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2021 ◽  
Vol 15 (3) ◽  
pp. 93-100
Author(s):  
Joachim Gruber
Keyword(s):  

Abstract Im Jahr 2018 jährte sich zum 50. Mal der Mord an Stevan Markovic Dazu J.-P. Méfret, Une sale affaire. Markovic, Marcantoni, Delon, Pompidou et les autres … (2007). Zur Sicht des Beteiligten Pompidou siehe dessen posthum herausgegebene Autobiographie: G. Pompidou, Pour rétablir une vérité (1982); die Markovic-Affäre wird ausführlich auf S. 251 ff. behandelt. Ferner fr.wikipedia.org unter „Affaire Markovic“; eine kürzere Darstellung findet sich auf der deutschsprachigen Wikipedia-Seite unter „Markovic-Affäre“. . Aus diesem Mordfall entwickelte sich eine der mysteriösesten Nachkriegs-Affären Frankreichs, die in Deutschland In Frankreich ist dieser Fall so bekannt, dass Léo Malet in seinem 1971 veröffentlichten Kriminalroman „Nestor Burma court la poupée“ (Titel der deutschen Übersetzung: Blutbad in Boulogne) eine entsprechende Anspielung untergebracht hat. Sein Held, der Privatdetektiv Nestor Burma, wird bei einem Besuch bei der Kriminalpolizei von einem Polizisten angestarrt. Malet legt Burma die Äußerung in den Mund: „Hat man endlich den Mörder von Markovic identifiziert und sehe ich ihm ähnlich?“ (die Äußerung findet sich in der Ausgabe Editions Laffont, 2007, Bd. 4, S. 463). allerdings wenig bekannt ist, obwohl sowohl die Beteiligten als auch die Vorgänge äußerst schillernd sind Einige Elemente dieser Affäre wurden im Drehbuch des Films „Il n´y pas de fumée sans feu“ (1973, Regie André Cayatte) aufgegriffen, in dem u. a. Mireille Darc (15. Mai 1938 bis 28. August 2017) mitspielte, die langjährige (1968–1983) Freundin von Alain Delon. . Da dieser Fall auch politische Auswirkungen hatte (fast wäre die Wahl von Georges Pompidou zum französischen Staatspräsidenten durch die Begleitumstände der Ermittlungen verhindert worden), sollen die Begebenheiten im Folgenden geschildert werden.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Enrico Callegari ◽  
Jūratė Šaltytė Benth ◽  
Geir Selbæk ◽  
Cato Grønnerød ◽  
Sverre Bergh

Abstract Background In this longitudinal study, we describe how psychotropic drugs (PTDs) are prescribed in nursing home (NH) patients from admission and over a 3-year period, to understand which clinical and environmental factors are associated with PTD prescription. Methods We used data from the Resource Use and Disease Course in Dementia – Nursing Home (REDIC-NH) study, examining physical and mental health, dementia, and PTD prescription during a 3-year period from admission to a NH. Data were collected every six months. At baseline, we included 696 participants from 47 Norwegian NHs. We presented prevalence, incidence, and deprescribing rates of PTD prescriptions for each assessment point. We calculated the odds of receiving PTDs and used a generalized linear mixed model to analyze the variables associated with a change in odds throughout the 3-year period. Results PTD prescriptions were frequent throughout the 3-year period. Antidepressants had the highest prescription rates (28.4%–42.2%). Every PTD category had the highest incidence rate between admission and six months, and antipsychotics had the highest values (49.4%). Deprescribing rates were comparable between assessment points. The odds of antipsychotic prescriptions were lower for older people (OR = 0.96, 95%CI:0.92–0.99, p = 0.023). People with more severe dementia had lower odds of being prescribed sedatives/hypnotics (OR = 0.89, 95%CI:0.85–0.94, p < 0.001). Conclusions PTDs, particularly antidepressants, are widely prescribed over time to NH patients. Older patients are less likely to receive antipsychotics. A higher severity of dementia decreases the odds of being prescribed sedatives/hypnotics. Close attention should be paid to PTD prescriptions during long-term NH stay to avoid prolonged and excessive treatment with these types of drugs. Trial registration ClinicalTrials.gov Identifier: NCT01920100.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
David M. Long ◽  
Jane Fitzpatrick

Abstract Background Osteoarthritis (OA) is the most prevalent form of joint disease and commonly affects the hip. Hip OA is associated with a high socioeconomic burden. Intra-articular hyaluronic acid (HA) injection may be of benefit but quality evidence for HA use in hip OA is lacking. The purpose of this study was to assess the safety and efficacy of ultrasound guided injection of a high molecular weight, non-animal derived, stabilised HA (NASHA) in patients with mild to moderate hip OA. Methods This single site study is an analysis of prospectively collected outcome data for 87 consecutive patients over a 2-year period who received a single HA (Durolane) injection for symptomatic hip OA. Inclusion criteria were male or female patients over 18-years of age with mild to moderate hip OA on x-ray. Patients with severe hip OA were excluded. The primary outcome measure was a modified Harris Hip Score (mHHS) questionnaire at baseline and 6-weeks with a minimal clinically important difference (MCID) of 10 points. All adverse events were recorded and assessed. Results Data from 87 patients, 49 women and 38 men with mean age of 54 (SD = 10.8) were analysed. At baseline, mean mHHS was 58.47 (SD 14.31). At the 6 week follow up, mean mHHS improved to 71.30 (SD 16.46), a difference of 12.83 (p < 0.01). This was greater than the MCID of 10. No significant adverse events were encountered. Five patients reported short-lived injection site pain. Conclusion A single injection of HA (NASHA) in the setting of hip joint OA was both safe and efficacious in this 87 patient cohort. Improvement in pain and function as measured with mHHS was statistically significant and reached the MCID of 10. Trial registration The study was retrospectively registered on the 1st of February 2021 in the Australian New Zealand Clinical Trials Registry with registry number ACTRN12621000098831. All research was performed in accordance with the Declaration of Helsinki.


2021 ◽  
pp. archdischild-2021-322586
Author(s):  
Thomas Waterfield ◽  
Mark D Lyttle ◽  
Charlotte Munday ◽  
Steven Foster ◽  
Marc McNulty ◽  
...  

ObjectiveTo report the performance of clinical practice guidelines (CPG) in the diagnosis of serious/invasive bacterial infections (SBI/IBI) in infants presenting with a fever to emergency care in the UK and Ireland. Two CPGs were from the National Institutes for Health and Care Excellence (NICE guidelines NG51 and NG143) and one was from the British Society for Antimicrobial Chemotherapy (BSAC).DesignRetrospective multicentre cohort study.PatientsFebrile infants aged 90 days or less attending between the 31 August 2018 to 1 September 2019.Main outcome measuresThe sensitivity, specificity and predictive values of CPGs in identifying SBI and IBI.SettingSix paediatric Emergency Departments in the UK/Ireland.Results555 participants were included in the analysis. The median age was 53 days (IQR 32 to 70), 447 (81%) underwent blood testing and 421 (76%) received parenteral antibiotics. There were five participants with bacterial meningitis (1%), seven with bacteraemia (1%) and 66 (12%) with urinary tract infections. The NICE NG51 CPG was the most sensitive: 1.00 (95% CI 0.95 to 1.00). This was significantly more sensitive than NICE NG143: 0.91 (95% CI 0.82 to 0.96, p=0.0233) and BSAC: 0.82 (95% 0.72 to 0.90, p=0.0005). NICE NG51 was the least specific 0.0 (95% CI 0.0 to 0.01), and this was significantly lower than the NICE NG143: 0.09 (95% CI 0.07 to 0.12, p<0.0001) and BSAC: 0.14 (95% CI 0.1 to 0.17, p<0.0001).ConclusionNone of the studied CPGs demonstrated ideal performance characteristics. CPGs should be improved to guide initial clinical decision making.Trial registration numberNCT04196192.


2021 ◽  
Vol 17 (9) ◽  
pp. e1009411
Author(s):  
Juan L. Trincado ◽  
Marina Reixachs-Solé ◽  
Judith Pérez-Granado ◽  
Tim Fugmann ◽  
Ferran Sanz ◽  
...  

Immunotherapies provide effective treatments for previously untreatable tumors and identifying tumor-specific epitopes can help elucidate the molecular determinants of therapy response. Here, we describe a pipeline, ISOTOPE (ISOform-guided prediction of epiTOPEs In Cancer), for the comprehensive identification of tumor-specific splicing-derived epitopes. Using RNA sequencing and mass spectrometry for MHC-I associated proteins, ISOTOPE identified neoepitopes from tumor-specific splicing events that are potentially presented by MHC-I complexes. Analysis of multiple samples indicates that splicing alterations may affect the production of self-epitopes and generate more candidate neoepitopes than somatic mutations. Although there was no difference in the number of splicing-derived neoepitopes between responders and non-responders to immune therapy, higher MHC-I binding affinity was associated with a positive response. Our analyses highlight the diversity of the immunogenic impacts of tumor-specific splicing alterations and the importance of studying splicing alterations to fully characterize tumors in the context of immunotherapies. ISOTOPE is available at https://github.com/comprna/ISOTOPE.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yeon Joo Kim ◽  
Jesang Yu ◽  
Sung Pyo Park ◽  
Seung Hae Lee ◽  
Young Seok Kim

Abstract Background Radiation induced enteropathy is a common complication of radiotherapy for pelvic tumors and adversely affects patient quality of life. Probiotics are thought to restore bowel microflora to optimal levels and reinforce intestinal barrier capacity. Although probiotics are effective in the treatment of radiation induced enteropathy, less is known about their efficacy to prevent radiation induced enteropathy. Methods This double-blind randomized placebo-controlled study will investigate the efficacy of probiotics to prevent radiation-induced enteropathy in patients with gynecologic or urologic cancer who received pelvic radiotherapy. The study is designed to enroll 248 eligible patients, who will be randomized 1:1 to a probiotic or placebo group. Toxicities will be evaluated using Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Discussion The primary aim of this study is to provide high level evidence for the ability of probiotics to prevent acute radiation induced enteropathy. The secondary aims are to determine the effects of probiotics on the incidence of chronic radiation induced enteropathy and the safety of probiotics in patients with gynecologic or urologic cancer. Trial registration ClinicalTrials.gov (NCT03978949, Registered on 7 June 2019).


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Long Liu ◽  
Jingze Zhang ◽  
Mei Wu ◽  
Haiming Xu

Abstract Background To illustrate the mechanism of miRNA and mRNA in coronary artery diseasen (CAD), differentially expressed microRNAs (DEmiRNAs) and genes (DEGs) were analyzed. Methods The mRNA transcription profiles of GSE20680 (including 87 blood samples of CAD and 52 blood samples of control), GSE20681 (including 99 blood samples of CAD and 99 blood samples of control) and GSE12288 (including 110 blood samples of CAD and 112 blood samples of control) and the miRNA transcription profiles of GSE59421 (including 33 blood samples of CAD and 37 blood samples of control), GSE49823 (including 12 blood samples of CAD and 12 blood samples of control) and GSE28858 (including 13 blood samples of CAD and 13 blood samples of control) were downloaded from Gene Expression Omnibus (GEO; http://www.ncbi.nlm.nih.gov/geo/). Then, the homogenous expressed mRNAs and miRNAs across the three mRNA transcription profiles and three miRNA transcription profiles were screened using the Fishers exact test in MetaDE. ES package. The weighted gene co-expression network analysis (WGCNA) was used to analyze gene modules. Additionally, the integrated miRNAs–targets regulatory network using the DEmiRNA and their targets was constructed using Cytoscape. Results A total of 1201 homogenously statistically significant DEGs were identified including 879 up-regulated and 322 down-regulated DEGs, while a total of 47 homogenously statistically significant DEmiRNAs including 37 up-regulated and 10 down-regulated DEmiRNAs in CAD compared with the controls across the three mRNA transcription profiles and the three miRNA transcription profiles. A total of 5067 genes were clustered into 9 modules in the training dataset, among which, 8 modules were validated. In the miRNAs-targets network, there existed 267 interaction relationships among 5 miRNAs (hsa-miR-361-5p, hsa-miR-139-5p, hsa-miR-146b-5p, hsa-miR-502-5p and hsa-miR-501-5p) and 213 targets. CAV1 could be the target of hsa-miR-361-5 while HSF2 was the target of both hsa-miR-361-5p and hsa-miR-146b-5p. CAV1 was significantly enriched in the GO term of regulation of cell proliferation. Conclusion hsa-miR-361-5p, has-miR-146b-5p, CAV1 and HSF2 could play an important role in CAD.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
A. Hasenburg ◽  
D. Eichkorn ◽  
F. Vosshagen ◽  
E. Obermayr ◽  
A. Geroldinger ◽  
...  

Abstract Background Trial on five plasma biomarkers (CA125, HE4, OPN, leptin, prolactin) and their possible role in differentiating benign from malignant ovarian tumors. Methods In this unicentric prospective trial preoperative blood samples of 43 women with ovarian masses determined for ovarian surgery were analyzed. 25 patients had pathologically confirmed benign, 18 malignant ovarian tumors. Blood plasma was analyzed for CA125, HE4, OPN, leptin, prolactin and MIF by multiplex immunoassay analysis. Each single protein and a logistical regression model including all the listed proteins were tested as preoperative predictive marker for suspect ovarian masses. Results Plasma CA125 was confirmed as a highly accurate tumor marker in ovarian cancer. HE4, OPN, leptin and prolactin plasma levels differed significantly between benign and malignant ovarian masses. With a logistical regression model a formula including CA125, HE4, OPN, leptin and prolactin was developed to predict malignant ovarian tumors. With a discriminatory AUC of 0.96 it showed to be a highly sensitive and specific diagnostic test for a malignant ovarian tumor. Conclusions The calculated formula with the combination of CA125, HE4, OPN, leptin and prolactin plasma levels surpasses each single marker in its diagnostic value to discriminate between benign and malignant ovarian tumors. The formula, applied to our patient population was highly accurate but should be validated in a larger cohort. Trial registration Clinical Trials.gov under NCT01763125, registered Jan. 8, 2013.


Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Ken-ichi Okada ◽  
Manabu Kawai ◽  
Seiko Hirono ◽  
Masayuki Sho ◽  
Masaji Tani ◽  
...  

Abstract Background Radical antegrade modular pancreatosplenectomy (RAMPS) is an isolation procedure in pancreatosplenectomy for pancreatic body/tail cancer. Connective tissues around the bifurcation of the celiac axis are dissected, followed by median-to-left retroperitoneal dissection. This procedure has the potential to isolate blood and lymphatic flow to the area of the pancreatic body/tail and the spleen to be excised. This is achieved by division of the inflow artery, transection of the pancreas, and then division of the outflow vein in the early phases of surgery. In cases of pancreatic ductal adenocarcinoma (PDAC), the procedure has been shown to decrease intraoperative blood loss and increase R0 resection rate by complete clearance of the lymph nodes. This trial investigates whether the isolation procedure can prolong the survival of patients with pancreatic ductal adenocarcinoma who undergo distal pancreatosplenectomy (DPS) compared with those that undergo the conventional approach. Methods/design Patients with PDAC scheduled to undergo DPS are randomized before surgery to undergo either a conventional procedure (arm A) or to undergo the isolation procedure (arm B). In arm A, the pancreatic body, tail, and spleen are mobilized, followed by removal of the regional lymph nodes. The splenic vein is transected at the end of the procedure. The timing of division of the splenic artery (SA) is not restricted. In arm B, regional lymph nodes are dissected, then we transect the root of the SA, the pancreas, then the splenic vein. At the end of the procedure, the pancreatic body/tail and spleen are mobilized and removed. In total, 100 patients from multiple Japanese high-volume centers will be randomized. The primary endpoint is 2-year recurrence-free survival by intention-to-treat analysis. Secondary endpoints include intraoperative blood loss, R0 resection rate, and overall survival. Discussion If this trial shows that the isolation procedures can improve survival with a similar R0 rate and with a similar number of lymph node dissections to the conventional procedure, the isolation procedure is expected to become a standard procedure during DPS for PDAC. Conversely, if there were no significant differences in endpoints between the groups, it would demonstrate justification of either procedure from surgical and oncological points of view. Trial registration UMIN Clinical Trials Registry UMIN000041381. Registered on 10 August 2020. ClinicalTrials.gov NCT04600063. Registered on 22 October 2020.


Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Lourdes R. Carhuapoma ◽  
Winter M. Thayer ◽  
Catherine E. Elmore ◽  
Jane Gildersleeve ◽  
Tanmay Singh ◽  
...  

Abstract Background Metastatic prostate cancer remains a lethal malignancy that warrants novel supportive interventions for patients and their decision partners and proxies. Decision aids have been applied primarily to patients with localized disease, with minimal inclusion of patients with advanced prostate cancer and their decision partners. The use of a community patient navigator (CPN) has been shown to have a positive supportive role in health care, particularly with individuals from minority populations. Research is needed to evaluate decision support interventions tailored to the needs of advanced prostate cancer patients and their decision partners in diverse populations. Methods Guided by Janis and Mann’s Conflict Model of Decision Making, the Cancer Health Aid to Manage Preferences and Improve Outcomes through Navigation (CHAMPION) is a randomized controlled trial to assess the feasibility and acceptability of a mobile health (mHealth), CPN-administered decision support intervention designed to facilitate communication between patients, their decision partners, and the healthcare team. Adult prostate cancer patients and their decision partners at three mid-Atlantic hospitals in the USA were randomized to receive enhanced usual care or the decision intervention. The CHAMPION intervention includes a theory-based decision-making process tutorial, immediate and health-related quality of life graphical summaries over time (using mHealth), values clarification via a balance sheet procedure with the CPN support during difficult decisions, and facilitated discussions with providers to enhance informed, shared decision-making. Discussion The CHAMPION intervention is designed to leverage dynamic resources, such as CPN teams, mHealth technology, and theory-based information, to support decision-making for advanced prostate cancer patients and their decision partners. This intervention is intended to engage decision partners in addition to patients and represents a novel, sustainable, and scalable way to build on individual and community strengths. Patients from minority populations, in particular, may face unique challenges during clinical communication. CHAMPION emphasizes the inclusion of decision partners and CPNs as facilitators to help address these barriers to care. Thus, the CHAMPION intervention has the potential to positively impact patient and decision partner well-being by reducing decisional conflict and decision regret related to complex, treatment-based decisions, and to reduce cancer health disparities. Trial registration ClinicalTrials.govNCT03327103. Registered on 31 October 2017—retrospectively registered. World Health Organization Trial Registration Data Set included in Supplementary Materials.


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