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1.
Clin Transplant ; 38(1): e15245, 2024 01.
Article in English | MEDLINE | ID: mdl-38289884

ABSTRACT

INTRODUCTION: SARS-CoV-2 infection has had a significant impact on vulnerable individuals including transplant patients. Socioeconomic deprivation negatively affects outcomes of many health conditions. The aim of this study was to evaluate the effect of socioeconomic deprivation on the incidence and severity of SARS-CoV-2 infection among Welsh transplant patients. METHODS: This study is a retrospective, cross-sectional study on the transplant population of Wales. The Welsh Index of Multiple Deprivation (WIMD) was used to assess the influence of socioeconomic deprivation on outcomes of Welsh transplant patients who developed SARS-CoV-2 infection. Outcome measures were the incidence of SARS-CoV-2 infection, rates of hospital and ICU admission, development of acute kidney injury (AKI) and mortality. A logistic binomial regression analysis was used to correlate the various risk factors with the incidence of SARS-CoV-2 infection. RESULTS: Two hundred and sixty-six (25%) of regular follow up patients had SARS-CoV-2 infection; of these 55 (20.7%) were admitted, 15 (5.6%) to ICU, 37 (13.9%) developed AKI, and 23 (8.6%) died. In a regression analysis, patients of younger age were associated with more (p = .001) and those with SPK (simultaneous pancreas kidney) transplant less chance of infection (p = .038), whereas social deprivation was not associated with the chance of infection (p = .14). In regression analysis increased social deprivation was associated with higher chance of AKI post SARS-CoV-2 (p = .049). CONCLUSIONS: Socioeconomic deprivation did not affect the rates or severity of SARS-CoV-2 infection apart from the degree of AKI in Welsh Transplant patients. Adherence to the preventive measures for this high-risk population must continue to remain a priority.


Subject(s)
Acute Kidney Injury , COVID-19 , Humans , SARS-CoV-2 , COVID-19/epidemiology , Wales/epidemiology , Retrospective Studies , Cross-Sectional Studies , Socioeconomic Factors , Acute Kidney Injury/epidemiology , Acute Kidney Injury/etiology
2.
Diabetes Obes Metab ; 25(2): 468-478, 2023 02.
Article in English | MEDLINE | ID: mdl-36200477

ABSTRACT

AIMS: Evaluate the effects of once-weekly subcutaneous semaglutide 2.4 mg on cardiometabolic risk factors in people with overweight/obesity without diabetes in the STEP 1 and 4 trials. MATERIALS AND METHODS: STEP 1 and 4 were phase III, 68-week, placebo-controlled trials of once-weekly semaglutide 2.4 mg combined with lifestyle intervention; STEP 4 had a 20-week semaglutide run-in and 48-week randomized withdrawal period. Participants had a body mass index ≥30 kg/m2 or ≥27 kg/m2 with one or more weight-related comorbidity, without diabetes. Pre-specified endpoints were changes in waist circumference, systolic/diastolic blood pressure (SBP/DBP), lipids, fasting plasma glucose (FPG), fasting serum insulin and antihypertensive/lipid-lowering medication use. Post-hoc assessments included non-high-density lipoprotein (HDL) cholesterol, homeostatic model assessment of insulin resistance (HOMA-IR; STEP 1 only), atherosclerotic cardiovascular disease (ASCVD) risk (American College of Cardiology/American Heart Association algorithm; STEP 1 only) and cardiometabolic risk factors by weight loss achieved (<5%, 5% to <10%, 10% to <15%, or ≥15%) (STEP 1 only). RESULTS: Of the 1961 participants in STEP 1 and 803 in STEP 4, most had one or more complication/comorbidity at baseline, with dyslipidaemia and hypertension most prevalent. In STEP 1, reductions in waist circumference, SBP, DBP, FPG, fasting serum insulin, lipids and HOMA-IR were greater with semaglutide versus placebo (p ≤ .001). Reductions in SBP, non-HDL cholesterol, low-density lipoprotein cholesterol and FPG were generally greater with semaglutide than placebo within weight-loss categories. Non-significant ASCVD risk reductions were observed with semaglutide versus placebo (p > .05). In STEP 4, improvements in waist circumference, SBP, FPG, fasting serum insulin and lipids during the semaglutide run-in (week 0-20) were maintained over week 20-68 with continued semaglutide, but deteriorated following the switch to placebo (p < .001 [week 20-68]). Net reductions in antihypertensive/lipid-lowering medication use occurred with semaglutide versus placebo (both trials). CONCLUSIONS: Semaglutide may improve cardiometabolic risk factors and reduce antihypertensive/lipid-lowering medication use versus placebo in adults with overweight/obesity without diabetes. These potential benefits were not maintained after treatment discontinuation. GOV NUMBERS: STEP 1 NCT03548935, STEP 4 NCT03548987.


Subject(s)
Diabetes Mellitus, Type 2 , Insulins , Humans , Adult , Overweight/complications , Overweight/drug therapy , Overweight/chemically induced , Cardiometabolic Risk Factors , Antihypertensive Agents/therapeutic use , Obesity/complications , Obesity/drug therapy , Obesity/chemically induced , Glucagon-Like Peptides , Weight Loss , Lipids , Diabetes Mellitus, Type 2/drug therapy
3.
Australas Psychiatry ; 31(1): 27-33, 2023 02.
Article in English | MEDLINE | ID: mdl-36772936

ABSTRACT

OBJECTIVE: Prescribers' expectations of Zuclopethixol Acetate's (ZA) efficacy and tolerability are shaped by clinical experience and organisational culture; however, these expectations may not be consistent with current evidence and best practice. METHODS: Quality improvement project (QIP) through a process audit of ZA prescribing, monitoring and patient outcomes (adverse events) in order to identify issues requiring intervention to align with service standards and practices. RESULTS: QIP interventions resulted in a statistically significant shift in psychiatrist oversight, identifying high dose ZA with adverse outcomes and cessation of prescribing/administration within the Emergency Department. Clinically significant changes in patterns of prescribing were observed between pre-post intervention audits. CONCLUSION: Entrenching an evidence-based QIP approach to clinical practice can effect clinically significant patterns of practice change to improve safe prescribing and drug monitoring.


Subject(s)
Clopenthixol , Quality Improvement , Humans , Clopenthixol/adverse effects , Health Services , Practice Patterns, Physicians'
4.
Medicina (Kaunas) ; 60(1)2023 Dec 25.
Article in English | MEDLINE | ID: mdl-38256300

ABSTRACT

Background and Objectives: The aim of this review is to explore the recent surgical innovations in tracheal reconstruction by evaluating the uses of synthetic material fabrication when dealing with tracheomalacia or stenotic pathologies, then discussing the challenges holding back these innovations. Materials and Methods: A targeted non-systematic review of published literature relating to tracheal reconstruction was performed within the PubMed database to help identify how synthetic materials are utilised to innovate tracheal reconstruction. Results: The advancements in 3D printing to aid synthetic material fabrication have unveiled promising alternatives to conventional approaches. Achieving successful tracheal reconstruction through this technology demands that the 3D models exhibit biocompatibility with neighbouring tracheal elements by encompassing vasculature, chondral foundation, and immunocompatibility. Tracheal reconstruction has employed grafts and scaffolds, showing a promising beginning in vivo. Concurrently, the integration of resorbable models and stem cell therapy serves to underscore their viability and application in the context of tracheal pathologies. Despite this, certain barriers hinder its advancement in surgery. The intricate tracheal structure has posed a challenge for researchers seeking novel approaches to support its growth and regeneration. Conclusions: The potential of synthetic material fabrication has shown promising outcomes in initial studies involving smaller animals. Yet, to fully realise the applicability of these innovative developments, research must progress toward clinical trials. These trials would ascertain the anatomical and physiological effects on the human body, enabling a thorough evaluation of post-operative outcomes and any potential complications linked to the materials or cells implanted in the trachea.


Subject(s)
Plastic Surgery Procedures , Animals , Humans , Databases, Factual , Postoperative Period , PubMed
5.
Transpl Int ; 35: 10127, 2022.
Article in English | MEDLINE | ID: mdl-35387396

ABSTRACT

The aim of this study is to evaluate the effect of SARS-CoV-2 infection on serum tacrolimus levels. Tacrolimus levels of 34 transplant patients diagnosed with SARS-CoV-2 in 2020 were compared with their pre-infection values and those of a control group with alternative infections. 20 out of 34 (59%) had high levels. At diagnosis, median tacrolimus level in the SARS-CoV-2 cohort was 9.6 µg/L (2.7-23) compared to 7.9 µg/L in the control group (p = 0.07, 95% CI for difference -0.3-5.8). The ratio of post-infection to pre-infection tacrolimus values was higher in the SARS-CoV-2 group (1.7) compared to the control group (1.25, p = 0.018, 95% CI for difference 0.08-0.89). The acute kidney injury rate was 65% (13 of 20) in SARS-CoV-2 patients with a level >8 µg/dl, compared to 29% (4 of 14) in those with lower levels (p = 0.037). Median length of stay was 10 days among SARS-CoV-2 infected patients with high tacrolimus levels compared to 0 days in the rest (p = 0.04). Four patients with high levels died compared to 2 in the control group. Clinicians should be aware of this potential effect on tacrolimus levels and take appropriate measures.


Subject(s)
COVID-19 , Kidney Transplantation , Cohort Studies , Humans , SARS-CoV-2 , Tacrolimus
6.
JAMA ; 327(2): 138-150, 2022 01 11.
Article in English | MEDLINE | ID: mdl-35015037

ABSTRACT

Importance: Phase 3 trials have not compared semaglutide and liraglutide, glucagon-like peptide-1 analogues available for weight management. Objective: To compare the efficacy and adverse event profiles of once-weekly subcutaneous semaglutide, 2.4 mg, vs once-daily subcutaneous liraglutide, 3.0 mg (both with diet and physical activity), in people with overweight or obesity. Design, Setting, and Participants: Randomized, open-label, 68-week, phase 3b trial conducted at 19 US sites from September 2019 (enrollment: September 11-November 26) to May 2021 (end of follow-up: May 11) in adults with body mass index of 30 or greater or 27 or greater with 1 or more weight-related comorbidities, without diabetes (N = 338). Interventions: Participants were randomized (3:1:3:1) to receive once-weekly subcutaneous semaglutide, 2.4 mg (16-week escalation; n = 126), or matching placebo, or once-daily subcutaneous liraglutide, 3.0 mg (4-week escalation; n = 127), or matching placebo, plus diet and physical activity. Participants unable to tolerate 2.4 mg of semaglutide could receive 1.7 mg; participants unable to tolerate 3.0 mg of liraglutide discontinued treatment and could restart the 4-week titration. Placebo groups were pooled (n = 85). Main Outcomes and Measures: The primary end point was percentage change in body weight, and confirmatory secondary end points were achievement of 10% or more, 15% or more, and 20% or more weight loss, assessed for semaglutide vs liraglutide at week 68. Semaglutide vs liraglutide comparisons were open-label, with active treatment groups double-blinded against matched placebo groups. Comparisons of active treatments vs pooled placebo were supportive secondary end points. Results: Of 338 randomized participants (mean [SD] age, 49 [13] years; 265 women [78.4%]; mean [SD] body weight, 104.5 [23.8] kg; mean [SD] body mass index, 37.5 [6.8]), 319 (94.4%) completed the trial, and 271 (80.2%) completed treatment. The mean weight change from baseline was -15.8% with semaglutide vs -6.4% with liraglutide (difference, -9.4 percentage points [95% CI, -12.0 to -6.8]; P < .001); weight change with pooled placebo was -1.9%. Participants had significantly greater odds of achieving 10% or more, 15% or more, and 20% or more weight loss with semaglutide vs liraglutide (70.9% of participants vs 25.6% [odds ratio, 6.3 {95% CI, 3.5 to 11.2}], 55.6% vs 12.0% [odds ratio, 7.9 {95% CI, 4.1 to 15.4}], and 38.5% vs 6.0% [odds ratio, 8.2 {95% CI, 3.5 to 19.1}], respectively; all P < .001). Proportions of participants discontinuing treatment for any reason were 13.5% with semaglutide and 27.6% with liraglutide. Gastrointestinal adverse events were reported by 84.1% with semaglutide and 82.7% with liraglutide. Conclusions and Relevance: Among adults with overweight or obesity without diabetes, once-weekly subcutaneous semaglutide compared with once-daily subcutaneous liraglutide, added to counseling for diet and physical activity, resulted in significantly greater weight loss at 68 weeks. Trial Registration: ClinicalTrials.gov Identifier: NCT04074161.


Subject(s)
Body Weight/drug effects , Glucagon-Like Peptides/administration & dosage , Hypoglycemic Agents/administration & dosage , Liraglutide/administration & dosage , Overweight/drug therapy , Diabetes Mellitus , Diet Therapy , Drug Administration Schedule , Exercise , Female , Glucagon-Like Peptides/adverse effects , Humans , Hypoglycemic Agents/adverse effects , Injections, Subcutaneous , Liraglutide/adverse effects , Male , Middle Aged , Obesity/drug therapy , Obesity/therapy , Odds Ratio , Overweight/therapy , Patient Dropouts/statistics & numerical data , Placebos/administration & dosage , Treatment Outcome , United States , Weight Loss
7.
World Econ ; 45(2): 386-408, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34230757

ABSTRACT

This paper makes an innovative contribution to the extant literature by analysing the determinants of economic stimulus packages implemented by governments in response to the COVID-19 pandemic. In particular, we explore whether stock market declines observed in many countries can predict the size of COVID-19 stimulus packages. Moreover, we explore whether a country's level of income can augment the underlying relationship between stock market declines and stimulus packages. The findings reveal that a larger stock market decline results in a larger stimulus package; however, this effect is only observed in countries that have an income level greater than the mean and/or median per capita gross domestic product (GDP). Moreover, our results show that monetary policy is more responsive to a stock market decline than fiscal policy. Thus, our results underscore the importance of international donor agencies such as the World Bank and International Monetary Fund (IMF) in supporting less affluent countries in coping with the adverse impacts of the COVID-19 pandemic on their economies.

8.
Am J Pathol ; 190(6): 1236-1255, 2020 06.
Article in English | MEDLINE | ID: mdl-32201263

ABSTRACT

Hyaluronidase (HYAL)-2 is a weak, acid-active, hyaluronan-degrading enzyme broadly expressed in somatic tissues. Aberrant HYAL2 expression is implicated in diverse pathology. However, a significant proportion of HYAL2 is enzymatically inactive; thus the mechanisms through which HYAL2 dysregulation influences pathobiology are unclear. Recently, nonenzymatic HYAL2 functions have been described, and nuclear HYAL2 has been shown to influence mRNA splicing to prevent myofibroblast differentiation. Myofibroblasts drive fibrosis, thereby promoting progressive tissue damage and leading to multimorbidity. This study identifies a novel HYAL2 cytoplasmic function in myofibroblasts that is unrelated to its enzymatic activity. In fibroblasts and myofibroblasts, HYAL2 interacts with the GTPase-signaling small molecule ras homolog family member A (RhoA). Transforming growth factor beta 1-driven fibroblast-to-myofibroblast differentiation promotes HYAL2 cytoplasmic relocalization to bind to the actin cytoskeleton. Cytoskeletal-bound HYAL2 functions as a key regulator of downstream RhoA signaling and influences profibrotic myofibroblast functions, including myosin light-chain kinase-mediated myofibroblast contractility, myofibroblast migration, myofibroblast collagen/fibronectin deposition, as well as connective tissue growth factor and matrix metalloproteinase-2 expression. These data demonstrate that, in certain biological contexts, the nonenzymatic effects of HYAL2 are crucial in orchestrating RhoA signaling and downstream pathways that are important for full profibrotic myofibroblast functionality. In conjunction with previous data demonstrating the influence of HYAL2 on RNA splicing, these findings begin to explain the broad biological effects of HYAL2.


Subject(s)
Fibroblasts/metabolism , Hyaluronoglucosaminidase/metabolism , Myofibroblasts/metabolism , Signal Transduction/physiology , rhoA GTP-Binding Protein/metabolism , Animals , Fibrosis/metabolism , Humans , Male , RNA Splicing , Rats
9.
J Pak Med Assoc ; 71(7): 1730-1735, 2021 Jul.
Article in English | MEDLINE | ID: mdl-34410236

ABSTRACT

OBJECTIVE: To investigate the effects of design parameters on the user experience of virtual reality medical training. METHODS: The quantitative study was conducted at Punjab (Pakistan) from July 2018 to October 2018, and comprised final year students from eight medical colleges in Pakistan. Each respondent was given to experience laparoscopy operation in text, video and virtual reality-based learning methodologies. User experience and usefulness was assessed against a pre-validated scale and compared with the three learning methodologies. RESULTS: Of the 87, students, 50(57.5%) were male and 37(42.5%) were female. The overall mean age was 22.5±4 years. Result of virtual reality was better than others (p<0.05). Data was analysed using SPSS 20. CONCLUSIONS: Virtual reality-based learning provided better user experience than traditional learning methodologies.


Subject(s)
Laparoscopy , Virtual Reality , Adolescent , Adult , Clinical Competence , Female , Humans , Male , Pakistan , User-Computer Interface , Young Adult
10.
Am J Transplant ; 18(6): 1380-1387, 2018 06.
Article in English | MEDLINE | ID: mdl-29275542

ABSTRACT

Socioeconomic deprivation is associated with poorer outcomes in chronic diseases. The aim of this study was to investigate the effect of socioeconomic deprivation on outcomes following pancreas transplantation among patients transplanted in England. We included all 1270 pancreas recipients transplanted between 2004 and 2012. We used the English Index of Multiple Deprivation (EIMD) score to assess the influence of socioeconomic deprivation on patient and pancreas graft survival. Higher scores mean higher deprivation status. Median EIMD score was 18.8, 17.7, and 18.1 in patients who received simultaneous pancreas and kidney (SPK), pancreas after kidney (PAK), and pancreas transplant alone (PTA), respectively (P = .56). Pancreas graft (censored for death) survival was dependent on the donor age (P = .08), cold ischemic time (CIT; P = .0001), the type of pancreas graft (SPK vs. PAK or PTA, P = .0001), and EIMD score (P = .02). The 5-year pancreas graft survival of the most deprived patient quartile was 62% compared to 75% among the least deprived (P = .013), and it was especially evident in the SPK group. EIMD score also correlated with patient survival (P = .05). When looking at the impact of individual domains of deprivation, we determined that "Environment" (P = .037) and "Health and Disability" (P = .035) domains had significant impact on pancreas graft survival. Socioeconomic deprivation, as expressed by the EIMD is an independent factor for pancreas graft and patient survival.


Subject(s)
Pancreas Transplantation , Registries , Social Class , Treatment Outcome , Adolescent , Adult , Aged , England , Female , Graft Survival , Humans , Kidney Transplantation , Male , Middle Aged , Young Adult
11.
Arterioscler Thromb Vasc Biol ; 36(5): 1043-8, 2016 05.
Article in English | MEDLINE | ID: mdl-27079879

ABSTRACT

OBJECTIVE: Abdominal aortic aneurysm (AAA) is a complex multifactorial disease associated with a high morbidity and mortality. Increased inflammation including T-helper 17 cell-mediated effects has been implicated in AAA pathogenesis. Psoriasis is considered to be a T-helper 17-driven chronic inflammatory disease and in view of potentially overlapping inflammatory mechanisms, we investigated the risk of AAA in patients with psoriasis in a nationwide cohort. APPROACH AND RESULTS: The study comprised all Danish residents aged ≥18 years followed up from January 1, 1997, until diagnosis of AAA, December 31, 2011, migration or death. Information on comorbidity, concomitant medication, and socioeconomic status was identified by individual-level linkage of administrative registers. Incidence rates for AAA were calculated and incidence rate ratios adjusted for age, sex, comorbidity, medications, socioeconomic status, and smoking were estimated in Poisson regression models. A total of 5 495 203 subjects were eligible for analysis. During the study period, we identified 59 423 patients with mild psoriasis and 11 566 patients with severe psoriasis. The overall incidence rates of AAA were 3.72, 7.30, and 9.87 per 10 000 person-years for the reference population (23 696 cases), mild psoriasis (240 cases), and severe psoriasis (50 cases), respectively. The corresponding adjusted incidence rate ratios for AAA were increased in patients with psoriasis with incidence rate ratios of 1.20 (95% confidence interval, 1.03-1.39) and 1.67 (confidence interval, 1.21-2.32) for subjects with mild and severe disease, respectively. CONCLUSIONS: In a nationwide cohort, psoriasis was associated with a disease severity-dependent increased risk of AAA. The mechanisms and consequences of this novel finding require further investigation.


Subject(s)
Aortic Aneurysm, Abdominal/epidemiology , Psoriasis/epidemiology , Adult , Aortic Aneurysm, Abdominal/diagnosis , Comorbidity , Denmark/epidemiology , Drug Prescriptions , Female , Humans , Incidence , Male , Middle Aged , Psoriasis/diagnosis , Registries , Retrospective Studies , Risk Assessment , Risk Factors , Severity of Illness Index , Smoking/adverse effects , Smoking/epidemiology , Socioeconomic Factors , Time Factors , Young Adult
13.
Clin Transplant ; 30(2): 99-104, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26660281

ABSTRACT

Hypothermic machine perfusion is effective in improving outcome following kidney transplantation. Molecular analyses of hypothermic machine perfusate (HMP) have the potential to identify biomarkers of organ viability prior to transplantation, offering significant advantages to the transplant surgeon, and leading to a potential increase in the organ donor pool. MicroRNAs are emerging as important biomarkers in the context of kidney injury and transplantation. Recent data demonstrate increased microRNA-21 (miR-21) expression in the kidney following acute kidney injury. This study investigated the potential of miR-21 detected in HMP to act as a sentinel for early kidney transplant outcomes. MiR-21 was found to be readily detectable in HMP by RT-qPCR. Eleven ECD kidneys were maintained on a hypothermic machine perfusion system for a median 627 (range 117-1027) minutes, and evaluation of flow and resistance characteristics suggested stability on the machine from 60 min post-perfusion. MiR-21 quantification at 60 min post-perfusion correlated with eGFR at 6 and 12 months post-transplantation. These data suggest that miR-21 expression in HMP may be predictive of early outcomes following kidney transplantation. In the era of ECD kidneys, a reliable measure of organ quality is urgently needed, and this study suggests miR-21 may be such a marker.


Subject(s)
Biomarkers/analysis , Graft Rejection/genetics , Graft Survival/physiology , Hypothermia, Induced/instrumentation , Kidney Transplantation , Kidney/physiology , MicroRNAs/genetics , Organ Preservation/methods , Tissue Donors , Adult , Aged , Female , Follow-Up Studies , Glomerular Filtration Rate , Graft Rejection/diagnosis , Graft Rejection/epidemiology , Humans , Hypothermia, Induced/methods , Male , Middle Aged , Perfusion/instrumentation , Perfusion/methods , Prognosis , Tissue and Organ Procurement , United Kingdom/epidemiology
15.
Acta Derm Venereol ; 96(2): 218-21, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26280176

ABSTRACT

Psoriasis is associated with depression, myocardial infarction (MI) and stroke. Patients with depression have increased cardiovascular risk. However, the link between psoriasis, depression and cardiovascular disease is unclear. This link was investigated in a nationwide Danish cohort of patients with psoriasis (n = 29,406). Incidence rates were calculated, and incidence rate ratios (IRRs) adjusted for age, gender, socio-economic status, medication and comorbidity were estimated by Poisson regression models. Risk of MI (IRR 1.57, 95% confidence interval (95% CI) 1.07-2.29), stroke (IRR 1.95, 95% CI 1.43-2.66), and cardiovascular death (IRR 2.24, 95% CI 1.53-3.26) were increased significantly during acute depression, and risk of stroke (IRR 1.51, 95% CI 1.19-1.90) was increased significantly in chronic depression. During remission from depression, only the risk of stroke was increased. In conclusion, in patients with psoriasis, depression is associated with increased risk of MI, stroke and cardiovascular death, especially during acute depression.


Subject(s)
Depression/epidemiology , Myocardial Infarction/epidemiology , Psoriasis/epidemiology , Stroke/epidemiology , Case-Control Studies , Cause of Death , Denmark/epidemiology , Depression/diagnosis , Depression/mortality , Health Surveys , Humans , Incidence , Myocardial Infarction/diagnosis , Myocardial Infarction/mortality , Prognosis , Psoriasis/diagnosis , Psoriasis/mortality , Risk Factors , Stroke/diagnosis , Stroke/mortality , Time Factors
16.
Eur Heart J ; 36(32): 2177-83, 2015 Aug 21.
Article in English | MEDLINE | ID: mdl-26059725

ABSTRACT

AIM: Psoriasis is a chronic inflammatory disease associated with increased risk of cardiovascular disease including atherosclerosis. The pathogenesis of aortic valve stenosis (AS) also includes an inflammatory component. We therefore investigated the risk of AS in patients with psoriasis compared with the general population in a nationwide cohort. METHODS: The study comprised the entire Danish population aged ≥18 years followed from 1 January 1997 until diagnosis of AS, 31 December 2011, or death. Information on comorbidity, concomitant medication, and socioeconomic status was identified by individual-level linkage of administrative registers. Incidence rates for AS were calculated and incidence rate ratios (IRRs) adjusted for age, gender, calendar year, comorbidity, medications, and socioeconomic status, were estimated in Poisson regression models. RESULTS: A total of 5 107 624 subjects were eligible for analysis. During the study period, we identified 58 747 patients with mild psoriasis and 11 918 patients with severe psoriasis. The overall incidence rates for AS were 8.09, 16.07, and 20.08 per 10 000 person-years for the reference population (48 539 cases [mean follow-up 12.3 years]), mild psoriasis (509 cases [mean follow-up 6.2 years]), and severe psoriasis (99 cases [mean follow-up 5.4 years]), respectively. Correspondingly, the fully adjusted IRRs for AS were markedly increased in patients with psoriasis with IRR 1.22 (95% confidence interval [CI] 1.12-1.33) and IRR 1.61 (CI 1.32-1.96) for subjects with mild and severe disease, respectively. CONCLUSION: In a nationwide cohort, psoriasis was associated with a disease severity-dependent increased risk of AS. The mechanisms underlying this novel finding require further study.


Subject(s)
Aortic Valve Stenosis/etiology , Psoriasis/complications , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , Aortic Valve Stenosis/epidemiology , Denmark/epidemiology , Epidemiologic Methods , Female , Humans , Male , Middle Aged , Psoriasis/epidemiology , Sex Distribution , Young Adult
17.
Clin Transplant ; 29(5): 409-14, 2015 May.
Article in English | MEDLINE | ID: mdl-25711958

ABSTRACT

Socioeconomic deprivation is an important factor in determining poor health and is associated with a higher prevalence of many chronic diseases including diabetes and renal failure, with poorer outcomes of their treatments. The influence of deprivation on outcomes following pancreas transplantation has not previously been reported. The Welsh Index of Multiple Deprivation was used to assess the influence of socioeconomic deprivation on outcomes for 119 consecutive pancreas transplant recipients from a single center in the United Kingdom, transplanted between 2004 and 2013. Outcomes measured were rate of acute rejection and graft survival. Thirty-five (29.4%) patients experienced at least one episode of acute rejection following their transplant. Rejection rates in least deprived were 37% and most deprived 24% (p = 0.29). Within the individual domains, rejection rate was higher for the "physical environment" domain (least deprived 40% vs. most deprived 17% (p = 0.053). Five-year graft survival for least and most deprived groups was 75% and 88%, respectively (log-rank test p-value 0.24). This study has not demonstrated any significant differences in outcomes following pancreas transplantation in Wales in relation to socioeconomic deprivation with the exception possibly of the "physical environment" domain. Further studies with larger patient population or concentrating on physical environment deprivation would be of interest.


Subject(s)
Graft Rejection/epidemiology , Pancreas Transplantation/economics , Pancreatic Diseases/economics , Poverty , Socioeconomic Factors , Tissue and Organ Procurement/economics , Adolescent , Adult , Child , Female , Follow-Up Studies , Graft Survival , Health Services Accessibility , Humans , Male , Middle Aged , Pancreatic Diseases/surgery , Postoperative Complications , Prevalence , Prognosis , Prospective Studies , Risk Factors , Young Adult
19.
Biochem Soc Trans ; 42(4): 1219-23, 2014 Aug.
Article in English | MEDLINE | ID: mdl-25110028

ABSTRACT

miRNAs are small, endogenous, post-transcriptional regulators of gene expression. AKI (acute kidney injury) of various aetiologies, including trauma, sepsis and IRI (ischaemia/reperfusion injury) in the context of kidney transplantation, or drug toxicity, has a high morbidity and mortality rate and presents a significant burden to health services worldwide. AKI primarily affects the renal cortex, in particular PTCs (proximal tubular epithelial cells). Current research demonstrates causality between G2/M cell cycle arrest of PTCs and AKI. Recent findings from our laboratory and others presented in this review implicate miRNA regulation of the cell cycle in the pathology of AKI.


Subject(s)
Acute Kidney Injury/metabolism , MicroRNAs/metabolism , Acute Kidney Injury/genetics , Animals , Cell Cycle/genetics , Cell Cycle/physiology , Humans , Kidney Tubules, Proximal/metabolism , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism
20.
Europace ; 16(4): 477-84, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24108228

ABSTRACT

AIMS: Inflammation is considered to play a role in the development of atrial fibrillation (AF). Hence inflammatory bowel disease (IBD) may be associated with AF. We therefore examined the incidence of AF and stroke in patients with IBD. METHODS AND RESULTS: From Danish nationwide registries 1996-2011, we identified 24 499 patients with new-onset IBD and 236 275 age- and sex-matched controls. Poisson regression analyses with continuously updated covariates were used to estimate incidence rate ratios (IRRs) of AF and stroke. Disease activity stages of flare (new disease activity), persistent activity, and remission were defined by corticosteroid prescriptions, IBD hospital admissions, and biological treatment. Inflammatory bowel disease patients had a mean age of 43.9 years, 53.9% were women, and mean follow-up was 6.8 years. Among IBD patients, 685 had AF and 549 had a stroke, corresponding to incidence rates per 1000 person-years of 4.16 vs. 2.70 for AF and 3.33 vs. 2.44 for stroke, compared with matched controls. Overall IBD-associated risk of AF corresponded to IRR 1.26 (1.16-1.36), but was driven by increased AF incidence during IBD flares [IRR 2.63 (2.26-3.06)] and persistent activity [IRR 2.06 (1.67-2.55)], whereas no increased AF risk was observed in remission periods [IRR 0.97 (0.88-1.08)]. Likewise increased stroke risk was exclusively found during active IBD [IRRs: 1.57 (1.27-1.93), 1.71 (1.32-2.21), and 1.04 (0.93-1.15) for flares, persistent activity, and remission, respectively]. CONCLUSION: Active IBD is associated with increased risk of AF and stroke. These findings may be relevant to clinical practice.


Subject(s)
Atrial Fibrillation/epidemiology , Colitis, Ulcerative/epidemiology , Crohn Disease/epidemiology , Stroke/epidemiology , Adrenal Cortex Hormones/therapeutic use , Adult , Atrial Fibrillation/diagnosis , Biological Products/therapeutic use , Case-Control Studies , Colitis, Ulcerative/diagnosis , Colitis, Ulcerative/drug therapy , Crohn Disease/diagnosis , Crohn Disease/drug therapy , Denmark/epidemiology , Disease Progression , Female , Hospitalization , Humans , Incidence , Male , Middle Aged , Odds Ratio , Registries , Remission Induction , Risk Assessment , Risk Factors , Severity of Illness Index , Stroke/diagnosis , Time Factors , Treatment Outcome
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