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1.
Zhonghua Liu Xing Bing Xue Za Zhi ; 41(12): 2149-2159, 2020 Dec 10.
Artigo em Chinês | MEDLINE | ID: mdl-33378831

RESUMO

This paper introduces the conducting systematic reviews and Meta-analyses of observational studies of etiology (COSMOS-E) and illustrates the critical issues of COSMOS-E with a published systematic review. This document provides researchers with guidance on all steps in systematic reviews of observational studies of etiology, from shaping the research question, defining exposure and outcomes, to assessing the risk of bias and statistical analysis.


Assuntos
Metanálise como Assunto , Estudos Observacionais como Assunto , Revisões Sistemáticas como Assunto , Humanos , Estudos Observacionais como Assunto/métodos , Estudos Observacionais como Assunto/normas , Viés de Seleção
3.
PLoS Med ; 17(8): e1003280, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32845900

RESUMO

BACKGROUND: Experimental and observational research has suggested the potential for increased type 2 diabetes (T2D) risk among populations taking statins for the primary prevention of atherosclerotic cardiovascular disease (ASCVD). However, few studies have directly compared statin-associated benefits and harms or examined heterogeneity by population subgroups or assumed treatment effect. Thus, we compared ASCVD risk reduction and T2D incidence increases across 3 statin treatment guidelines or recommendations among adults without a history of ASCVD or T2D who were eligible for statin treatment initiation. METHODS AND FINDINGS: Simulations were conducted using Markov models that integrated data from contemporary population-based studies of non-Hispanic African American and white adults aged 40-75 years with published meta-analyses. Statin treatment eligibility was determined by predicted 10-year ASCVD risk (5%, 7.5%, or 10%). We calculated the number needed to treat (NNT) to prevent one ASCVD event and the number needed to harm (NNH) to incur one incident case of T2D. The likelihood to be helped or harmed (LHH) was calculated as ratio of NNH to NNT. Heterogeneity in statin-associated benefit was examined by sex, age, and statin-associated T2D relative risk (RR) (range: 1.11-1.55). A total of 61,125,042 U.S. adults (58.5% female; 89.4% white; mean age = 54.7 years) composed our primary prevention population, among whom 13-28 million adults were eligible for statin initiation. Overall, the number of ASCVD events prevented was at least twice as large as the number of incident cases of T2D incurred (LHH range: 2.26-2.90). However, the number of T2D cases incurred surpassed the number of ASCVD events prevented when higher statin-associated T2D RRs were assumed (LHH range: 0.72-0.94). In addition, females (LHH range: 1.74-2.40) and adults aged 40-50 years (LHH range: 1.00-1.14) received lower absolute benefits of statin treatment compared with males (LHH range: 2.55-3.00) and adults aged 70-75 years (LHH range: 3.95-3.96). Projected differences in LHH by age and sex became more pronounced as statin-associated T2D RR increased, with a majority of scenarios projecting LHHs < 1 for females and adults aged 40-50 years. This study's primary limitation was uncertainty in estimates of statin-associated T2D risk, highlighting areas in which additional clinical and public health research is needed. CONCLUSIONS: Our projections suggest that females and younger adult populations shoulder the highest relative burden of statin-associated T2D risk.


Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Cadeias de Markov , Guias de Prática Clínica como Assunto/normas , Adulto , Idoso , Aterosclerose/diagnóstico , Aterosclerose/tratamento farmacológico , Aterosclerose/epidemiologia , Doenças Cardiovasculares/diagnóstico , Diabetes Mellitus Tipo 2/diagnóstico , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Observacionais como Assunto/métodos , Estudos Observacionais como Assunto/normas , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/normas , Resultado do Tratamento
5.
Br J Anaesth ; 125(3): 393-397, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32600803

RESUMO

Graphical models have emerged as a tool to map out the interplay between multiple measured and unmeasured variables, and can help strengthen the case for a causal association between exposures and outcomes in observational studies. In Part 1 of this methods series, we will introduce the reader to graphical models for causal inference in perioperative medicine, and set the framework for Part 2 of the series involving advanced methods for causal inference.


Assuntos
Pesquisa Biomédica/métodos , Modelos Estatísticos , Estudos Observacionais como Assunto/métodos , Medicina Perioperatória/métodos , Pesquisa Biomédica/estatística & dados numéricos , Humanos , Estudos Observacionais como Assunto/estatística & dados numéricos , Medicina Perioperatória/estatística & dados numéricos
9.
Medicine (Baltimore) ; 99(24): e20733, 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32541525

RESUMO

INTRODUCTION: To investigate the gene rearrangement and mutation of lymphoma biomarkers including (Immunoglobulin H (IgH), Immunoglobulin kappa (IGK), Immunoglobulin lambda (IGL), and TCR) in the lymphoma diagnosis. METHODS AND ANALYSIS: Paraffin tissue samples from 240 cases diagnosed as suspected lymphoma in the department of pathology, Deyang City People's Hospital from June 2020 to June 2021 will be enrolled. Deoxyribonucleic acid extraction and Polymerase Chain Reaction (PCR) amplification will be performed in these paraffin tissue samples. Immunoglobulin and T cell receptor (TCR) rearrangement will be analyzed by hetero-double chain gel electrophoresis and BioMed-2 standardized immunoglobulin gene rearrangement detection system. In this study protocol IGH gene rearrangement, IGK gene rearrangement, both IGH and IGL gene rearrangement, both IGH and IGK gene rearrangement, both IGK and IGL gene rearrangement, both IGH, IGK and IGL gene rearrangement, TCR gene rearrangement and positive Ig/TCR rearrangement will be analyzed. DISCUSSION: In this study, we will use B and T cell lymphoma analysis focusing on IgH, IGK, IGL, and TCR gene rearrangement, so as to provide early guidance for the diagnosis of lymphoma. Second generation sequencing technology is helpful in the differential diagnosis of lymphoma. TRIAL REGISTRATION: Chinese Clinical trial registry: ChiCTR2000032366.


Assuntos
Rearranjo Gênico , Linfoma/genética , Mutação , Estudos Observacionais como Assunto/métodos , Projetos de Pesquisa , Humanos , Estudos Prospectivos
10.
J Gen Intern Med ; 35(9): 2698-2706, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32556875

RESUMO

BACKGROUND: Infection with coronavirus SARS-CoV-2, causing COVID-19 disease, leads to inflammation and a prothrombotic state. OBJECTIVE: This rapid systematic review aims to synthesize evidence on thromboembolism incidence and outcomes with antithrombotic therapies in COVID-19. DATA SOURCES: We searched MEDLINE (Ovid), Cochrane Rapid Reviews, PROSPERO, and the WHO COVID-19 Database from January 1, 2003, to April 22, 2020, for studies meeting pre-specified inclusion criteria. STUDY SELECTION, DATA EXTRACTION, AND SYNTHESIS: One investigator identified articles for inclusion, abstracted data, and performed quality assessment, with second reviewer checking. RESULTS: Incidence of thromboembolism among hospitalized patients with COVID-19 ranged from 25 to 53% in 4 retrospective series. We identified 3 studies (1 retrospective cohort study, 1 prospective uncontrolled observational study, and 1 case series) examining outcomes among COVID-19 patients who received antithrombotic therapies. These studies all included different interventions (thromboprophylaxis with unfractionated heparin (UFH) or low molecular-weight heparin (LMWH); an intensive thromboprophylaxis protocol with LMWH, antithrombin, and clopidogrel; and salvage therapy with tissue plasminogen activator and heparin). These studies are overall poor quality due to methodological limitations including unclear patient selection protocols, lack of reporting or adjustment for patient baseline characteristics, inadequate duration of follow-up, and partial reporting of outcomes. CONCLUSIONS: New evidence on thromboembolism in COVID-19 does not warrant a change in current guidance on thromboprophylaxis among hospitalized patients. Prospective trials of antithrombotic treatment strategies among patients with COVID-19 are urgently needed.


Assuntos
Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Fibrinolíticos/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/epidemiologia , Anticoagulantes/uso terapêutico , Humanos , Estudos Observacionais como Assunto/métodos , Pandemias , Estudos Prospectivos , Estudos Retrospectivos
11.
Br J Anaesth ; 125(3): 398-405, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32527658

RESUMO

Although RCTs represent the gold standard in clinical research, most clinical questions cannot be answered using this technique, because of ethical considerations, time, and cost. The goal of observational research in clinical medicine is to gain insight into the relationship between a clinical exposure and patient outcome, in the absence of evidence from RCTs. Observational research offers additional benefit when compared with data from RCTs: the conclusions are often more generalisable to a heterogenous population, which may be of greater value to everyday clinical practice. In Part 2 of this methods series, we will introduce the reader to several advanced methods for supporting the case for causality between an exposure and outcome, including: mediation analysis, natural experiments, and joint effects methods.


Assuntos
Pesquisa Biomédica/métodos , Estudos Observacionais como Assunto/métodos , Medicina Perioperatória/métodos , Humanos
12.
PLoS Med ; 17(4): e1003100, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32353039

RESUMO

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease worldwide. Many individuals have risk factors associated with NAFLD, but the majority do not develop advanced liver disease: cirrhosis, hepatic decompensation, or hepatocellular carcinoma. Identifying people at high risk of experiencing these complications is important in order to prevent disease progression. This review synthesises the evidence on metabolic risk factors and their potential to predict liver disease outcomes in the general population at risk of NAFLD or with diagnosed NAFLD. METHODS AND FINDINGS: We conducted a systematic review and meta-analysis of population-based cohort studies. Databases (including MEDLINE, EMBASE, the Cochrane Library, and ClinicalTrials.gov) were searched up to 9 January 2020. Studies were included that reported severe liver disease outcomes (defined as liver cirrhosis, complications of cirrhosis, or liver-related death) or advanced fibrosis/non-alcoholic steatohepatitis (NASH) in adult individuals with metabolic risk factors, compared with individuals with no metabolic risk factors. Cohorts selected on the basis of a clinically indicated liver biopsy were excluded to better reflect general population risk. Risk of bias was assessed using the QUIPS tool. The results of similar studies were pooled, and overall estimates of hazard ratio (HR) were obtained using random-effects meta-analyses. Of 7,300 unique citations, 22 studies met the inclusion criteria and were of sufficient quality, with 18 studies contributing data suitable for pooling in 2 random-effects meta-analyses. Type 2 diabetes mellitus (T2DM) was associated with an increased risk of incident severe liver disease events (adjusted HR 2.25, 95% CI 1.83-2.76, p < 0.001, I2 99%). T2DM data were from 12 studies, with 22.8 million individuals followed up for a median of 10 years (IQR 6.4 to 16.9) experiencing 72,792 liver events. Fourteen studies were included in the meta-analysis of obesity (BMI > 30 kg/m2) as a prognostic factor, providing data on 19.3 million individuals followed up for a median of 13.8 years (IQR 9.0 to 19.8) experiencing 49,541 liver events. Obesity was associated with a modest increase in risk of incident severe liver disease outcomes (adjusted HR 1.20, 95% CI 1.12-1.28, p < 0.001, I2 87%). There was also evidence to suggest that lipid abnormalities (low high-density lipoprotein and high triglycerides) and hypertension were both independently associated with incident severe liver disease. Significant study heterogeneity observed in the meta-analyses and possible under-publishing of smaller negative studies are acknowledged to be limitations, as well as the potential effect of competing risks on outcome. CONCLUSIONS: In this review, we observed that T2DM is associated with a greater than 2-fold increase in the risk of developing severe liver disease. As the incidence of diabetes and obesity continue to rise, using these findings to improve case finding for people at high risk of liver disease will allow for effective management to help address the increasing morbidity and mortality from liver disease. TRIAL REGISTRATION: PROSPERO CRD42018115459.


Assuntos
Doenças Metabólicas/epidemiologia , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Estudos Observacionais como Assunto/métodos , Vigilância da População , Humanos , Incidência , Hepatopatias/sangue , Hepatopatias/diagnóstico , Hepatopatias/epidemiologia , Doenças Metabólicas/sangue , Doenças Metabólicas/diagnóstico , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Vigilância da População/métodos , Fatores de Risco
13.
Pediatrics ; 145(6)2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32371428

RESUMO

CONTEXT: The World Health Organization recommends tummy time for infants because of the benefits of improved motor development and reduced likelihood of plagiocephaly. Because of poor uptake of these recommendations, the association of tummy time with other health outcomes requires further investigation. OBJECTIVE: To review existing evidence regarding the association of tummy time with a broad and specific range of infant health outcomes. DATA SOURCES: Electronic databases were searched between June 2018 and April 2019. STUDY SELECTION: Peer-reviewed English-language articles were included if they investigated a population of healthy infants (0 to 12 months), using an observational or experimental study design containing an objective or subjective measure of tummy time which examined the association with a health outcome (adiposity, motor development, psychosocial health, cognitive development, fitness, cardiometabolic health, or risks/harms). DATA EXTRACTION: Two reviewers independently extracted data and assessed their quality. RESULTS: Sixteen articles representing 4237 participants from 8 countries were included. Tummy time was positively associated with gross motor and total development, a reduction in the BMI-z score, prevention of brachycephaly, and the ability to move while prone, supine, crawling, and rolling. An indeterminate association was found for social and cognitive domains, plagiocephaly, walking, standing, and sitting. No association was found for fine motor development and communication. LIMITATIONS: Most studies were observational in design and lacked the robustness of a randomized controlled trial. High selection and performance bias were also present. CONCLUSIONS: These findings guide the prioritization of interventions aimed at assisting parents meet the global and national physical activity guidelines.


Assuntos
Desenvolvimento Infantil/fisiologia , Saúde do Lactente/tendências , Decúbito Ventral/fisiologia , Humanos , Lactente , Recém-Nascido , Estudos Observacionais como Assunto/métodos , Plagiocefalia/epidemiologia , Plagiocefalia/prevenção & controle
14.
Ann Rheum Dis ; 79(7): 883-890, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32381560

RESUMO

OBJECTIVES: Target trial emulation is an intuitive design framework that encourages investigators to formulate their comparative effectiveness research (CER) question as a hypothetical randomised controlled trial (RCT). Our aim was to systematically review CER studies in rheumatoid arthritis (RA) to provide examples of design limitations that could be avoided using target trial emulation, and how these limitations might introduce bias. METHODS: We searched for head-to-head CER studies of biologic disease modifying anti-rheumatic drugs (DMARDs) in RA. Study designs were reviewed for seven components of the target trial emulation framework: eligibility criteria, treatment strategies, assignment procedures, follow-up period, outcome, causal contrasts of interest (ie, intention-to-treat (ITT) or per-protocol effect) and analysis plan. Hypothetical trials corresponding to the reported methods were assessed to identify design limitations that would have been avoided with an explicit target trial protocol. Analysis of the primary effectiveness outcome was chosen where multiple analyses were performed. RESULTS: We found 31 CER studies, of which 29 (94%) had at least one design limitation belonging to seven components. The most common limitations related to: (1) eligibility criteria: 19/31 (61%) studies used post-baseline information to define baseline eligibility; (2) causal contrasts: 25 (81%) did not define whether ITT or per-protocol effects were estimated and (3) assignment procedures: 13 (42%) studies did not account for confounding by indication or relied solely on statistical confounder selection. CONCLUSIONS: Design limitations were found in 94% of observational CER studies in RA. Target trial emulation is a structured approach for designing observational CER studies that helps to avoid potential sources of bias.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Pesquisa Comparativa da Efetividade/estatística & dados numéricos , Estudos Observacionais como Assunto/estatística & dados numéricos , Projetos de Pesquisa , Pesquisa Comparativa da Efetividade/métodos , Humanos , Estudos Observacionais como Assunto/métodos
15.
Clin Neurol Neurosurg ; 194: 105921, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32422545

RESUMO

BACKGROUND: Increasing research reports neurological manifestations of COVID-19 patients. SARS-CoV-2 shares homology with other human coronaviruses that have also had nervous system involvement. OBJECTIVE: To review the neurological aspects of SARS-cov2 and other coronavirus, including transmission pathways, mechanisms of invasion into the nervous system, and mechanisms of neurological disease. METHODS: We conducted a systematic review of articles in PubMed, SCOPUS and EMBASE data bases. Reviewed evidence is presented in sections of this manuscript which includes pathogenesis, neuro-invasion, encephalitis, Guillain-Barré, ADEM, multiple sclerosis, polyneuropathy, and cerebrovascular disease. RESULTS: A total 67 studies were included in the final analysis of experimental studies, case reports, series of cases, cohort studies, and systematic reviews related to neurological manifestations of SARS- CoV-2 and other human coronavirus infections. The SARS-CoV-2 receptor is expressed in the nervous system. Common reported symptoms included hyposmia, headaches, weakness, altered consciousness. Encephalitis, demyelination, neuropathy, and stroke have been associated with COVID-19. Infection through the cribriform plate and olfactory bulb and dissemination through trans-synaptic transfer are some of the mechanisms proposed. Invasion of the medullary cardiorespiratory center by SARS-CoV-2 may contribute to the refractory respiratory failure observed in critically-ill COVID-19 patients. CONCLUSION: An increasing number of reports of COVID-19 patients with neurological disorders add to emergent experimental models with neuro-invasion as a reasonable concern that SARS-CoV-2 is a new neuropathogen. How it may cause acute and chronic neurologic disorders needs to be clarified in future research.


Assuntos
Betacoronavirus , Infecções por Coronavirus/diagnóstico por imagem , Infecções por Coronavirus/epidemiologia , Doenças do Sistema Nervoso/diagnóstico por imagem , Doenças do Sistema Nervoso/epidemiologia , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/epidemiologia , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Encéfalo/virologia , Infecções por Coronavirus/metabolismo , Humanos , Doenças do Sistema Nervoso/metabolismo , Estudos Observacionais como Assunto/métodos , Pandemias , Pneumonia Viral/metabolismo
16.
Psychiatry Res ; 288: 112959, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32335466

RESUMO

Schizophrenia is a heterogeneous disorder in which there is an interaction between genetic and environmental factors. Accumulating data show that there may be an association between vitamin D deficiency and schizophrenia. We conducted an updated meta-analysis to investigate the relationship between schizophrenia and blood vitamin D level. All published observational articles have been searched from five databases until September 2019. In total, 36 articles with a total of 12528 participants were included in this study. Patients with schizophrenia have significantly lower levels of vitamin D than controls. The subgroup analyses based on study design, hospitalization status, quality score, type of biomarker [25-hydroxyvitamin D or 25-hydroxyvitamin D3], and the country did not explain between-study heterogeneity; however, meta-regression on match factors indicted that match of BMI could account for some degree of heterogeneity. No significant differences in publication bias were observed. Also, subjects with schizophrenia were more likely to have vitamin D deficiency or insufficiency compared to controls. In conclusion, our analyses are consistent with the hypothesis that vitamin D deficiency is associated with schizophrenia. More well-designed randomized control trials are needed to determine whether this association is causal.


Assuntos
Estudos Observacionais como Assunto/métodos , Esquizofrenia/sangue , Esquizofrenia/epidemiologia , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/epidemiologia , Vitamina D/análogos & derivados , Biomarcadores/sangue , Humanos , Vitamina D/sangue
17.
Pain Physician ; 23(2): E163-E174, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32214293

RESUMO

BACKGROUND: Acute pain management in patients on buprenorphine opioid agonist therapy (BOAT) can be challenging. It is unclear whether BOAT should be continued or interrupted for optimization of postoperative pain control. OBJECTIVES: To determine an evidence-based approach for pain management in patients on BOAT in the perioperative setting, particularly whether BOAT should be continued or interrupted with or without bridging to another mu opioid agonist and to identify benefits and harms of either perioperative strategy. STUDY DESIGN: Systematic literature review with qualitative data synthesis. SETTING: Hospital, perioperative. METHODS: The study protocol was registered on PROSPERO (Registration number 9030276355). Medline via OVID, EMBASE, CINAHL, and the Cochrane CENTRAL register of trials were searched for prospective or retrospective observational or controlled studies, case series, and case reports that described perioperative or acute pain care for patients on BOAT. References of narrative and systematic reviews addressing acute pain management in patients on BOAT and references of included articles were hand-searched to identify additional original articles for inclusion. The full text of publications were reviewed for final inclusion, and data were extracted using a standardized data extraction form. Results were summarized qualitatively. Primary outcomes were postoperative pain intensity and total opioid use and identification of benefits and harms of perioperative strategies. RESULTS: Eighteen publications presenting data on the perioperative management of patients on BOAT were identified: 10 case reports, 5 case series, and 3 retrospective cohort studies. Eleven articles reported continuation of BOAT, 2 concerned bridging BOAT, and 4 articles described stopping BOAT without planned bridging. In one retrospective cohort study, BOAT was continued in half and interrupted in half of patients. Patients on BOAT may have pain that is more difficult to treat than those who are not on OAT. There is no clear evidence that one particular strategy provides superior postoperative pain control, but interruption of BOAT may result in harm, including failure to return to baseline BOAT doses, continuing non-BOAT opioid use, or relapse of opioid use disorder. LIMITATIONS: There were a limited number of articles relevant to the study question consisting of case reports and retrospective observational studies. Some omitted relevant details. No prospective studies were found. CONCLUSIONS: There is no clear benefit to bridging or stopping BOAT but failure to restart it may pose concerns for relapse. We recommend continuing BOAT in the perioperative period when possible and incorporating an interdisciplinary approach with multimodal analgesia. KEY WORDS: Opioid use disorder, opiate substitution treatment, buprenorphine, buprenorphine-naloxone, buprenorphine opioid agonist therapy, postoperative pain, acute pain, multimodal analgesia.


Assuntos
Analgésicos Opioides/administração & dosagem , Buprenorfina/administração & dosagem , Tratamento de Substituição de Opiáceos/métodos , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Manejo da Dor/métodos , Dor Pós-Operatória/tratamento farmacológico , Esquema de Medicação , Humanos , Estudos Observacionais como Assunto/métodos , Tratamento de Substituição de Opiáceos/tendências , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Dor Pós-Operatória/epidemiologia , Estudos Prospectivos , Estudos Retrospectivos
18.
Dtsch Arztebl Int ; 116(7): 101-107, 2020 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-32164822

RESUMO

BACKGROUND: In clinical medical research, causality is demonstrated b controlled trials (RCTs). Often, however, an RCT cannot be conducted for ethical reasons, and sometimes for practical reasons as well. In such cases, knowledge can be derived from an observational study instead. In this article, we present two methods that have not been widely used in medical research to date. METHODS: The methods of assessing causal inferences in observational studies are described on the basis of publications retrieved by a selective literature search. RESULTS: Two relatively new approaches-regression-discontinuity methods and interrupted time series-can be used to demonstrate a causal relationship under certain circumstances. The regression-discontinuity design is a quasi-experimental approach that can be applied if a continuous assignment variable is used with a threshold value. Patients are assigned to different treatment schemes on the basis of the threshold value. For assignment variables that are subject to random measurement error, it is assumed that, in a small interval around a threshold value, e.g., cholesterol values of 160 mg/dL, subjects are assigned essentially at random to one of two treatment groups. If patients with a value above the threshold are given a certain treatment, those with values below the threshold can serve as control group. Interrupted time series are a special type of regression-discontinuity design in which time is the assignment variable, and the threshold is a cutoff point. This is often an external event, such as the imposition of a smoking ban. A before-and-after comparison can be used to determine the effect of the intervention (e.g., the smoking ban) on health parameters such as the frequency of cardiovascular disease. CONCLUSION: The approaches described here can be used to derive causal inferences ies. They should only be applied after the prerequisites for their use have been carefully checked.


Assuntos
Causalidade , Estudos Observacionais como Assunto/métodos , Humanos
20.
Fertil Steril ; 113(1): 21-50, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-32033719

RESUMO

Post-finasteride syndrome (PFS) is a constellation of serious adverse side effects manifested in clinical symptoms that develop and persist in patients during and/or after discontinuing finasteride treatment in men with pattern hair loss (androgenetic alopecia) or benign prostatic hyperplasia. These serious adverse side effects include persistent or irreversible sexual, neurological, physical and mental side effects. To date, there are no evidence-based effective treatments for PFS. Although increasing number of men report persistent side effects, the medical community has yet to recognize this syndrome nor are there any specific measures to address this serious and debilitating symptoms. Here we evaluate the scientific and clinical evidence in the contemporary medical literature to address the very fundamental question: Is PFS a real clinical condition caused by finasteride use or are the reported symptoms only incidentally associated with but not caused by finasteride use? One key indisputable clinical evidence noted in all reported studies with finasteride and dutasteride was that use of these drugs is associated with development of sexual dysfunction, which may persist in a subset of men, irrespective of age, drug dose or duration of study. Also, increased depression, anxiety and suicidal ideation in a subset of men treated with these drugs were commonly reported in a number of studies. It is important to note that many clinical studies suffer from incomplete or inadequate assessment of adverse events and often limited or inaccurate data reporting regarding harm. Based on the existing body of evidence in the contemporary clinical literature, the author believes that finasteride and dutasteride induce a constellation of persistent sexual, neurological and physical adverse side effects, in a subset of men. These constellations of symptoms constitute the basis for PFS in individuals predisposed to epigenetic susceptibility. Indeed, delineating the pathophysiological mechanisms underlying PFS will be of paramount importance to the understanding of this syndrome and to development of potential novel therapeutic modalities.


Assuntos
Inibidores de 5-alfa Redutase/efeitos adversos , Finasterida/efeitos adversos , Disfunções Sexuais Fisiológicas/induzido quimicamente , Disfunções Sexuais Fisiológicas/diagnóstico , Suspensão de Tratamento/tendências , Alopecia/tratamento farmacológico , Alopecia/fisiopatologia , Ensaios Clínicos como Assunto/métodos , Humanos , Masculino , Estudos Observacionais como Assunto/métodos , Hiperplasia Prostática/tratamento farmacológico , Hiperplasia Prostática/fisiopatologia , Disfunções Sexuais Fisiológicas/fisiopatologia , Síndrome
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