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1.
Br J Dermatol ; 185(5): 978-987, 2021 11.
Article in English | MEDLINE | ID: mdl-33991338

ABSTRACT

BACKGROUND: New technologies have enabled the potential for stratified medicine in psoriasis. It is important to understand patients' preferences to enable the informed introduction of stratified medicine, which is likely to involve a number of individual tests that could be collated into a prescribing algorithm for biological drug selection to be used in clinical practice. OBJECTIVES: To quantify patient preferences for an algorithm-based approach to prescribing biologics ('biologic calculator') in psoriasis. METHODS: An online survey comprising a discrete choice experiment (DCE) was conducted to elicit the preferences of two purposive samples of adults living with psoriasis in the UK, identified from a psoriasis patient organization (Psoriasis Association) and an online panel provider (Dynata). Respondents chose between two biologic calculators and conventional prescribing described using five attributes: treatment delay; positive predictive value; negative predictive value; risk of infection; and cost saving to the National Health Service. Each participant selected their preferred alternative from six hypothetical choice sets. Additional data, including sociodemographic characteristics, were collected. Choice data were analysed using conditional logit and fully correlated random parameters logit models. RESULTS: Data from 212 respondents (67 from the Psoriasis Association and 145 from Dynata) were analysed. The signs of all estimated coefficients were consistent with a priori expectations. Respondents had a strong preference for a high predictive accuracy and avoiding serious infection, but there was evidence of systematic differences in preferences between the samples. CONCLUSIONS: This study indicates that individuals with psoriasis would value a biologic calculator and suggested that such a biologic calculator should have sufficient accuracy to predict future response and risk of serious infection from the biologic.


Subject(s)
Patient Preference , Psoriasis , Adult , Choice Behavior , Humans , Logistic Models , Psoriasis/drug therapy , State Medicine , Surveys and Questionnaires
2.
Osteoarthritis Cartilage ; 28(6): 819-823, 2020 06.
Article in English | MEDLINE | ID: mdl-32173628

ABSTRACT

OBJECTIVE: Shared decision-making supported by patient decisions aids may improve care and reduce healthcare costs for persons considering total joint replacement. Observational studies and randomized controlled trials (RCTs) have evaluated the short-term impact of decision aids on uptake of surgery and costs, however the long-term effects are unclear. This analysis aimed to evaluate the effect of patient decision aids on 1) use of joint replacement up to 7-years of follow-up, and 2) osteoarthritis-related health system costs. METHODS: 324 participants in a Canadian RCT with 2-years follow-up who were randomized to either a decision aid (n = 161) or usual care (n = 163) had their trial and health administrative data linked. The proportion undergoing surgery up to 7-years were compared using cumulative incidence plots and competing risk regression. Mean per-patient costs were compared using two sample t-tests. RESULTS: At 2-years, 119 of 161 (73.9%) patients in the decision aid arm and 129 of 163 (79.1%) patients in the usual care arm had surgery. Between two and 7-years, 17 additional patients in both the decision aid (of 42, 40.4%) and usual care (of 34, 50.0%) arms underwent surgery. At 7-years, patients exposed to decision aids had a similar likelihood of undergoing surgery (HR = 0.92, 95% CI:0.73 to 1.17, p = 0.49) and mean per-patient costs ($21,965 vs $23,681, incremental cost: -$1,717, 95% CI:-$5,631 to $2,198) compared to those in usual care. CONCLUSIONS: This is the first study to assess the long-term impact of decision aids on use of joint replacement and healthcare costs. These results are not conclusive but can inform future trial design. CLINICAL TRIAL REGISTRATION: The full trial protocol is available at ClinicalTrials.Gov (NCT00911638).


Subject(s)
Arthroplasty, Replacement/economics , Arthroplasty, Replacement/statistics & numerical data , Decision Support Techniques , Health Care Costs , Osteoarthritis/economics , Osteoarthritis/surgery , Patient Participation , Procedures and Techniques Utilization/statistics & numerical data , Aged , Female , Follow-Up Studies , Humans , Male , Middle Aged , Single-Blind Method , Time Factors
3.
Lupus ; 28(11): 1337-1343, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31423896

ABSTRACT

OBJECTIVE: We evaluated the effects of the B-cell activating factor (BAFF)-targeting antibody Belimumab on human nonmemory B-cell pools. Human B-cell pools were identified using surface markers adapted from mouse studies that specifically assessed reductions in immature B cells due to BAFF depletion. Patients with systemic lupus erythematosus (SLE) have high levels of both BAFF and immature B cells. Mechanistic mouse studies provide a framework for understanding human responses to therapies that target B cells. METHODS: Peripheral blood mononuclear cells were isolated from healthy donors and SLE patients on Belimumab or standard-of-care therapy (SCT). Cells were stained for flow cytometry to identify B-cell subsets based on CD21/CD24. Differences in subset proportions were determined by one-way ANOVA and Tukey's post hoc test. RESULTS: Patients treated with Belimumab show alterations in the nonmemory B-cell pool characterized by a decrease in the Transitional 2 (T2) subset (p = 0.002), and an increase in the proportion of Transitional 1 (T1) cells (p = 0.005) as compared with healthy donors and SCT patients. The naïve B-cell compartment showed no significant differences between the groups (p = 0.293). CONCLUSION: Using a translational approach, we show that Belimumab-mediated BAFF depletion reduces the T2 subset in patients, similar to observations in mouse models with BAFF depletion.


Subject(s)
Antibodies, Monoclonal, Humanized/pharmacology , B-Cell Activating Factor/immunology , Immunosuppressive Agents/pharmacology , Lupus Erythematosus, Systemic/drug therapy , Adult , Animals , B-Lymphocyte Subsets/immunology , Female , Humans , Leukocytes, Mononuclear/immunology , Lupus Erythematosus, Systemic/immunology , Male , Mice , Middle Aged , Precursor Cells, B-Lymphoid/immunology , Species Specificity , Young Adult
4.
Clin Genet ; 93(4): 752-761, 2018 04.
Article in English | MEDLINE | ID: mdl-28881385

ABSTRACT

Diagnostic exome sequencing (DES) has aided delineation of the phenotypic spectrum of rare genetic etiologies of intellectual disability (ID). A SET domain containing 5 gene (SETD5) phenotype of ID and dysmorphic features has been previously described in relation to patients with 3p25.3 deletions and in a few individuals with de novo sequence alterations. Herein, we present additional patients with pathogenic SETD5 sequence alterations. The majority of patients in this cohort and previously reported have developmental delay, behavioral/psychiatric issues, and variable hand and skeletal abnormalities. We also present an apparently unaffected carrier mother of an affected individual and a carrier mother with normal intelligence and affected twin sons. We suggest that the phenotype of SETD5 is more complex and variable than previously presented. Therefore, many features and presentations need to be considered when evaluating a patient for SETD5 alterations through DES.


Subject(s)
Body Dysmorphic Disorders/genetics , Developmental Disabilities/genetics , Intellectual Disability/genetics , Methyltransferases/genetics , Adolescent , Adult , Body Dysmorphic Disorders/diagnosis , Body Dysmorphic Disorders/physiopathology , Child , Child, Preschool , Chromosome Deletion , Chromosomes, Human, Pair 3/genetics , Developmental Disabilities/diagnosis , Developmental Disabilities/physiopathology , Female , Humans , Infant , Intellectual Disability/diagnosis , Intellectual Disability/physiopathology , Male , Middle Aged , Mutation/genetics , Penetrance , Phenotype , Exome Sequencing , Young Adult
5.
Br J Dermatol ; 177(3): 828-836, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28386916

ABSTRACT

BACKGROUND: The Psoriasis Stratification to Optimise Relevant Therapy (PSORT) consortium has a collective aim to develop a prescribing algorithm to help stratify eligible patients with psoriasis to the most appropriate biological treatment. To facilitate the adoption of a stratified approach, it is necessary to first understand the factors driving the choice of first-line biological therapy. OBJECTIVES: To identify and quantify factors that influence the selection of the first-line biological therapy for people with psoriasis. METHODS: Multinomial logistic regression was used to determine the factors that influenced the probability of treatment selection, using data from the British Association of Dermatologists Biologic Interventions Register from January 2012 to December 2015. Sensitivity analyses were performed to assess the robustness of the findings to key assumptions. RESULTS: The main analysis was based on a dataset comprising 3040 people with psoriasis. The identified factors affecting first-line biological selection within the available therapies were: presence of psoriatic arthritis; patient weight; employment status; country of registration; and baseline disease severity. Importantly, the analysis showed a general shift in prescribing behaviour over time. These results were robust to sensitivity analysis. CONCLUSIONS: This study offers important insights into the factors influencing current prescribing practice for first-line biological therapies for people with psoriasis. It provides baseline data to inform the evaluation of future potential changes that may affect prescribing behaviour, such as stratified medicine.


Subject(s)
Biological Factors/therapeutic use , Biological Therapy/methods , Psoriasis/drug therapy , Adult , Algorithms , Female , Humans , Interleukins/antagonists & inhibitors , Male , Practice Patterns, Physicians' , Prescription Drugs/therapeutic use , Prospective Studies , Treatment Outcome , Tumor Necrosis Factor-alpha/antagonists & inhibitors
6.
Surg Endosc ; 30(10): 4613-8, 2016 10.
Article in English | MEDLINE | ID: mdl-26895915

ABSTRACT

BACKGROUND: Prior studies have demonstrated that existing risk stratification guidelines for the evaluation of suspected choledocholithiasis lack accuracy, leading to the overutilization of endoscopic retrograde cholangiopancreatography (ERCP). The aim of our study was to evaluate the performance characteristics of published guidelines in predicting choledocholithiasis and to determine the impact of laboratory trends on diagnostic accuracy. METHODS: We identified patients with suspected choledocholithiasis hospitalized over a 5-year period (2009-2014) at a tertiary care academic medical center. Among eligible patients, we assessed the performance characteristics of the American Society for Gastrointestinal Endoscopy (ASGE) guidelines predicting the presence of choledocholithiasis, confirmed by endoscopic ultrasound, magnetic resonance cholangiography, ERCP, or intra-operative cholangiography. We also evaluated whether a second set of liver function tests improved the accuracy of the guidelines. RESULTS: On presentation, 71 of the 173 eligible patients (41.4 %) met ASGE high-probability criteria for choledocholithiasis. Of these, only 39 (54.9 %) were found to have a choledocholithiasis on confirmatory testing. Conversely, of the 102 patients (58.6 %) who were classified as low or intermediate probability, 32 (31.4 %) had choledocholithiasis. Overall, the accuracy of the guidelines was 63 % (sensitivity 54.9 %; specificity 68.6 %). Incorporating a second set of laboratory tests did not improve accuracy (62.7 %), and a significant decline in liver function tests did not reliably predict spontaneous stone passage. CONCLUSIONS: Existing guidelines performed suboptimally for predicting choledocholithiasis in our patient population, similar to other validation studies. These findings further underscore the importance of developing alternate risk stratification tools for choledocholithiasis, aiming to minimize unnecessary diagnostic ERCP.


Subject(s)
Alanine Transaminase/blood , Bilirubin/blood , Choledocholithiasis/diagnostic imaging , Lipase/blood , Cholangiography , Cholangiopancreatography, Endoscopic Retrograde , Cholangiopancreatography, Magnetic Resonance , Choledocholithiasis/blood , Choledocholithiasis/surgery , Endoscopy, Gastrointestinal , Endosonography , Female , Humans , Liver Function Tests , Logistic Models , Male , Middle Aged , Multivariate Analysis , Retrospective Studies , Risk , Risk Assessment , Sensitivity and Specificity , Ultrasonography
7.
J Oral Pathol Med ; 43(4): 239-44, 2014 Apr.
Article in English | MEDLINE | ID: mdl-23750566

ABSTRACT

Oral epithelial dysplasia grading is currently recognised as the most useful prognostic indicator for predicting conversion of potentially malignant disorders of the oral cavity to squamous cell carcinoma. It is also used as a basis for deciding management options. However, the diagnosis of oral epithelial dysplasia is subjective and thus unreliable. Surgery is currently recommended for removal of high-risk lesions; however, the evidence for its success is lacking, and in some cases, there have been reports of increased recurrence of malignancy following surgical excision. Molecular and genetic markers have been identified and show promising results in identifying which potential malignant disorders are at risk of malignant transformation. The current evidence available for prognosis of potential malignant disorders and its treatment is based on observational and retrospective data. No randomised control trials have been conducted to date to assess the efficacy of surgery in oral epithelial dysplasia. Until good quality evidence is available from well-designed randomised control trials, experts still recommend the surgical removal of potential malignant disorders which are regarded as high risk.


Subject(s)
Mouth Neoplasms/surgery , Precancerous Conditions/surgery , Biomarkers, Tumor/analysis , Cell Transformation, Neoplastic/pathology , Epithelial Cells/pathology , Genetic Markers , Humans , Mouth Mucosa/pathology , Mouth Neoplasms/pathology , Precancerous Conditions/pathology , Prognosis , Risk Factors , Treatment Outcome
8.
Int J Colorectal Dis ; 29(10): 1203-10, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25080148

ABSTRACT

PURPOSE: This study aimed to elicit EuroQol Quality of Life 5-Dimensions (EQ-5D) utility values from patients with second-line metastatic colorectal cancer (mCRC) pre- and post-progression. METHODS: A cross-sectional study was conducted in five hospitals in the Netherlands and the UK. Patients with mCRC were eligible if prescribed a second or subsequent line of therapy or best supportive care (BSC), received prior oxaliplatin in first-line therapy, and had Eastern Cooperative Oncology Group (ECOG) performance status scores of 0-2 at second-line initiation. Patients completed the EuroQol Quality of Life 5-Dimensions 3-levels (EQ-5D-3L) questionnaire and were categorized as pre- or post-progression. Chart data including patient demographics, clinical history, prior/current treatments and serious adverse events (SAEs) were collected. Mean utilities were estimated; uni- and multivariate analyses were conducted. RESULTS: Seventy-five patients were enrolled; 42 were pre-progression defined as second line or third line following an AE on second line and 33 were post-progression defined as third or subsequent therapy lines or BSC. Patient/disease characteristics and number of SAEs were similar between cohorts. Mean utility scores were 0.741 (SD = 0.230) and 0.731 (SD = 0.292) for pre- and post-progression cohorts, respectively. Compared to pre-progression, more patients reported increased anxiety/depression (36 vs. 12 %) and fewer problems with daily activities (64 vs. 38 %) post-progression. More patients pre-progression were on active treatment at enrolment (83 vs. 42 %) compared to post-progression. CONCLUSIONS: This is the first real-world study to collect utilities for patients with second-line mCRC pre- and post-disease progression. Utility values were similar pre- and post-progression. To further explore the effect of radiological progression on utilities, longitudinal research is required that includes patients in palliative care centres.


Subject(s)
Colorectal Neoplasms/psychology , Quality of Life , Surveys and Questionnaires , Activities of Daily Living , Antineoplastic Agents/therapeutic use , Anxiety/etiology , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/secondary , Cross-Sectional Studies , Depression/etiology , Disease Progression , Female , Humans , Male , Middle Aged , Netherlands , Organoplatinum Compounds/therapeutic use , Oxaliplatin , Pain/etiology , Palliative Care , United Kingdom
9.
Eur J Dent Educ ; 18(2): 98-103, 2014 May.
Article in English | MEDLINE | ID: mdl-24118643

ABSTRACT

INTRODUCTION: Oral and maxillofacial surgery (OMFS) trainees in the UK have traditionally completed their dental undergraduate studies prior to returning to medical school. Recently, there have been increasing numbers of medical graduates who return to dental school before embarking on OMFS specialist training. There is limited research into the career motivation within this group and little guidance on how they may integrate the dental undergraduate course into their postgraduate training path. This study aims to evaluate these factors in more detail. METHODS: Questionnaires and focus groups were used to evaluate prior surgical experience of qualified medics who return to dental school with the intention of pursuing a career in OMFS, along with the factors that affect the timing of their return to dental school. RESULTS: The average age of medical graduates entering dental school decreased during the study period. The average number of months each cohort of students spent as a practicing doctor prior to starting dentistry also reduced. Postgraduate experience in OMFS was highly variable, but the numbers of students who received alternative exposure to OMFS, such as undergraduate special study modules, medical school elective or taster weeks, increased. The key barriers that were carefully considered by these trainees before returning to university included the perceived increase in the length of training, trainees' prior surgical experience, financial implications and the impact on quality of life. CONCLUSIONS: A trainee's decision to return to study dentistry is a multifactorial process. Understanding when trainees decide to return to sit their dental degree is vital not only to provide guidance for future trainees but also to assist future workforce planning, thus aiding training, education and development within OMFS.


Subject(s)
Career Choice , Decision Making , Education, Dental, Graduate , Surgery, Oral/education , Adult , Clinical Competence , Education, Dental, Graduate/economics , Female , Focus Groups , Humans , London , Male , Quality of Life , Surveys and Questionnaires , Time Factors
10.
Public Health ; 127(7): 653-60, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23810318

ABSTRACT

OBJECTIVES: To conduct an initial evaluation of a behaviour change programme called 'Making Every Contact Count' (MECC). STUDY DESIGN: Retrospective interview study. METHODS: In depth qualitative interviews with key stakeholders engaged in the delivery of MECC which were digitally recorded, transcribed and analysed thematically using framework analysis. RESULTS: The responses of those involved were generally favourable and although the 'intuitive' nature of the idea of Making Every Contact Count clearly resonated with interviewees, the take up was variable across different organisations. CONCLUSIONS: The approach to MECC described here was based on some of the principles outlined in the NICE Guidance on behaviour change published in 2007. The report shows that MECC has considerable potential for changing staff behaviour in relation promoting health enhancing behaviour among members of the general public coming into contact with services.


Subject(s)
Health Behavior , Health Promotion/methods , Health Promotion/organization & administration , Interpersonal Relations , Guidelines as Topic , Humans , Program Evaluation , Qualitative Research , Retrospective Studies , United Kingdom
13.
Osteoarthritis Cartilage ; 19(8): 1058-65, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21571082

ABSTRACT

OBJECTIVE: To test the hypothesis that in vivo transgene expression mediated by single intra-articular injection of adeno-associated virus serotype 2 (AAV2) persists within intra-articular tissues 1 year post-injection and can be externally controlled using an AAV2-based tetracycline-inducible gene regulation system containing the tetracycline response element (TRE) promoter. METHODS: Sprague Dawley rats received intra-articular injections of AAV2-cytomegalovirus (CMV)-enhanced green fluorescent protein (GFP) and AAV2-CMV-luciferase (Luc) into their right and left knees, respectively. Luciferase expression was evaluated over 1 year using bioluminescence imaging. After sacrifice, tissues were analyzed for GFP+ cells by fluorescent microscopy. To study external control of intra-articular AAV-transgene expression, another set of rats was co-injected with AAV2-TRE-Luc and AAV2-CMV-reverse-tetracycline-controlled transactivator (rtTA) into the right knees, and AAV2-CMV-Luc and AAV2-CMV-rtTA into the left knees. Rats received oral doxycycline (Dox), an analog of tetracycline, for 7 days. Luciferase expression was assessed by bioluminescence imaging. RESULTS: Luciferase expression was localized to the injected joint and persisted throughout the 1-year study period. Abundant GFP+ cells were observed within intra-articular soft tissues. Transgene expression in AAV2-TRE-Luc injected joints was upregulated by oral administration of Dox, and downregulated following its removal, at 14 days and 13 months post-AAV injection. CONCLUSIONS: This longitudinal in vivo study shows that sustained and stable AAV-mediated intra-articular transgene expression can be achieved through a single intra-articular injection and can be controlled using a tetracycline-controlled inducible AAV system in a normal rat knee model. Highly regulatable long-term intra-articular transgene expression is of potential clinical utility for development of treatment strategies for chronic intra-articular disease processes such as inflammatory and degenerative arthritis.


Subject(s)
Dependovirus/metabolism , Doxycycline/pharmacology , Hindlimb/metabolism , Transgenes/drug effects , Animals , Cartilage, Articular/metabolism , Disease Models, Animal , Doxycycline/administration & dosage , Gene Expression Regulation , Gene Transfer Techniques , Green Fluorescent Proteins/metabolism , Injections, Intra-Articular , Longitudinal Studies , Luciferases/metabolism , Male , Microscopy, Fluorescence , Rats , Rats, Sprague-Dawley , Tetracycline/pharmacology , Trans-Activators/pharmacology
14.
Int J Clin Pract ; 65(10): 1043-54, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21923845

ABSTRACT

AIM: The aim of this study was to characterise the natural course of smoking cessation behaviour in a web-based survey of current and former cigarette smokers (CS and FS) in the United States. METHODS: A web-based survey of CS and FS was conducted in April 2009; demographic and socioeconomic characteristics and smoking history (including the number of lifetime and length of latest quit attempts, aids used and time to relapse) were collated. The surveyed cohort was selected from prescreened CS and FS panellists and matched for age, race and education, to be representative of the US population. Descriptive statistics and time-to-event analyses using Kaplan-Meier curves were applied in the analysis of this report. RESULTS: The final cohort comprised 512 CS and 566 FS (n = 1078). A larger proportion of FS than CS reported a longest smoke-free period of > 1 year (78.8% vs. 22.4%, respectively). As a greater variety of smoking cessation products became available over time, the proportion of unassisted quit attempts decreased from 76.1% prior to 1983 to 43.9% after 2006 for CS and from 79.3% to 50.3% for FS. The cumulative proportion of subjects relapsing was 31.3% by 1 week and 79.3% by 6 months. The estimated median time to next quit attempt was approximately 360 days. CONCLUSIONS: These data confirm that relapse is common and that as the variety of cessation modalities increase, the proportion of unassisted quit attempts decreases. Self-help or cold-turkey methods still provide significant alternatives even when pharmacotherapy is available. This study provides data related to the smoking history and smoking cessation patterns of a large, nationally representative sample of CS and FS.


Subject(s)
Smoking Cessation/psychology , Smoking/psychology , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , Attitude to Health , Cross-Sectional Studies , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Recurrence , Socioeconomic Factors , Time Factors , Tobacco Use Cessation Devices/statistics & numerical data , Young Adult
15.
Gut ; 59(4): 452-60, 2010 Apr.
Article in English | MEDLINE | ID: mdl-19996326

ABSTRACT

OBJECTIVE: An aberrant immunophenotype and monoclonality of intraepithelial lymphocytes (IELs) are frequently found in refractory coeliac disease (RCD). However, the utility of continual monitoring of IEL immunophenotype and clonality in the surveillance of RCD remains to be studied. DESIGN: The diagnostic and follow-up biopsies from 33 patients with CD, 7 with suspected RCD, 41 with RCD and 20 with enteropathy-associated T cell lymphoma (EATL) (including 11 evolved from RCD) were investigated by CD3epsilon/CD8 double immunohistochemistry and PCR-based clonality analysis of the rearranged T cell receptor (TCR) genes. RESULTS: An aberrant immunophenotype (CD3epsilon(+)CD8(-) IELs > or =40%) and monoclonality were detected occasionally in CD biopsies, either transiently in patients with CD not compliant with a gluten-free diet or in those who subsequently developed suspected RCD, RCD or EATL. In contrast, the aberrant immunophenotype and monoclonality were found in 30 of 41 (73%) and 24 of 37 (65%) biopsies, respectively, at the time of RCD diagnosis. Among the patients with RCD who did not show these abnormalities in their diagnostic biopsies, 8 of 10 (80%) and 5 of 11 (45%) cases gained an aberrant immunophenotype and monoclonality, respectively, during follow-up. Irrespective of whether detected in diagnostic or follow-up biopsies, persistence of both abnormalities was characteristic of RCD. Importantly, the presence of concurrent persistent monoclonality and aberrant immunophenotype, especially > or =80% CD3epsilon(+)CD8(-) IELs, was a strong predictor of EATL development in patients with RCD (p=0.001). CONCLUSIONS: Continual monitoring of both immunophenotype and clonality of IELs is more important than snapshot analysis for RCD diagnosis and follow-up, and could provide a useful tool for surveillance of patients at risk of EATL.


Subject(s)
Celiac Disease/immunology , Intestinal Mucosa/immunology , T-Lymphocyte Subsets/immunology , Adolescent , Adult , Aged , Celiac Disease/complications , Female , Follow-Up Studies , Humans , Immunity, Mucosal , Immunophenotyping , Intestinal Neoplasms/etiology , Intestinal Neoplasms/immunology , Lymphoma, T-Cell/etiology , Lymphoma, T-Cell/immunology , Male , Middle Aged , Population Surveillance/methods , Stem Cells/immunology , Young Adult
16.
Br J Cancer ; 103(3): 315-23, 2010 Jul 27.
Article in English | MEDLINE | ID: mdl-20661248

ABSTRACT

BACKGROUND: Accurate description of current practice within advanced colorectal cancer (CRC) specialties were needed to inform an economic evaluation of the UGT1A1 pharmacogenetic test for irinotecan in the United Kingdom. METHODS: The study was based on a literature review and elicitation of expert opinion. The expert panel comprised 44 consultant oncologists in NHS Hospital Trusts across England. RESULTS: Ten first-line, 10 second-line and 12 third-line chemotherapy regimens were reported, reflecting wide variations in treatment pathways. Predominant pathways emerged with: first-line treatment with oxaliplatin-based regimens, second-line treatment with irinotecan-based regimens and third-line treatment with mitomycin-based regimens. Experts estimated the frequency of febrile neutropaenia 8.4% (95% CI: 6.7-10.0), septic neutropaenia 4.7% (95% CI: 3.4-6.0) and severe diarrhoea 13.1% (95% CI: 10.8-15.5). Approaches for the clinical management of neutropaenia within the NHS were described. CONCLUSIONS: This study identified wide variations in the clinical management of advanced CRC patients. Descriptions of current treatment pathways are necessary for economic evaluations. Variations in clinical practice must be reflected in the model to ensure the findings from an economic evaluation of UGT1A1 testing are sufficient to inform policy regarding the cost-effective use of NHS resources.


Subject(s)
Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/economics , Glucuronosyltransferase/analysis , Neutropenia/chemically induced , Antibiotics, Antineoplastic/therapeutic use , Antineoplastic Agents/therapeutic use , Antineoplastic Agents, Phytogenic/therapeutic use , Camptothecin/adverse effects , Camptothecin/analogs & derivatives , Camptothecin/therapeutic use , Colorectal Neoplasms/enzymology , Colorectal Neoplasms/pathology , Diarrhea/chemically induced , Fluorouracil/therapeutic use , Glucuronosyltransferase/genetics , Health Surveys , Humans , Irinotecan , Mitomycin/adverse effects , Mitomycin/therapeutic use , Neutropenia/classification , Organoplatinum Compounds/adverse effects , Organoplatinum Compounds/therapeutic use , Pyridines/adverse effects , Pyridines/therapeutic use , Risk Factors , State Medicine , United Kingdom
17.
Osteoarthritis Cartilage ; 18(5): 705-13, 2010 May.
Article in English | MEDLINE | ID: mdl-20171308

ABSTRACT

OBJECTIVE: Damaged articular cartilage does not heal well and can progress to osteoarthritis (OA). Human bone marrow stem cells (BMC) are promising cells for articular cartilage repair, yet age- and sex-related differences in their chondrogenesis have not been clearly identified. The purpose of this study is to test whether the chondrogenic potential of human femoral BMC varies based on the sex and/or age of the donor. DESIGN: BMC were isolated from 21 males (16-82 years old (y.o.)) and 20 females (20-77 y.o.) during orthopaedic procedures. Cumulative population doubling (CPD) was measured and chondrogenesis was evaluated by standard pellet culture assay in the presence or absence of transforming growth factor beta 1 (TGFbeta1). Pellet area was measured, and chondrogenic differentiation was determined by Toluidine blue and Safranin O-Fast green histological grading using the Bern score and by glycosaminoglycan (GAG) content. RESULTS: No difference in CPD was observed due to donor sex or age. The increase in pellet area with addition of TGFbeta1 and the Bern score significantly decreased with increasing donor age in male BMC, but not in female BMC. A significant reduction in GAG content per pellet was also observed with increasing donor age in male BMC. This was not observed in female BMC. CONCLUSIONS: This study showed an age-related decline in chondroid differentiation with TGFbeta1 stimulation in male BMC, but not in female BMC. Understanding the mechanisms for these differences will contribute to improved clinical use of autologous BMC for articular cartilage repair, and may lead to the development of customized age- or sex-based treatments to delay or prevent the onset of OA.


Subject(s)
Bone Marrow Cells/drug effects , Chondrogenesis/drug effects , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Bone Marrow Cells/chemistry , Bone Marrow Cells/cytology , Cell Differentiation/drug effects , Cells, Cultured , Chondrogenesis/physiology , Female , Femur/cytology , Glycosaminoglycans/analysis , Humans , Male , Middle Aged , Sex Factors , Young Adult
18.
Gastrointest Endosc ; 72(3): 558-63, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20638060

ABSTRACT

BACKGROUND: Benign biliary strictures are typically managed endoscopically whereby an increasing size or number of plastic stents is placed at ERCP. Stents are often changed every 3 to 4 months based on the known median patency of a single biliary stent, but patency data for multiple biliary stents are lacking. OBJECTIVE: To assess the incidence of occlusion-free survival of multiple plastic biliary stents and the rate of premature occlusion if left in longer than 6 months. DESIGN: Retrospective. SETTING: Tertiary-care medical center (Charleston, SC). PATIENTS: Consecutive patients who received multiple plastic stents for benign nonhilar biliary strictures from 1994 to 2008 were identified. INTERVENTIONS: Exchange of multiple plastic biliary stents within 6 months (group 1) or 6 months or longer (group 2) after placement. MAIN OUTCOME MEASUREMENTS: Symptomatic stent occlusion. RESULTS: Seventy-nine patients with nonhilar extrahepatic benign biliary stricture underwent 125 ERCPs with multiple plastic biliary stents. Stents were scheduled for removal/exchange within 6 months in 52 patients (86 ERCPs) compared with after 6 months in 22 patients (26 ERCPs). The median interval between multiple stent placement and removal/exchange was 90 days for group 1 and 242 days for group 2. Premature stent occlusion occurred in 4 of 52 (7.7%) patients in group 1 versus 1 of 22 (4.5%) in group 2, with significantly longer occlusion-free survival in group 2 (log-rank P < .0001). LIMITATIONS: Retrospective study at a single tertiary referral center. CONCLUSION: Multiple plastic biliary stents for benign nonhilar strictures were associated with a low rate of premature symptomatic stent occlusion at more than 6 months and a longer occlusion-free survival.


Subject(s)
Cholestasis, Extrahepatic/therapy , Equipment Failure Analysis , Plastics , Stents , Adult , Aged , Cholangiopancreatography, Endoscopic Retrograde , Cholestasis, Extrahepatic/etiology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Retreatment , Retrospective Studies , Secondary Prevention
19.
Res Dev Disabil ; 104: 103681, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32474231

ABSTRACT

Cyber-dependent offending, i.e. criminal behaviour reliant on computing and the online domain, has been reportedly associated with particular characteristics and motivations such as being young, male, autistic and motivated by challenge. These associations are anecdotal however and empirical evidence is limited. The present study investigated reasons for engaging or declining to commit cyber-dependent offending in cyber-skilled non-offenders (n = 175) and offenders (n = 7) via an online survey measuring cyber-dependent criminality. The potential role of autism and autistic traits was also considered. Qualitative interviews about motivations for offending were carried out with the offenders. The cyber-dependent offenders reported seven main reasons for engaging in cyber-dependent offending: (1) lack of understanding; (2) entertainment; (3) peer influence; (4) experience and career; (5) anonymity and risk perception; (6) life events; and (7) morals. Twenty-nine (approximately 17 %) of the non-offenders had been asked to engage in cyber-dependent offending but had declined. Their reasons and motivations for declining to commit cyber-dependent offences were compared with the cyber-dependent offenders reasons and motivations for engaging in cybercrime. Seven main reasons for declining to offend were identified: (1) moral principles; (2) perception of risk; (3) fear of consequences; (4) not wanting to; (5) wanting to adhere to the law; (6) behaviour being too complicated; and (7) price being too low. Implications for practise are discussed.


Subject(s)
Autistic Disorder , Criminals , Humans , Male , Motivation , Self Report , Surveys and Questionnaires
20.
Gastrointest Endosc ; 69(7): 1271-5, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19246037

ABSTRACT

BACKGROUND: Pancreatic sphincterotomy is one of several factors associated with an increased risk of post-ERCP pancreatitis (PEP). The needle-knife pancreatic sphincterotomy technique (NKS) is purported to result in less-frequent post-ERCP pancreatitis compared with a standard pull-type sphincterotomy (PTS). OBJECTIVE: Our purpose was to analyze the experience with both endoscopic pancreatic sphincterotomy (EPS) techniques with respect to post-ERCP pancreatitis at a single tertiary-level referral center. DESIGN: Retrospective analysis. SETTING: Tertiary-care medical center (Charleston, South Carolina). PATIENTS: Patients without chronic pancreatitis and with normal retrograde pancreatogram who underwent EPS between 1994 and 2007 were identified. Patients were excluded for the following reasons: pancreatic stent not placed, both sphincterotomy techniques used, any balloon dilation of the ampullary orifice, precut or access papillotomy, pancreas divisum. RESULTS: A total of 481 patients were identified and underwent 510 ERCPs. Indications for ERCP were recurrent pancreatic-type pain (n = 353) or pancreatitis (n = 157). NKS was used for 395 of 510 (77.5%) cases versus 115 of 510 (22.5%) in which PTS was used. The incidence of post-ERCP pancreatitis was no different between NKS (25/395, 6.4%) and PTS (9/115, 7.8%). Most cases were mild pancreatitis; a single episode of severe PEP occurred in each group. CONCLUSIONS: The risk of post-ERCP pancreatitis does not differ between EPS techniques when performed at a high-volume pancreaticobiliary referral center when using routine prophylactic pancreatic duct stent placement.


Subject(s)
Cholangiopancreatography, Endoscopic Retrograde/adverse effects , Pancreatitis/epidemiology , Sphincterotomy, Endoscopic/adverse effects , Sphincterotomy, Endoscopic/methods , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Incidence , Male , Middle Aged , Pancreatitis/etiology , Retrospective Studies , South Carolina , Young Adult
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