Risk Relationship Research Articles

In vitro fertilization and perinatal outcomes of patients with advanced maternal age after single frozen euploid embryo transfer: a propensity score-matched analysis of autologous and donor cycles

ObjectiveTo evaluate in vitro fertilization (IVF) and perinatal outcomes of donor egg and autologous cycles in advanced reproductive-aged patients after undergoing single, frozen euploid embryo transfer (SET/FET). DesignA retrospective, multicenter cohort study. SettingUniversity-affiliated and private IVF centers. Patient(s)Patients between 39-46 years old undergoing IVF with intracytoplasmic sperm injection (ICSI) and preimplantation genetic testing for aneuploidy (PGT-A) using whole-chromosome sequencing with donor (n=278) or autologous (n=278) oocytes between October 2017 and October 2021. Intervention(s)SET/FET with donor or autologous euploid embryo Main outcome measure(s)The live birth rate after the first embryo transfer, calculated per embryo transfer. Secondary outcomes included implantation rate, ectopic pregnancy rate, miscarriage rate, and gestational age and birthweight at the time of delivery. Result(s)Patients using donor or autologous oocytes had a similar likelihood of implantation57.91% (51.87-63.78) versus 57.19% (51.15-63.09), p=0.93 and live birth rate 41.01% (95% CI:35.17-47.04) versus 42.45% (95% CI:36.56-48.49), p=0.86. Furthermore, there were no significant differences in ectopic pregnancy rate [0.72% (0.09-2.57) versus 0.36% (0.01-1.99), p=1] or miscarriage rate [16.19% (12.06-21.05) versus 14.39% (95% CI:10.48-19.08), p=0.98], gestational age [38.50 weeks (38.08-38.92) versus 39.16 weeks (38.25-40.07), p=0.19], or birthweight of infants [2982.25 kg (2606.69-3357.81) versus 3128.24 kg (2962.30-3294.17), p=0.95]. The univariate analysis showed no association of advanced maternal age on the live birth rate [risk relative (RR) 1.03 (IC95%: 0.84-1.25); p=0.79]. Multivariate analysis using putative confounders for embryo competency found no associations with live birth rate [adjusted risk relative (aRR) 1.22 (IC95%: 0.75-1.98); p=0.42] Conclusion(s)Patients with euploid blastocysts derived from donor or autologous oocytes did not reveal statistically significant differences in live birth rate, implantation rate, ectopic pregnancy rate, miscarriage rate, duration of gestation, or infant birthweight. These findings suggest that age-related reproductive decline and/or poor IVF outcomes associated with advanced reproductive-aged women undergoing IVF are heavily driven by embryonic aneuploidy.

Impact of switching between reference biologics and biosimilars of tumour necrosis factor inhibitors for rheumatoid arthritis: a systematic review and network meta-analysis

What is the impact of switching between biologics and biosimilars of adalimumab, etanercept, and infliximab on efficacy and safety for rheumatoid arthritis? A systematic review and network meta-analysis were performed to compare switching and non-switching groups of treatments. Pooled Risk Relative (RR) or standardised mean differences (SMD) with 95% credible intervals (95% CrIs) were obtained. Seventeen randomized trials with a switching phase involving 6,562 patients were included. Results showed that a single switch from biologics to biosimilars compared to continuing biologics had comparable effects for primary and co-primary outcomes, the American College of Rheumatology criteria with 20% response (ACR20) (7 trials, 1,926 patients, RR 0.98, 95% CrIs 0.93 to 1.03) and the Health Assessment Questionnaire—Disability Index (HAQ-DI) (5 trials, 1,609 patients, SMD − 0.07, 95% CrIs − 0.23 to 0.1), and within the equivalence margins: ACR20 [RR 0.94, 1.06] and HAQ-DI [SMD − 0.22, 0.22]. The risk of treatment-emergent adverse events, discontinuation, and positive anti-drug antibodies were comparable after switching. Safety results were imprecise, and the follow-up period might not be sufficient to evaluate long-term effects, especially malignancies. Overall, the practice of single switching between approved biologics and biosimilars of Tumour Necrosis Factor inhibitors is efficacious and safe for rheumatoid arthritis.

Simple Risk Index Score and Hospitalization Mortality in Patients with ST-Elevation Myocardial Infarction

Introduction: Hospitalization mortality in ST-elevation Myocardial Infarction (STEMI) patients areaffected by several factors, including initial identification of the risks at hospital admission. Riskscore tools as a predictor of STEMI complication and death event in STEMI patients is a simple riskindex score. The aim of this study was to determine the association between simple risk index scoreand hospitalization mortality in STEMI patients.Methods: We retrospectively enrolled 60 consecutive patients who were admitted to our hospitaldiagnosed with STEMI. The simple risk index score was calculated for each patient using equation:heart rate x [age/10]2/systolic blood pressure. The patients were assigned into 2 groups according tothis score, high score and low score group. Incidence of death during hospitalization in STEMIpatients was recorded.Results: The total subjects were 60 people. The subjects consisted of 30 patients with low score and30 subjects with high score. The incidence of death during hospitalization in the group of high simplerisk index score were 26 patients, and in the group of low simple risk index score were 13 patients.The association between the simple risk index score and the deaths during hospitalization in STEMIpatients based on statistical analysis was significant (p= 0.00) and value of risk relative (RR) is 2.167;95% CI: 1.368-3.433; (p=0.000).Conclusion: Simple risk index score is associated with hospitalization mortality in ST-elevationmyocardial Infarction (STEMI) patients.

Dietary Glycemic Index and Load and the Risk of Type 2 Diabetes: A Systematic Review and Updated Meta-Analyses of Prospective Cohort Studies.

Published meta-analyses indicate significant but inconsistent incident type-2 diabetes (T2D)-dietary glycemic index (GI) and glycemic load (GL) risk ratios or risk relations (RR). It is now over a decade ago that a published meta-analysis used a predefined standard to identify valid studies. Considering valid studies only, and using random effects dose–response meta-analysis (DRM) while withdrawing spurious results (p < 0.05), we ascertained whether these relations would support nutrition guidance, specifically for an RR > 1.20 with a lower 95% confidence limit >1.10 across typical intakes (approximately 10th to 90th percentiles of population intakes). The combined T2D–GI RR was 1.27 (1.15–1.40) (p < 0.001, n = 10 studies) per 10 units GI, while that for the T2D–GL RR was 1.26 (1.15–1.37) (p < 0.001, n = 15) per 80 g/d GL in a 2000 kcal (8400 kJ) diet. The corresponding global DRM using restricted cubic splines were 1.87 (1.56–2.25) (p < 0.001, n = 10) and 1.89 (1.66–2.16) (p < 0.001, n = 15) from 47.6 to 76.1 units GI and 73 to 257 g/d GL in a 2000 kcal diet, respectively. In conclusion, among adults initially in good health, diets higher in GI or GL were robustly associated with incident T2D. Together with mechanistic and other data, this supports that consideration should be given to these dietary risk factors in nutrition advice. Concerning the public health relevance at the global level, our evidence indicates that GI and GL are substantial food markers predicting the development of T2D worldwide, for persons of European ancestry and of East Asian ancestry.

Coronary Heart Disease and Dietary Carbohydrate, Glycemic Index, and Glycemic Load: Dose-Response Meta-analyses of Prospective Cohort Studies.

ObjectiveTo clarify the role of dietary carbohydrate, glycemic index (GI), and glycemic load (GL) in progression from health to coronary heart disease (CHD) by determining disease-nutrient risk relation (RR) values needed for intake ranges within jurisdictions and across the globe.MethodsWe performed a literature search of MEDLINE and EMBASE for prospective cohort studies that used truly valid dietary instruments in heathy adults published from January 1, 2000, to June 5, 2018. Relevant observations were extracted by 2 reviewers independently. We used dose-response meta-analysis accounting for nonindependence of results within studies. Bradford-Hill criteria were used to assess causality.ResultsEligible studies had a mean follow-up of 11 years (range, 5-19 years), were conducted in North America, Europe, and East Asia, and yielded combined RRs of 1.44 (95% CI, 1.25-1.65) per 65 g/d GL (11 studies) and 1.24 (95% CI, 1.12-1.38) per 10 U GI (10 studies) (glucose scale). The CHD-carbohydrate RR on GI was 1.66 (95% CI, 1.23-2.25) per 98 g/d of carbohydrates per 10 units GI. The 65 g/d GL, 10 U GI, and 98 g/d carbohydrate values corresponded to oral intakes from the 10th to the 90th percentiles within sampled populations. Inconsistencies were minor (I2≤20%), as were small-study effects (P=.61 for GL and P=.26 for GI). Funnel plots were symmetric. Cubic spline dose-response meta-analysis yielded RRs as follows: across the global range for GL (55-290 g/d), 5.5 (95% CI, 3.1-9.8) (I2=0); for GI (47-82 U), 2.71 (95% CI, 1.47-4.40) (I2=0); and for the CHD-carbohydrate dependence on GI (50-80 U), 4.57 (95% CI, 1.86-11.4) (I2=16%). Bradford-Hill criteria indicated that these relations were probably causal.ConclusionStrong and probably causal CHD-GL and GI RRs exist within populations. The RRs were remarkably higher across global exposures. The results support the consideration of these markers of carbohydrate food quality in dietary guidelines for general populations.Trial RegistrationPROSPERO Identifier: CRD42013004504

Commentary on Costanzo et al. (2019): The need for secondary analyses of prospective cohort studies—creating a better understanding of alcohol consumption and hospitalization

The risk relationsip between alcohol consumption and disease occurrence often differs depending on whether the end-point used is mortality or morbidity. More studies using morbidity as an end-point are required to avoid incorrect results when estimating the burden of alcohol-related harm. Cohort study networks offer opportunities for conducting such studies. Alcohol consumption is a leading risk factor for the burden of disease 1, 2, and a large proportion of the alcohol-attributable burden is due to disability and impaired functioning 1-3. However, the majority of cohort studies which examine the risk relationship (RR) between alcohol consumption and disease occurrence use mortality as an end-point 4 because mortality is easier to assess as its recording is often mandated by law, while the measurement of non-fatal end-points are more resource-intensive to collect and often are not mandated by law 4, 5. For example, studies using hospitalization as an end-point require a central collection and collation of hospitalization records, and for these records to be linked to a unique personal identifier. However, in many countries and regions, hospitalization services are administered by multiple companies with different data access and data organization policies. Under such circumstances, the resources needed to collect and harmonize hospitalization data from multiple sources are often cost- and resource-prohibitive. Consequently, for meta-analyses, data on the effects of alcohol on morbidity alone are not sufficiently available to produce accurate and precise RR estimates. Accordingly, for most disease conditions, meta-analyses combine studies which use mortality and morbidity as end-points 3, 4. Previous studies have found evidence that the alcohol RRs for various chronic diseases 6-9 may differ depending on whether mortality or morbidity is used as the end-point. In line with this, the Moli-sani study differs from mortality-based studies 3, 19 in that heavy alcohol consumers were found not to be at an increased risk of hospitalization from ischaemic heart disease and cerebrovascular accidents. These differences in the RRs by disease end-point are due to potentially confounding factors (e.g. the stage at which the diseases are diagnosed and treated, access to health care, heavy drinkers avoiding hospitals due to stigmatization by health-care workers 10-14 and/or factors affected by alcohol consumption (e.g. adherence to treatment regimens 15. Therefore, the combining of mortality and morbidity RRs may lead to incorrect results in studies which utilize both these RRs, such as the 2018 Global Status Report on Alcohol and Health 1, the 2017 Global Burden of Disease study 2 and other studies which have estimated hospitalizations and hospitalization costs attributable to alcohol 16-18. The data analysis of the Moli-sani study by Costanzo and colleagues 19 demonstrates the availability of opportunities to perform analyses of cohort studies which are linked to hospital discharge registries. As a result of the observation that there are different alcohol RRs for morbidity and mortality, there is a need for additional analyses of cohort studies linked to hospitalization records to examine the association of alcohol with specific alcohol-related diseases. Such analyses could take advantage of existing cohort study networks. An example of a large cohort study network is the European Prospective Investigation into Cancer and Nutrition (of which the Moli-sani study is a participant). Although this cohort study network was originally designed to examine the RRs for various risk factor exposures and the development of cancer, such a network can be used for the secondary purpose of assessing the RR for alcohol consumption and hospitalization. These sorts of analyses will lead to improvements in our understanding of how alcohol consumption leads to disease occurrence and, further, will improve the evidence base for studies which model how best to reduce morbidity, hospitalizations and hospital costs due to alcohol consumption. None. K.D.S. receives funding from the 2018 Canadian Institutes of Health Research - Institute of Population and Public Health Trailblazer Award in Population and Public Health Research.

Spatial analysis for bovine viral diarrhea virus and bovine herpesvirus type 1 infections in the state of Para\xedba, northeastern Brazil

BackgroundBovine Viral Diarrhea Virus (BVDV) and Bovine Herpesvirus type 1 (BoHV-1) cause reproductive problems in cattle and restrictions on international trade in animals worldwide. Both infections were detected in cattle herds in the Paraíba state, Northeastern Brazil, however, the spatial distribution and geographic identification of positive herds for these viruses has never been examined. Therefore, the aim of this study was to describe the spatial pattern of apparent prevalence estimate and to identify spatial clustering of positive herds of BVDV and BoHV-1 infections in cattle herds from the state of Paraíba, Northeastern Brazil.ResultsThe herd-level prevalence for BVDV and BoHV-1 infections in Paraíba were, respectively, 65.5% (95% CI: 61.1–69.7) and 87.8% (95% CI: 84.5–90.5). The average apparent within-herd prevalence of BVDV was 31.8% and of BoHV-1 was 62.4%. The predicted prevalence was highest (0.42–0.75) for BVDV in the west, north and eastern part of Sertão and in the central and eastern part of Agreste/Zona da Mata. For BoHV-1, the highest predicted prevalence (0.74–0.97) was in some local areas across Sertão and throughout the eastern part of Agreste/Zona da Mata. Six significant clusters were detected for BVDV, a primary cluster covering the eastern Sertão region, with 11 herds, radius of 24.10 km and risk relative (RR) of 2.21 (P < 0.001) and five smaller significant clusters, involving one or two herds in Agreste/Zona da Mata region with a high RR. A significant clustering of BoHV-1 positive herds (P < 0.001) was detected in Agreste/Zona da Mata region with a radius of 77.17 km and a RR of 1.27, with 103 cases. Consistency was found between kriging and SatScan results for identification of risk areas for BVDV and BoHV-1 infections.ConclusionsThe clusters detected contemplated different areas of the state, with BVDV cluster located in the Sertão and BoHV-1 in Agreste/Zona da Mata stratum. Through the risk mapping, it was possible to identify the areas in which the risk is significantly elevated, coincided with areas where there are borders with other states and in which there is a high movement of animals.

Alcohol consumption as a risk factor for tuberculosis: meta-analyses and burden of disease.

Meta-analyses of alcohol use, alcohol dosage and alcohol-related problems as risk factors for tuberculosis incidence were undertaken. The global alcohol-attributable tuberculosis burden of disease was also re-estimated.Systematic searches were conducted, reference lists were reviewed and expert consultations were held to identify studies. Cohort and case-control studies were included if there were no temporal violations of exposure and outcome. Risk relations (RRs) were pooled by using categorical and dose-response meta-analyses. The alcohol-attributable tuberculosis burden of disease was estimated by using alcohol-attributable fractions.36 of 1108 studies were included. RRs for alcohol use and alcohol-related problems were 1.35 (95% CI 1.09–1.68; I2: 83%) and 3.33 (95% CI 2.14–5.19; 87%), respectively. Concerning alcohol dosage, tuberculosis risk rose as ethanol intake increased, with evidence of a threshold effect. Alcohol consumption caused 22.02 incident cases (95% CI 19.70–40.77) and 2.35 deaths (95% CI 2.05–4.79) per 100 000 people from tuberculosis in 2014. Alcohol-attributable tuberculosis incidence increased between 2000 and 2014 in most high tuberculosis burden countries, whereas mortality decreased.Alcohol consumption was associated with an increased risk of tuberculosis in all meta-analyses. It was consequently a major contributor to the tuberculosis burden of disease.

An Approach To Using Data Mining To Support Early Identification Of Acromegaly

Data mining using insurance claims presents an opportunity to incorporate new analytic techniques in identifying rare conditions. This study aims to identify dyads of clinical conditions associated with acromegaly that may, with further validation and testing, be used to initially identify and diagnose this rare disease more accurately and efficiently. This case-control study used two claims databases to identify acromegaly patients (cases) (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM]: 253.0) from 2008-2013. Each case was assigned two nonacromegaly controls (same age, gender, and region). Matched patients were randomly split into development and validation datasets. With expert clinician input, we isolated common associated conditions using ICD-9-CM codes. We identified all 2-way combinations of these conditions (dyads) and calculated the rate and risk relative (RR) to controls. Dyads meeting certain criteria (case rate ≥5% [or ≥1% if RR ≥5] or observed RR > expected) were replicated in the validation dataset to confirm results. We identified 3,731 cases and 7,462 controls: mean age 41.8 (SD, 16.1) years, 51.8% female. A total of 32 and 38 dyads, reduced from 630, met study criteria. Among replicated dyads, case rates varied -15.9% (hypertension and metabolic disorder) to 0.6% (arthritis and menstrual abnormalities). The highest RRs (e.g., valvular insufficiency and colon polyps [RR, 13.5; rate, 0.7%]) also exceeded expected values. Replication showed similar RR direction and size. This novel analytic approach revealed several dyads that were significantly associated with an acromegaly diagnosis. Presence of high-risk condition pairs, if verified by a detailed data source (e.g., medical charts), may be incorporated into screening tools or serve as potential markers for physicians to consider an acromegaly diagnosis. ICD-9-CM = International Classification of Diseases, Ninth Revision, Clinical Modification ID = identification RR = relative risk.

Artéria radial versus veia safena para revascularização do miocárdio: metanálise (não houve diferença estatisticamente significante)

OBJETIVO: Comparar a efetividade do enxerto de arteria radial com o enxerto de veia safena para revascularizacao do miocardio, em associacao com a arteria toracica interna. METODO: Realizou-se uma revisao sistematica da literatura, utilizando uma estrategia de busca de artigos aplicada as bases de dados da MEDLINE e LILACS. Dois pesquisadores independentes realizaram a selecao dos artigos identificados, avaliando criteriosamente a metodologia dos artigos considerados relevantes para o tema. Somente os ensaios clinicos controlados e randomizados com adequado sistema de aleatorizacao foram incluidos. Em todas as situacoes em que ocorreu discordância entre os pesquisadores, foi realizada uma reuniao de consenso. Nao foi estipulada restricao quanto ao periodo pos-operatorio para avaliacao angiografica do enxerto, o vaso tratado cirurgicamente e as caracteristicas dos pacientes incluidos. Os resultados sao expressos como Risco Relativo (RR), com 95% de Intervalo de Confianca (CI), da comparacao da efetividade entre a arteria radial e a veia safena. RESULTADOS: Com base nesses criterios foram incluidos tres estudos. Nao foi detectada diferenca estatistica entre a perviabilidade dos enxertos estudados (RR 0,53 [95% IC 0,13 - 2,18]). CONCLUSAO: Apesar dos estudos serem de boa qualidade metodologica, nao houve resultado estatisticamente significativo beneficiando um dos enxertos. O poder estatistico da metanalise e baixo. Portanto, sao necessarios novos ensaios clinicos controlados e randomizados, com tamanho de amostra adequado para detectar possiveis diferencas entre os tratamentos propostos.

Pre-AIDS mortality from natural causes associated with HIV disease progression: evidence from the European Seroconverter Study among injecting drug users.

To study differences in pre-AIDS mortality between European cohorts of injecting drug users (IDU) and to evaluate whether pre-AIDS mortality increased with time since HIV seroconversion and decreasing CD4 count. The study population consisted of 664 IDU with documented intervals of HIV seroconversion from eight cohort studies. Differences in pre-AIDS mortality were studied between European sites; an evaluation of whether pre-AIDS mortality increased with time since HIV seroconversion and decreasing CD4 count was carried out using Poisson regression. One hundred and seven IDU died, of whom 57 did not have AIDS. Pre-AIDS causes of death were overdose/suicide (49%), natural causes such as bacterial infections/cirrhosis (40%), and unintentional injuries/unknown (11%). Considering pre-AIDS death and AIDS as competing risks, 14.7% were expected to have died without AIDS and 17.3% to have developed AIDS at 7 years from seroconversion. No statistically significant differences in pre-AIDS mortality were found between European regions, men and women, age categories and calendar time periods. Overall pre-AIDS mortality did not increase with time since seroconversion, but did increase with decreasing CD4 count. Evaluating cause-specific mortality, only pre-AIDS mortality from natural causes appeared to be associated with time since seroconversion as well as immunosuppression. For natural causes, the death rate per 100 person-years was 0.13 the first 2 years after seroconversion, 0.73 in years 2-4 [risk relative (RR) to years 0-2, 5.6], 1.83 in years 4-6 (RR, 14.0) and 1.54 for > or = 6 years (RR, 11.7). This rate was 0 for a CD4 cell count > or = 500 x 10(6)/l, 1.06 for 200-500 x 10(6)/l and 4.06 for < 200 x 10(6)/l (RR versus > or = 200 x 10(6)/l, 7.0). In multivariate analysis, both CD4 count and time since seroconversion appeared to be independently associated with death from natural causes; CD4 count appeared to be the strongest predictor (adjusted RR, 5.9). A high pre-AIDS mortality rate was observed among IDU. No significant differences were observed across European sites. Pre-AIDS mortality from natural causes but not from overdose and suicide was associated with HIV disease progression.

Components of the crude risk ratio.

Miettinen, O. S. (Harvard School of Public Health, Boston, Mass. 02115). Components of the ratio. Am J Epidemiol 96: 168-172, 1972.—Both in cohort and case-control studies the estimate of the factors into two important and easily derived components. One is a measure of the strength of confounding, and the other is an estimate of the residual in terms of the standardized morbidity (mortality) ratio. For case-control studies the latter seems to be a new and useful summary relative risk. epidemiologic methods; biometry Risk (relative (RR)) is a parameter of central interest in epidemiology. It is denned as the of the among the exposed to that among the nonexposed, with risk referring to some measure of morbidity or mortality and exposure and nonexposure distinguishing between a pair of alternative experiences or characteristi cs. The data-layouts for its estimation in cohort and case-control studies, respectively, are presented in table 1. With a cohort study the crude RR is estimated naturally by the of the two observed rates, i.e., by f>e = (e/F)/(g/H) = eH/gF. The equivalent formula for case-control studies, introduced by Cornfield (1), is the odds ratio fic = ad/bc as long as the compared series are independent (unmatched) and the disease is rare among exposed as well as nonexposed individuals. These estimates of the RR are useful for predictive purposes, but in etiologic research it is necessary to make a distinction between two components of the parameter—one resulting from recognizaAbbreviations: ML, maximum likelihood; RR, ratio; SMR, standard morbidity (mortality)