BACKGROUND Glucagon-like peptide-1 receptor agonists(GLP-1RA)and sodium-glucose co-transporter-2 inhibitors(SGLT-2I)are associated with significant cardiovascular benefit in type 2 diabetes(T2D).However,GLP-1RA or SGL...BACKGROUND Glucagon-like peptide-1 receptor agonists(GLP-1RA)and sodium-glucose co-transporter-2 inhibitors(SGLT-2I)are associated with significant cardiovascular benefit in type 2 diabetes(T2D).However,GLP-1RA or SGLT-2I alone may not improve some cardiovascular outcomes in patients with prior cardiovascular co-morbidities.AIM To explore whether combining GLP-1RA and SGLT-2I can achieve additional benefit in preventing cardiovascular diseases in T2D.METHODS The systematic review was conducted according to PRISMA recommendations.The protocol was registered on PROSPERO(ID:42022385007).A total of 107049 participants from eligible cardiovascular outcomes trials of GLP-1RA and SGLT-2I were included in network meta-regressions to estimate cardiovascular benefit of the combination treatment.Effect modification of prior myocardial infarction(MI)and heart failure(HF)was also explored to provide clinical insight as to when the INTRODUCTION The macro-and micro-vascular benefits of glucagon-like peptide-1 receptor agonists(GLP-1RA)and sodium-glucose co-transporter-2 inhibitors(SGLT-2I)are independent of their glucose-lowering effects[1].In patients with type 2 diabetes(T2D),the major cardiovascular outcome trials(CVOT)showed that dipeptidyl peptidase-4 inhibitors(DPP-4I)did not improve cardiovascular outcomes[2],whereas cardiovascular benefit of GLP-1RA or SGLT-2I was significant[3,4].Further subgroup analyses indicated that the background cardiovascular risk should be considered when examining the cardiovascular outcomes of these newer glucose-lowering medications.For instance,prevention of major adverse cardiovascular events(MACE)was only seen in those patients with baseline atherosclerotic cardiovascular disease[3,4].Moreover,a series of CVOT conducted in patients with heart failure(HF)have demonstrated that(compared with placebo)SGLT-2I significantly reduced risk of hospitalization for HF or cardiovascular death,irrespective of their history of T2D[5-8].However,similar cardiovascular benefits were not observed in those with myocardial infarction(MI)[9,10].Cardiovascular co-morbidities are not only approximately twice as common but are also associated with dispropor-tionately worse cardiovascular outcomes in patients with T2D,compared to the general population[11].Therefore,it is of clinical importance to investigate whether the combination treatment of GLP-1RA and SGLT-2I could achieve greater cardiovascular benefit,particularly when considering patients with cardiovascular co-morbidities who may not gain sufficient cardiovascular protection from the monotherapies.This systematic review with multiple network meta-regressions was mainly aimed to explore whether combining GLP-1RA and SGLT-2I can provide additional cardiovascular benefit in T2D.Cardiovascular outcomes of these newer antidiabetic medications were also estimated under effect modification of prior cardiovascular diseases.This was to provide clinical insight as to when the combination treatment might be prioritized.展开更多
Hepatocellular carcinoma (HCC) is one of the commonest cancers worldwide, particularly in parts of the developing world, and is increasing in incidence. This article reviews the current modalities employed for the dia...Hepatocellular carcinoma (HCC) is one of the commonest cancers worldwide, particularly in parts of the developing world, and is increasing in incidence. This article reviews the current modalities employed for the diagnosis of HCC, including serum markers, radiological techniques and histological evaluation, and summarises international guidelines for the diagnostic approach to HCC.展开更多
AIM： To assess the effectiveness of the current UK clinical practice in reducing hepatic fat （IHCL）.METHODS： Whole body MRI and IH MRS were obtained, before and after 6 mo nutritional counselling, from liver, sole...AIM： To assess the effectiveness of the current UK clinical practice in reducing hepatic fat （IHCL）.METHODS： Whole body MRI and IH MRS were obtained, before and after 6 mo nutritional counselling, from liver, soleus and tibialis muscles in 10 subjects with non-alcoholic fatty liver disease （NAFLD）.RESULTS： A 500 Kcal-restricted diet resulted in an average weight loss of 4% （-3.4 kg,） accompanied by significant reductions in most adipose tissue （AT） depots, including subcutaneous （-9.9%）, abdominal subcutaneous （-10.2%） and intra-abdominal- AT （-11.4%）. Intramyocellular lipids （IMCL） were significantly reduced in the tibialis muscle （-28.2%）. Decreases in both IHCL （-39.9%） and soleus IMCL （-12.2%） content were also observed, although these were not significant. Several individuals showed dramatic decreases in IHCL, while others paradoxically showed increases in IHCL content. Changes in body composition were accompanied by improvements in certain liver function tests： serum aspartate aminotransferase （AST） and alanine aminotransferase （ALT）. Significant correlations were found between decreases in IHCL and reductions in both intra-abdominal and abdominal subcutaneous AT. Improvements in liver function tests were associated with reductions in intra-abdominal AT, but not with changes in IHCL. CONCLUSION： This study shows that even a very modest reduction in body weight achieved through lifestyle modification can result in changes in body fat depots and improvements in LETs.展开更多
AIM： To evaluate the safety and clinical efficacy of a new immunotherapy using both α-Gal epitope-pulsed dendritic cells （DCs） and cytokine-induced killer cells. METHODS： Freshly collected hepatocellular carcino...AIM： To evaluate the safety and clinical efficacy of a new immunotherapy using both α-Gal epitope-pulsed dendritic cells （DCs） and cytokine-induced killer cells. METHODS： Freshly collected hepatocellular carcinoma （HCC） tumor tissues were incubated with a mixture of neuraminidase and recombinant αl,3-galactosyltrans- ferase （αI,3GT） to synthesize α-Gal epitopes on car- bohydrate chains of the glycoproteins of tumor mem- branes. The subsequent incubation of the processed membranes in the presence of human natural anti-Gal IgG resulted in the effective phagocytosis to the tumor membrane by DCs. Eighteen patients aged 38-78 years with stage 111 primary HCC were randomly chosen for the study; 9 patients served as controls, and 9 patients were enrolled in the study group.RESULTS： The evaluation demonstrated that the pro- cedure was safe; no serious side effects or autoimmune diseases were observed. The therapy significantly pro- longed the survival of treated patients as compared with the controls （17.1 ± 2.01 mo vs 10.1 ±4.5 mo, P = 0.00121）. After treatment, all patients in the study group had positive delayed hypersensitivity and robust systemic cytotoxicity in response to tumor lysate as measured by interferon-y-expression in peripheral blood mononuclear cells using enzyme-linked immunosorbent spot assay. They also displayed increased numbers of CD8-, CD45RO- and CD56-positive cells in the peripheral blood and decreased α-fetoprotein level in the se- rum. CONCLUSION： This new tumor-specific immunotherapy is safe, effective and has a great potential for the treat- ment of tumors.展开更多
OBJECTIVE To investigate the effect of microRNA-32 on cold-induced thermogenesis and brown adipocyte energy metabolism.METHODS To apply the cold-induced thermogenesis model in mice,8-10 week old male C57Bl6 mice were ...OBJECTIVE To investigate the effect of microRNA-32 on cold-induced thermogenesis and brown adipocyte energy metabolism.METHODS To apply the cold-induced thermogenesis model in mice,8-10 week old male C57Bl6 mice were placed within a 6℃fridge for 7d.Control microRNA inhibitor or miR-32 inhibitor(10mg·kg-1)was administered via intraperitoneal injection 16 hbefore the mice were placed in the fridge.Daily core body temperatures were taken using a rectal temperature probe.Mice were euthanized after 7dand brown adipose tissue(BAT),inguinal and epididymal white adipose tissue(WAT),skeletal muscle and liver tissue analysed for changes in morphology and gene expression.RESULTS miR-32 inhibition in vivoinhibits the emergence of beige cells,which function like BAT cells,within WAT.In silico prediction and gene ontology analysis identified Tob1 as a likely target gene of miR-32.miR-32 inhibition led to increased expression of Tob1 whilst mutation of target sequence abolished this effect.Expression of brown adipose markers such as Ucp1,Pgc1α,Pparαand Prdm16 were significantly reduced in inguinal white adipose tissue(P<0.05).There was also a significant decrease in serumfgf21 levels due to the inhibition of Fgf21 expression in BAT(P<0.05).p38/MAPK signalling in brown adipose tissue was also significantly inhibited within brown adipose tissue leading to decreased fgf21 expression and secretion.CONCLUSION Our study shows that miR-32 plays a crucial role in stimulating beige cell emergence by activating p38/MAPK signalling during cold thermogenesis.miR-32 may prove effective as a treatment for obesity by activating cold-induced thermogenesis leading to increased energy metabolism.展开更多
Giardia is an enteric protozoan that infects a wide range of vertebrate hosts, being considered a major causative agent of gastrointestinal disease in humans in both developing and developed countries. Giardia infecti...Giardia is an enteric protozoan that infects a wide range of vertebrate hosts, being considered a major causative agent of gastrointestinal disease in humans in both developing and developed countries. Giardia infection has also a significant impact on livestock health, causing diarrhoea and resulting in significant economic lost. Transmission is either direct, through the faecal-oral route, or indirect, through ingestion of contaminated water or food. In this article, we review current knowledge about the epidemiology of giardiasis in different populations in Spain, including humans, livestock, companion animals, and wildlife. Environmental contamination of surface waters and raw foods by Giardia cysts is also addressed. Special relevance has been given to the data available on the molecular characterization of the Giardia isolates obtained from clinical and environmental samples, as determining thespecies/assemblages and subassemblages involved is essential for accurately identifying the parasite and assessing zoonotic transmission. The public health significance of these findings has also been thoroughly discussed.展开更多
Background and aims: The potentially high costs of care associated with inflammatory bowel disease (IBD) are recognised but we have little knowledge of the scale, profile, or determinants of these costs in the UK. Thi...Background and aims: The potentially high costs of care associated with inflammatory bowel disease (IBD) are recognised but we have little knowledge of the scale, profile, or determinants of these costs in the UK. This study aimed to describe costs of illness for a group of IBD patients and determine factors associated with increased healthcare costs. Setting: A university hospital serving a target population of approximately 330 000. Patients and methods: A six month cohort of IBD patients receiving any form of secondary care was identified, comprising 307 cases of ulcerative (or indeterminate) colitis and 172 cases of Crohns disease. Demographic and clinical data were abstracted from clinical records and individual resource use was itemised for all attributable costs (including extraintestinal manifestations). Item costs were derived from national and local sources. Cost data were expressed as mean six month costs per patient (with 95%confidence interval (CI)) obtained using non parametric bootstrapping. Determinants of cost were analysed using generalised linear regression modelling. A postal survey of patients was undertaken to examine indirect costs, out of pocket expenses, and primary care visits. Results: Inpatient services (medical and/or surgical) were required by 67 patients (14%) but accounted for 49%of total secondary care costs. Drug costs accounted for less than a quarter of total costs. Individual patient costs ranged from ￡73 to ￡33 254 per six months. Mean (95%CI) six month costs per patient were ￡1256 (￡988, ￡1721) for colitis and ￡1652 (￡1221, ￡2239) for Crohns disease. Hospitalisation, disease severity grade, and disease extent correlated positively with cost of illness but costs were independent of age or sex. Comparedwith quiescent cases of IBD, disease relapse was associated with a 2-3-fold increase in costs for non hospitalised cases and a 20-fold increase in costs for hospitalised cases. Survey data suggested average six month costs were< ￡30 per patient for primary care visits (both diseases) and median loss of earnings were ￡239 for colitis and ￡299 for Crohns disease. Conclusions: This study represents the first detailed characterisation of the scale and determinants of costs of illness for IBD in a British hospital. Hospitalisation affected a minority of sufferers but accounted for half of the total direct costs falling on the healthcare system.展开更多
Background: Oligodendroglial neoplasms with combined loss of chromosomes 1p a nd 19q may have a good prognosis and respond to procarbazine- lomustine (CCNU) - vincristine (PCV)- chemotherapy. Objective: To determine w...Background: Oligodendroglial neoplasms with combined loss of chromosomes 1p a nd 19q may have a good prognosis and respond to procarbazine- lomustine (CCNU) - vincristine (PCV)- chemotherapy. Objective: To determine whether single voxe l magnetic resonance spectroscopy (SV- MRS) obtained through routine clinical p ractice distinguishes between histopathologic and genetic subtypes of oligodendr oglial tumors. Methods: Forty- eight patients with oligodendroglial tumors (19 oligodendrogliomas and 29 oligoastrocytomas) underwent molecular genetic analysis to determine allelic imbalance in chromoso mes 1p36 and 19q13. SV- MRS was obtained pretherapy to determine tumor metaboli te ratios. Results: Grade III oligodendroglial tumors had higher choline (Mann- Whitney; p=0.002), methyl lipid (Mann- Whitney; p=0.002), and combined methyle ne lipid and lactate ratios (Mann- Whitney; p < 0.001)- than grade II tumors. Lactate did not distinguish between tumor types (Fisher exact test; p=0.342) or grade (Fisher exact test; p=0.452). There were no significant associations when tumors were analyzed according to histopathology or genetic subtypes. Conclusion : As a noninvasive diagnostic tool used in routine clinical practice, SV- MRS h as the potential benefit of determining oligodendroglial tumor grade but not sub types classified by histopathology or molecular genetics. MRS may be useful for determining the timing of therapy but is unlikely to predict chemosensitivity.展开更多
Objectives: The aetiology of the cognitive changes seen in Parkinson’s disease (PD) is multifactorial but it is likely that a significant contribution arises from the disruption of dopaminergic pathways. This study a...Objectives: The aetiology of the cognitive changes seen in Parkinson’s disease (PD) is multifactorial but it is likely that a significant contribution arises from the disruption of dopaminergic pathways. This study aimed to investigate the contribution of the dopaminergic system to performance on two executive tasks using 18F-6-fluorodopa positron emission tomography (F-dopa PET) in PD subjects with early cognitive changes. Methods: 16 non-demented, non-depressed PD subjects were evaluated with the Tower of London (TOL) spatial planning task, a verbal working memory task (VWMT) and 18F-dopa PET, all known to be affected in early PD. Statistical parametric mapping (SPM) localised brain regions in which 18F-dopa uptake covaried with performance scores. Frontal cortical resting glucose metabolism was assessed with 18F-fluoro-2-deoxy-D-glucose (18F-FDG) PET. Results: SPM localised significant covariation between right caudate 18F-dopa uptake (Ki) and TOL scores and between left anterior putamen Ki and VWMT performance. No significant covariation was found between task scores and F-dopa Ki values in either limbic or cortical regions. Frontal cortical glucose metabolism was preserved in all cases. Conclusions: These findings support a causative role of striatal dopaminergic depletion in the early impairment of executive functions seen in PD. They suggest that spatial and verbal executive tasks require integrity of the right and left striatum, respectively, and imply that the pattern of cognitive changes manifest by a patient with PD may reflect differential dopamine loss in the two striatal complexes.展开更多
基金Supported by China Scholarship Council,No.202006920018Key Talent Program for Medical Applications of Nuclear Technology,No.XKTJ-HRC2021007+2 种基金the Second Affiliated Hospital of Soochow University,No.SDFEYBS1815 and No.SDFEYBS2008National Natural Science Foundation of China,No.82170831The Jiangsu Innovation&Career Fund for PhD 2019.
文摘BACKGROUND Glucagon-like peptide-1 receptor agonists(GLP-1RA)and sodium-glucose co-transporter-2 inhibitors(SGLT-2I)are associated with significant cardiovascular benefit in type 2 diabetes(T2D).However,GLP-1RA or SGLT-2I alone may not improve some cardiovascular outcomes in patients with prior cardiovascular co-morbidities.AIM To explore whether combining GLP-1RA and SGLT-2I can achieve additional benefit in preventing cardiovascular diseases in T2D.METHODS The systematic review was conducted according to PRISMA recommendations.The protocol was registered on PROSPERO(ID:42022385007).A total of 107049 participants from eligible cardiovascular outcomes trials of GLP-1RA and SGLT-2I were included in network meta-regressions to estimate cardiovascular benefit of the combination treatment.Effect modification of prior myocardial infarction(MI)and heart failure(HF)was also explored to provide clinical insight as to when the INTRODUCTION The macro-and micro-vascular benefits of glucagon-like peptide-1 receptor agonists(GLP-1RA)and sodium-glucose co-transporter-2 inhibitors(SGLT-2I)are independent of their glucose-lowering effects[1].In patients with type 2 diabetes(T2D),the major cardiovascular outcome trials(CVOT)showed that dipeptidyl peptidase-4 inhibitors(DPP-4I)did not improve cardiovascular outcomes[2],whereas cardiovascular benefit of GLP-1RA or SGLT-2I was significant[3,4].Further subgroup analyses indicated that the background cardiovascular risk should be considered when examining the cardiovascular outcomes of these newer glucose-lowering medications.For instance,prevention of major adverse cardiovascular events(MACE)was only seen in those patients with baseline atherosclerotic cardiovascular disease[3,4].Moreover,a series of CVOT conducted in patients with heart failure(HF)have demonstrated that(compared with placebo)SGLT-2I significantly reduced risk of hospitalization for HF or cardiovascular death,irrespective of their history of T2D[5-8].However,similar cardiovascular benefits were not observed in those with myocardial infarction(MI)[9,10].Cardiovascular co-morbidities are not only approximately twice as common but are also associated with dispropor-tionately worse cardiovascular outcomes in patients with T2D,compared to the general population[11].Therefore,it is of clinical importance to investigate whether the combination treatment of GLP-1RA and SGLT-2I could achieve greater cardiovascular benefit,particularly when considering patients with cardiovascular co-morbidities who may not gain sufficient cardiovascular protection from the monotherapies.This systematic review with multiple network meta-regressions was mainly aimed to explore whether combining GLP-1RA and SGLT-2I can provide additional cardiovascular benefit in T2D.Cardiovascular outcomes of these newer antidiabetic medications were also estimated under effect modification of prior cardiovascular diseases.This was to provide clinical insight as to when the combination treatment might be prioritized.
基金Supported by The NIHR Biomedical Research Centre funding scheme and the following for authors’ funding and supportAIG is funded by a scholarship from the Egyptian Government+5 种基金SAK is supported by a grant from the Higher Education Funding Council for England (HEFCE)SDTR is funded by grants from the British Medical Research Council (MRC), London, United KingdomThe British Engineering, Physics and Science Research Council (EPSRC), Swindon, United KingdomThe Alan Morement Memorial Fund AMMF, Essex, United KingdomBroad Foundation, Los Angeles, United StatesPfizer Global Research and Development Inc, Sandwich, United Kingdom and GlaxoSmithKline, Ware, United Kingdom
文摘Hepatocellular carcinoma (HCC) is one of the commonest cancers worldwide, particularly in parts of the developing world, and is increasing in incidence. This article reviews the current modalities employed for the diagnosis of HCC, including serum markers, radiological techniques and histological evaluation, and summarises international guidelines for the diagnostic approach to HCC.
基金Supported by the British Medical Research Council, United Kingdom, No. MRC CEG G99000178
文摘AIM： To assess the effectiveness of the current UK clinical practice in reducing hepatic fat （IHCL）.METHODS： Whole body MRI and IH MRS were obtained, before and after 6 mo nutritional counselling, from liver, soleus and tibialis muscles in 10 subjects with non-alcoholic fatty liver disease （NAFLD）.RESULTS： A 500 Kcal-restricted diet resulted in an average weight loss of 4% （-3.4 kg,） accompanied by significant reductions in most adipose tissue （AT） depots, including subcutaneous （-9.9%）, abdominal subcutaneous （-10.2%） and intra-abdominal- AT （-11.4%）. Intramyocellular lipids （IMCL） were significantly reduced in the tibialis muscle （-28.2%）. Decreases in both IHCL （-39.9%） and soleus IMCL （-12.2%） content were also observed, although these were not significant. Several individuals showed dramatic decreases in IHCL, while others paradoxically showed increases in IHCL content. Changes in body composition were accompanied by improvements in certain liver function tests： serum aspartate aminotransferase （AST） and alanine aminotransferase （ALT）. Significant correlations were found between decreases in IHCL and reductions in both intra-abdominal and abdominal subcutaneous AT. Improvements in liver function tests were associated with reductions in intra-abdominal AT, but not with changes in IHCL. CONCLUSION： This study shows that even a very modest reduction in body weight achieved through lifestyle modification can result in changes in body fat depots and improvements in LETs.
基金Supported by Hong Kong Wang Kuan Cheng GrantInner Mongolia Stem Cell Grant, No. kjk10jhg
文摘AIM： To evaluate the safety and clinical efficacy of a new immunotherapy using both α-Gal epitope-pulsed dendritic cells （DCs） and cytokine-induced killer cells. METHODS： Freshly collected hepatocellular carcinoma （HCC） tumor tissues were incubated with a mixture of neuraminidase and recombinant αl,3-galactosyltrans- ferase （αI,3GT） to synthesize α-Gal epitopes on car- bohydrate chains of the glycoproteins of tumor mem- branes. The subsequent incubation of the processed membranes in the presence of human natural anti-Gal IgG resulted in the effective phagocytosis to the tumor membrane by DCs. Eighteen patients aged 38-78 years with stage 111 primary HCC were randomly chosen for the study; 9 patients served as controls, and 9 patients were enrolled in the study group.RESULTS： The evaluation demonstrated that the pro- cedure was safe; no serious side effects or autoimmune diseases were observed. The therapy significantly pro- longed the survival of treated patients as compared with the controls （17.1 ± 2.01 mo vs 10.1 ±4.5 mo, P = 0.00121）. After treatment, all patients in the study group had positive delayed hypersensitivity and robust systemic cytotoxicity in response to tumor lysate as measured by interferon-y-expression in peripheral blood mononuclear cells using enzyme-linked immunosorbent spot assay. They also displayed increased numbers of CD8-, CD45RO- and CD56-positive cells in the peripheral blood and decreased α-fetoprotein level in the se- rum. CONCLUSION： This new tumor-specific immunotherapy is safe, effective and has a great potential for the treat- ment of tumors.
基金The project supported by Singapore Institute for Clinical Sciences(SICS)A*STAR Singapore and BMRC Young Investigator Grant
文摘OBJECTIVE To investigate the effect of microRNA-32 on cold-induced thermogenesis and brown adipocyte energy metabolism.METHODS To apply the cold-induced thermogenesis model in mice,8-10 week old male C57Bl6 mice were placed within a 6℃fridge for 7d.Control microRNA inhibitor or miR-32 inhibitor(10mg·kg-1)was administered via intraperitoneal injection 16 hbefore the mice were placed in the fridge.Daily core body temperatures were taken using a rectal temperature probe.Mice were euthanized after 7dand brown adipose tissue(BAT),inguinal and epididymal white adipose tissue(WAT),skeletal muscle and liver tissue analysed for changes in morphology and gene expression.RESULTS miR-32 inhibition in vivoinhibits the emergence of beige cells,which function like BAT cells,within WAT.In silico prediction and gene ontology analysis identified Tob1 as a likely target gene of miR-32.miR-32 inhibition led to increased expression of Tob1 whilst mutation of target sequence abolished this effect.Expression of brown adipose markers such as Ucp1,Pgc1α,Pparαand Prdm16 were significantly reduced in inguinal white adipose tissue(P<0.05).There was also a significant decrease in serumfgf21 levels due to the inhibition of Fgf21 expression in BAT(P<0.05).p38/MAPK signalling in brown adipose tissue was also significantly inhibited within brown adipose tissue leading to decreased fgf21 expression and secretion.CONCLUSION Our study shows that miR-32 plays a crucial role in stimulating beige cell emergence by activating p38/MAPK signalling during cold thermogenesis.miR-32 may prove effective as a treatment for obesity by activating cold-induced thermogenesis leading to increased energy metabolism.
基金Supported by A grant from the Department of Health,Basque Government,Spain,Exp.No.2007111002
文摘Giardia is an enteric protozoan that infects a wide range of vertebrate hosts, being considered a major causative agent of gastrointestinal disease in humans in both developing and developed countries. Giardia infection has also a significant impact on livestock health, causing diarrhoea and resulting in significant economic lost. Transmission is either direct, through the faecal-oral route, or indirect, through ingestion of contaminated water or food. In this article, we review current knowledge about the epidemiology of giardiasis in different populations in Spain, including humans, livestock, companion animals, and wildlife. Environmental contamination of surface waters and raw foods by Giardia cysts is also addressed. Special relevance has been given to the data available on the molecular characterization of the Giardia isolates obtained from clinical and environmental samples, as determining thespecies/assemblages and subassemblages involved is essential for accurately identifying the parasite and assessing zoonotic transmission. The public health significance of these findings has also been thoroughly discussed.
文摘Background and aims: The potentially high costs of care associated with inflammatory bowel disease (IBD) are recognised but we have little knowledge of the scale, profile, or determinants of these costs in the UK. This study aimed to describe costs of illness for a group of IBD patients and determine factors associated with increased healthcare costs. Setting: A university hospital serving a target population of approximately 330 000. Patients and methods: A six month cohort of IBD patients receiving any form of secondary care was identified, comprising 307 cases of ulcerative (or indeterminate) colitis and 172 cases of Crohns disease. Demographic and clinical data were abstracted from clinical records and individual resource use was itemised for all attributable costs (including extraintestinal manifestations). Item costs were derived from national and local sources. Cost data were expressed as mean six month costs per patient (with 95%confidence interval (CI)) obtained using non parametric bootstrapping. Determinants of cost were analysed using generalised linear regression modelling. A postal survey of patients was undertaken to examine indirect costs, out of pocket expenses, and primary care visits. Results: Inpatient services (medical and/or surgical) were required by 67 patients (14%) but accounted for 49%of total secondary care costs. Drug costs accounted for less than a quarter of total costs. Individual patient costs ranged from ￡73 to ￡33 254 per six months. Mean (95%CI) six month costs per patient were ￡1256 (￡988, ￡1721) for colitis and ￡1652 (￡1221, ￡2239) for Crohns disease. Hospitalisation, disease severity grade, and disease extent correlated positively with cost of illness but costs were independent of age or sex. Comparedwith quiescent cases of IBD, disease relapse was associated with a 2-3-fold increase in costs for non hospitalised cases and a 20-fold increase in costs for hospitalised cases. Survey data suggested average six month costs were< ￡30 per patient for primary care visits (both diseases) and median loss of earnings were ￡239 for colitis and ￡299 for Crohns disease. Conclusions: This study represents the first detailed characterisation of the scale and determinants of costs of illness for IBD in a British hospital. Hospitalisation affected a minority of sufferers but accounted for half of the total direct costs falling on the healthcare system.
文摘Background: Oligodendroglial neoplasms with combined loss of chromosomes 1p a nd 19q may have a good prognosis and respond to procarbazine- lomustine (CCNU) - vincristine (PCV)- chemotherapy. Objective: To determine whether single voxe l magnetic resonance spectroscopy (SV- MRS) obtained through routine clinical p ractice distinguishes between histopathologic and genetic subtypes of oligodendr oglial tumors. Methods: Forty- eight patients with oligodendroglial tumors (19 oligodendrogliomas and 29 oligoastrocytomas) underwent molecular genetic analysis to determine allelic imbalance in chromoso mes 1p36 and 19q13. SV- MRS was obtained pretherapy to determine tumor metaboli te ratios. Results: Grade III oligodendroglial tumors had higher choline (Mann- Whitney; p=0.002), methyl lipid (Mann- Whitney; p=0.002), and combined methyle ne lipid and lactate ratios (Mann- Whitney; p < 0.001)- than grade II tumors. Lactate did not distinguish between tumor types (Fisher exact test; p=0.342) or grade (Fisher exact test; p=0.452). There were no significant associations when tumors were analyzed according to histopathology or genetic subtypes. Conclusion : As a noninvasive diagnostic tool used in routine clinical practice, SV- MRS h as the potential benefit of determining oligodendroglial tumor grade but not sub types classified by histopathology or molecular genetics. MRS may be useful for determining the timing of therapy but is unlikely to predict chemosensitivity.
文摘Objectives: The aetiology of the cognitive changes seen in Parkinson’s disease (PD) is multifactorial but it is likely that a significant contribution arises from the disruption of dopaminergic pathways. This study aimed to investigate the contribution of the dopaminergic system to performance on two executive tasks using 18F-6-fluorodopa positron emission tomography (F-dopa PET) in PD subjects with early cognitive changes. Methods: 16 non-demented, non-depressed PD subjects were evaluated with the Tower of London (TOL) spatial planning task, a verbal working memory task (VWMT) and 18F-dopa PET, all known to be affected in early PD. Statistical parametric mapping (SPM) localised brain regions in which 18F-dopa uptake covaried with performance scores. Frontal cortical resting glucose metabolism was assessed with 18F-fluoro-2-deoxy-D-glucose (18F-FDG) PET. Results: SPM localised significant covariation between right caudate 18F-dopa uptake (Ki) and TOL scores and between left anterior putamen Ki and VWMT performance. No significant covariation was found between task scores and F-dopa Ki values in either limbic or cortical regions. Frontal cortical glucose metabolism was preserved in all cases. Conclusions: These findings support a causative role of striatal dopaminergic depletion in the early impairment of executive functions seen in PD. They suggest that spatial and verbal executive tasks require integrity of the right and left striatum, respectively, and imply that the pattern of cognitive changes manifest by a patient with PD may reflect differential dopamine loss in the two striatal complexes.
