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1.
BMJ Open ; 9(8): e028201, 2019 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-31391190

RESUMO

OBJECTIVES: To assess the impact of both the Committee on Safety of Medicines (CSM) warning (December 2003) and the National Institute for Health and Care Excellence (NICE) guidance (September 2005) on antidepressant prescription rates in children and adolescents within the UK primary care service. SETTING: Population based study of primary care antidepressant prescribing using the Clinical Practice Research Datalink (CPRD). PARTICIPANTS: Under-18s presenting to primary care with a depressive disorder or related diagnostic code recorded in the CPRD. PRIMARY OUTCOME MEASURE: Antidepressant prescription rates per month per 100 000 depressed 4-17 year olds. RESULTS: Following the CSM warning, the prior trend towards increased prescribing rates for selective serotonin reuptake inhibitors (SSRIs) in children was significantly reversed (ß for change in trend -12.34 (95% CI -18.67 to -6.00, p<0.001)). However, after the publication of the NICE guidelines the prior trend towards increased prescribing resumed for those SSRIs mentioned as potential treatments in the guidance (fluoxetine, citalopram and sertraline) (ß for change in trend 11.52 (95% CI 5.32 to 17.73, p<0.001)). Prescribing of other SSRIs and tricyclics remained low. CONCLUSIONS: Despite a strong emphasis on psychosocial interventions for child and adolescent depression, it may be that the NICE guidelines inadvertently encouraged further antidepressant prescribing, at least for those SSRIs cited. Although the guidelines gave cautions and caveats for the use of antidepressants, practitioners may have interpreted these recommendations as endorsing their use in young people with depression and related conditions. However, more accurate prevalence trend estimates for depression in this age group, and information on the use of psychosocial interventions would be needed to rule out other reasons underlying this increase in prescribing.

2.
Trials ; 20(1): 463, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31358032

RESUMO

BACKGROUND: Differentiating infection from inflammation in acute pancreatitis is difficult, leading to overuse of antibiotics. Procalcitonin (PCT) measurement is a means of distinguishing infection from inflammation as levels rise rapidly in response to a pro-inflammatory stimulus of bacterial origin and normally fall after successful treatment. Algorithms based on PCT measurement can differentiate bacterial sepsis from a systemic inflammatory response. The PROCalcitonin-based algorithm for antibiotic use in Acute Pancreatitis (PROCAP) trial tests the hypothesis that a PCT-based algorithm to guide initiation, continuation and discontinuation of antibiotics will lead to reduced antibiotic use in patients with acute pancreatitis and without an adverse effect on outcome. METHODS: This is a single-centre, randomised, controlled, single-blind, two-arm pragmatic clinical and cost-effectiveness trial. Patients with a clinical diagnosis of acute pancreatitis will be allocated on a 1:1 basis to intervention or standard care. Intervention will involve the use of a PCT-based algorithm to guide antibiotic use. The primary outcome measure will be the binary outcome of antibiotic use during index admission. Secondary outcome measures include: safety non-inferiority endpoint all-cause mortality; days of antibiotic use; clinical infections; new isolates of multiresistant bacteria; duration of inpatient stay; episode-related mortality and cause; quality of life (EuroQol EQ-5D); and cost analysis. A 20% absolute change in antibiotic use would be a clinically important difference. A study with 80% power and 5% significance (two-sided) would require 97 patients in each arm (194 patients in total): the study will aim to recruit 200 patients. Analysis will follow intention-to-treat principles. DISCUSSION: When complete, PROCAP will be the largest randomised trial of the use of a PCT algorithm to guide initiation, continuation and cessation of antibiotics in acute pancreatitis. PROCAP is the only randomised trial to date to compare standard care of acute pancreatitis as defined by the International Association of Pancreatology/American Pancreatic Association guidelines to patients having standard care but with all antibiotic prescribing decisions based on PCT measurement. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number, ISRCTN50584992. Registered on 7 February 2018.


Assuntos
Algoritmos , Antibacterianos/uso terapêutico , Técnicas de Apoio para a Decisão , Monitoramento de Medicamentos/métodos , Pancreatite/tratamento farmacológico , Pró-Calcitonina/sangue , Antibacterianos/efeitos adversos , Antibacterianos/economia , Biomarcadores/sangue , Tomada de Decisão Clínica , Ensaios Clínicos Fase III como Assunto , Redução de Custos , Análise Custo-Benefício , Custos de Medicamentos , Monitoramento de Medicamentos/economia , Inglaterra , Humanos , Pancreatite/sangue , Pancreatite/diagnóstico , Pancreatite/economia , Ensaios Clínicos Pragmáticos como Assunto , Valor Preditivo dos Testes , Método Simples-Cego , Fatores de Tempo , Resultado do Tratamento
6.
BMJ Open ; 7(6): e015018, 2017 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-28601828

RESUMO

INTRODUCTION: Colorectal cancer is the fourth most common cancer in the UK and an important cause of cancer-related death. In 20% of patients, there is metastasis to the liver or beyond at the time of diagnosis. The management of synchronous disease is complex. Conventional surgery removes the colorectal primary first, followed by chemotherapy, with resection of liver metastases as a final step. Advances in the availability and safety of liver surgery, anaesthesia and critical care have made two alternative options feasible. The first is synchronous resection of the primary and liver metastases. The second is resection of the metastatic disease as the first step, termed the reverse or liver-first approach. Currently, evidence is inadequate to inform the selection of care pathway for patients with colorectal cancer and synchronous liver-limited metastases. Specifically, optimal pathways are not defined and there is a dearth of prospectively recorded cohort-defining factors influencing treatment selection or outcome. METHODS AND ANALYSIS: Colorectal cancer with Synchronous liver-limited Metastases: an Inception Cohort (CoSMIC) is an inception cohort study of patients with a new diagnosis of colorectal cancer with synchronous liver-limited metastases. The sequence of treatment received, and factors influencing treatment decisions, will be evaluated against European Society of Medical Oncology guidelines. Clinical data will be collected, and quality of life, morbidity, mortality and long-term outcome compared for different treatment sequences adjusted for prognostic factors. Disease-free survival or progression will be measured at 1, 2 and 5 years. A nested qualitative study will ascertain patient experiences and clinician perspectives on delivery of care. ETHICS AND DISSEMINATION: The full study protocol was independently peer reviewed by Professor Kees de Jong (University of Maastricht, Holland). CoSMIC has ethical approval from the National Health Service Research Ethics Committee (14/NW/1397). Results will be disseminated to healthcare professionals and patient groups, and may be used to design a definitive trial addressing areas of equipoise in treatment pathways, as well as optimising current pathways to improve outcomes and experiences. TRIAL REGISTRATION NUMBER: NCT02456285, pre-results.


Assuntos
Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Estudos de Coortes , Colectomia , Procedimentos Clínicos , Hepatectomia , Humanos , Guias de Prática Clínica como Assunto , Qualidade de Vida , Projetos de Pesquisa , Fatores de Tempo , Resultado do Tratamento
7.
Dermatol Ther (Heidelb) ; 7(3): 383-393, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28616853

RESUMO

INTRODUCTION: Patient eczema severity time (PEST) is a new atopic dermatitis (AD) scoring system based on patients' own perception of their disease. Conventional scales such as SCORing of atopic dermatitis (SCORAD) reflect the clinician's observations during the clinic visit. Instead, the PEST score captures eczema severity, relapse and recovery as experienced by the patient or caregiver on a daily basis, promoting patient engagement, compliance with treatment and improved outcomes. This study aims to determine the correlation between carer-assessed PEST and clinician-assessed SCORAD in paediatric AD patients after 12 weeks of treatment using a ceramide-dominant therapeutic moisturizer. METHODS: Prospective, open-label, observational, multi-centre study in which children with AD aged 6 months to 6 years were treated with a ceramide dominant therapeutic moisturizer twice daily for 12 weeks; 58 children with mild-to-moderate AD were included. Correlation between the 7-day averaged PEST and SCORAD scores for assessment of AD severity was measured within a general linear model. PEST and SCORAD were compared in week 4 and week 12. RESULTS: At week 12, a moderate correlation was found between the SCORAD and PEST scores (r = 0.51). The mean change in SCORAD and PEST scores from baseline to week 12 was -11.46 [95% confidence interval (CI) -14.99 to -7.92, p < 0.0001] and -1.33 (95% CI -0.71 to -0.10, p < 0.0001) respectively. PEST demonstrated greater responsiveness to change (33.3% of scale) compared to SCORAD (13.8% of scale). CONCLUSION: The PEST score correlates well with the SCORAD score and may have improved sensitivity when detecting changes in the severity of AD. The ceramide-dominant therapeutic moisturizer used was safe and effective in the management of AD in young children. FUNDING: Hyphens Pharma Pte Ltd. TRIAL REGISTRATION: clinicaltrials.gov identifier, NCT02073591.

8.
Genetics ; 206(1): 451-465, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28258181

RESUMO

Meiotic drive occurs when a selfish element increases its transmission frequency above the Mendelian ratio by hijacking the asymmetric divisions of female meiosis. Meiotic drive causes genomic conflict and potentially has a major impact on genome evolution, but only a few drive loci of large effect have been described. New methods to reliably detect meiotic drive are therefore needed, particularly for discovering moderate-strength drivers that are likely to be more prevalent in natural populations than strong drivers. Here, we report an efficient method that uses sequencing of large pools of backcross (BC1) progeny to test for deviations from Mendelian segregation genome-wide with single-nucleotide polymorphisms (SNPs) that distinguish the parental strains. We show that meiotic drive can be detected by a characteristic pattern of decay in distortion of SNP frequencies, caused by recombination unlinking the driver from distal loci. We further show that control crosses allow allele-frequency distortion caused by meiotic drive to be distinguished from distortion resulting from developmental effects. We used this approach to test whether chromosomes with extreme telomere-length differences segregate at Mendelian ratios, as telomeric regions are a potential hotspot for meiotic drive due to their roles in meiotic segregation and multiple observations of high rates of telomere sequence evolution. Using four different pairings of long and short telomere strains, we find no evidence that extreme telomere-length variation causes meiotic drive in Drosophila However, we identify one candidate meiotic driver in a centromere-linked region that shows an ∼8% increase in transmission frequency, corresponding to a ∼54:46 segregation ratio. Our results show that candidate meiotic drivers of moderate strength can be readily detected and localized in pools of BC1 progeny.


Assuntos
Evolução Molecular , Genoma de Inseto/genética , Meiose/genética , Modelos Genéticos , Animais , Centrômero/genética , Drosophila melanogaster/genética , Frequência do Gene , Polimorfismo de Nucleotídeo Único , Sequências Repetitivas de Ácido Nucleico/genética , Telômero/genética
9.
Trials ; 18(1): 139, 2017 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-28340625

RESUMO

BACKGROUND: Constipation affects up to 20% of adults. Chronic constipation (CC) affects 1-2% of adults. Patient dissatisfaction is high; nearly 80% feel that laxative therapy is unsatisfactory and symptoms have significant impact on quality of life. There is uncertainty about the value of specialist investigations and whether equipment-intensive therapies using biofeedback confer additional benefit when compared with specialist conservative advice. METHODS/DESIGN: A three-arm, parallel-group, multicentre randomised controlled trial. OBJECTIVES: to determine whether standardised specialist-led habit training plus pelvic floor retraining using computerised biofeedback is more clinically effective than standardised specialist-led habit training alone; to determine whether outcomes are improved by stratification based on prior investigation of anorectal and colonic pathophysiology. Primary outcome measure is response to treatment, defined as a 0.4-point (10% of scale) or greater reduction in Patient Assessment of Constipation-Quality of Life (PAC-QOL) score 6 months after the end of treatment. Other outcomes up to 12 months include symptoms, quality of life, health economics, psychological health and qualitative experience. HYPOTHESES: (1) habit training (HT) with computer-assisted direct visual biofeedback (HTBF) results in an average reduction in PAC-QOL score of 0.4 points at 6 months compared to HT alone in unselected adults with CC, (2) stratification to either HT or HTBF informed by pathophysiological investigation (INVEST) results in an average 0.4-point reduction in PAC-QOL score at 6 months compared with treatment not directed by investigations (No-INVEST). Inclusion: chronic constipation in adults (aged 18-70 years) defined by self-reported symptom duration of more than 6 months; failure of previous laxatives or prokinetics and diet and lifestyle modifications. Consenting participants (n = 394) will be randomised to one of three arms in an allocation ratio of 3:3:2: [1] habit training, [2] habit training and biofeedback or [3] investigation-led allocation to one of these arms. Analysis will be on an intention-to-treat basis. DISCUSSION: This trial has the potential to answer some of the major outstanding questions in the management of chronic constipation, including whether costly invasive tests are warranted and whether computer-assisted direct visual biofeedback confers additional benefit to well-managed specialist advice alone. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number: ISRCTN11791740. Registered on 16 July 2015.


Assuntos
Canal Anal/fisiopatologia , Biorretroalimentação Psicológica/métodos , Colo/fisiopatologia , Constipação Intestinal/terapia , Defecação , Hábitos , Diafragma da Pelve/fisiopatologia , Terapia Assistida por Computador/métodos , Percepção Visual , Adolescente , Adulto , Idoso , Doença Crônica , Protocolos Clínicos , Gráficos por Computador , Constipação Intestinal/diagnóstico , Constipação Intestinal/fisiopatologia , Constipação Intestinal/psicologia , Feminino , Humanos , Análise de Intenção de Tratamento , Masculino , Manometria , Pessoa de Meia-Idade , Satisfação do Paciente , Qualidade de Vida , Recuperação de Função Fisiológica , Projetos de Pesquisa , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento , Reino Unido , Adulto Jovem
10.
Gut ; 66(5): 887-895, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-27196576

RESUMO

BACKGROUND: Accurate optical characterisation and removal of small adenomas (<10 mm) at colonoscopy would allow hyperplastic polyps to be left in situ and surveillance intervals to be determined without the need for histopathology. Although accurate in specialist practice the performance of narrow band imaging (NBI), colonoscopy in routine clinical practice is poorly understood. METHODS: NBI-assisted optical diagnosis was compared with reference standard histopathological findings in a prospective, blinded study, which recruited adults undergoing routine colonoscopy in six general hospitals in the UK. Participating colonoscopists (N=28) were trained using the NBI International Colorectal Endoscopic (NICE) classification (relating to colour, vessel structure and surface pattern). By comparing the optical and histological findings in patients with only small polyps, test sensitivity was determined at the patient level using two thresholds: presence of adenoma and need for surveillance. Accuracy of identifying adenomatous polyps <10 mm was compared at the polyp level using hierarchical models, allowing determinants of accuracy to be explored. FINDINGS: Of 1688 patients recruited, 722 (42.8%) had polyps <10 mm with 567 (78.5%) having only polyps <10 mm. Test sensitivity (presence of adenoma, N=499 patients) by NBI optical diagnosis was 83.4% (95% CI 79.6% to 86.9%), significantly less than the 95% sensitivity (p<0.001) this study was powered to detect. Test sensitivity (need for surveillance) was 73.0% (95% CI 66.5% to 79.9%). Analysed at the polyp level, test sensitivity (presence of adenoma, N=1620 polyps) was 76.1% (95% CI 72.8% to 79.1%). In fully adjusted analyses, test sensitivity was 99.4% (95% CI 98.2% to 99.8%) if two or more NICE adenoma characteristics were identified. Neither colonoscopist expertise, confidence in diagnosis nor use of high definition colonoscopy independently improved test accuracy. INTERPRETATION: This large multicentre study demonstrates that NBI optical diagnosis cannot currently be recommended for application in routine clinical practice. Further work is required to evaluate whether variation in test accuracy is related to polyp characteristics or colonoscopist training. TRIAL REGISTRATION NUMBER: The study was registered with clinicaltrials.gov (NCT01603927).


Assuntos
Adenoma/diagnóstico por imagem , Pólipos do Colo/diagnóstico por imagem , Neoplasias Colorretais/diagnóstico por imagem , Imagem de Banda Estreita , Vigilância da População , Adenoma/patologia , Idoso , Competência Clínica , Pólipos do Colo/patologia , Colonoscopia , Neoplasias Colorretais/patologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Estudos Prospectivos , Sensibilidade e Especificidade , Fatores de Tempo
11.
J Am Acad Dermatol ; 75(6): 1216-1220.e2, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27742168

RESUMO

BACKGROUND: Pyoderma gangrenosum is a rare inflammatory skin condition. Two prospective studies have evaluated treatments for pyoderma gangrenosum using a primary outcome of healing speed at 6 weeks. OBJECTIVE: Using data from both studies we assessed the predictive value of 3 early predictors for healing at 6 months: speed of healing, Investigator Global Assessment (IGA), and resolution of inflammation, recorded at 2 and 6 weeks. METHODS: Logistic regression models were applied and the effectiveness of the 3 measures was assessed through estimating the positive and negative predictive values and the area under the receiver operating characteristic curve. RESULTS: The positive and negative predictive value at 6 weeks were, respectively, 63.5% (95% confidence interval [CI] 52.4%-73.7%) and 74.6% (95% CI 62.5%-84.5%) for speed of healing; 80% (95% CI 68.7%-88.6%) and 74.2% (95% CI 64.1%-82.7%) for IGA; and 72.1% (95% CI 59.9%-82.3%) and 68.1% (95% CI 57.7%-77.3%) for resolution of inflammation. IGA had the best combined positive predictive value, negative predictive value, and area under the receiver operating characteristic curve at 2 and 6 weeks. LIMITATIONS: We were limited by data available from existing datasets. CONCLUSION: Speed of healing, IGA, and resolution of inflammation were all shown to be good predictors of eventual healing of pyoderma gangrenosum.


Assuntos
Pioderma Gangrenoso/tratamento farmacológico , Índice de Gravidade de Doença , Cicatrização , Adulto , Idoso , Área Sob a Curva , Determinação de Ponto Final , Feminino , Humanos , Inflamação/tratamento farmacológico , Inflamação/etiologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Pioderma Gangrenoso/complicações , Curva ROC , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo , Resultado do Tratamento
12.
J Am Acad Dermatol ; 75(5): 940-949, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27502313

RESUMO

BACKGROUND: Pyoderma gangrenosum (PG) is an uncommon dermatosis with a limited evidence base for treatment. OBJECTIVE: We sought to estimate the effectiveness of topical therapies in the treatment of patients with PG. METHODS: This was a prospective cohort study of UK secondary care patients with a clinical diagnosis of PG that was suitable for topical treatment (recruited between July 2009 and June 2012). Participants received topical therapy after normal clinical practice (primarily topical corticosteroids [classes I-III] and tacrolimus 0.03% or 0.1%). The primary outcome was speed of healing at 6 weeks. Secondary outcomes included the following: proportion healed by 6 months; time to healing; global assessment; inflammation; pain; quality of life; treatment failure; and recurrence. RESULTS: Sixty-six patients (22-85 years of age) were enrolled. Clobetasol propionate 0.05% was the most commonly prescribed therapy. Overall, 28 of 66 (43.8%) ulcers healed by 6 months. The median time to healing was 145 days (95% confidence interval, 96 days to ∞). Initial ulcer size was a significant predictor of time to healing (hazard ratio, 0.94 [95% confidence interval, 0.88-1.00); P = .043). Four patients (15%) had a recurrence. LIMITATIONS: Our study did not include a randomized comparator. CONCLUSION: Topical therapy is potentially an effective first-line treatment for PG that avoids the possible side effects associated with systemic therapy. It remains unclear whether more severe disease will respond adequately to topical therapy alone.


Assuntos
Anti-Inflamatórios/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Pioderma Gangrenoso/tratamento farmacológico , Administração Cutânea , Adulto , Idoso , Anti-Inflamatórios/administração & dosagem , Clobetasol/administração & dosagem , Clobetasol/uso terapêutico , Fármacos Dermatológicos/administração & dosagem , Feminino , Humanos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Estudos Prospectivos , Pioderma Gangrenoso/complicações , Qualidade de Vida , Recidiva , Úlcera Cutânea/tratamento farmacológico , Úlcera Cutânea/etiologia , Tacrolimo/administração & dosagem , Tacrolimo/uso terapêutico , Resultado do Tratamento
13.
Chromosoma ; 125(1): 65-73, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26162505

RESUMO

Telomerase and telomerase-generated telomeric DNA sequences are widespread throughout eukaryotes, yet they are not universal. Neither telomerase nor the simple DNA repeats associated with telomerase have been found in some plant and animal species. Telomerase was likely lost from Diptera before the divergence of Diptera and Siphonaptera, some 260 million years ago. Even so, Diptera is one of the most successful animal orders, making up 11% of known animal species. In addition, many species of Coleoptera and Hemiptera seem to lack canonical telomeric repeats at their chromosome ends. These and other insects that appear to lack canonical terminal repeat sequences account for another 10-15% of animal species. Conversely, the silk moth Bombyx mori maintains canonical telomeric sequences at its chromosome ends but seems to lack a functional telomerase. We speculate that a telomere-specific capping complex that recognizes the telomeric repeats and protects chromosome ends is the determining factor in maintaining canonical telomeric sequences and that telomerase is an early and efficacious mechanism for satisfying the needs of capping complex. There are alternate mechanisms for maintaining chromosome ends that do not depend on telomerase, such as recombination found in some human cancer cells and yeast mutants. These mechanisms may maintain the canonical telomeric repeats or allow the terminal sequence to evolve when specificity of the capping complex for terminal repeat sequences is weak.


Assuntos
Evolução Molecular , Deleção de Genes , Insetos/enzimologia , Telomerase/genética , Telômero/metabolismo , Animais , Recombinação Homóloga , Insetos/genética , Sequências Repetidas Terminais
14.
Pancreatology ; 15(6): 635-41, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26547592

RESUMO

OBJECTIVE: Patients with severe acute pancreatitis were excluded from major trials of human recombinant activated protein C (Xigris) because of concern about pancreatic haemorrhage although these individuals have an intense systemic inflammatory response that may benefit from treatment. The object of this study was to provide initial safety data evaluating Xigris in severe acute pancreatitis. DESIGN: Prospective clinical trial recruiting between November 2009 and October 2011. Patients received human recombinant activated protein C (Xigris) for 24 h by intravenous infusion (24 µg/kg/h) in addition to standard clinical care. A matched historical control group treated within the same hospital unit were used to compare outcomes. Of 166 consecutive admitted patients, 43 met the screening criteria for severe acute pancreatitis and 19 were recruited, all contributing to the analyses. RESULTS: Compared to historical controls, there were fewer bleeding events in the Xigris group although the finding did not reach significance (Xigris 0% vs. Control 21%, p = 0.13), similarly further intervention appeared less frequent (11% vs. 47%, p = 0.07) in the treatment group. Length of stay was shorter for patients receiving Xigris (19 vs. 41 days, p = 0.03) as was inotrope use (5% vs. 32%, p = 0.02); mortality and incidence of infections in both groups were similar. Biomarker protein C increased while IL-6 decreased following infusion. CONCLUSIONS: A 24-hr infusion of Xigris appears safe when used in patients with severe acute pancreatitis. TRIAL REGISTRATION: Eudract Number 2007-003635-23.


Assuntos
Anti-Infecciosos/uso terapêutico , Pancreatite/tratamento farmacológico , Proteína C/uso terapêutico , Doença Aguda , Adulto , Idoso , Anti-Infecciosos/administração & dosagem , Biomarcadores , Esquema de Medicação , Feminino , Humanos , Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Proteína C/administração & dosagem , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/uso terapêutico
15.
BMC Gastroenterol ; 15: 139, 2015 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-26474758

RESUMO

BACKGROUND: Trans-anal irrigation (TAI) is used widely to treat bowel dysfunction, although evidence for its use in adult chronic functional constipation remains unclear. Long-term outcome data are lacking, and the effectiveness of therapy in this patient group is not definitively known. METHODS: Evidence for effectiveness and safety was reviewed and the quality of studies was assessed. Primary research articles of patients with chronic functional constipation, treated with TAI as outpatients and published in English in indexed journals were eligible. Searching included major bibliographical databases and search terms: bowel dysfunction, defecation, constipation and irrigation. Fixed- and random-effect meta-analyses were performed. RESULTS: Seven eligible uncontrolled studies, including 254 patients, of retrospective or prospective design were identified. The definition of treatment response varied and was investigator-determined. The fixed-effect pooled response rate (the proportion of patients with a positive outcome based on investigator-reported response for each study) was 50.4 % (95 % CI: 44.3-56.5 %) but featured substantial heterogeneity (I(2) = 67.1 %). A random-effects estimate was similar: 50.9 % (95 % CI: 39.4-62.3 %). Adverse events were inconsistently reported but were commonplace and minor. CONCLUSIONS: The reported success rate of irrigation for functional constipation is about 50 %, comparable to or better than the response seen in trials of pharmacological therapies. TAI is a safe treatment benefitting some patients with functional constipation, which is a chronic refractory condition. However findings for TAI vary, possibly due to varying methodology and context. Well-designed prospective trials are required to improve the current weak evidence base.


Assuntos
Canal Anal , Constipação Intestinal/terapia , Irrigação Terapêutica/estatística & dados numéricos , Adulto , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Irrigação Terapêutica/métodos , Resultado do Tratamento
16.
PLoS One ; 10(10): e0139745, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26461954

RESUMO

OBJECTIVE: Patients with inflammatory bowel disease (IBD) demonstrate an inflammatory response which bears some similarities to that seen in ischaemic heart disease (IHD). The nature of the association of IBD with IHD is uncertain. We aimed to define the extent and direction of that association. DESIGN: This retrospective cohort study examined records from patients aged ≥ 15 years with IBD from 1987-2009 (n = 19163) who were age and gender matched with patients without IBD (n = 75735) using the General Practice Research Database. The primary outcome was the hazard ratio for IHD. RESULTS: A higher proportion of IBD patients had a recorded diagnosis of IHD ever, 2220 (11.6%) compared with 6504 (8.6%) of controls. However, the majority (4494, 51.5%) developed IHD prior to IBD diagnosis (1404 (63.2%) of IBD cases and 3090 (47.5%) of controls). There was increased IHD incidence in the first year after IBD diagnosis. Mean age at IHD diagnosis was statistically similar across all IBD groups apart from for those with Ulcerative Colitis (UC) who were slightly younger at diagnosis of angina compared to controls (64.5y vs. 67.0y, p = 0.008) and coronary heart disease (65.7y vs.67.9y, p = 0.015). Of those developing IHD following IBD diagnosis, UC patients were at higher risk of IHD (unadjusted HR 1.3 (95% CI 1.1-1.5), p<0.001) or MI (unadjusted HR 1.4 (95% CI 1.1-1.6), p = 0.004). CONCLUSION: Although IHD prevalence was higher in IBD patients, most IHD diagnoses predated the diagnosis of IBD. This implies a more complex relationship than previously proposed between the inflammatory responses associated with IHD and IBD, and alternative models should be considered.


Assuntos
Bases de Dados como Assunto , Medicina Geral , Doenças Inflamatórias Intestinais/complicações , Isquemia Miocárdica/etiologia , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/diagnóstico , Modelos de Riscos Proporcionais , Fatores de Tempo , Adulto Jovem
17.
BMJ ; 350: h2958, 2015 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-26071094

RESUMO

OBJECTIVE: To determine whether ciclosporin is superior to prednisolone for the treatment of pyoderma gangrenosum, a painful, ulcerating skin disease with a poor evidence base for management. DESIGN: Multicentre, parallel group, observer blind, randomised controlled trial. SETTING: 39 UK hospitals, recruiting from June 2009 to November 2012. PARTICIPANTS: 121 patients (73 women, mean age 54 years) with clinician diagnosed pyoderma gangrenosum. Clinical diagnosis was revised in nine participants after randomisation, leaving 112 participants in the analysis set (59 ciclosporin; 53 prednisolone). INTERVENTION: Oral prednisolone 0.75 mg/kg/day compared with ciclosporin 4 mg/kg/day, to a maximum dose of 75 and 400 mg/day, respectively. MAIN OUTCOME MEASURES: The primary outcome was speed of healing over six weeks, captured using digital images and assessed by blinded investigators. Secondary outcomes were time to healing, global treatment response, resolution of inflammation, self reported pain, quality of life, number of treatment failures, adverse reactions, and time to recurrence. Outcomes were assessed at baseline and six weeks and when the ulcer had healed (to a maximum of six months). RESULTS: Of the 112 participants, 108 had complete primary outcome data at baseline and six weeks (57 ciclosporin; 51 prednisolone). Groups were balanced at baseline. The mean (SD) speed of healing at six weeks was -0.21 (1.00) cm(2)/day in the ciclosporin group compared with -0.14 (0.42) cm(2)/day in the prednisolone group. The adjusted mean difference showed no between group difference (0.003 cm(2)/day, 95% confidence interval -0.20 to 0.21; P=0.97). By six months, ulcers had healed in 28/59 (47%) participants in the ciclosporin group compared with 25/53 (47%) in the prednisolone group. In those with healed ulcers, eight (30%) receiving ciclosporin and seven (28%) receiving prednisolone had a recurrence. Adverse reactions were similar for the two groups (68% ciclosporin and 66% prednisolone), but serious adverse reactions, especially infections, were more common in the prednisolone group. CONCLUSION: Prednisolone and ciclosporin did not differ across a range of objective and patient reported outcomes. Treatment decisions for individual patients may be guided by the different side effect profiles of the two drugs and patient preference. Trial registration Current Controlled Trials ISRCTN35898459.


Assuntos
Ciclosporina/administração & dosagem , Fármacos Dermatológicos/administração & dosagem , Prednisolona/administração & dosagem , Pioderma Gangrenoso/tratamento farmacológico , Úlcera Varicosa/tratamento farmacológico , Cicatrização/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Pioderma Gangrenoso/patologia , Qualidade de Vida , Recidiva , Fatores de Tempo , Resultado do Tratamento , Reino Unido , Úlcera Varicosa/patologia
18.
PLoS One ; 10(3): e0116231, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25739018

RESUMO

OBJECTIVE: The contraceptive needs of illicit opioid users differ from non-drug users but are poorly understood. The aim of this study was to describe contraceptive use and pregnancy outcomes in opioid-using women, and to examine their association with a range of risk factors. METHOD: This retrospective cohort study used UK general practice records, Treatment Outcomes Profile and National Drug Treatment Monitoring System data, and a nested data validation exercise. A cohort of 376 women aged 20-61 years were in active treatment for opioid addiction in October 2010 at two specialised primary care practices in North-East England. Outcomes were age-adjusted prevalence estimates for contraceptive use and pregnancy outcomes in users of illicit opioids. The association between lifestyle-related risk factors and contraception was explored. RESULTS: Drug-using women made lower use of planned (non-condom) contraception (24% vs 50%, p<0.001), had more frequent pregnancy terminations (0.46 vs. 0.025, p = 0.004) and higher annual incidence of chlamydia (1.1% vs. 0.33%, p<0.001), when compared with age-matched population data. Specifically, there was low use of oral contraceptives (4% vs. 25%, p<0.001), IUCD (1% vs. 6%, p<0.001), and sterilisation (7% vs. 6%, p = 0.053), but higher rates of injectable contraceptives (6% vs. 3%, p = 0.003). A total of 64% of children aged <16 years born to this group did not live with their mother. No individual risk factor (such as sex-working) significantly explained the lower use or type of non-condom contraception. CONCLUSIONS: This is the first study to describe planned contraceptive use among drug-users, as well as the association with a range of risk factors and pregnancy outcomes. The low uptake of planned contraception, set against high rates of terminations and sexually transmitted disease demonstrates the urgent clinical need to improve contraceptive services, informed by qualitative work to explore the values and beliefs influencing low contraceptive uptake.


Assuntos
Anticoncepção/estatística & dados numéricos , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Resultado da Gravidez/epidemiologia , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Gravidez , Estudos Retrospectivos
19.
J Orthop Traumatol ; 16(1): 27-34, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25091616

RESUMO

BACKGROUND: Tranexamic acid (TXA) has been successfully used to reduce bleeding in joint replacement. Recently local TXA has been advocated to reduce blood loss in total knee or hip replacement; however, this raised concerns about potential adverse effects of TXA upon the artificial joint replacement. MATERIALS AND METHODS: In this biomechanical study we compared the effects of TXA and saline upon the following biomechanical properties of artificial joint materials-(1) tensile properties (ultimate strength, stiffness and Young's modulus), (2) the wear rate using a multi-directional pin-on-plate machine, and (3) the surface topography of pins and plates before and after wear rate testing. RESULTS: There were no significant differences in tensile strength, wear rates or surface topography of either ultra-high-molecular-weight polyethylene pins or cobalt chromium molybdenum metal plates between specimens soaked in TXA and specimens soaked in saline. CONCLUSION: Biomechanical testing shows that there are no biomechanical adverse affects on the properties of common artificial joint materials from using topical TXA. LEVEL OF EVIDENCE: V.


Assuntos
Artroplastia de Quadril , Artroplastia do Joelho , Teste de Materiais/métodos , Polietilenos/química , Ácido Tranexâmico/farmacologia , Antifibrinolíticos/farmacologia , Materiais Biocompatíveis , Fenômenos Biomecânicos/efeitos dos fármacos , Humanos , Resistência à Tração
20.
Acta Orthop ; 86(1): 32-40, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25301437

RESUMO

BACKGROUND AND PURPOSE: There has been a recent trend towards the use of greater femoral head sizes in an attempt to improve function and enhance stability after primary hip replacement. This has been associated with the use of alternative bearings, theoretically to reduce wear and improve implant longevity. METHODS: We examined the influence of these variables on patient-reported outcome measures (PROMs) for a consecutive series of primary hip replacements using National Joint Registry (NJR) and PROMs-linked data. To minimize the confounding influence of implant design factors, the single most commonly used brand in England and Wales (DePuy Corail Pinnacle) was examined. Improvement in patient hip-specific outcomes (Oxford hip score, OHS), general health outcomes (Euroqol, EQ-5D), and rates of self-reported complications (bleeding, wound problems, re-admission, and reoperation) were compared for different head sizes (28-mm, 32-mm, and 36-mm) and bearings (metal-on-polyethylene (MoP), ceramic-on-polyethylene (CoP), and ceramic-on-ceramic (CoC)), adjusting for differences in case mix. RESULTS: At a mean follow-up of 7 months, improvements in OHS and EQ5D index were similar for 28-mm and 36-mm heads. A 32-mm head was associated with poorer function (OHS: 20, 99% CI: 19-21, p = 0.002; EQ5D index: 0.39, 99% CI: 0.36-0.42, p = 0.004), although these small differences may not be of clinical importance. There were no statistically significant benefits of either CoP or CoC bearings compared to a MoP bearing. Complication rates were similar within comparisons of head sizes or bearings. INTERPRETATION: In this short-term study, we did not find any functional benefits of larger head sizes or alternative bearings, after adjusting for other influences. We question their use in routine primary hip replacement given the lack of evidence of improved long-term survival in the literature.


Assuntos
Artroplastia de Quadril/métodos , Prótese de Quadril , Osteoartrite do Quadril/cirurgia , Desenho de Prótese , Sistema de Registros , Adulto , Idoso , Idoso de 80 Anos ou mais , Cerâmica , Estudos de Coortes , Inglaterra , Feminino , Humanos , Masculino , Metais , Pessoa de Meia-Idade , Avaliação de Resultados da Assistência ao Paciente , Polietileno , Resultado do Tratamento , País de Gales
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