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1.
J Autoimmun ; : 102417, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32035746

RESUMO

IL-12 and IL-18 synergize to promote TH1 responses and have been implicated as accelerators of autoimmune pathogenesis in type 1 diabetes (T1D). We investigated the influence of these cytokines on immune cells involved in human T1D progression: natural killer (NK) cells, regulatory T cells (Tregs), and cytotoxic T lymphocytes (CTL). NK cells from T1D patients exhibited higher surface CD226 versus controls and lower CD25 compared to first-degree relatives and controls. Changes in NK cell phenotype towards terminal differentiation were associated with cytomegalovirus (CMV) seropositivity, while possession of IL18RAP, IFIH1, and IL2RA T1D-risk variants impacted NK cell activation as evaluated by immuno-expression quantitative trait loci (eQTL) analyses. IL-12 and IL-18 stimulated NK cells from healthy donors exhibited enhanced specific killing of myelogenous K562 target cells. Moreover, activated NK cells increased expression of NKG2A, NKG2D, CD226, TIGIT and CD25, which enabled competition for IL-2 upon co-culture with Tregs, resulting in Treg downregulation of FOXP3, production of IFNγ, and loss of suppressive function. We generated islet-autoreactive CTL "avatars", which upon exposure to IL-12 and IL-18, upregulated IFNγ and Granzyme-B leading to increased lymphocytotoxicity of a human ß-cell line in vitro. These results support a model for T1D pathogenesis wherein IL-12 and IL-18 synergistically enhance CTL and NK cell cytotoxic activity and disrupt immunoregulation by Tregs.

3.
J Econ Entomol ; 2020 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-31982916

RESUMO

Use of heated air to create lethal temperatures within infested wood serves as a nonchemical treatment option against western drywood termites, Incisitermes minor (Hagen). When treating a whole or large portion of the structure, however, the presence of hard-to-heat areas (structural heat sinks) and potential risk of damaging heat-sensitive items are recognized as important challenges. To address these challenges, we tested if the incorporation of a volatile essential oil would increase the overall efficacy of heat treatments against the drywood termites. To choose an essential oil for use, we tested the volatile action of several candidate compounds against individual termites using a fumigant toxicity assay. As a proof-of-concept experiment, field-collected termites were housed in small wooden arenas and subsequently subjected to 2-h heat treatment at various air temperatures within a gas chromatography oven. A simulated heat sink and essential oil treatment was also included in the experimental design. Analyses of lethal temperatures (LTemp50 and LTemp99 values), probabilities of mortality, and survivorship data over time suggested that 1) the presence of a heat sink significantly increased the minimum air temperature needed for complete kill of the termites and 2) the volatile essential oil added at the site of a heat sink effectively counteracted the impact of the heat sink. The use of volatile essential oils makes it possible to effectively kill drywood termites even in areas which might not reach lethal temperatures (~50°C), potentially improving the overall efficacy of heat treatments while reducing the risk of heat damage.

4.
Sci Rep ; 10(1): 672, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31959869

RESUMO

In this study, we sought to fill an important gap in fundamental immunology research by conducting a comprehensive systems immunology analysis of daily variation in the normal human peripheral immune system. Although variation due to circadian rhythmicity was not a significant source of variation in daily B-cell levels or any CD4+ functional subset, it accounted for more than 25% of CD4+ regulatory T-cell variation and over 50% of CD8+ central memory variation. Circadian rhythmicity demonstrated phase alignment within functional phenotypes. In addition, we observed that previously-described mechanistic relationships can also appear in the peripheral system as phase shifting in rhythmic patterns. We identified a set of immune factors which are ubiquitously correlated with other factors and further analysis also identified a tightly-correlated "core" set whose relational structure persisted after analytically removing circadian-related variation. This core set consisted of CD8+ and its subpopulations and the NK population. In sum, the peripheral immune system can be conceptualized as a dynamic, interconnected wave-field repeating its pattern on a daily basis. Our data provide a comprehensive inventory of synchronization and correlation within this wave-field and we encourage use of our data to discover unknown mechanistic relationships which can then be tested in the laboratory.

5.
JAMA ; 322(23): 2323-2333, 2019 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-31846019

RESUMO

Importance: Hip osteoarthritis (OA) is a common cause of pain and disability. Objective: To identify the clinical findings that are most strongly associated with hip OA. Data Sources: Systematic search of MEDLINE, PubMed, EMBASE, and CINAHL from inception until November 2019. Study Selection: Included studies (1) quantified the accuracy of clinical findings (history, physical examination, or simple tests) and (2) used plain radiographs as the reference standard for diagnosing hip OA. Data Extraction and Synthesis: Studies were assigned levels of evidence using the Rational Clinical Examination scale and assessed for risk of bias using the Quality Assessment of Diagnostic Accuracy Studies tool. Data were extracted using individual hips as the unit of analysis and only pooled when findings were reported in 3 or more studies. Main Outcomes and Measures: Sensitivity, specificity, and likelihood ratios (LRs). Results: Six studies were included, with data from 1110 patients and 1324 hips, of which 509 (38%) showed radiographic evidence of OA. Among patients presenting to primary care physicians with hip or groin pain, the affected hip showed radiographic evidence of OA in 34% of cases. A family history of OA, personal history of knee OA, or pain on climbing stairs or walking up slopes all had LRs of 2.1 (sensitivity range, 33%-68%; specificity range, 68%-84%; broadest LR range: 95% CI, 1.1-3.8). To identify patients most likely to have OA, the most useful findings were squat causing posterior pain (sensitivity, 24%; specificity, 96%; LR, 6.1 [95% CI, 1.3-29]), groin pain on passive abduction or adduction (sensitivity, 33%; specificity, 94%; LR, 5.7 [95% CI, 1.6-20]), abductor weakness (sensitivity, 44%; specificity, 90%; LR, 4.5 [95% CI, 2.4-8.4]), and decreased passive hip adduction (sensitivity, 80%; specificity, 81%; LR, 4.2 [95% CI, 3.0-6.0]) or internal rotation (sensitivity, 66%; specificity, 79%; LR, 3.2 [95% CI, 1.7-6.0]) as measured by a goniometer or compared with the contralateral leg. The presence of normal passive hip adduction was most useful for suggesting the absence of OA (negative LR, 0.25 [95% CI, 0.11-0.54]). Conclusions and Relevance: Simple tests of hip motion and observing for pain during that motion were helpful in distinguishing patients most likely to have OA on plain radiography from those who will not. A combination of findings efficiently detects those most likely to have severe hip OA.


Assuntos
Articulação do Quadril/diagnóstico por imagem , Osteoartrite do Quadril/diagnóstico , Exame Físico , Radiografia , Diagnóstico Diferencial , Feminino , Articulação do Quadril/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Quadril/diagnóstico por imagem , Dor/etiologia , Amplitude de Movimento Articular , Sensibilidade e Especificidade
6.
SICOT J ; 5: 41, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31769752

RESUMO

BACKGROUND: To perform a bibliometric analysis and quantify the amount of orthopaedic and trauma literature published from low-income countries (LICs). METHODS AND METHODS: The Web of Science database was utilised to identify all indexed orthopaedic journals. All articles published in the 76 orthopaedics journals over the last 10 years were reviewed, to determine their geographic origin. RESULTS: A total of 131 454 articles were published across 76 orthopaedic journals over the last 10 years. Of these, 132 (0.1%) were published from LICs and 3515 (2.7%) were published from lower middle-income countries (LMICs); 85.7% (n = 112 716) of published orthopaedic research was undertaken in a high-income setting. The majority of the studies (n = 90, 74.4%) presented level IV evidence. Only 7.4% (n = 9) were high-quality evidence (level I or II). Additionally, the majority of research (74 articles, 56%) was published in partnership with high-income countries (HICs). CONCLUSIONS: There is a stark mismatch between the publication of scientific reports on orthopaedic research and the geographical areas of greatest clinical need. We believe there is an urgent need for orthopaedic research to be carried out in low-income settings to guide treatment and improve outcomes, rather than assuming that evidence from high-income settings will translate into this environment. LEVEL OF EVIDENCE: IV.

7.
Cardiol Clin ; 37(4): 497-503, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31587790

RESUMO

Carcinoid heart disease is the collective term for all cardiac manifestations that develop in patients with carcinoid. The cardiac manifestations of carcinoid tumors are attributed to the paraneoplastic effects of vasoactive substances released by the malignant cells. The clinical manifestations of carcinoid heart disease include valvular destruction leading to valvular regurgitation and stenosis, right-sided heart failure, and metastatic carcinoid disease. A combination of biomarkers and cardiac imaging is used in screening and diagnosis of carcinoid heart disease in patients with carcinoid syndrome. The management of carcinoid heart disease involves medical and surgical treatment and requires a multidisciplinary approach for optimized care.

10.
BMC Med Res Methodol ; 19(1): 115, 2019 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-31170931

RESUMO

BACKGROUND: Comorbidity measures, such as the Charlson Comorbidity Index (CCI) and Elixhauser Method (EM), are frequently used for risk-adjustment by healthcare researchers. This study sought to create CCI and EM lists of Read codes, which are standard terminology used in some large primary care databases. It also aimed to describe and compare the predictive properties of the CCI and EM amongst patients with hip fracture (and matched controls) in a large primary care administrative dataset. METHODS: Two researchers independently screened 111,929 individual Read codes to populate the 17 CCI and 31 EM comorbidity categories. Patients with hip fractures were identified (together with age- and sex-matched controls) from UK primary care practices participating in the Clinical Practice Research Datalink (CPRD). The predictive properties of both comorbidity measures were explored in hip fracture and control populations using logistic regression models fitted with 30- and 365-day mortality as the dependent variables together with tests of equality for Receiver Operating Characteristic (ROC) curves. RESULTS: There were 5832 CCI and 7156 EM comorbidity codes. The EM improved the ability of a logistic regression model (using age and sex as covariables) to predict 30-day mortality (AUROC 0.744 versus 0.686). The EM alone also outperformed the CCI (0.696 versus 0.601). Capturing comorbidities over a prolonged period only modestly improved the predictive value of either index: EM 1-year look-back 0.645 versus 5-year 0.676 versus complete record 0.695 and CCI 0.574 versus 0.591 versus 0.605. CONCLUSIONS: The comorbidity code lists may be used by future researchers to calculate CCI and EM using records from Read coded databases. The EM is preferable to the CCI but only marginal gains should be expected from incorporating comorbidities over a period longer than 1 year.

11.
BMC Musculoskelet Disord ; 20(1): 226, 2019 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-31101041

RESUMO

BACKGROUND: Displaced intracapsular hip fractures are typically treated with hemiarthroplasty (HA) or total hip arthroplasty (THA). A number of professional bodies recommend considering THA for patients that were independently mobile and cognitively intact before injury. The aim of this study was to compare the outcomes between HA and THA for independently mobile older adults with hip fractures. METHODS: A systematic review and meta-analysis of RCTs was undertaken alongside analysis of a propensity score matched national cohort of older adults (aged > 60) with hip fractures. Participants were identified for the propensity score matched cohort from the National Hip Fracture Database (NHFD), which was linked to Hospital Episode Statistics (HES) and civil death registration data. The primary outcomes were 12-month dislocation, revision, and mortality. The secondary outcomes were length of stay, discharge home, unplanned re-admission, functional outcomes, and health-related quality of life. RESULTS: Five RCTs reported higher THA dislocation but this was not statistically significant (THA risk ratio [RR] 2.77, 95% CI 0.81 to 9.48). However, THA dislocation was significantly higher in the national observational dataset (sub-distribution hazard ratio [SHR] 1.73, 95% CI 1.24 to 2.41). Meta-analysis of data from four RCTs did not identify a significant difference in terms of revision (RR 1.52, 95% CI 0.56 to 4.14). However, THA revision was significantly lower in the national dataset (SHR 0.66, 95% CI 0.48 to 0.90). Meta-analysis of data from 5 RCTs suggested higher mortality amongst patients undergoing HA (RR 0.63, 95% CI 0.38 to 1.04), which was also observed within the national registry dataset (hazard ratio 0.45, 95% CI 0.37 to 0.54). CONCLUSIONS: National clinical registries can provide important context when interpreting RCT data, which may alone be inadequate for comparing the safety profile of surgical interventions. These data suggest that THA is at significantly higher risk of dislocation but lower risk of revision within 12 months. The finding from both RCT and clinical registry data that THA is associated with lower 12-month mortality amongst the fittest patients with hip fractures requires urgent further study to determine whether or not this can be replicated in other balanced populations.


Assuntos
Artroplastia de Quadril/efeitos adversos , Cabeça do Fêmur/lesões , Fratura-Luxação/cirurgia , Hemiartroplastia/efeitos adversos , Fraturas do Quadril/cirurgia , Complicações Pós-Operatórias/epidemiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Artroplastia de Quadril/métodos , Fratura-Luxação/mortalidade , Hemiartroplastia/métodos , Fraturas do Quadril/mortalidade , Humanos , Vida Independente , Pessoa de Meia-Idade , Seleção de Pacientes , Complicações Pós-Operatórias/etiologia , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Sistema de Registros/estatística & dados numéricos , Reoperação/estatística & dados numéricos , Fatores de Risco , Reino Unido/epidemiologia
12.
Glob Pediatr Health ; 6: 2333794X19835235, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30993152

RESUMO

Aim. To determine the social, physical, and emotional impact of living with Perthes' disease on affected children and their family (caregivers). Patients and Methods. Through a mixed methods approach, we interviewed 18 parents and explored the perspectives of 12 children affected by Perthes' disease (mean = 7.1 years, SD = ±4.1 years) using a survey tool. Thematic analysis of parents' interviews provided an insight into disease-specific factors influencing patients and family's daily life activities. Using the childhood survey tool, good and bad day scores were analyzed using MANOVA (multivariate analysis of variance). Results. Thematic analysis of the parent interviews (main themes n = 4) identified a marked effect of the disease on many facets of the child's life, particularly pain and the impact on sleep, play, and school attendance. In addition, the interviews identified a negative effect on the family life of the parents and siblings. Children indicated that activities of daily living were affected even during "good days" (P < .05), but pain was the key limiting factor. Conclusion. Perthes' disease negatively affects the social, physical, and emotional well-being of children and their family. These findings provide outcome domains that are important to measure in day-to-day care and add in-depth insight into the challenges caused by this disease for health care professionals involved in clinical management.

13.
J Card Fail ; 2019 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-30753933

RESUMO

BACKGROUND: Resting oxygen consumption (VO2) is often estimated and frequently used to guide therapeutic decisions in symptomatic heart failure (HF) patients. The relationship between resting VO2 and symptomatic HF and the accuracy of estimations of VO2 in this population are unknown. METHODS AND RESULTS: We performed a cross-sectional study of HF patients (n = 691) and healthy control subjects (n = 77). VO2 was measured with the use of a metabolic cart, and estimated VO2 was calculated with the use of the Dehmer, LaFarge, and Bergstra formulas and the thermodilution method. The measured and estimated VO2 were compared and the potential impact of estimations determined. In the multivariable model, resting VO2 decreased with increasing New York Heart Association (NYHA) functional class in a stepwise fashion (ß NYHA functional class IV vs control = -36 mL O2/min; P < .001). Estimations of VO2 with the use of derived equations diverged from measured values, particularly for patients with NYHA functional class IV limitations. The percentage difference of measured VO2 versus estimated VO2 was >25% in 39% (n = 271), 25% (n = 170), 82% (n = 566), and 39% (n = 271) of HF patients when using the Dehmer, LaFarge, Bergstra, and thermodilution-derived estimations of VO2 respectively. CONCLUSIONS: Resting VO2 decreases with increasing NYHA functional class and is lower than in control subjects. Using estimations of VO2 to calculate CO may introduce clinically important error.

14.
BMJ Open ; 9(12): e033233, 2019 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-31892663

RESUMO

OBJECTIVE: To identify and prioritise research questions concerning the elective surgical management of children with conditions affecting the lower limb by engaging patients, carers and healthcare professionals. DESIGN: A modified nominal group technique. SETTING: UK. PARTICIPANTS: 388 individuals (29 patients, 155 parents/carers, 204 healthcare professionals) were recruited through hospital clinics, patient charities and professional organisations and participated in the initial prioritisation survey; 234 individuals took part in the interim prioritisation survey. 33 individuals (3 patients, 9 parents/carers, 11 healthcare professionals, 7 individuals representing the project's steering group and 3 James Lind Alliance (JLA) facilitators) attended the final face-to-face workshop to rank the top 10 research priorities. INTERVENTIONS: Surveys were distributed using various media resources such as newsletters, internet messaging boards and the 'Paediatric Lower Limb Surgery Priority Setting Partnership (PSP) website. Printed copies of the questionnaire were also made available to families in outpatient clinics. OUTCOME MEASURES: Survey results, top 10 and top 26 priority rankings RESULTS: The process took 18 months to complete (July 2017-January 2019); 388 people generated 1023 questions; a total of 801 research questions were classified as true uncertainties. Following the JLA methodology, 75 uncertainties were developed from the initial 801 questions. Twenty six of those were selected through a second survey and were taken to the final face-to-face workshop where the top 10 research priorities were selected. The top10 priorities included questions on cerebral palsy, common hip conditions (ie, Perthes' disease and developmental dysplasia of the hip) as well as rehabilitation techniques and methods to improve shared decision-making between clinicians and patients/families. CONCLUSIONS: This is the first JLA PSP in children's orthopaedic surgery, a particularly under-researched and underfunded area. We have identified important research topics which will guide researchers and funders and direct their efforts in future research.

15.
Pediatrics ; 142(5)2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30348751

RESUMO

: media-1vid110.1542/5828355774001PEDS-VA_2018-1067Video Abstract BACKGROUND: Slipped capital femoral epiphysis (SCFE) is believed to be associated with childhood obesity, although the strength of the association is unknown. METHODS: We performed a cohort study using routine data from health screening examinations at primary school entry (5-6 years old) in Scotland, linked to a nationwide hospital admissions database. A subgroup had a further screening examination at primary school exit (11-12 years old). RESULTS: BMI was available for 597 017 children at 5 to 6 years old in school and 39 468 at 11 to 12 years old. There were 4.26 million child-years at risk for SCFE. Among children with obesity at 5 to 6 years old, 75% remained obese at 11 to 12 years old. There was a strong biological gradient between childhood BMI at 5 to 6 years old and SCFE, with the risk of disease increasing by a factor of 1.7 (95% confidence interval [CI] 1.5-1.9) for each integer increase in BMI z score. The risk of SCFE was almost negligible among children with the lowest BMI. Those with severe obesity at 5 to 6 years old had 5.9 times greater risk of SCFE (95% CI 3.9-9.0) compared with those with a normal BMI; those with severe obesity at 11 to 12 years had 17.0 times the risk of SCFE (95% CI 5.9-49.0). CONCLUSIONS: High childhood BMI is strongly associated with SCFE. The magnitude of the association, temporal relationship, and dose response added to the plausible mechanism offer the strongest evidence available to support a causal association.


Assuntos
Obesidade Pediátrica/complicações , Escorregamento das Epífises Proximais do Fêmur/etiologia , Índice de Massa Corporal , Criança , Pré-Escolar , Estudos de Coortes , Bases de Dados Factuais , Feminino , Humanos , Incidência , Masculino , Programas de Rastreamento , Medição de Risco/métodos , Fatores de Risco , Escócia/epidemiologia , Escorregamento das Epífises Proximais do Fêmur/epidemiologia
16.
Curr Diab Rep ; 18(10): 90, 2018 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-30168021

RESUMO

PURPOSE OF REVIEW: The immunosuppressive agent cyclosporine was first reported to lower daily insulin dose and improve glycemic control in patients with new-onset type 1 diabetes (T1D) in 1984. While renal toxicity limited cyclosporine's extended use, this observation ignited collaborative efforts to identify immunotherapeutic agents capable of safely preserving ß cells in patients with or at risk for T1D. RECENT FINDINGS: Advances in T1D prediction and early diagnosis, together with expanded knowledge of the disease mechanisms, have facilitated trials targeting specific immune cell subsets, autoantigens, and pathways. In addition, clinical responder and non-responder subsets have been defined through the use of metabolic and immunological readouts. Herein, we review emerging T1D biomarkers within the context of recent and ongoing T1D immunotherapy trials. We also discuss responder/non-responder analyses in an effort to identify therapeutic mechanisms, define actionable pathways, and guide subject selection, drug dosing, and tailored combination drug therapy for future T1D trials.


Assuntos
Diabetes Mellitus Tipo 1/imunologia , Autoimunidade , Biomarcadores/sangue , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/terapia , Humanos , Imunoterapia , Prevenção Primária , Linfócitos T/imunologia
17.
Cochrane Database Syst Rev ; 9: CD004538, 2018 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-30188566

RESUMO

BACKGROUND: It is becoming increasingly common to publish information about the quality and performance of healthcare organisations and individual professionals. However, we do not know how this information is used, or the extent to which such reporting leads to quality improvement by changing the behaviour of healthcare consumers, providers, and purchasers. OBJECTIVES: To estimate the effects of public release of performance data, from any source, on changing the healthcare utilisation behaviour of healthcare consumers, providers (professionals and organisations), and purchasers of care. In addition, we sought to estimate the effects on healthcare provider performance, patient outcomes, and staff morale. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and two trials registers on 26 June 2017. We checked reference lists of all included studies to identify additional studies. SELECTION CRITERIA: We searched for randomised or non-randomised trials, interrupted time series, and controlled before-after studies of the effects of publicly releasing data regarding any aspect of the performance of healthcare organisations or professionals. Each study had to report at least one main outcome related to selecting or changing care. DATA COLLECTION AND ANALYSIS: Two review authors independently screened studies for eligibility and extracted data. For each study, we extracted data about the target groups (healthcare consumers, healthcare providers, and healthcare purchasers), performance data, main outcomes (choice of healthcare provider, and improvement by means of changes in care), and other outcomes (awareness, attitude, knowledge of performance data, and costs). Given the substantial degree of clinical and methodological heterogeneity between the studies, we presented the findings for each policy in a structured format, but did not undertake a meta-analysis. MAIN RESULTS: We included 12 studies that analysed data from more than 7570 providers (e.g. professionals and organisations), and a further 3,333,386 clinical encounters (e.g. patient referrals, prescriptions). We included four cluster-randomised trials, one cluster-non-randomised trial, six interrupted time series studies, and one controlled before-after study. Eight studies were undertaken in the USA, and one each in Canada, Korea, China, and The Netherlands. Four studies examined the effect of public release of performance data on consumer healthcare choices, and four on improving quality.There was low-certainty evidence that public release of performance data may make little or no difference to long-term healthcare utilisation by healthcare consumers (3 studies; 18,294 insurance plan beneficiaries), or providers (4 studies; 3,000,000 births, and 67 healthcare providers), or to provider performance (1 study; 82 providers). However, there was also low-certainty evidence to suggest that public release of performance data may slightly improve some patient outcomes (5 studies, 315,092 hospitalisations, and 7502 providers). There was low-certainty evidence from a single study to suggest that public release of performance data may have differential effects on disadvantaged populations. There was no evidence about effects on healthcare utilisation decisions by purchasers, or adverse effects. AUTHORS' CONCLUSIONS: The existing evidence base is inadequate to directly inform policy and practice. Further studies should consider whether public release of performance data can improve patient outcomes, as well as healthcare processes.


Assuntos
Informação de Saúde ao Consumidor/métodos , Hospitais/normas , Disseminação de Informação , Garantia da Qualidade dos Cuidados de Saúde/métodos , Melhoria de Qualidade , Canadá , Tomada de Decisão Clínica , Estudos de Avaliação como Assunto , Sistemas Pré-Pagos de Saúde/normas , Necessidades e Demandas de Serviços de Saúde/normas , Humanos , Medicaid , Inovação Organizacional , Ensaios Clínicos Controlados Aleatórios como Assunto , Reprodutibilidade dos Testes , Resultado do Tratamento , Estados Unidos
18.
Trop Doct ; 48(4): 359-365, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30153770

RESUMO

In low-income countries, where surgical expertise and resources are limited, displaced supracondylar fractures of the distal humerus are routinely managed with traction or closed reduction and casting. This is in contrast to high-income nations, where percutaneous K-wire fixation forms the mainstay of treatment. The aim of our study is to present the published evidence regarding the outcome of conservatively managed displaced supracondylar fractures in children. A systematic review of the literature was performed identifying 46 studies evaluating the outcome of displaced supracondylar fractures managed non-operatively. Our results show management by traction is equivalent to percutaneous pinning, whereas outcomes following closed reduction and casting were inconsistent. Traction therefore remains a viable option in low- and middle-income countries (LMICs). However, at present there are few data from LMICs, limiting the transferability of our conclusions.


Assuntos
Moldes Cirúrgicos , Redução Fechada/normas , Tratamento Conservador , Articulação do Cotovelo/lesões , Fraturas do Úmero/terapia , Tração , Humanos
19.
Trials ; 19(1): 374, 2018 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-30005667

RESUMO

BACKGROUND: Perthes' disease is an idiopathic osteonecrosis of a developmental hip that is most frequent in Northern Europe. Currently, the absence of a common set of standardised outcomes makes comparisons between studies of different interventions challenging. This study aims to summarise the outcomes used in clinical research of interventions for Perthes' disease and define a set of core outcomes (COS) to ensure that the variables of primary importance are measured and reported in future research studies investigating Perthes' disease. METHODS: A systematic review of the current literature will be used to identify a list of outcomes reported in previous studies. Additional important outcomes will be sought by interviewing a group of children with Perthes' disease, adults who were treated with the disease in infancy and parents of children with the disease. This list will then be evaluated by experts in Perthes' disease using a Delphi survey divided into two rounds to ascertain the importance of each outcome. The final outcomes list obtained from the Delphi survey will be then discussed during a consensus meeting of representative key stakeholders in order to define the COS to be reported in future clinical trials related to Perthes' disease. DISCUSSION: The absence of high-quality research and clear guidelines concerning the management of Perthes' disease is, at least in part, due to the difficulties in the comparing the results from previous studies. The development of a COS seeks to standardise outcomes collected in future research studies to enable comparisons between studies to be made and to facilitate meta-analyses of results. TRIAL REGISTRATION: Core Outcome Measures in Effectiveness Trials Initiative (COMET), 1003 . Registered on 20 July 2017. Prospero International Prospective Register of Systematic Reviews, CRD 42017069742 . Registered on 10 July 2017.


Assuntos
Determinação de Ponto Final , Doença de Legg-Calve-Perthes/terapia , Projetos de Pesquisa , Adolescente , Adulto , Criança , Pré-Escolar , Consenso , Conferências de Consenso como Assunto , Técnica Delfos , Feminino , Humanos , Doença de Legg-Calve-Perthes/diagnóstico , Doença de Legg-Calve-Perthes/fisiopatologia , Masculino , Revisão Sistemática como Assunto , Resultado do Tratamento
20.
Sci Rep ; 8(1): 4529, 2018 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-29540798

RESUMO

Prior studies identified HLA class-II and 57 additional loci as contributors to genetic susceptibility for type 1 diabetes (T1D). We hypothesized that race and/or ethnicity would be contextually important for evaluating genetic risk markers previously identified from Caucasian/European cohorts. We determined the capacity for a combined genetic risk score (GRS) to discriminate disease-risk subgroups in a racially and ethnically diverse cohort from the southeastern U.S. including 637 T1D patients, 46 at-risk relatives having two or more T1D-related autoantibodies (≥2AAb+), 790 first-degree relatives (≤1AAb+), 68 second-degree relatives (≤1 AAb+), and 405 controls. GRS was higher among Caucasian T1D and at-risk subjects versus ≤ 1AAb+ relatives or controls (P < 0.001). GRS receiver operating characteristic AUC (AUROC) for T1D versus controls was 0.86 (P < 0.001, specificity = 73.9%, sensitivity = 83.3%) among all Caucasian subjects and 0.90 for Hispanic Caucasians (P < 0.001, specificity = 86.5%, sensitivity = 84.4%). Age-at-diagnosis negatively correlated with GRS (P < 0.001) and associated with HLA-DR3/DR4 diplotype. Conversely, GRS was less robust (AUROC = 0.75) and did not correlate with age-of-diagnosis for African Americans. Our findings confirm GRS should be further used in Caucasian populations to assign T1D risk for clinical trials designed for biomarker identification and development of personalized treatment strategies. We also highlight the need to develop a GRS model that accommodates racial diversity.


Assuntos
Autoanticorpos/sangue , Diabetes Mellitus Tipo 1/etnologia , Diabetes Mellitus Tipo 1/genética , Antígeno HLA-DR3/genética , Antígeno HLA-DR4/genética , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Diabetes Mellitus Tipo 1/imunologia , Feminino , Florida/etnologia , Predisposição Genética para Doença , Genética Populacional , Antígenos HLA-DQ/genética , Humanos , Masculino , Modelos Teóricos , Curva ROC , Medição de Risco , Adulto Jovem
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