| 11. |
- Holmer, Hampus
(författare)
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Measuring global surgery, obstetrics and anaesthesia from health systems to patients
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundWorldwide, an estimated 5 billion people lack access to safe, affordable surgical care when needed. This leads to millions of avertable deaths and unnecessary morbidity each year. To change this situation, urgent action is needed at many levels, but indicators and data have been lacking to guide improvement.AimsThe aim of this thesis was to describe and evaluate measurement of surgical public health. Organised according to the Lancet Commission on Global Surgery indicator framework, the thesis specifically aimed to: I. quantify global access to emergency obstetric care; II. describe the global distribution of specialist surgeons, anaesthesiologists and obstetricians; III. measure the rate and mortality of Caesarean sections in Sierra Leone, the country with the world’s highest maternal mortality; IV. to propose a new study design for collecting data on surgical outcomes; V. calculate the cost-effectiveness of surgical care, as exemplified by Ponseti club foot repair, and; VI. critically review the global data collection efforts of the six Lancet global surgery indicators.MethodsTo address these aims, a range of methodologies were employed: I. Available reports of national and sub-national data on the met need for emergency obstetric care were collected, reviewed and analysed; II. National data on the number and distribution of the specialist surgical workforce were collected; III. The rate and outcomes of Caesarean sections in Sierra Leone were analysed based on data from facilities and from the national Maternal Death Surveillance and Response system; IV. A protocol for collecting data on perioperative mortality of emergency abdominal surgery was developed; V. Cost effectiveness analysis was carried out for club foot repair; VI. Data on the six indicators proposed by the Lancet Commission on Global Surgery in 2015 were collected, and indicators analysed and critically reviewed.ResultsThe global met need for emergency obstetric care was 45% [interquartile range 28–57%], and the met need was significantly correlated with the proportion of births attended by skilled birth attendants. There were an estimated two million specialist surgeons, obstetricians and anaesthesiologists, of which only 20% serve the poorest half of the world. In 2016, the Sierra Leonean Caesarean section rate was 2.9% of all deliveries, with a perioperative mortality rate of 1.5%. A multicentre, international, prospective cohort study protocol for the measurement of perioperative mortality of emergency abdominal surgery was published. Clubfoot repair by the Ponseti method was highly cost-effective at 22 USD per averted Disability Adjusted Life Year. The six indicators proposed by The Lancet Commission on Global Surgery have been implemented to varying degrees, with definitional challenges as well as lack of commitment and structures for data collection.SignificanceMeasuring global surgery, obstetrics and anaesthesia – from health systems to patients explores methods of measuring surgical care in the context of a growing recognition of the need to increase access to safe, affordable surgical care around the globe. This research has provided baseline data on several indicators, some of which have been adopted by the WHO and the World Bank. Furthermore, it has critically reviewed the six indicators proposed for global implementation, and made suggestions for further improvement. Good quality indicators are paramount for guiding further efforts in global surgery, obstetrics and anaesthesia, with potential impact for surgical patients, families and societies today and in the future.
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| 12. |
- Malmström, Annika, 1957-
(författare)
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Studies for Better Treatment of Patients with Glioma
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In Sweden annually over 500 people will be diagnosed with the malignant brain tumor glioma. They are graded from I-IV. The majority are glioblastoma (grade IV) (GBM), these being the most aggressive type. Median survival for those treated with standard of care is expected to be around 15 months. This tumor will mainly affect those 60 years or older.The studies in this thesis focus on treatment of patients with malignant gliomas grade III and IV. The aim of the studies is to improve the care of glioma patients. Papers I and II explored different therapeutic options in randomized trials, to facilitate individualized treatment recommendations. Findings from studies I and II, together with additional trials, demonstrated the importance of analyzing the tumor marker O6-methylguanine DNA methyltransferase (MGMT) methylation status for survival of GBM patients treated with Temozolomide (TMZ). The third paper investigated how the analysis of this marker is implemented internationally.The first study (paper I, Nordic trial) investigated treatment options for patients 60 years or older with GBM. The trial compared standard radiotherapy (SRT) over 6 weeks versus hypofractionated radiotherapy (HRT) over 2 weeks versus single agent TMZ administered in up to six 4 weekly cycles. In all, 342 patients were included in the trial. This study demonstrated that those randomized to TMZ had superior survival as compared to SRT. In addition, quality of life (QoL) data also suggested a better QoL for TMZ treatment than for radiotherapy. The benefit of TMZ treatment seemed to be limited to those with the tumor molecular marker MGMT methylated (inactivated).The second trial (paper II, Neoadjuvant trial) studied whether integrating TMZ treatment with SRT for patients younger than 60 years with GBM (grade IV) and astrocytoma grade III would confer a survival benefit, if administered postoperatively, before the start of SRT (neoadjuvant). TMZ was provided for 2-3 four weekly cycles followed by SRT to patients randomized to neoadjuvant treatment and was compared to postoperative SRT alone. Although this trial could not illustrate any advantage of delaying the start of SRT while administering TMZ for the study cohort in general, for those included as astrocytoma grade III the median survival was found to be superior by 5 years when randomized to neoadjuvant TMZ. This trial also confirmed the importance of MGMT promoter methylation for the efficacy of TMZ.The third study (paper III) investigated international practices for analyzing tumor MGMT promoter methylation status. MGMT analysis can be conducted by various laboratory methods, which in some cases can provide opposing results regarding the MGMT methylation status of the patient´s tumor. This can lead to incorrect treatment recommendations. To establish which methods and cut-offs that are regularly used to determine tumor MGMT status in the clinic, an international survey was provided to those working in the field. We also inquired about opinions regarding an international consensus on how MGMT should be tested. The 152 respondents reported several methodologies and different cut-off levels also for the same method. A majority of respondents warrant international guidelines.In conclusion, the results of the 2 randomized trials contribute to individualized treatment recommendations for patients affected by GBM or astrocytoma grade III. The results of the survey regarding analyses of MGMT clarify the current problematic situation. The request of the respondents regarding international guidelines might contribute to their future development, so that personalized treatment recommendations can be improved.
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| 13. |
- Ali, Muhaddisa Barat, 1986, et al.
(författare)
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Multi-stream Convolutional Autoencoder and 2D Generative Adversarial Network for Glioma Classification
- 2019
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Ingår i: Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics). - Cham : Springer International Publishing. - 1611-3349 .- 0302-9743. ; 11678 LNCS, s. 234-245
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Konferensbidrag (refereegranskat)abstract
- Diagnosis and timely treatment play an important role in preventing brain tumor growth. Deep learning methods have gained much attention lately. Obtaining a large amount of annotated medical data remains a challenging issue. Furthermore, high dimensional features of brain images could lead to over-fitting. In this paper, we address the above issues. Firstly, we propose an architecture for Generative Adversarial Networks to generate good quality synthetic 2D MRIs from multi-modality MRIs (T1 contrast-enhanced, T2, FLAIR). Secondly, we propose a deep learning scheme based on 3-streams of Convolutional Autoencoders (CAEs) followed by sensor information fusion. The rational behind using CAEs is that it may improve glioma classification performance (as comparing with conventional CNNs), since CAEs offer noise robustness and also efficient feature reduction hence possibly reduce the over-fitting. A two-round training strategy is also applied by pre-training on GAN augmented synthetic MRIs followed by refined-training on original MRIs. Experiments on BraTS 2017 dataset have demonstrated the effectiveness of the proposed scheme (test accuracy 92.04%). Comparison with several exiting schemes has provided further support to the proposed scheme.
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| 14. |
- Huvila, J., et al.
(författare)
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Combined ASRGL1 and p53 immunohistochemistry as an independent predictor of survival in endometrioid endometrial carcinoma
- 2018
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Ingår i: Gynecologic Oncology. - : Academic Press Inc.. - 0090-8258 .- 1095-6859. ; 149:1, s. 173-180
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Tidskriftsartikel (refereegranskat)abstract
- Objective: In clinical practise, prognostication of endometrial cancer is based on clinicopathological risk factors. The use of immunohistochemistry-based markers as prognostic tools is generally not recommended and a systematic analysis of their utility as a panel is lacking. We evaluated whether an immunohistochemical marker panel could reliably assess endometrioid endometrial cancer (EEC) outcome independent of clinicopathological information. Methods: A cohort of 306 EEC specimens was profiled using tissue microarray (TMA). Cost- and time-efficient immunohistochemical analysis of well-established tissue biomarkers (ER, PR, HER2, Ki-67, MLH1 and p53) and two new biomarkers (L1CAM and ASRGL1) was carried out. Statistical modelling with embedded variable selection was applied on the staining results to identify minimal prognostic panels with maximal prognostic accuracy without compromising generalizability. Results: A panel including p53 and ASRGL1 immunohistochemistry was identified as the most accurate predictor of relapse-free and disease-specific survival. Within this panel, patients were allocated into high- (5.9%), intermediate- (29.5%) and low- (64.6%) risk groups where high-risk patients had a 30-fold risk (P < 0.001) of dying of EEC compared to the low-risk group. Conclusions: P53 and ASRGL1 immunoprofiling stratifies EEC patients into three risk groups with significantly different outcomes. This simple and easily applicable panel could provide a useful tool in EEC risk stratification and guiding the allocation of treatment modalities.
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| 15. |
- Aulin, Cecilia, 1979-
(författare)
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Extracellular Matrix Based Materials for Tissue Engineering
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The extracellular matrix is (ECM) is a network of large, structural proteins and polysaccharides, important for cellular behavior, tissue development and maintenance. Present thesis describes work exploring ECM as scaffolds for tissue engineering by manipulating cells cultured in vitro or by influencing ECM expression in vivo. By culturing cells on polymer meshes under dynamic culture conditions, deposition of a complex ECM could be achieved, but with low yields. Since the major part of synthesized ECM diffused into the medium the rate limiting step of deposition was investigated. This quantitative analysis showed that the real rate limiting factor is the low proportion of new proteins which are deposited as functional ECM. It is suggested that cells are pre-embedded in for example collagen gels to increase the steric retention and hence functional deposition. The possibility to induce endogenous ECM formation and tissue regeneration by implantation of growth factors in a carrier material was investigated. Bone morphogenetic protein-2 (BMP-2) is a growth factor known to be involved in growth and differentiation of bone and cartilage tissue. The BMP-2 processing and secretion was examined in two cell systems representing endochondral (chondrocytes) and intramembranous (mesenchymal stem cells) bone formation. It was discovered that chondrocytes are more efficient in producing BMP-2 compared to MSC. The role of the antagonist noggin was also investigated and was found to affect the stability of BMP-2 and modulate its effect. Finally, an injectable gel of the ECM component hyaluronan has been evaluated as delivery vehicle in cartilage regeneration. The hyaluronan hydrogel system showed promising results as a versatile biomaterial for cartilage regeneration, could easily be placed intraarticulary and can be used for both cell based and cell free therapies.
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| 16. |
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| 17. |
- Sundbom, Magnus, et al.
(författare)
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Substantial Decrease in Comorbidity 5 Years After Gastric Bypass: A Population-based Study From the Scandinavian Obesity Surgery Registry.
- 2017
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Ingår i: Annals of Surgery. - Philadelphia PA, USA : Lippincott Williams & Wilkins. - 0003-4932 .- 1528-1140. ; 265:6, s. 1166-1171
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate effect on comorbid disease and weight loss 5 years after Roux-en-Y gastric bypass (RYGB) surgery for morbid obesity in a large nationwide cohort. Background: The number patients having surgical procedures to treat obesity and obesity-related disease are increasing. Yet, population-based, long-term outcome studies are few. Methods: Data on 26,119 individuals [75.8% women, 41.0 years, and body mass index (BMI) 42.8 kg/m2] undergoing primary RYGB between May 1, 2007 and June 30, 2012, were collected from 2 Swedish quality registries: Scandinavian Obesity Surgery Registry and the Prescribed Drug Registry. Weight, remission of type 2 diabetes mellitus, hypertension, dyslipidemia, depression, and sleep apnea, and changes in corresponding laboratory data were studied. Five-year follow-up was 100% (9774 eligible individuals) for comorbid diseases. Results: BMI decreased from 42.8 ± 5.5 to 31.2 ± 5.5 kg/m2 at 5 years, corresponding to 27.7% reduction in total body weight. Prevalence of type 2 diabetes mellitus (15.5%–5.9%), hypertension (29.7%–19.5%), dyslipidemia (14.0%–6.8%), and sleep apnea (9.6%–2.6%) was reduced. Greater weight loss was a positive prognostic factor, whereas increasing age or BMI at baseline was a negative prognostic factor for remission. The use of antidepressants increased (24.1%–27.5%). Laboratory status was improved, for example, fasting glucose and glycated hemoglobin decreased from 6.1 to 5.4 mmol/mol and 41.8% to 37.7%, respectively. Conclusions: In this nationwide study, gastric bypass resulted in large improvements in obesity-related comorbid disease and sustained weight loss over a 5-year period. The increased use of antidepressants warrants further investigation. Studies with long-term results after bariatric surgery are surprisingly rare, 1–5 especially in the light of the large number of procedures performed worldwide. In most studies there is a 1 to 2-year follow-up, 6 and at such an early point in time, it is impossible to evaluate the true effect of gastric bypass, because patients have just reached their nadir in weight. Moreover, for this group of patients, the longstanding remission of obesity-related comorbidities, for example, diabetes mellitus, hypertension, dyslipidemia, and sleep apnea, are of utmost importance. The Scandinavian Obesity Surgery Registry (SOReg) was launched in 2007 as a quality registry for the expanding number of bariatric surgeries in Sweden. 7 In 2015, SOReg contained more than 50,000 bariatric procedures (>98% national coverage), with all 43 operating centers reporting to the registry. There has been an expansion of bariatric surgery, with 3300 bariatric procedures performed in 2008, 4800 in 2009, 7800 in 2010, and 8600 in 2011. There has been a slight decrease in procedures, and currently approximately 7000 performed annually, and approximately 95% of the reported procedures have been primary laparoscopic gastric bypass. 8 Perioperative complication rates (eg, 1.2% leaks) and mortality are low (0.04%), the latter validated with the Swedish Population Register. Regular audits are performed by randomly comparing data in SOReg with patient charts at the surgical centers, demonstrating a high validity with less than 2% incorrect values. 7 Furthermore, by cross-linkage with the national Prescribed Drug Registry (PDR), a 100% follow-up of the occurrence of comorbid disease (defined as medical treatment) can be achieved. The present study reports outcome in weight and obesity-related comorbid disease in a nationwide cohort of 26,119 individuals over 5 years after primary Roux-en-Y gastric bypass (RYGB) in Sweden, using the prospective SOReg database with cross-linkage with the PDR.
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| 18. |
- Ge, Chenjie, 1991, et al.
(författare)
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Cross-Modality Augmentation of Brain Mr Images Using a Novel Pairwise Generative Adversarial Network for Enhanced Glioma Classification
- 2019
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Ingår i: Proceedings - International Conference on Image Processing, ICIP. - 1522-4880.
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Konferensbidrag (refereegranskat)abstract
- © 2019 IEEE. Brain Magnetic Resonance Images (MRIs) are commonly used for tumor diagnosis. Machine learning for brain tumor characterization often uses MRIs from many modalities (e.g., T1-MRI, Enhanced-T1-MRI, T2-MRI and FLAIR). This paper tackles two issues that may impact brain tumor characterization performance from deep learning: insufficiently large training dataset, and incomplete collection of MRIs from different modalities. We propose a novel pairwise generative adversarial network (GAN) architecture for generating synthetic brain MRIs in missing modalities by using existing MRIs in other modalities. By improving the training dataset, we aim to mitigate the overfitting and improve the deep learning performance. Main contributions of the paper include: (a) propose a pairwise generative adversarial network (GAN) for brain image augmentation via cross-modality image generation; (b) propose a training strategy to enhance the glioma classification performance, where GAN-augmented images are used for pre-training, followed by refined-training using real brain MRIs; (c) demonstrate the proposed method through tests and comparisons of glioma classifiers that are trained from mixing real and GAN synthetic data, as well as from real data only. Experiments were conducted on an open TCGA dataset, containing 167 subjects for classifying IDH genotypes (mutation or wild-type). Test results from two experimental settings have both provided supports to the proposed method, where glioma classification performance has consistently improved by using mixed real and augmented data (test accuracy 81.03%, with 2.57% improvement).
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| 19. |
- Pourhamidi, Kaveh, et al.
(författare)
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Evaluation of clinical tools and their diagnostic use in distal symmetric polyneuropathy
- 2014
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Ingår i: Primary care diabetes. - : Elsevier. - 1878-0210 .- 1751-9918. ; 8:1, s. 77-84
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: To compare the diagnostic usefulness of tuning fork, monofilament, biothesiometer and skin biopsies in peripheral neuropathy in individuals with varying glucose metabolism.METHODS: Normoglycaemic, impaired glucose tolerance (IGT) and type 2 diabetes (T2DM) individuals were recruited. Nerve conduction studies (NCS) and thermal threshold tests were performed. Vibrotactile sense was tested with a biothesiometer and a 128-Hz tuning fork. Touch/pressure perception was examined with a 10-g monofilament. Skin biopsies were performed and intraepidermal nerve fibres were quantified. Distal symmetric polyneuropathy (DSPN) was defined as neuropathy disability score ≥2 and abnormal NCS. Thermal threshold tests were used to define small nerve fibre neuropathy (sDSPN) in cases where NCS (large nerve fibres) were normal.RESULTS: The prevalence of DSPN and sDSPN in the whole group (n=119) was 18% and 23%, respectively. For the biothesiometer, a cut-off of ≥24.5V had a sensitivity of 82% and specificity of 70% (AUC=0.81, 95% CI 0.71-0.91) when evaluating DSPN. An intraepidermal nerve fibre density cut-off of ≤3.39fibres/mm showed a sensitivity of 74% and specificity of 70% in the detection of sDSPN, whereas the sensitivity of the tuning fork and the biothesiometer were relatively low, 46% and 67%, respectively. When combining skin biopsies with the tuning fork, 10 more sDSPN cases were identified. Adding skin biopsy to the combination of the tuning fork and biothesiometer increased the sensitivity of finding sDSPN cases, but not DSPN, from 81% to 93%.CONCLUSION: Using a biothesiometer in clinical routine might be a sensitive method to detect large nerve fibre dysfunction in the lower extremity, whereas skin biopsies in combination with methods measuring vibrotactile sense could increase the diagnostic sensitivity of detecting peripheral neuropathy at an early stage.
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| 20. |
- Farahmand, Dan, et al.
(författare)
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Intracranial pressure in hydrocephalus: impact of shunt adjustments and body positions
- 2015
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Ingår i: Journal of Neurology Neurosurgery and Psychiatry. - : BMJ. - 0022-3050 .- 1468-330X. ; 86:2, s. 222-228
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Tidskriftsartikel (refereegranskat)abstract
- Background The association between intracranial pressure (ICP) and different shunt valve opening pressures in relation to body positions is fundamental for understanding the physiological function of the shunt. Objective To analyse the ICP and ICP wave amplitude (AMP) at different shunt settings and body positions in patients with hydrocephalus. Methods In this prospective study 15 patients with communicating hydrocephalus were implanted with a ligated adjustable ventriculoperitoneal shunt. They also received a portable intraparenchymatous ICP-monitoring device. Postoperative ICP and AMP were recorded with the patients in three different body positions (supine, sitting and walking) and with the shunt ligated and open at high, medium and low valve settings. In each patient 12 10 min segments were coded, blinded and analysed for mean ICP and mean AMP using an automated computer algorithm. Results Mean ICP and mean AMP were lower at all three valve settings compared with the ligated shunt state (p<0.001). Overall, when compared with the supine position, mean ICP was 11.5 +/- 1.1 (mean +/- SD) mm Hg lower when sitting and 10.5 +/- 1.1 mm Hg lower when walking (p<0.001). Mean ICP was overall 1.1 mm Hg higher (p=0.042) when walking compared with sitting. The maximal adjustability difference (highest vs lowest valve setting) was 4.4 mm Hg. Conclusions Changing from a supine to an upright position reduced ICP while AMP only increased at trend level. Lowering of the shunt valve opening pressure decreased ICP and AMP but the difference in mean ICP in vivo between the highest and lowest opening pressures was less than half that previously observed in vitro.
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