Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 236
Filtrar
1.
Ann Intern Med ; 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33587686

RESUMO

BACKGROUND: Because immune checkpoint inhibition (ICI) can cause immune-related adverse events (irAEs) mimicking immunologic diseases, patients with preexisting autoimmune disease (AID) have been excluded from clinical trials. OBJECTIVE: To evaluate the safety and efficacy of ICI in patients with advanced melanoma with and without AID. DESIGN: Nationwide cohort study. SETTING: The Netherlands. PATIENTS: 4367 patients with advanced melanoma enrolled in the Dutch Melanoma Treatment Registry (DMTR) between July 2013 and July 2018 and followed through February 2019. MEASUREMENTS: Patient, clinical, and treatment characteristics; irAEs of grade 3 or higher; treatment response; and survival. RESULTS: A total of 415 patients (9.5%) had AID, categorized as rheumatologic AID (n = 227), endocrine AID (n = 143), inflammatory bowel disease (IBD) (n = 55), or "other" (n = 8). Of these, 228 patients (55%) were treated with ICI (vs. 2546 [58%] without AID); 87 were treated with anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4), 187 with anti-programmed cell death 1 (PD-1), and 34 with the combination. The incidences of irAEs of grade 3 or higher in patients with AID were 30% (95% CI, 21% to 41%) with anti-CTLA-4, 17% (CI, 12% to 23%) with anti-PD-1, and 44% (CI, 27% to 62%) with combination therapy; for patients without AID, the incidences were 30% (CI, 27% to 33%) (n = 916), 13% (CI, 12% to 15%) (n = 1540), and 48% (CI, 43% to 53%) (n = 388), respectively. Patients with AID more often discontinued anti-PD-1 treatment because of toxicity than patients without AID (17% [CI, 12% to 23%] vs. 9% [CI, 8% to 11%]). Patients with IBD were more prone to anti-PD-1-induced colitis (6 / 31 = 19% [CI, 7% to 37%]) than patients with other AIDs (3% [CI, 0% to 6%]) and patients without AID (2% [CI, 2% to 3%]). The objective response rate was similar in patients with versus without AID who were treated with anti-CTLA-4 (10% [CI, 5% to 19%] vs. 16% [CI, 14% to 19%]), anti-PD-1 (40% [CI, 33% to 47%] vs. 44% [CI, 41% to 46%]), or the combination (39% [CI, 20% to 59%] vs. 43% [CI, 38% to 49%]). Survival did not differ between patients with and those without AID (median, 13 months [CI, 10 to 16 months] vs. 14 months [CI, 13 to 15 months]). LIMITATION: Information was limited on AID severity and immunosuppressive treatment. CONCLUSION: Response to ICI with anti-CTLA-4, anti-PD-1, or their combination for advanced melanoma and overall incidence of any irAEs of grade 3 or higher were similar in patients with and without preexisting AID. However, severe colitis and toxicity requiring early discontinuation of treatment occurred more frequently among patients with preexisting IBD, warranting close follow-up. PRIMARY FUNDING SOURCE: The Netherlands Organization for Health Research and Development.

2.
Eur J Endocrinol ; 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33449912

RESUMO

Glucocorticoids are, besides non-steroidal anti-inflammatory drugs, the most widely used anti-inflammatory medications. Prevalence studies indicate substantial use of both systemic and locally acting agents. A recognized adverse effect of glucocorticoid treatment is adrenal insufficiency, which is highly prevalent based on biochemical testing, but its clinical implications are poorly understood. Current evidence, including randomized trials and observational studies, indicates substantial variation among patients in both risk and course of glucocorticoid-induced adrenal insufficiency, but both are currently unpredictable. Oral and intra-articular formulations, as well as long-term and high-dose treatments, carry the highest risk of glucocorticoid-induced adrenal insufficiency defined by biochemical tests. However, no route of administration, treatment duration, or dose can be considered without risk. More research is needed to estimate the risk and temporal pattern of glucocorticoid-induced adrenal insufficiency, to investigate its clinical implications, and to identify predictors of risk and prognosis. Randomized trials are required to evaluate whether hydrocortisone replacement therapy mitigates risk and symptoms of glucocorticoid-induced adrenal insufficiency in patients discontinuing glucocorticoid treatment. This review aims to provide an overview of available evidence, pointing to knowledge gaps and unmet needs.

3.
Eur J Endocrinol ; 184(2): E5-E9, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33410763

RESUMO

Diagnostic accuracy studies are fundamental for the assessment of diagnostic tests. Researchers need to understand the implications of their chosen design, opting for comparative designs where possible. Researchers should analyse test accuracy studies using the appropriate methods, acknowledging the uncertainty of results and avoiding overstating conclusions and ignoring the clinical situation which should inform the trade-off between sensitivity and specificity. Test accuracy studies should be reported with transparency using the STAndards for the Reporting of Diagnostic accuracy studies (STARD) checklist.


Assuntos
Técnicas de Diagnóstico Endócrino/normas , Testes Diagnósticos de Rotina/métodos , Testes Diagnósticos de Rotina/normas , Lista de Checagem , Humanos , Distribuição Aleatória , Valores de Referência , Projetos de Pesquisa , Tamanho da Amostra , Sensibilidade e Especificidade
4.
Eur J Endocrinol ; 184(1): E1-E4, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33112276

RESUMO

Immortal time bias should always be considered in an observational study if exposure status is determined based on a measurement or event that occurs after baseline. This bias can lead to an overestimation of an effect, but also to an underestimation, which is explained. Several approaches are illustrated that can be used to avoid immortal time bias in the analysis phase of the study; a time-dependent analysis to avoid immortal time bias optimizes the use of available information.


Assuntos
Estudos Observacionais como Assunto , Viés , Fatores de Tempo
5.
Artigo em Inglês | MEDLINE | ID: mdl-33255540

RESUMO

Rare disease (RD) registries are important platforms that facilitate communication between health care professionals, patients and other members of the multidisciplinary team. RD registries enable data sharing and promotion of research and audits, often in an international setting, with the overall aim of improving patient care. RD registries also have a fundamental role in supporting the work of clinical networks such as the European Reference Networks (ERNs) for rare diseases. With the recent expansion of RD registries, it has become even more essential to outline standards of good practice in relation to governance, infrastructure, documentation, training, audits and adopting the Findable, Accessible, Interoperable and Reusable (FAIR) data principles to maintain registries of high quality. For the purpose of this paper, we highlight vital aspects of data access and data governance policies for RD registries, using the European Registries for Rare Endocrine Conditions (EuRRECa) as an example of a project that aims to promote good standards of practice for improving the quality of utilization of RD registries.

6.
Eur J Endocrinol ; 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33300887

RESUMO

In almost all medical research, more than a single hypothesis is being tested or more than a single relation is being estimated. Testing multiple hypotheses increases the risk of drawing a false-positive conclusion. We briefly discuss this phenomenon, which is often called multiple testing. Also, methods to mitigate the risk of false-positive conclusions are discussed.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33306249

RESUMO

OBJECTIVE: Data on sex differences in acromegaly at the time of diagnosis vary considerably between studies. DESIGN: A nationwide cohort study including all incident cases of acromegaly (1978-2010, n=596) and a meta-analysis on sex differences in active acromegaly (40 studies) were performed. METHOD: Sex-dependent differences in prevalence, age at diagnosis, diagnostic delay, pituitary adenoma size, insulin-like growth factor 1 (IGF-I), and growth hormone (GH) concentrations were estimated. RESULTS: The cohort study identified a balanced gender distribution (49.6% females) and a comparable age (years) at diagnosis (48.2 CI95% 46.5-49.8 (males) vs. 47.2 CI95% 45.5-48.9 (females), p = 0.4). The incidence rate significantly increased during the study period (R2 =0.42, P<0.01) and the gender ratio (F/M) changed from female predominance to an even ratio (SR: 1.4 vs. 0.9, P=0.03). IGF-ISDS was significantly lower in females compared to males, whereas neither nadir GH nor pituitary adenoma size differed between males and females. In the meta-analysis the weighted percentage female was 53.3% (CI95% 51.5-55.2) with considerable heterogeneity (I2 =85%) among the studies. The mean age difference at diagnosis between genders was 3.1 years (CI95% 1.9-4.4) and the diagnostic delay was longer in females by 0.9 years (CI95% -0.4-2.1). Serum IGF-I levels were significantly lower in female patients, whereas nadir GH, and pituitary adenoma size were comparable. CONCLUSION: There is only a minor sex differences in the epidemiology of acromegaly at the time of diagnosis except that female patients are slightly older and exhibit lower IGF-I concentrations and a longer diagnostic delay.

8.
Pituitary ; 2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33230695

RESUMO

OBJECTIVE: Full blood count (FBC) and serum inflammation-based scores reflect systemic inflammation and predict outcomes in cancer, but little is known in pituitary adenomas (PAs). We aimed to characterise FBC and inflammation-based scores in PA patients and investigate their usefulness in predicting challenging disease course. METHODS: We studied 424 PA patients first operated at our centre with available pre-operative biochemical data. Patients with infection, malignancies, autoimmune or haematological conditions were excluded. Inflammation-based scores studied: Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), Lymphocyte-to-Monocyte Ratio (LMR), Systemic Immune-Inflammation Index (SII), Neutrophil-Platelet Score (NPS), Prognostic Nutrition Index (PNI), and Glasgow Prognostic Score (GPS). RESULTS: Cushing's disease patients had more platelets, leucocytes, neutrophils and monocytes, and higher NLR, NPS and SII. Serum inflammation-based scores didn't differ among non-Cushing PA subtypes. The glucocorticoid excess severity influenced leucocyte, eosinophil, basophil and platelet counts, and GPS in Cushing's disease. Patients with functioning non-Cushing PAs with suprasellar extension, cavernous sinus invasion and hypopituitarism had GPS ≥ 1, while NPS ≥ 1 was associated with suprasellar extension. More invasive and difficult to treat corticotrophinomas were associated with fewer platelets pre-operatively (< 299.5 × 109/L predicting multimodal treatment). Non-functioning PA patients who suffered apoplexy had more leucocytes, neutrophils and monocytes, higher GPS ≥ 1 and fewer platelets; re-operated cases had fewer lymphocytes, higher NLR and PLR. CONCLUSIONS: Serum inflammation-based scores may predict invasive/refractory PAs: GPS and PNI in non-functioning and functioning non-Cushing PAs; NPS in functioning non-Cushing PAs; NLR and PLR in non-functioning PAs. Platelets < 299.5 × 109/L predict multimodal treatment in Cushing's disease. Further studies are needed to confirm these observations.

9.
Artigo em Inglês | MEDLINE | ID: mdl-33135721

RESUMO

INTRODUCTION: Multiple Endocrine Neoplasia type 1 (MEN1)-related neuroendocrine tumors (NETs) of the lung are mostly indolent with a good prognosis. Nevertheless, cases of aggressive lung NET do occur, and therefore the management of individual patients is challenging. AIM: To assess tumor growth and survival of patients with MEN1-related lung NETs at long-term follow-up. METHODS: The population based Dutch MEN1 Study Group (DMSG) database (n = 446) was used to identify lung NETs by histopathological and radiological examinations. Tumor diameter was assessed. Linear mixed models and the Kaplan-Meier method were used for analyzing tumor growth and survival. Molecular analyses were performed on a lung NET showing particularly aggressive behavior. RESULTS: In 102 patients (22.9% of the total MEN1 cohort), 164 lesions suspect of lung NETs were identified and followed for a median of 6.6 years. Tumor diameter increased 6.0% per year. The overall 15-yr survival was 78.0% (95% confidence interval (CI): 64.6% - 94.2%) without lung NET-related death. No prognostic factors for tumor growth or survival could be identified. A somatic c.3127A>G (p.Met1043Val) PIK3CA driver mutation was found in a case of rapid growing lung NET after six years of indolent disease, presumably explaining the sudden change in course. CONCLUSION: MEN1-related lung NETs are slow-growing and have a good prognosis. No accurate risk factors for tumor growth could be identified. Lung NET screening should therefore be based on well-informed shared decision-making, balancing between the low absolute risk of an aggressive tumor in individuals and the potential harms of frequent thoracic imaging.

10.
Artigo em Inglês | MEDLINE | ID: mdl-33245343

RESUMO

BACKGROUND: While biochemical response is often used as primary study outcome, improvement in symptoms and health-related quality of life (HRQoL) is the relevant goal for patients to consider treatment successful. We performed a systematic review and meta-analysis to assess the effect of treatment on symptoms and HRQoL in acromegaly. METHODS: Seven electronic databases were searched for longitudinal studies assessing patient-reported symptoms or HRQoL in acromegaly. Meta-analyses were performed to assess differences during treatment for the Acromegaly Quality of Life Questionnaire (AcroQoL) and Patient-Assessed Acromegaly Symptom Questionnaire (PASQ), and standardized mean difference (SMD) for individual symptoms (interpretation: 0.2 small, 0.5 moderate, and 0.8 large effect). Treatment naive and previously treated patients were assessed separately. RESULTS: Forty-six studies with 3301 patients were included; 24 contributed to quantitative analyses. Thirty-six studies used medication as main treatment, one transsphenoidal adenomectomy, and nine various treatments. Both symptoms and HRQoL improved: AcroQoL increased: 2.9 (95% CI: 0.5, 5.3) points, PASQ decreased: -2.3 (95% CI: -1.3, -3.3) points, and individual symptom scores decreased: paresthesia -0.9 (95% CI: -0.6, -1.2), hyperhidrosis -0.4 (95% CI: -0.1, -0.6), fatigue -0.3 (95% CI: -0.1, -0.6), arthralgia -0.3 (95% CI: -0.1, -0.5), headache -0.3 (95% CI: 0.0, -0.6), and soft tissue swelling -0.2 (95% CI: 0.0, -0.4). CONCLUSION: Symptoms and HRQoL improved during acromegaly treatment. Consensus is needed on which symptoms should be included in a potential Core Outcome Set, taking into account symptom frequency, severity, and sensitivity to change, which can be used in clinical practice and as outcome in trials.

11.
Eur J Epidemiol ; 2020 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-33247797

RESUMO

Risk prediction is one of the central goals of medicine. However, ultimate prediction-perfectly predicting whether individuals will actually get a disease-is still out of reach for virtually all conditions. One crucial assumption of ultimate personalized prediction is that individual risks in the relevant sense exist. In the present paper we argue that perfect prediction at the individual level will fail-and we will do so by providing pragmatic, epistemic, conceptual, and ontological arguments.

12.
Breast Cancer Res ; 22(1): 106, 2020 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-33050919

RESUMO

BACKGROUND: Breast cancer survivors (BCS) may have increased risk of hypothyroidism, but risk according to treatment modality is unclear. We estimated the incidence of hypothyroidism in women with breast cancer, and according to cancer treatment. METHODS: Using nationwide registries, we identified all Danish women aged ≥ 35 years diagnosed with non-metastatic breast cancer (1996-2009). We matched up to five cancer-free women (controls) for each BCS. We excluded women with prevalent thyroid disease. Cancer treatment was chemotherapy with or without radiotherapy (RT) targeting the breast/chest wall only, or also the lymph nodes (RTn). We identified hypothyroidism using diagnostic codes, and/or levothyroxine prescriptions. We calculated the cumulative incidence, incidence rates (IR) per 1000 person-years, and used Cox regression to estimate hazard ratios (HR) and associated 95% confidence intervals (CIs) of hypothyroidism, adjusting for comorbidities. RESULTS: We included 44,574 BCS and 203,306 matched controls with 2,631,488 person-years of follow-up. BCS had a slightly higher incidence of hypothyroidism than controls [5-year cumulative incidence, 1.8% (95%CI = 1.7-1.9) and 1.6% (95%CI = 1.5-1.6), respectively]. The overall IR was 4.45 (95%CI = 4.25-4.67) and 3.81 (95%CI = 3.73-3.90), corresponding to an adjusted HR = 1.17 (95%CI = 1.11-1.24). BCS who received RTn with chemotherapy (HR = 1.74, 95%CI = 1.50-2.02) or without chemotherapy (HR = 1.31, 95%CI = 1.14-1.51) had an elevated risk of hypothyroidism compared with matched controls and compared with BCS who underwent surgery alone [HR = 1.71, 95%CI = 1.45-2.01 and HR = 1.36, 95%CI = 1.17-1.58, respectively]. CONCLUSIONS: BCS have an excess risk of hypothyroidism compared with age-matched controls. BCS and those working in cancer survivorship settings ought to be aware that this risk is highest in women treated with radiation therapy to the lymph nodes and chemotherapy.

13.
Eur J Clin Nutr ; 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33087892

RESUMO

Dietary macronutrient composition may affect hepatic liver content and its associated diseases, but the results from human intervention trials have been equivocal or underpowered. We aimed to assess the effects of dietary macronutrient composition on liver fat content by conducting a systematic review and meta-analysis of randomized controlled trials in adults. Four databases (PubMed, Embase, Web of Science, and COCHRANE Library) were systematically searched for trials with isocaloric diets evaluating the effect of dietary macronutrient composition (energy percentages of fat, carbohydrates, and protein, and their specific types) on liver fat content as assessed by magnetic resonance techniques, computed tomography or liver biopsy. Data on change in liver fat content were pooled by random or fixed-effects meta-analyses and expressed as standardized mean difference (SMD). We included 26 randomized controlled trials providing data for 32 comparisons on dietary macronutrient composition. Replacing dietary fat with carbohydrates did not result in changes in liver fat (12 comparisons, SMD 0.01 (95% CI -0.36; 0.37)). Unsaturated fat as compared with saturated fat reduced liver fat content (4 comparisons, SMD -0.80 (95% CI -1.09; -0.51)). Replacing carbohydrates with protein reduced liver fat content (5 comparisons, SMD -0.33 (95% CI -0.54; -0.12)). Our meta-analyses showed that replacing carbohydrates with total fat on liver fat content was not effective, while replacing carbohydrates with proteins and saturated fat with unsaturated fat was. More well-performed and well-described studies on the effect of types of carbohydrates and proteins on liver fat content are needed, especially studies comparing proteins with fats.

14.
Eur J Endocrinol ; 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33112281

RESUMO

N/A.

15.
Eur J Endocrinol ; 183(6): E11-E13, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33055302

RESUMO

The name of the study should properly reflect the actual conduct and analysis of the study. This short paper provides guidance on how to properly name the study design. The first distinction is between a trial (intervention given to patients to study its effect) and an observational study. For observational studies, it should further be decided whether it is cross-sectional or whether follow-up time is taken into account (cohort or case-control study). The distinction prospective-retrospective has two disadvantages: prospective is often seen as marker of higher quality, which is not necessarily true; there is no unifying definition that makes a proper distinction between retrospective and prospective possible.


Assuntos
Ensaios Clínicos como Assunto/classificação , Estudos Transversais/classificação , Estudos Observacionais como Assunto/classificação , Terminologia como Assunto , Estudos de Casos e Controles , Estudos de Coortes , Humanos , Estudos Prospectivos , Projetos de Pesquisa , Estudos Retrospectivos
16.
Diagnostics (Basel) ; 10(9)2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32961994

RESUMO

[18F]-FDG-PET/CT ([18F]-fluoro-deoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT)) is increasingly used as a diagnostic tool in suspected infectious or inflammatory conditions. Studies on the value of FDG-PET/CT in children are scarce. This study assesses the role of FDG-PET/CT in suspected infection or inflammation in children. In this multicenter cohort study, 64 scans in 59 children with suspected infection or inflammation were selected from 452 pediatric FDG-PET/CT scans, performed in five hospitals between January 2016 and August 2017. Main outcomes were diagnostic information provided by FDG-PET/CT for diagnostic scans and impact on clinical management for follow-up scans. Of these 64 scans, 50 were performed for primary diagnosis and 14 to monitor disease activity. Of the positive diagnostic scans, 23/27 (85%) contributed to establishing a diagnosis. Of the negative diagnostic scans, 8/21 (38%) contributed to the final diagnosis by narrowing the differential or by providing information on the disease manifestation. In all follow-up scans, FDG-PET/CT results guided management decisions. CRP was significantly higher in positive scans than in negative scans (p = 0.004). In 6% of diagnostic scans, relevant incidental findings were identified. In conclusion, FDG-PET/CT performed in children with suspected infection or inflammation resulted in information that contributed to the final diagnosis or helped to guide management decisions in the majority of cases. Prospective studies assessing the impact of FDG-PET/CT results on diagnosis and patient management using a structured diagnostic protocol are feasible and necessary.

17.
Clin Kidney J ; 13(4): 550-563, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32897278

RESUMO

Background: Acute kidney injury (AKI) can affect hospitalized patients with coronavirus disease 2019 (COVID-19), with estimates ranging between 0.5% and 40%. We performed a systematic review and meta-analysis of studies reporting incidence, mortality and risk factors for AKI in hospitalized COVID-19 patients. Methods: We systematically searched 11 electronic databases until 29 May 2020 for studies in English reporting original data on AKI and kidney replacement therapy (KRT) in hospitalized COVID-19 patients. Incidences of AKI and KRT and risk ratios for mortality associated with AKI were pooled using generalized linear mixed and random-effects models. Potential risk factors for AKI were assessed using meta-regression. Incidences were stratified by geographic location and disease severity. Results: A total of 3042 articles were identified, of which 142 studies were included, with 49 048 hospitalized COVID-19 patients including 5152 AKI events. The risk of bias of included studies was generally low. The pooled incidence of AKI was 28.6% [95% confidence interval (CI) 19.8-39.5] among hospitalized COVID-19 patients from the USA and Europe (20 studies) and 5.5% (95% CI 4.1-7.4) among patients from China (62 studies), whereas the pooled incidence of KRT was 7.7% (95% CI 5.1-11.4; 18 studies) and 2.2% (95% CI 1.5-3.3; 52 studies), respectively. Among patients admitted to the intensive care unit, the incidence of KRT was 20.6% (95% CI 15.7-26.7; 38 studies). Meta-regression analyses showed that age, male sex, cardiovascular disease, diabetes mellitus, hypertension and chronic kidney disease were associated with the occurrence of AKI; in itself, AKI was associated with an increased risk of mortality, with a pooled risk ratio of 4.6 (95% CI 3.3-6.5). Conclusions: AKI and KRT are common events in hospitalized COVID-19 patients, with estimates varying across geographic locations. Additional studies are needed to better understand the underlying mechanisms and optimal treatment of AKI in these patients.

18.
Clin J Am Soc Nephrol ; 15(8): 1103-1111, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32723805

RESUMO

BACKGROUND AND OBJECTIVES: The histopathologic classification for ANCA-associated GN distinguishes four classes on the basis of patterns of injury. In the original validation study, these classes were ordered by severity of kidney function loss as follows: focal, crescentic, mixed, and sclerotic. Subsequent validation studies disagreed on outcomes in the crescentic and mixed classes. This study, driven by the original investigators, provides several analyses in order to determine the current position of the histopathologic classification of ANCA-associated GN. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A validation study was performed with newly collected data from 145 patients from ten centers worldwide, including an analysis of interobserver agreement on the histopathologic evaluation of the kidney biopsies. This study also included a meta-analysis on previous validation studies and a validation of the recently proposed ANCA kidney risk score. RESULTS: The validation study showed that kidney failure at 10-year follow-up was significantly different between the histopathologic classes (P<0.001). Kidney failure at 10-year follow-up was 14% in the crescentic class versus 20% in the mixed class (P=0.98). In the meta-analysis, no significant difference in kidney failure was also observed when crescentic class was compared with mixed class (relative risk, 1.15; 95% confidence interval, 0.94 to 1.41). When we applied the ANCA kidney risk score to our cohort, kidney survival at 3 years was 100%, 96%, and 77% in the low-, medium-, and high-risk groups, respectively (P<0.001). These survival percentages are higher compared with the percentages in the original study. CONCLUSIONS: The crescentic and mixed classes seem to have a similar prognosis, also after adjusting for differences in patient populations, treatment, and interobserver agreement. However, at this stage, we are not inclined to merge the crescentic and mixed classes because the reported confidence intervals do not exclude important differences in prognosis and because an important histopathologic distinction would be lost.

19.
Res Synth Methods ; 11(6): 780-794, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32643264

RESUMO

Meta-analysis of individual participant data (IPD) is considered the "gold-standard" for synthesizing clinical study evidence. However, gaining access to IPD can be a laborious task (if possible at all) and in practice only summary (aggregate) data are commonly available. In this work we focus on meta-analytic approaches of comparative studies where aggregate data are available for continuous outcomes measured at baseline (pre-treatment) and follow-up (post-treatment). We propose a method for constructing pseudo individual baselines and outcomes based on the aggregate data. These pseudo IPD can be subsequently analysed using standard analysis of covariance (ANCOVA) methods. Pseudo IPD for continuous outcomes reported at two timepoints can be generated using the sufficient statistics of an ANCOVA model, i.e., the mean and standard deviation at baseline and follow-up per group, together with the correlation of the baseline and follow-up measurements. Applying the ANCOVA approach, which crucially adjusts for baseline imbalances and accounts for the correlation between baseline and change scores, to the pseudo IPD, results in identical estimates to the ones obtained by an ANCOVA on the true IPD. In addition, an interaction term between baseline and treatment effect can be added. There are several modeling options available under this approach, which makes it very flexible. Methods are exemplified using reported data of a previously published IPD meta-analysis of 10 trials investigating the effect of antihypertensive treatments on systolic blood pressure, leading to identical results compared with the true IPD analysis and of a meta-analysis of fewer trials, where baseline imbalance occurred.

20.
Int J Clin Pract ; 74(11): e13601, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32603544

RESUMO

OBJECTIVE: A cornerstone in the management of Staphylococcus aureus bacteraemia (SAB) is the differentiation between a complicated and an uncomplicated SAB course. The ability to early and accurately identify patients with - and without - complicated bacteraemia may optimise the utility of diagnostics and prevent unnecessary prolonged antibiotic therapy. METHODS: Development and validation of a prediction score in SAB using demographic, clinical, and laboratory data from two independent Dutch cohorts; estimating the risk of complicated disease at the time of the first positive blood culture. Models were developed using logistic regression and evaluated by c-statistics, ie area under the ROC-curve, and negative predictive values (NPV). RESULTS: The development- and validation cohorts included 150 and 183 patients, respectively. The most optimal prediction model included: mean arterial pressure, signs of metastatic infection on physical examination, leucocyte count, urea level and time to positivity of blood cultures (c-statistic 0.82, 95% CI 0.74-0.89). In the validation cohort, the c-statistic of the prediction score was 0,77 (95% CI 0.69-0.84). The NPV for complicated disease for patients with a score of ≤2 was 0.83 (95% CI 0.68-0.92), with a negative likelihood ratio of 0.14 (95% CI 0.06-0.31). CONCLUSION: The early SAB risk score helps to identify patients with high probability of uncomplicated SAB. However, the risk score's lacked absolute discriminative power to guide decisions on the management of all patients with SAB on its own. The heterogenicity of the disease and inconsistency in definitions of complicated SAB are important challenges in the development of clinical rules to guide the management of SAB.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA