untypischem Zellbild nicht eindeutig sein. Verwechslungen mit Knochenzysten oder Enchondromen sind möglich. Erst der molekularpathologische Nachweis der Mutation konnte die Diagnose sichern.Die fibröse Dysplasie mit Manifestation am proximalen Femur stellt eine operative Herausforderung dar. Wesentlich für die erfolgreiche Therapie scheint die Beseitigung der Coxa vara durch eine valgisierende Osteotomie zu sein. Das optimale Osteosyntheseverfahren kann noch nicht abschließend empfohlen werden. Zur Diagnosesicherung sollte immer der Mutationsnachweis des GNAS1-Gens erfolgen.
Global Epidemiology of Tuberculosis
Authors: Floyd Katherine , Raviglione Mario , Glaziou Philippe 
Published: August 2018

AbstractTuberculosis (TB) was the underlying cause of 1.3 million deaths among human immunodeficiency virus (HIV)-negative people in 2016, exceeding the global number of HIV/acquired immune deficiency syndrome (AIDS) deaths. In addition, TB was a contributing cause of 374,000 HIV deaths. Despite the success of chemotherapy over the past seven decades, TB is the top infectious killer globally. In 2016, 10.4 million new cases arose, a number that has remained stable since the beginning of the 21th century, frustrating public health experts tasked to design and implement interventions to reduce the burden of TB disease worldwide. Ambitious targets for reductions in the epidemiological burden of TB have been set within the context of the Sustainable Development Goals (SDGs) and the End TB Strategy. Achieving these targets is the focus of national and international efforts, and demonstrating whether or not they are achieved is of major importance to guide future and sustainable investments. This article reviews epidemiological facts about TB, trends in the magnitude of the burden of TB and factors contributing to it, and the effectiveness of the public health response.
Diagnostic Challenge of Tuberculosis Heterogeneity
Authors: Nemes Elisa , Meermeier Erin , Scriba Thomas , Walzl Gerhard , Malherbe Stephanus , Lewinsohn David 
Published: August 2018

AbstractFor the ICU physician, the failure to consider, diagnose, and treat tuberculosis (TB) results in increased morbidity and mortality, and poses risks to both patients and health care providers. At present, the diagnosis of TB depends on the detection of either mycobacteria or mycobacterial products from clinical specimens. Given the risks posed to both the patient and health care providers by undiagnosed and/or untreated TB, the ability to diagnose TB rapidly in the ICU cannot be understated. In this regard, nucleic acid amplification tests provide relatively quick information about the presence of Mycobacterium tuberculosis (Mtb) DNA. If available, a blood-based test that would accurately identify persons with TB would be of use in the ICU. Currently available tests such as the T-Spot.TB or QuantiFERON-TB Gold In-Tube can discern infection with Mtb, but are not recommended for the ICU as they cannot rule out TB. In this review, we will discuss the increasing literature that would suggest that a blood-based diagnostic that reflects the host response to TB could be used to diagnose TB in the ICU.
Updates in the Treatment of Active and Latent Tuberculosis
Authors: Belknap Robert , Haas Michelle 
Published: August 2018

AbstractFirst-line therapy for active tuberculosis (TB) has remained unchanged for nearly 40 years. Isoniazid, rifampin, pyrazinamide, and ethambutol for the initial two-month phase followed by isoniazid and rifampin for 4 to 7 months is standard treatment for people at low risk for drug-resistant disease. Directly-observed therapy (DOT) remains the standard of care for pulmonary TB. Virtual treatment monitoring using digital technologies is becoming more common as a way to provide a more patient-centered approach to care. Attempts to shorten treatment duration have been unsuccessful based on recent clinical trials evaluating the role of fluoroquinolones. Treatment-shortening trials using higher doses of rifamycins are currently underway. Recently approved medications for TB treatment are recommended only for drug-resistant disease, but novel agents in varying stages of development are being evaluated. Rifamycin-based regimens for latent TB infection (LTBI) have been successful in preventing progression to TB disease. Once-weekly isoniazid and rifapentine for 12 weeks by DOT was shown to be safe and effective compared with 9 months of isoniazid. The same regimen was shown to have acceptable treatment completion when given self-administered. Newer studies are investigating even shorter LTBI treatment with durations of less than 2 months. Treatment of LTBI in people likely infected with multidrug resistant TB is very limited, but one observational study found that fluoroquinolones appear to be effective. The first randomized trials for treating LTBI in contacts to MDR-TB are currently enrolling.
FXa-α2-Macroglobulin Complex Neutralizes Direct Oral Anticoagulants Targeting FXa In Vitro and In Vivo
Authors: Jourdi Georges , Gouin-Thibault Isabelle , Siguret Virginie , Gandrille Sophie , Gaussem Pascale , Le Bonniec Bernard 
Published: August 2018

Increasing number of patients are treated with direct oral anticoagulants (DOAC). An antidote for dabigatran inhibiting thrombin (idarucizumab) is available but no antidote is yet approved for the factor Xa (FXa) inhibitors (xabans). We hypothesized that a complex between Gla-domainless FXa and α2-macroglobulin (GDFXa-α2M) may neutralize the xabans without interfering with normal blood coagulation.Purified α2M was incubated with GDFXa to form GDFXa-α2M. Affinity of apixaban and rivaroxaban for GDFXa-α2M was only slightly decreased compared to FXa. Efficacy and harmlessness of GDFXa-α2M were tested in vitro and in vivo. Stoichiometric excess of GDFXa-α2M neutralized rivaroxaban and apixaban as attested by clot waveform assay and rotational thromboelastometry, whereas GDFXa-α2M alone had no effect on these assays. Efficacy and pro-thrombotic potential of GDFXa-α2M were also assessed in vivo. Half-life of GDFXa-α2M in C57BL6 mice was 4.9 ± 1.1 minutes, but a 0.5 mg/mouse dose resulted in uptake saturation such that 50% persistence was still observed after 170 minutes. Single administration of GDFXa-α2M significantly decreased the rivaroxaban-induced bleeding time (p < 0.001) and blood loss (p < 0.01). GDFXa-α2M did not increase D-dimer or thrombin–antithrombin complex formation, suggesting a lack of pro-thrombotic potential.GDFXa-α2M is therefore an attractive candidate for xaban neutralization neither pro- nor anticoagulant in vitro as well as in vivo.
Scientific instrument curators in Britain
Authors: Alberti Samuel J M M 
Published: August 2018

Abstract
From the mid-1960s a new breed of scientific instrument curators emerged in the United Kingdom. This small community of practice developed in parallel to but distinctly from the expanding generation of university historians of science and other cognate museum sub-professions. Presenting the trajectories, experiences and practices of personnel in British scientific instrument collections, especially the Royal Scottish Museum in Edinburgh, this article explores how networks of interest around collections shaped the museum sector in later twentieth-century Britain. With particular objects – especially eighteenth-century instruments – the ‘brass brigade’ built a discipline.
Thoracolumbar Injury Classification and Severity Score in Children: A Validity Study
Authors: Dawkins Ross L , Miller Joseph H , Menacho Sarah T , Ramadan Omar I , Lysek Michael C , Kuhn Elizabeth N , Tubbs R Shane , Walker Marion L , Walters Beverly C , Agee Bonita S , Rozzelle Curtis J 
Published: August 2018

Abstract

BACKGROUND
The Thoracolumbar Injury Classification and Severity Score (TLICS) has been shown to be a valid tool for assessing the need for surgical intervention in adult patients. There is limited insight into its usefulness in children.

OBJECTIVE
To assess the validity of the TLICS system in pediatric patients.

METHODS
The medical records for pediatric patients with acute, traumatic thoracolumbar fractures at two Level 1 trauma centers were reviewed retrospectively. A TLICS score was calculated for each patient using computed tomography and magnetic resonance images, along with the neurological examination recorded in the patient's medical record. TLICS scores were compared with the type of treatment received. Receiver operating characteristic (ROC) curve analysis was employed to quantify the validity of the TLICS scoring system.

RESULTS
TLICS calculations were completed for 165 patients. The mean TLICS score was 2.9 (standard deviation ± 2.7). Surgery was the treatment of choice for 23% of patients. There was statistically significant agreement between the TLICS suggested treatment and the actual treatment received (P < 0.001). The ROC curve calculated using multivariate logistic regression analysis of the TLICS system's parameters as a tool for predicting treatment demonstrated excellent discriminative ability, with an area under the ROC curve of 0.96, which was also statistically significant (P < 0.001).

CONCLUSION
The TLICS system demonstrates good validity for selecting appropriate thoracolumbar fracture treatment in pediatric patients.
Mitochondrial electron transport chain complex III sustains hepatitis E virus replication and represents an antiviral target
Authors: Qu Changbo , Zhang Shaoshi , Wang Wenshi , Li Meng , Wang Yijin , van der Heijde-Mulder Marieke , Shokrollahi Ehsan , Hakim Mohamad S. , Raat Nicolaas J. H. , Peppelenbosch Maikel P. , Pan Qiuwei 
Published: August 2018

ABSTRACTHepatitis E virus (HEV) infection has emerged as a global health problem. However, no approved medication is available, and the infection biology remains largely elusive. Electron transport chain (ETC), a key component of the mitochondria, is the main site that produces ATP and reactive oxygen species (ROS). By profiling the role of the different complexes of the mitochondrial ETC, we found that pharmacological inhibition of complex III, a well‐defined drug target for the treatment of malaria and Pneumocystis pneumonia, potently restricts HEV replication. This effect demonstrated in our HEV models is equivalent to the anti‐HEV potency of ribavirin, a widely used off‐label treatment for patients with chronic HEV. Mechanistically, we found that this effect is independent of ATP production, ROS level, and pyridine depletion. By using pharmacological inhibitors and genetic approaches, we found that mitochondrial permeability transition pore (MPTP), a newly identified component of ETC, provides basal defense against HEV infection. HEV interferes with the opening of the MPTP. Furthermore, inhibition of the MPTP attenuated the anti‐HEV effect of complex III inhibitors, suggesting that the MPTP mediates the antiviral effects of these inhibitors. These findings reveal new insights on HEV–host interactions and provide viable anti‐HEV targets for therapeutic development.—Qu, C., Zhang, S., Wang, W., Li, M., Wang, Y., van der Heijde‐Mulder, M., Shokrollahi, E., Hakim, M. S., Raat, N. J. H., Peppelenbosch, M. P., Pan, Q. Mitochondrial electron transport chain complex III sustains hepatitis E virus replication and represents an antiviral target. FASEB J. 33, 1008–1019 (2019). www.fasebj.org
Influence of Dose and Antiepileptic Comedication on Lacosamide Serum Concentrations in Patients With Epilepsy of Different Ages
Authors: May Theodor W. , Helmer Renate , Bien Christian G. , Brandt Christian 
Published: August 2018

Background:
Lacosamide (LCM) is a new antiepileptic drug (AED). The purpose of the study was to investigate the effects of LCM dose, body weight, height, sex, age, and concomitant AEDs on LCM trough serum concentrations (at a steady state) in patients with epilepsy.

Methods:
A total number of 3154 blood samples of 973 consecutive patients of the Mara Hospital (Bethel Epilepsy Centre) were evaluated. Generalized estimating equation (GEE) models were used for statistical analyses.

Results:
GEE analyses showed that LCM trough serum concentrations were significantly correlated with the body weight–normalized LCM dose (range: 0.44–25.7 mg/kg; 45–1050 mg) and significantly dependent on comedication and age. Compared with adults (18–60 years), the LCM trough serum concentrations of children aged 6–12 years and children younger than 6 years were significantly lower (−21% to −38%, respectively) and those of elderly patients (>60 years) were significantly higher (+20%). Sex had no significant influence. Carbamazepine, phenytoin, primidone, phenobarbital, and methsuximide decreased LCM trough serum concentrations significantly by 30%, 32%, 34%, 39%, and 41%, respectively, whereas other AEDs (eg, oxcarbazepine, eslicarbazepine acetate, valproate) had no significant or only a minor impact (zonisamide) on LCM trough concentrations. In children, the effect of enzyme-inducing AEDs was more marked. Of note, the number of blood samples (n = 151) of patients younger than 12 (n = 78) was comparatively low. Alternative GEE models confirmed the effect of comedication, whereas the effect of age, especially in children, depended on adjustment of LCM dosage to body weight, body surface area, or approximated volume of distribution.

Conclusions:
In accordance with previous therapeutic drug monitoring studies, our results confirmed that enzyme inducers reduce the LCM trough serum concentrations by 30%–40%. In children, the effects of comedication are more pronounced but should be confirmed by further studies.
Choosing outcomes for clinical trials: a pragmatic perspective
Authors: Iwashyna Theodore J. , McPeake Joanne 
Published: August 2018

Purpose of review
The turn to evidence-based medicine in critical care has lead to a dramatic increase in the number of randomized clinical trials. Yet many of these trials are not showing differences on an appropriately prespecified primary outcome. In light of this, there have been some heated arguments as to what sorts of clinical trials should be conducted. We synthesize pragmatic recommendations from two governing bases: rigorous statistical practice and a commitment to insuring trials provide information that should help guide patient-centered decision-making.

Recent findings
We suggest six principles for the selection of an randomized clinical trial primary outcome: (1) your intervention should plausibly change your primary outcome. (2) The primary outcome should be cared about by your audience. (3) The primary outcome should be relevant to patients. (4) The primary outcome should be measured efficiently. (5) The primary outcome should be measured reliably. (6) When possible, use a well understood continuous scale. In addition, principles for selecting secondary outcomes are described.

Summary
It may be of value, when proposing a trial, to present preliminary evidence documenting the extent to which a proposed primary outcome actually accords each of these principles.