The association between survey timing and patient-reported experiences with hospitals: results of a national postal survey

<p>Abstract</p> <p>Background</p> <p>Research on the effect of survey timing on patient-reported experiences and patient satisfaction with health services has produced contradictory results. The objective of this study was thus to assess the association between survey timing and patient-reported experiences with hospitals.</p> <p>Methods</p> <p>Secondary analyses of a national inpatient experience survey including 63 hospitals in the 5 health regions in Norway during the autumn of 2006. 10,912 (45%) patients answered a postal questionnaire after their discharge from hospital. Non-respondents were sent a reminder after 4 weeks. Multilevel linear regression analysis was used to assess the association between survey timing and patient-reported experiences, both bivariate analysis and multivariate analysis controlling for other predictors of patient experiences.</p> <p>Results</p> <p>Multivariate multilevel regression analysis revealed that survey time was significantly and negatively related to three of six patient-reported experience scales: doctor services (Beta = -0.424, <it>p</it>< 0.05), information about examinations (Beta = -0.566, <it>p </it>< 0.05) and organization (Beta = -0.528, <it>p </it>< 0.05). Patient age, self-perceived health and type of admission were significantly related to all patient-reported experience scales (better experiences with higher age, better health and routine admission), and all other predictors had at least one significant association with patient-reported experiences.</p> <p>Conclusions</p> <p>Survey time was significantly and negatively related to three of the six scales for patient-reported experiences with hospitals. Large differences in survey time across hospitals could be problematic for between-hospital comparisons, implying that survey time should be considered as a potential adjustment factor. More research is needed on this topic, including studies with other population groups, other data collection modes and a longer time span.</p

The actin-myosin regulatory MRCK kinases: regulation, biological functions and associations with human cancer

The contractile actin-myosin cytoskeleton provides much of the force required for numerous cellular activities such as motility, adhesion, cytokinesis and changes in morphology. Key elements that respond to various signal pathways are the myosin II regulatory light chains (MLC), which participate in actin-myosin contraction by modulating the ATPase activity and consequent contractile force generation mediated by myosin heavy chain heads. Considerable effort has focussed on the role of MLC kinases, and yet the contributions of the myotonic dystrophy-related Cdc42-binding kinases (MRCK) proteins in MLC phosphorylation and cytoskeleton regulation have not been well characterized. In contrast to the closely related ROCK1 and ROCK2 kinases that are regulated by the RhoA and RhoC GTPases, there is relatively little information about the CDC42-regulated MRCKα, MRCKβ and MRCKγ members of the AGC (PKA, PKG and PKC) kinase family. As well as differences in upstream activation pathways, MRCK and ROCK kinases apparently differ in the way that they spatially regulate MLC phosphorylation, which ultimately affects their influence on the organization and dynamics of the actin-myosin cytoskeleton. In this review, we will summarize the MRCK protein structures, expression patterns, small molecule inhibitors, biological functions and associations with human diseases such as cancer

Deep Learning for the detection of microsatellite instability from histology images in colorectal cancer: a systematic literature review

Microsatellite instability (MSI) or deficient mismatch repair (dMMR) is a clinically important genetic feature affecting 10-15% of colorectal cancer (CRC) patients. Patients with metastatic MSI/dMMR CRC are eligible for therapy with immune checkpoint inhibitors, making MSI/dMMR the most important immuno-oncological biomarker in CRC. Gold standard tests for detection of MSI/dMMR in CRC are based on wet laboratory tests such as immunohistochemistry (IHC) or DNA extraction with subsequent polymerase chain reaction (PCR). However, since 2019, advances in Deep Learning (DL), an Artificial Intelligence (AI) technology, have enabled the prediction of MSI/dMMR directly from digitized routine haematoxylin and eosin (H&E) histopathology slides with high accuracy. In addition to the initial proof-of-concept publication in 2019, twelve subsequent studies have refined, improved, and further validated this approach. At this moment, MSI/dMMR prediction using Deep Learning has become a widely used benchmark task for academic studies in the field of computational pathology. Beyond academic use, this assay has attracted commercial interest from companies with the possibility of approval as a diagnostic device in the near future. In this review, we summarize and quantitatively compare the existing evidence on Deep-Learning-based detection of MSI/dMMR in CRC and discuss the need for further improvement and potential for integration into routine pathological workflows. Ultimately, this DL-based method could facilitate the identification of patients eligible for treatment with immune checkpoint inhibitors by pre-screening or replacement of current methods

Boerhaave syndrome as a complication of colonoscopy preparation: a case report

<p>Abstract</p> <p>Introduction</p> <p>Colonoscopy is one of the most frequently performed elective and invasive diagnostic interventions. For every colonoscopy, complete colon preparation is mandatory to provide the best possible endoluminal visibility; for example, the patient has to drink a great volume of a non-resorbable solution to flush out all feces. Despite the known possible nauseating side effects of colonoscopy preparation and despite the knowledge that excessive vomiting can cause rupture of the distal esophagus (Boerhaave syndrome), which is a rare but severe complication with high morbidity and mortality, it is not yet a standard procedure to provide a patient with an anti-emetic medication during a colon preparation process. This is the first report of Boerhaave syndrome induced by colonoscopy preparation, and this case strongly suggests that the prospect of being at risk of a severe complication connected with an elective colonoscopy justifies a non-invasive, inexpensive yet effective precaution such as an anti-emetic co-medication during the colonoscopy preparation process.</p> <p>Case presentation</p> <p>A 73-year-old Caucasian woman was scheduled to undergo elective colonoscopy. For the colonoscopy preparation at home she received commercially available bags containing soluble polyethylene glycol powder. No anti-emetic medication was prescribed. After drinking the prepared solution she had to vomit excessively and experienced a sudden and intense pain in her back. An immediate computed tomography (CT) scan revealed a rupture of the distal esophagus (Boerhaave syndrome). After initial conservative treatment by endoluminal sponge vacuum therapy, she was taken to the operating theatre and the longitudinal esophageal rupture was closed by direct suture and gastric fundoplication (Nissen procedure). She recovered completely and was discharged three weeks after the initial event.</p> <p>Conclusions</p> <p>To the best of our knowledge, this is the first report of a case of Boerhaave syndrome as a complication of excessive vomiting caused by colonoscopy preparation. The case suggests that patients who are prepared for a colonoscopy by drinking large volumes of fluid should routinely receive an anti-emetic medication during the preparation process, especially when they have a tendency to nausea and vomiting.</p

Multiple thromboembolism with multiple causes in a 69-year-old woman: a case report

<p>Abstract</p> <p>Introduction</p> <p>Aggressive, recurrent embolisms require accurate etiologic diagnosis. We describe the case of a 69-year-old Italian Caucasian woman with recurrent arterial embolisms in whom several sources and triggers of thrombosis were detected.</p> <p>Case presentation</p> <p>The patient, a 69-year-old Italian Caucasian woman, presented with a systemic embolism that was initially attributed to atrial fibrillation. The recurrence of embolisms despite anti-thrombotic therapy prompted a re-evaluation of the clinical presentation. New potential causes of thrombosis emerged in this patient, including thrombocytosis associated with the <it>JAK2 V617F </it>mutation and the very rare mural thrombosis of the descending aorta. A mural thrombus in the pulmonary artery was detected contiguous with the aortic mural thrombosis, raising the possibility of a clinically silent ductus Botalli as the initiating event. The patient was treated with warfarin, aspirin, hydroxyurea, and surgery.</p> <p>Conclusions</p> <p>The diagnosis was achieved via systematic use of imaging procedures and reconsideration of blood tests performed to explore the diagnosis of thrombosis. This allowed a deeper and more detailed analysis of the case beyond the conventional approach, which would have aimed to identify one cause for the condition at hand, in this case, atrial fibrillation. The broader approach that we used resulted in the diagnosis of multiple embolisms from multiple sites and multiple causes.</p

Hf-based high-k materials for Si nanocrystal floating gate memories

Pure and Si-rich HfO2 layers fabricated by radio frequency sputtering were utilized as alternative tunnel oxide layers for high-k/Si-nanocrystals-SiO2/SiO2 memory structures. The effect of Si incorporation on the properties of Hf-based tunnel layer was investigated. The Si-rich SiO2 active layers were used as charge storage layers, and their properties were studied versus deposition conditions and annealing treatment. The capacitance-voltage measurements were performed to study the charge trapping characteristics of these structures. It was shown that with specific deposition conditions and annealing treatment, a large memory window of about 6.8 V is achievable at a sweeping voltage of ± 6 V, indicating the utility of these stack structures for low-operating-voltage nonvolatile memory devices

The Evaluation of a Rapid In Situ HIV Confirmation Test in a Programme with a High Failure Rate of the WHO HIV Two-Test Diagnostic Algorithm

BACKGROUND: Concerns about false-positive HIV results led to a review of testing procedures used in a Médecins Sans Frontières (MSF) HIV programme in Bukavu, eastern Democratic Republic of Congo. In addition to the WHO HIV rapid diagnostic test algorithm (RDT) (two positive RDTs alone for HIV diagnosis) used in voluntary counselling and testing (VCT) sites we evaluated in situ a practical field-based confirmation test against western blot WB. In addition, we aimed to determine the false-positive rate of the WHO two-test algorithm compared with our adapted protocol including confirmation testing, and whether weakly reactive compared with strongly reactive rapid test results were more likely to be false positives. METHODOLOGY/PRINCIPAL FINDINGS: 2864 clients presenting to MSF VCT centres in Bukavu during January to May 2006 were tested using Determine HIV-1/2 and UniGold HIV rapid tests in parallel by nurse counsellors. Plasma samples on 229 clients confirmed as double RDT positive by laboratory retesting were further tested using both WB and the Orgenics Immunocomb Combfirm HIV confirmation test (OIC-HIV). Of these, 24 samples were negative or indeterminate by WB representing a false-positive rate of the WHO two-test algorithm of 10.5% (95%CI 6.6-15.2). 17 of the 229 samples were weakly positive on rapid testing and all were negative or indeterminate by WB. The false-positive rate fell to 3.3% (95%CI 1.3-6.7) when only strong-positive rapid test results were considered. Agreement between OIC-HIV and WB was 99.1% (95%CI 96.9-99.9%) with no false OIC-HIV positives if stringent criteria for positive OIC-HIV diagnoses were used. CONCLUSIONS: The WHO HIV two-test diagnostic algorithm produced an unacceptably high level of false-positive diagnoses in our setting, especially if results were weakly positive. The most probable causes of the false-positive results were serological cross-reactivity or non-specific immune reactivity. Our findings show that the OIC-HIV confirmation test is practical and effective in field contexts. We propose that all double-positive HIV RDT samples should undergo further testing to confirm HIV seropositivity until the accuracy of the RDT testing algorithm has been established at programme level

Genomic and epigenomic EBF1 alterations modulate TERT expression in gastric cancer

Transcriptional reactivation of telomerase catalytic subunit (TERT) is a frequent hallmark of cancer, occurring in 90% of human malignancies. However, specific mechanisms driving TERT reactivation remain obscure for many tumor types and in particular gastric cancer (GC), a leading cause of global cancer mortality. Here, through comprehensive genomic and epigenomic analysis of primary GCs and GC cell lines, we identified the transcription factor early B cell factor 1 (EBF1) as a TERT transcriptional repressor and inactivation of EBF1 function as a major cause of TERT upregulation. Abolishment of EBF1 function occurs through 3 distinct (epi)genomic mechanisms. First, EBF1 is epigenetically silenced via DNA methyltransferase, polycomb-repressive complex 2 (PRC2), and histone deacetylase activity in GCs. Second, recurrent, somatic, and heterozygous EBF1 DNA–binding domain mutations result in the production of dominant-negative EBF1 isoforms. Third, more rarely, genomic deletions and rearrangements proximal to the TERT promoter remobilize or abolish EBF1-binding sites, derepressing TERT and leading to high TERT expression. EBF1 is also functionally required for various malignant phenotypes in vitro and in vivo, highlighting its importance for GC development. These results indicate that multimodal genomic and epigenomic alterations underpin TERT reactivation in GC, converging on transcriptional repressors such as EBF1

In vitro and in vivo characterization of highly purified Human Mesothelioma derived cells

<p>Abstract</p> <p>Background</p> <p>Malignant pleural mesothelioma is a rare disease known to be resistant to conventional therapies. A better understanding of mesothelioma biology may provide the rationale for new therapeutic strategies. In this regard, tumor cell lines development has been an important tool to study the biological properties of many tumors. However all the cell lines established so far were grown in medium containing at least 10% serum, and it has been shown that primary cell lines cultured under these conditions lose their ability to differentiate, acquire gene expression profiles that differ from that of tissue specific stem cells or the primary tumor they derive from, and in some cases are neither clonogenic nor tumorigenic. Our work was aimed to establish from fresh human pleural mesothelioma samples cell cultures maintaining tumorigenic properties.</p> <p>Methods</p> <p>The primary cell cultures, obtained from four human pleural mesotheliomas, were expanded in vitro in a low serum proliferation-permissive medium and the expression of different markers as well as the tumorigenicity in immunodeficient mice was evaluated.</p> <p>Results</p> <p>The established mesothelioma cell cultures are able to engraft, after pseudo orthotopic intraperitoneal transplantation, in immunodeficient mouse and maintain this ability to after serial transplantation. Our cell cultures were strongly positive for CD46, CD47, CD56 and CD63 and were also strongly positive for some markers never described before in mesothelioma cell lines, including CD55, CD90 and CD99. By real time PCR we found that our cell lines expressed high mRNA levels of typical mesothelioma markers as mesothelin (MSLN) and calretinin (CALB2), and of BMI-1, a stemness marker, and DKK1, a potent Wingless [WNT] inhibitor.</p> <p>Conclusions</p> <p>These cell cultures may provide a valuable in vitro and in vivo model to investigate mesothelioma biology. The identification of new mesothelioma markers may be useful for diagnosis and/or prognosis of this neoplasia as well as for isolation of mesothelioma tumor initiating cells.</p