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G-computation of average treatment effects on the treated and the untreated
No full textAbstract
Background
Average treatment effects on the treated (ATT) and the untreated (ATU) are useful when there is interest in: the evaluation of the effects of treatments or interventions on those who received them, the presence of treatment heterogeneity, or the projection of potential outcomes in a target (sub-) population. In this paper we illustrate the steps for estimating ATT and ATU using g-computation implemented via Monte Carlo simulation.
Methods
To obtain marginal effect estimates for ATT and ATU we used a three-step approach: fitting a model for the outcome, generating potential outcome variables for ATT and ATU separately, and regressing each potential outcome variable on treatment intervention.
Results
The estimates for ATT, ATU and average treatment effect (ATE) were of similar magnitude, with ATE being in between ATT and ATU as expected. In our illustrative example, the effect (risk difference [RD]) of a higher education on angina among the participants who indeed have at least a high school education (ATT) was \u22120.019 (95% CI: \u22120.040, \u22120.007) and that among those who have less than a high school education in India (ATU) was \u22120.012 (95% CI: \u22120.036, 0.010).
Conclusions
The g-computation algorithm is a powerful way of estimating standardized estimates like the ATT and ATU. Its use should be encouraged in modern epidemiologic teaching and practice
Assessing the performance of centralized waiting lists for patients without a regular family physician using clinical-administrative data
No full textAbstract
Background
With 4.6 million patients who do not have a regular family physician, Canada performs poorly compared to other OECD countries in terms of attachment to a family physician. To address this issue, several provinces have implemented centralized waiting lists to coordinate supply and demand for attachment to a family physician. Although significant resources are invested in these centralized waiting lists, no studies have measured their performance. In this article, we present a performance assessment of centralized waiting lists for unattached patients implemented in Quebec, Canada.
Methods
We based our approach on the Balanced Scorecard method. A committee of decision-makers, managers, healthcare professionals, and researchers selected five indicators for the performance assessment of centralized waiting lists, including both process and outcome indicators. We analyzed and compared clinical-administrative data from 86 centralized waiting lists (GACOs) located in 14 regions in Quebec, from April 1, 2013, to March 31, 2014.
Results
During the study period, although over 150,000 patients were attached to a family physician, new requests resulted in a 30% median increase in patients on waiting lists. An inverse correlation of average strength was found between the rates of patients attached to a family physician and the proportion of vulnerable patients attached to a family physician meaning that as more patients became attached to an FP through GACOs, the proportion of vulnerable patients became smaller ( r \u2009= \u22120.31, p \u2009<\u20090.005). The results showed very large performance variations both among GACOs of different regions and among those of a same region for all performance indicators.
Conclusions
Centralized waiting lists for unattached patients in Quebec seem to be achieving their twofold objective of attaching patients to a family physician and giving priority to vulnerable patients. However, the demand for attachment seems to exceed the supply and there appears to be a tension between giving priority to vulnerable patients and attaching of a large number of patients. Results also showed heterogeneity in the performance of centralized waiting lists across Quebec. Finally, our findings suggest it is critical that similar mechanisms should use available data to identify the best strategies for reducing ..
The cut-off value of tumor size and appropriate timing of follow-up for management of minimal EUS-suspected gastric gastrointestinal stromal tumors
No full textAbstract
Backgroud
The detectable rate of minimal gastric GISTs has continuously increased. While the surveillance and management of GIST <2\ua0cm have been deemed controversial or lack evidence-based approaches. \ua0The aim of the current study is to propose a cut-off value of tumor size for treatment policy and the appropriate timing for endoscopic ultrasonography (EUS) follow-up in the minimal EUS-suspected gastric GIST patients.
Methods
A single-institution retrospective study was performed. 69 patients with EUS-suspected gastric GISTs were studied from November 2008 to March 2015. 69 patients with minimal gastric GISTs \u22642\ua0cm diagnosed by EUS were followed for a mean period of 29\ua0months (range, 12 to 70). An at least 20% increase of the maximal diameter of the tumors was set as a significant change.
Results
During follow-up, Of the 69 minimal EUS-suspected GISTs, 16 (23.2%) showed significant changes in size. 11 out of 69 GISTs (15.9%), 6 out of 43 GISTs (14.0%), 7 out of 30 GISTs (23.3%) showed significant changes in size, at 1\ua0year, 2\ua0years, and more than 3\ua0years respectively. The receiver operating characteristic curve analysis showed that the tumor size cut-off was 9.5\ua0mm. Only 4.7 and 3.7% of gastric EUS-suspected GISTs of <9.5\ua0mm in size showed significant changes at 1\ua0year and 2\ua0years, while 9.5% at more than 3\ua0years. 34.6, 31.3 and 55.6% of gastric EUS-suspected GISTs of\u2009\u2265\u20099.5\ua0mm in size showed significant changes at 1\ua0year, 2\ua0years and more than 3\ua0years.
Conclusions
Minimal EUS-suspected GISTs, larger than 9.5\ua0mm may be associated with significant progression. The patients with a\u2009\u2265\u20099.5\ua0mm GIST should have a EUS 6\u201312months, while <9.5\ua0mm GIST may have a EUS extended to every 2\u20133 years
Single- and multiple viral respiratory infections in children: disease and management cannot be related to a specific pathogen
No full textAbstract
Background
The number of viral pathogens associated with pediatric acute respiratory tract infection (ARI) has grown since the introduction of reverse transcription real-time polymerase chain reaction (RT-PCR) assays. Multiple viruses are detected during a single ARI episode in approximately a quarter of all cases. The clinical relevance of these multiple detections is unclear, as is the role of the individual virus. We therefore investigated the correlation between clinical data and RT-PCR results in children with single- and multiple viral ARI.
Methods
Data from children with ARI were prospectively collected during two winter seasons. RT-PCR testing for 15 viruses was performed in 560 ARI episodes. In the patients with a single-viral etiology, clinical data, laboratory findings, patient management- and outcome data were compared between the different viruses. With this information, we compared data from children of whom RT-PCR data were negative, with children with single- and multiple viral positive results.
Results
The viral detection rate was 457/560 (81.6%) of which 331/560 (59.1%) were single infections and 126/560 (22.5%) were multiple infections. In single viral infections, some statistically significant differences in demographics, clinical findings, disease severity and outcome were found between children with different viral etiologies. However, no clinically recognizable pattern was established to be virus-specific. In a multivariate analysis, the only variables that were correlated with longer hospital stay were the use of oxygen and nebulizer therapy, irrespective of the viral pathogen. Children with RT-PCR positive test results had a significant higher disease severity, fever, length of hospital stay, days of extra oxygen supply, and days of antibiotic treatment than children with a negative RT-PCR test result. For children with single- versus children with multiple positive RT-PCR test results, these differences were not significant.
Conclusions
Disease (severity), management and outcome in pediatric ARI are not associated with a specific virus. Single- and multiple viral ARI do not significantly differ with regard to clinical outcome and patient management. For general pediatrics, RT-PCR assays should be restricted to pathogens for which therapy is available or otherwise may have clinical consequences. Further research with an extended panel of RT-PCR assays and a larger number of inclusions is necessary to further validate our findings
Screening of WT1 mutations in exon 8 and 9 in children with steroid resistant nephrotic syndrome from a single centre and establishment of a rapid screening assay using high-resolution melting analysis in a clinical setting
No full textAbstract
Background
Mutations in Wilm\u2019s tumor 1 ( WT1 ) gene is one of the commonly reported genetic mutations in children with steroid resistant nephrotic syndrome (SRNS). We report the results of direct sequencing of exons 8 and 9 of WT1 gene in 100 children with SRNS from a single centre. We standardized and validated High Resolution Melt (HRM) as a rapid and cost effective screening step to identify individuals with normal sequence and distinguish it from those with a potential mutation. Since only mutation positive samples identified by HRM will be further processed for sequencing it will help in reducing the sequencing burden and speed up the screening process.
Methods
One hundred SRNS children were screened for WT1 mutations in Exon 8 and 9 using Sanger sequencing. HRM assay was standardized and validated by performing analysis for exon 8 and 9 on 3 healthy control and 5 abnormal variants created by site directed mutagenesis and verified by sequencing. To further test the clinical applicability of the assay, we screened additional 91 samples for HRM testing and performed a blinded assessment.
Results
WT1 mutations were not observed in the cohort of children with SRNS. The results of HRM analysis were concordant with the sequencing results.
Conclusion
The WT1 gene mutations were not observed in the SRNS cohort indicating it has a low prevalence. We propose applying this simple, rapid and cost effective assay using HRM technique as the first step for screening the WT1 gene hot spot region in a clinical setting
Interaction among COX-2, P2Y1 and GPIIIa gene variants is associated with aspirin resistance and early neurological deterioration in Chinese stroke patients
No full textAbstract
Background
The effect of genetic variants on aspirin resistance (AR) remains controversial. We sought to assess the association of genetic variants with AR and early clinical outcomes in patients with acute ischemic stroke (IS).
Methods
A total of 850 acute IS patients were consecutively enrolled. Platelet aggregation was measured before and after a 7\u201310 day aspirin treatment. The sequences of 14 variants of COX-1, COX-2 , GPIb, GPIIIa, P2Y1 and P2Y12 were determined using matrix-assisted laser desorption/ionization time of flight mass spectrometry. Gene-gene interactions were analyzed using generalized multifactor dimensionality reduction (GMDR). The primary outcome was early neurological deterioration (END) within 10\ua0days of admission. The secondary outcome was a composite of early recurrent ischemic stroke (ERIS), myocardial infarction (MI) and death within 10\ua0days of admission.
Results
175 (20.6%) patients were AR, 45 (5.3%) were aspirin semi-resistant, 121 (14.2%) developed END, 17 (0.2%) had ERIS, 2 (0.2%) died, and 6 (0.7%) had MI. Single locus analysis indicated that only rs1371097 was associated with AR. However, GMDR analysis indicated that the following three sets of gene-gene interactions were significantly associated with AR: rs20417CC/rs1371097TT/rs2317676GG; rs20417CC/rs1371097TT/rs2317676GG; rs20417CC/rs1371097CT/rs2317676AG. END occurred significantly more frequently in patients with AR or high-risk interactive genotypes. Moreover, AR and high-risk interactive genotypes were independently associated with END.
Conclusion
Sensitivity of IS patients to aspirin and END may be multifactorial and is not significantly associated with a single gene polymorphism. Combinational analysis may useful for further insight into the genetic risks for AR
Subgroup identification of early preterm birth (ePTB): informing a future prospective enrichment clinical trial design
No full textAbstract
Background
Despite the widely recognized association between the severity of early preterm birth (ePTB) and its related severe diseases, little is known about the potential risk factors of ePTB and the sub-population with high risk of ePTB. Moreover, motivated by a future confirmatory clinical trial to identify whether supplementing pregnant women with docosahexaenoic acid (DHA) has a different effect on the risk subgroup population or not in terms of ePTB prevalence, this study aims to identify potential risk subgroups and risk factors for ePTB, defined as babies born less than 34\ua0weeks of gestation.
Methods
The analysis data ( N\u2009= \u20093,994,872) were obtained from CDC and NCHS\u2019 2014 Natality public data file. The sample was split into independent training and validation cohorts for model generation and model assessment, respectively. Logistic regression and CART models were used to examine potential ePTB risk predictors and their interactions, including mothers\u2019 age, nativity, race, Hispanic origin, marital status, education, pre-pregnancy smoking status, pre-pregnancy BMI, pre-pregnancy diabetes status, pre-pregnancy hypertension status, previous preterm birth status, infertility treatment usage status, fertility enhancing drug usage status, and delivery payment source.
Results
Both logistic regression models with either 14 or 10 ePTB risk factors produced the same C-index (0.646) based on the training cohort. The C-index of the logistic regression model based on 10 predictors was 0.645 for the validation cohort. Both C-indexes indicated a good discrimination and acceptable model fit. The CART model identified preterm birth history and race as the most important risk factors, and revealed that the subgroup with a preterm birth history and a race designation as Black had the highest risk for ePTB. The c-index and misclassification rate were 0.579 and 0.034 for the training cohort, and 0.578 and 0.034 for the validation cohort, respectively.
Conclusions
This study revealed 14 maternal characteristic variables that reliably identified risk for ePTB through either logistic regression model and/or a CART model. Moreover, both models efficiently identify risk subgroups for further enrichment clinical trial design
Concordance between PIK3CA mutations in endoscopic biopsy and surgically resected specimens of esophageal squamous cell carcinoma
No full textAbstract
Background
PIK3CA mutations are expected to be potential therapeutic targets for esophageal squamous cell carcinoma (ESCC). We aimed to clarify the concordance between PIK3CA mutations detected in endoscopic biopsy specimens and corresponding surgically resected specimens.
Methods
We examined five hotspot mutations in the PIK3CA gene (E542K, E545K, E546K, H1047R, and H1047L) in formalin-fixed and paraffin-embedded tissue sections of paired endoscopic biopsy and surgically resected specimens from 181 patients undergoing curative resection for ESCC between 2000 and 2011 using a Luminex technology-based multiplex gene mutation detection kit.
Results
Mutation analyses were successfully performed for both endoscopic biopsy and surgically resected specimens in all the cases. A PIK3CA mutation was detected in either type of specimen in 13 cases (7.2%, 95% confidence interval: 3.9\u201312.0). The overall concordance rate, positive predictive value, and negative predictive value were 98.3% (178/181), 90.9% (10/11), and 98.8% (168/170), respectively. Among patients with a PIK3CA mutation detected in both types of specimens, the concordance between PIK3CA mutation genotypes was 100%. There were three cases with a discordant mutation status between the types of specimens ( PIK3CA mutation in surgically resected specimen and wild-type in biopsy specimen in two cases, and the opposite pattern in one case), suggesting possible intratumoral heterogeneity in the PIK3CA mutation status.
Conclusions
The PIK3CA mutation status was highly concordant between endoscopic biopsy and surgically resected specimens from the same patient, suggesting that endoscopic biopsy specimens can be clinically used to detect PIK3CA mutations in patients with ESCC
Age of onset of substance use and psychosocial problems among individuals with substance use disorders
No full textAbstract
Background
Substance use is generally initiated in adolescence or early adulthood and is commonly associated with several physical, psychological, emotional and social problems. The objective of this study is to assess the age of onset of substance use differences on psychosocial problems among individuals with substance use disorders (SUDs) residing in drug rehabilitation centers.
Methods
A descriptive cross sectional research design was carried out. Probability Proportional to Size (PPS) sampling technique was used to select the drug rehabilitation centers and all the respondents meeting the inclusion criteria of the selected seven rehabilitation centers were taken as a sample and comprised of 221 diagnosed individuals with SUDs. A semi structured self administered questionnaires were used to collect the information regarding demographic and substance use related characteristics. A standard tool Drug Use Screening Inventory-Revised (DUSI-R) was used to assess the psychosocial problems among individuals with SUDs. Data were analyzed using both descriptive and inferential statistics. Multivariate general linear model (MANOVA and MANCOVA) was used to evaluate differences in psychosocial problems between early vs late onset substance users.
Result
The age of onset of substance use was significantly associated with psychosocial problems. The mean psychosocial problem scores were higher in early onset substance user (17\ua0years or younger) than late onset substance user (18\ua0years or higher) in various domains of DUSI-R even after controlling confounding factors. The two groups (early vs late) differed significantly in relation to age, gender, occupational status, current types of substance use, frequency of use, mode of substance use and relapse history.
Conclusion
The study indicated that early onset substance users are at higher risk for psychosocial problems in various areas of life such as Behavior Pattern, Psychiatric disorder, Family system, Peer relationship, Leisure/Recreation and Work adjustment compared to late onset substance users. It highlights the need for early prevention, screening, and timely intervention among those individuals
Metabolic syndrome and depressive symptoms among rural Northeast general population in China
No full textAbstract
Background
Previous researches aiming to estimate the association between metabolic syndrome and depressive symptoms come out with inconsistent results. Besides, most of them are conducted in the developed areas. There is lack of the data from rural China. The aim of this study is to confirm whether gender difference exists among the relationship between MetS, metabolic components and depressive symptoms in the rural Chinese population.
Methods
A cross-sectional analysis enrolled 11430 subjects\u2019 aged \u226535 from rural Northeast China. Metabolic and anthropometric indicators were measured according to standard methods. Depressive symptoms were defined using the Patient Health Questionnaire-9 (PHQ-9).
Results
The prevalence of depressive symptoms was 6% among rural Northeast general population and the prevalence of MetS and its components were 39.0% for MetS, 42.9% for abdominal obesity, 67.1% for elevated blood pressure, 47.1% for hyperglycemia, 32.1% for hypertriglyceridemia, 29.5% for low HDL-C. Depressive symptoms were associated with triglyceride component (OR\u2009=\u20091.24, 95%CI: 1.05\u20131.46, P\u2009= \u20090.01) but not MetS (OR\u2009=\u20091.11, 95%CI: 0.94\u20131.30, P \u2009=\u20090.23). Moreover, depressive symptoms were associated with triglyceride component (OR\u2009=\u20091.21, 95% CI\u2009=\u20091.00\u20131.47, P = 0.05) in women only. But once adjusted for menopause status, depressive symptoms were no longer statically associated with triglyceride component (OR\u2009=\u20091.20, 95% CI\u2009=\u20090.99\u20131.46, P = 0.07).
Conclusions
Depressive symptoms were associated with triglyceride component but not MetS in rural Chinese population. Routine lipid screening should be recommended among rural depressed residents especially among female