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- Adane, A, et al.
(författare)
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Exploring data quality and use of the routine health information system in Ethiopia: a mixed-methods study
- 2021
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:12, s. e050356-
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Tidskriftsartikel (refereegranskat)abstract
- A routine health information system (RHIS) enables decision making in the healthcare system. We aimed to analyse data quality at the district and regional level and explore factors and perceptions affecting the quality and use of routine data.DesignThis was a mixed-methods study. We used the WHO toolkit for analysing data quality and interviewed staff at the point of data generation and along with the flow of data. Data were analysed using the Performance of Routine Information System Management framework.SettingThis study was performed in eight districts in four regions of Ethiopia. The study was nested within a 2-year programme of the Operational Research and Coaching for government Analysts.ParticipantsWe visited 45 health posts, 1 district hospital, 16 health centres and 8 district offices for analysis of routine RHIS data and interviewed 117 staff members for the qualitative assessment.Outcome measuresWe assessed availability of source documents, completeness, timeliness and accuracy of reporting of routine data, and explored data quality and use perceptions.ResultsThere was variable quality of both indicator and data element. Data on maternal health and immunisation were of higher quality than data on child nutrition. Issues ranged from simple organisational factors, such as availability of register books, to intricate technical issues, like complexity of indicators and choice of denominators based on population estimates. Respondents showed knowledge of the reporting procedures, but also demonstrated limited skills, lack of supportive supervision and reporting to please the next level. We saw limited examples of the use of data by the staff who were responsible for data reporting.ConclusionWe identified important organisational, technical, behavioural and process factors that need further attention to improve the quality and use of RHIS data in Ethiopia.
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- Campieri, M, et al.
(författare)
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Oral budesonide is as effective as oral prednisolone in active Crohn's disease. The Global Budesonide Study Group
- 1997
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Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 41:2, s. 209-214
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Tidskriftsartikel (refereegranskat)abstract
- Background—The use of corticosteroids in active Crohn’s disease often becomes limited by side effects. Budesonide is a potent corticosteroid with low systemic bioavailability due to an extensive first pass liver metabolism.Aims—To compare the efficacy and safety of two dosage regimens of budesonide and prednisolone in patients with active Crohn’s disease affecting the ileum and/or the ascending colon.Patients and methods—One hundred and seventy eight patients were randomised to receive budesonide controlled ileal release (CIR) capsules 9 mg once daily or 4.5 mg twice daily, or prednisolone tablets 40 mg once daily. The treatment period was 12 weeks. The primary efficacy variable was clinical remission, defined as a Crohn’s Disease Activity Index (CDAI) of 150 or less.Results—After eight weeks of treatment, remission occurred in 60% of patients receiving budesonide once daily or prednisolone and in 42% of those receiving budesonide twice daily (p=0.062). The presence of glucocorticoid associated side effects was similar in all groups; however, moon face was more common in the prednisolone group (p=0.0005). The highest frequency of impaired adrenal function, as measured by a short ACTH test, was found in the prednisolone group (p=0.0023).Conclusions—Budesonide CIR, administered at 9 mg once daily or 4.5 mg twice daily, is comparable to prednisolone in inducing remission in active Crohn’s disease. The single dose administration is as promptly effective as prednisolone and represents a simpler and safer therapeutic approach, with a considerable reduction in side effects.
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- Del Chiaro, M, et al.
(författare)
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European evidence-based guidelines on pancreatic cystic neoplasms
- 2018
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 67:5, s. 789-804
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Tidskriftsartikel (refereegranskat)abstract
- Evidence-based guidelines on the management of pancreatic cystic neoplasms (PCN) are lacking. This guideline is a joint initiative of the European Study Group on Cystic Tumours of the Pancreas, United European Gastroenterology, European Pancreatic Club, European-African Hepato-Pancreato-Biliary Association, European Digestive Surgery, and the European Society of Gastrointestinal Endoscopy. It replaces the 2013 European consensus statement guidelines on PCN. European and non-European experts performed systematic reviews and used GRADE methodology to answer relevant clinical questions on nine topics (biomarkers, radiology, endoscopy, intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm (MCN), serous cystic neoplasm, rare cysts, (neo)adjuvant treatment, and pathology). Recommendations include conservative management, relative and absolute indications for surgery. A conservative approach is recommended for asymptomatic MCN and IPMN measuring <40 mm without an enhancing nodule. Relative indications for surgery in IPMN include a main pancreatic duct (MPD) diameter between 5 and 9.9 mm or a cyst diameter ≥40 mm. Absolute indications for surgery in IPMN, due to the high-risk of malignant transformation, include jaundice, an enhancing mural nodule >5 mm, and MPD diameter >10 mm. Lifelong follow-up of IPMN is recommended in patients who are fit for surgery. The European evidence-based guidelines on PCN aim to improve the diagnosis and management of PCN.
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- Hu, YZ, et al.
(författare)
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Neural network learning defines glioblastoma features to be of neural crest perivascular or radial glia lineages
- 2022
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Ingår i: Science advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 8:23, s. eabm6340-
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Tidskriftsartikel (refereegranskat)abstract
- Glioblastoma is believed to originate from nervous system cells; however, a putative origin from vessel-associated progenitor cells has not been considered. We deeply single-cell RNA–sequenced glioblastoma progenitor cells of 18 patients and integrated 710 bulk tumors and 73,495 glioma single cells of 100 patients to determine the relation of glioblastoma cells to normal brain cell types. A novel neural network–based projection of the developmental trajectory of normal brain cells uncovered two principal cell-lineage features of glioblastoma, neural crest perivascular and radial glia, carrying defining methylation patterns and survival differences. Consistently, introducing tumorigenic alterations in naïve human brain perivascular cells resulted in brain tumors. Thus, our results suggest that glioblastoma can arise from the brains’ vasculature, and patients with such glioblastoma have a significantly poorer outcome.
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- Pettersson, Helen, et al.
(författare)
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Arsenic trioxide is highly cytotoxic to small cell lung carcinoma cells.
- 2009
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Ingår i: Molecular Cancer Therapeutics. - 1538-8514 .- 1535-7163. ; 8:1, s. 160-170
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Tidskriftsartikel (refereegranskat)abstract
- Small cell lung carcinoma (SCLC) is an extremely aggressive form of cancer and current treatment protocols are insufficient. SCLC have neuroendocrine characteristics and show phenotypical similarities to the childhood tumor neuroblastoma. As multidrug-resistant neuroblastoma cells are highly sensitive to arsenic trioxide (As2O3) in vitro and in vivo, we here studied the cytotoxic effects of As2O3 on SCLC cells. As2O3 induced pronounced cell death in SCLC cells at clinically relevant concentrations, and also at hypoxia. SCLC cells were more sensitive than non-SCLC cells to As2O3. Cell death was mainly due to necrosis, although apoptotic responses were also seen. A significant in vivo effect of As2O3 on SCLC growth was shown in a nude mice-xenograft model, although a fraction of the treated tumor-bearing animals did not respond. The nonresponding SCLC tumors differed in morphology and cell organization compared with treatment-responsive tumors, which in turn, showed decreased vascularization and higher expression of neuroendocrine markers compared with control tumors. Our results suggest a potential clinical application of As2O3 in SCLC therapy. In addition to cell death induction, antiangiogenic induction of differentiation may also be part of the in vivo effect of As2O3 on SCLC growth, as suggested by an increase in neuroendocrine markers in cultured cells.
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- Saal, Lao, et al.
(författare)
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Recurrent gross mutations of the PTEN tumor suppressor gene in breast cancers with deficient DSB repair
- 2008
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:1, s. 102-107
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Tidskriftsartikel (refereegranskat)abstract
- Basal-like breast cancer (BBC) is a subtype of breast cancer with poor prognosis1, 2, 3. Inherited mutations of BRCA1, a cancer susceptibility gene involved in double-strand DNA break (DSB) repair, lead to breast cancers that are nearly always of the BBC subtype3, 4, 5; however, the precise molecular lesions and oncogenic consequences of BRCA1 dysfunction are poorly understood. Here we show that heterozygous inactivation of the tumor suppressor gene Pten leads to the formation of basal-like mammary tumors in mice, and that loss of PTEN expression is significantly associated with the BBC subtype in human sporadic and BRCA1-associated hereditary breast cancers. In addition, we identify frequent gross PTEN mutations, involving intragenic chromosome breaks, inversions, deletions and micro copy number aberrations, specifically in BRCA1-deficient tumors. These data provide an example of a specific and recurrent oncogenic consequence of BRCA1-dependent dysfunction in DNA repair and provide insight into the pathogenesis of BBC with therapeutic implications. These findings also argue that obtaining an accurate census of genes mutated in cancer will require a systematic examination for gross gene rearrangements, particularly in tumors with deficient DSB repair.
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- Zirath, Hanna, et al.
(författare)
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MYC inhibition induces metabolic changes leading to accumulation of lipid droplets in tumor cells
- 2013
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Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 110:25, s. 10258-10263
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Tidskriftsartikel (refereegranskat)abstract
- The MYC genes are the most frequently activated oncogenes in human tumors and are hence attractive therapeutic targets. MYCN amplification leads to poor clinical outcome in childhood neuroblastoma, yet strategies to modulate the function of MYCN do not exist. Here we show that 10058-F4, a characterized c-MYC/Max inhibitor, also targets the MYCN/Max interaction, leading to cell cycle arrest, apoptosis, and neuronal differentiation in MYCN-amplified neuroblastoma cells and to increased survival of MYCN transgenic mice. We also report the discovery that inhibition of MYC is accompanied by accumulation of intracellular lipid droplets in tumor cells as a direct consequence of mitochondrial dysfunction. This study expands on the current knowledge of how MYC proteins control the metabolic reprogramming of cancer cells, especially highlighting lipid metabolism and the respiratory chain as important pathways involved in neuroblastoma pathogenesis. Together our data support direct MYC inhibition as a promising strategy for the treatment of MYC-driven tumors.
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