37 research outputs found
The role of sex in precision medicine: novel methods in systematic reviews
Precision medicine is a term used to describe the treatment or interventions focusing on patients based on their individual characteristics, such as disease severity, genetic traits or sex. Sex plays an influential role in health and disease and using the characteristic of sex in precision medicine can improve outcomes for both males and females. Publications in health research are continuously increasing in amount and updating which makes it difficult for clinicians to keep updated with the best evidence. To address this challenge, systematic reviews (SRs) were developed and just as with every other area in research new methods for SRs are needed.
The primary objective of this PhD thesis is to highlight sex inequities in healthcare. This was done through an analysis of risk factors for pregnant women with Covid-19 in a living systematic review and by assessing the potential role of sex (being a male or a female) as a prognostic factor (PF) in patients with pulmonary embolism. As secondary objectives I looked at developing novel methods to aid in these reviews of risk factors and prognostic factors. This was done through the development of a prognostic factor search filter for use in systematic review searches and the modification and discussion of tools and methods employed in a prognostic factor systematic review.
Overall, this thesis found that: 1) Pregnant women are considered to be a high-risk group for covid-19 infection and those with the infection need extra medical attention as they are more likely to experience preterm birth or be admitted to the intensive care unit. 2) Preliminary results of the systematic review of sex as a prognostic factor in patients with pulmonary embolism show that there is no association between sex and mortality. However, we have still yet to rate the quality of the evidence, so more higher quality studies may be needed to confirm this. 3) The development of a PF search filter that is both sensitive and specific is not an easy task due to the poor indexing of PF studies in databases. Our filter yielded a sensitivity of 95% and a specificity of 41%, so more research is needed to increase the filters specificity. 4) When carrying out a systematic review investigating sex as a PF, researchers must keep in mind that various adaptations must be made to the review process. These adaptations include modifying the PF section of the data extraction template, adjusting certain sections of QUIPS (after ROB) and extracting data on the sex and gender terms used throughout the included studies.
This thesis highlighted the level of awareness and the role that sex plays in healthcare and health research. Sex should play a central role in personalized medical care. Although more studies providing sex specific evidence are being carried out, there still remains significant shortcomings in effectively implementing sex specific health care
Patient motivation as a predictor of digital health intervention effects: A meta-epidemiological study of cancer trials
The objective of this meta-epidemiological study was to develop a rating that captures participantsâ motivation at the study level in digital health intervention (DHI) randomised controlled trials (RCTs). The rating was used to investigate whether participantsâ motivation is associated with the effect estimates in DHI RCTs for cancer patients. The development of the rating was based on a bottom-up approach involving the collection of information that captures participantsâ baseline motivation in empirical studies from the Smartphone-RCCT Database. We specified three indicators for rating: indicator 1 captures whether the study team actively selects or enhances the motivation of the potential study participants; indicator 2 captures the study participantsâ active engagement before the treatment allocation; and indicator 3 captures the potential bond and trust between the study participants and the person/institution referring to the study. The rating of each indicator and the overall rating varies between high motivation, moderate motivation, and low motivation. We applied the rating across 27 DHI RCTs with cancer patients. We performed meta-regression analysis to examine the effect of patient motivation on quality of life (QoL), psychological outcomes, and attrition. The intraclass correlation coefficient (ICC) indicated moderate to poor inter-rater reliability. The meta-regression showed that cancer patientsâ overall motivation before engaging in the intervention was associated with the treatment effect of QoL. Patient motivation was not found to be associated with psychological outcomes or attrition. Subgroup analyses revealed that the clinical effects of DHIs were more prevalent in the high-motivation subgroups, whereas the low-motivation subgroups were unlikely to show intervention benefits. The likelihood of dropouts from DHIs seems to be especially high among the low-bond (indicator 3) subgroup. We suggest using single indicators since they reflect specific content. Better reporting about baseline motivation is required to enable meaningful interpretations in not only primary studies but also in evidence syntheses
Sex as a Prognostic Factor in Systematic Reviews: Challenges and Lessons Learned
Sex is a common baseline factor collected in studies that has the potential to be a prognostic
factor (PF) in several clinical areas. In recent years, research on sex as a PF has increased; however,
this influx of new studies frequently shows conflicting results across the same treatment or disease
state. Thus, systematic reviews (SRs) addressing sex as a PF may help us to better understand
diseases and further personalize healthcare. We wrote this article to offer insights into the challenges
we encountered when conducting SRs on sex as a PF and suggestions on how to overcome these
obstacles, regardless of the clinical domain. When carrying out a PF SR with sex as the index factor,
it is important to keep in mind the modifications that must be made in various SR stages, such as
modifying the PF section of CHARMS-PF, adjusting certain sections of QUIPS and extracting data on
the sex and gender terms used throughout the studies. In this paper, we provide an overview of the
lessons learned from carrying out our reviews on sex as a PF in different disciplines and now call on
researchers, funding agencies and journals to realize the importance of studying sex as a PF.Instituto de Salud Carlos III (Plan Estatal de I
+ D + i 2013â2016)European Development Regional Fund. âA way to achieve
Europeâ (ERDF) grant number PIE16/0005
Development and evaluation of a search filter to identify prognostic factor studies in Ovid MEDLINE
Background: Systematic reviews (SRs) are valuable resources as they address specific clinical questions by summarizing all existing relevant studies. However, finding all information to include in systematic reviews can be challenging. Methodological search filters have been developed to find articles related to specific clinical questions. To our knowledge, no filter exists for finding studies on the role of prognostic factor (PF). We aimed to develop and evaluate a search filter to identify PF studies in Ovid MEDLINE that has maximum sensitivity.
Methods: We followed current recommendations for the development of a search filter by first identifying a reference set of PF studies included in relevant systematic reviews on the topic, and by selecting search terms using a word frequency analysis complemented with an expert panel discussion. We evaluated filter performance using the relative recall methodology.
Result: We constructed a reference set of 73 studies included in six systematic reviews from a larger sample. After completing a word frequency analysis using the reference set studies, we compiled a list of 80 of the frequent methodological terms. This list of terms was evaluated by the Delphi panel for inclusion in the filter, resulting in a final set of 8 appropriate terms. The consecutive connection of these terms with the Boolean operator OR produced the filter. We then evaluated the filter using the relative recall method against the reference set, comparing the references included in the SRs with our new search using the filter. The overall sensitivity of the filter was calculated to be 95%, while the overall specificity was 41%. The precision of the filter varied considerably, ranging from 0.36 to 17%. The NNR (number needed to read) value varied largely from 6 to 278. The time saved by using the filter ranged from 13â70%.
Conclusions: We developed a search filter for OVID-Medline with acceptable performance that could be used in systematic reviews of PF studies. Using this filter could save as much as 40% of the title and abstract screening task. The specificity of the filter could be improved by defining additional terms to be included, although it is important to evaluate any modification to guarantee the filter is still highly sensitive
Development and evaluation of a search filter to identify prognostic factor studies in Ovid MEDLINE.
Background: Systematic reviews (SRs) are valuable resources as they address specific clinical questions by summarizing
all existing relevant studies. However, finding all information to include in systematic reviews can be challenging.
Methodological search filters have been developed to find articles related to specific clinical questions. To our
knowledge, no filter exists for finding studies on the role of prognostic factor (PF). We aimed to develop and evaluate
a search filter to identify PF studies in Ovid MEDLINE that has maximum sensitivity.
Methods: We followed current recommendations for the development of a search filter by first identifying a reference
set of PF studies included in relevant systematic reviews on the topic, and by selecting search terms using a
word frequency analysis complemented with an expert panel discussion. We evaluated filter performance using the
relative recall methodology.
Results: We constructed a reference set of 73 studies included in six systematic reviews from a larger sample. After
completing a word frequency analysis using the reference set studies, we compiled a list of 80 of the frequent methodological
terms. This list of terms was evaluated by the Delphi panel for inclusion in the filter, resulting in a final set of
8 appropriate terms. The consecutive connection of these terms with the Boolean operator OR produced the filter. We
then evaluated the filter using the relative recall method against the reference set, comparing the references included
in the SRs with our new search using the filter. The overall sensitivity of the filter was calculated to be 95%, while the
overall specificity was 41%. The precision of the filter varied considerably, ranging from 0.36 to 17%. The NNR (number
needed to read) value varied largely from 6 to 278. The time saved by using the filter ranged from 13â70%.
Conclusions: We developed a search filter for OVID-Medline with acceptable performance that could be used in
systematic reviews of PF studies. Using this filter could save as much as 40% of the title and abstract screening task.
The specificity of the filter could be improved by defining additional terms to be included, although it is important to
evaluate any modification to guarantee the filter is still highly sensitive.post-print1282 K
Sex as a prognostic factor for mortality in critically ill adults with sepsis: a systematic review and meta-analysis.
Objective To assess the role of sex as an independent
prognostic factor for mortality in patients with sepsis
admitted to intensive care units (ICUs).
Design Systematic review and meta-analysis.
Data sources MEDLINE, Embase, Web of Science,
ClinicalTrials. gov and the WHO Clinical Trials Registry from
inception to 17 July 2020.
Study selection Studies evaluating independent
associations between sex and mortality in critically ill
adults with sepsis controlling for at least one of five core
covariate domains prespecified following a literature
search and consensus among experts.
Data extraction and synthesis Two authors
independently extracted and assessed the risk of bias
using Quality In Prognosis Studies tool. Meta-analysis
was performed by pooling adjusted estimates. The Grades
of Recommendations, Assessment, Development and
Evaluation approach was used to rate the certainty of
evidence.
Results From 14 304 records, 13 studies (80 520
participants) were included. Meta-analysis
did not find
sex-based
differences in all-cause
hospital mortality (OR
1.02, 95% CI 0.79 to 1.32; very low-certainty
evidence)
and all-cause
ICU mortality (OR 1.19, 95% CI 0.79 to 1.78;
very low-certainty
evidence). However, females presented
higher 28-day
all-cause
mortality (OR 1.18, 95% CI 1.05
to 1.32; very low-certainty
evidence) and lower 1-year
all-cause
mortality (OR 0.83, 95% CI 0.68 to 0.98; low-certainty
evidence). There was a moderate risk of bias in
the domain adjustment for other prognostic factors in six
studies, and the certainty of evidence was further affected
by inconsistency and imprecision.
Conclusion The prognostic independent effect of sex on
all-cause
hospital mortality, 28-day
all-cause
mortality
and all-cause
ICU mortality for critically ill adults with
sepsis was uncertain. Female sex may be associated with
decreased 1-year
all-cause
mortality.post-print1281 K
Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta-analysis.
OBJECTIVE: To determine the clinical manifestations, risk factors, and maternal and perinatal outcomes in pregnant and recently pregnant women with suspected or confirmed coronavirus disease 2019 (covid-19). DESIGN: Living systematic review and meta-analysis. DATA SOURCES: Medline, Embase, Cochrane database, WHO COVID-19 database, China National Knowledge Infrastructure (CNKI), and Wanfang databases from 1 December 2019 to 26 June 2020, along with preprint servers, social media, and reference lists. STUDY SELECTION: Cohort studies reporting the rates, clinical manifestations (symptoms, laboratory and radiological findings), risk factors, and maternal and perinatal outcomes in pregnant and recently pregnant women with suspected or confirmed covid-19. DATA EXTRACTION: At least two researchers independently extracted the data and assessed study quality. Random effects meta-analysis was performed, with estimates pooled as odds ratios and proportions with 95% confidence intervals. All analyses will be updated regularly. RESULTS: 77 studies were included. Overall, 10% (95% confidence interval 7% to14%; 28 studies, 11â432 women) of pregnant and recently pregnant women attending or admitted to hospital for any reason were diagnosed as having suspected or confirmed covid-19. The most common clinical manifestations of covid-19 in pregnancy were fever (40%) and cough (39%). Compared with non-pregnant women of reproductive age, pregnant and recently pregnant women with covid-19 were less likely to report symptoms of fever (odds ratio 0.43, 95% confidence interval 0.22 to 0.85; I2=74%; 5 studies; 80â521 women) and myalgia (0.48, 0.45 to 0.51; I2=0%; 3 studies; 80â409 women) and were more likely to need admission to an intensive care unit (1.62, 1.33 to 1.96; I2=0%) and invasive ventilation (1.88, 1.36 to 2.60; I2=0%; 4 studies, 91â606 women). 73 pregnant women (0.1%, 26 studies, 11â580 women) with confirmed covid-19 died from any cause. Increased maternal age (1.78, 1.25 to 2.55; I2=9%; 4 studies; 1058 women), high body mass index (2.38, 1.67 to 3.39; I2=0%; 3 studies; 877 women), chronic hypertension (2.0, 1.14 to 3.48; I2=0%; 2 studies; 858 women), and pre-existing diabetes (2.51, 1.31 to 4.80; I2=12%; 2 studies; 858 women) were associated with severe covid-19 in pregnancy. Pre-existing maternal comorbidity was a risk factor for admission to an intensive care unit (4.21, 1.06 to 16.72; I2=0%; 2 studies; 320 women) and invasive ventilation (4.48, 1.40 to 14.37; I2=0%; 2 studies; 313 women). Spontaneous preterm birth rate was 6% (95% confidence interval 3% to 9%; I2=55%; 10 studies; 870 women) in women with covid-19. The odds of any preterm birth (3.01, 95% confidence interval 1.16 to 7.85; I2=1%; 2 studies; 339 women) was high in pregnant women with covid-19 compared with those without the disease. A quarter of all neonates born to mothers with covid-19 were admitted to the neonatal unit (25%) and were at increased risk of admission (odds ratio 3.13, 95% confidence interval 2.05 to 4.78, I2=not estimable; 1 study, 1121 neonates) than those born to mothers without covid-19. CONCLUSION: Pregnant and recently pregnant women are less likely to manifest covid-19 related symptoms of fever and myalgia than non-pregnant women of reproductive age and are potentially more likely to need intensive care treatment for covid-19. Pre-existing comorbidities, high maternal age, and high body mass index seem to be risk factors for severe covid-19. Preterm birth rates are high in pregnant women with covid-19 than in pregnant women without the disease. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020178076. READERS' NOTE: This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication
A multi-program analysis of cleft lip with cleft palate prevalence and mortality using data from 22 International Clearinghouse for Birth Defects Surveillance and Research programs, 1974-2014
Background
Cleft lip with cleft palate (CLP) is a congenital condition that affects both the oral cavity and the lips. This study estimated the prevalence and mortality of CLP using surveillance data collected from birth defect registries around the world.
Methods
Data from 22 population- and hospital-based surveillance programs affiliated with the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR) in 18 countries on live births (LB), stillbirths (SB), and elective terminations of pregnancy for fetal anomaly (ETOPFA) for CLP from 1974 to 2014 were analyzed. Prevalence and survival (survival for LB only) estimates were calculated for total and subclassifications of CLP and by pregnancy outcome.
Results
The pooled prevalence of total CLP cases was 6.4 CLP per 10,000 births. The prevalence of CLP and all of the pregnancy outcomes varied across programs. Higher ETOPFA rates were recorded in most European programs compared to programs in other continents. In programs reporting low ETOPFA rates or where there was no ascertainment of ETOPFA, the rate of CLP among LB and SB was higher compared to those where ETOPFA rates were ascertained. Overall survival for total CLP was 91%. For isolated CLP, the survival was 97.7%. CLP associated with multiple congenital anomalies had an overall survival of 77.1%, and for CLP associated with genetic/chromosomal syndromes, overall survival was 40.9%.
Conclusions
Total CLP prevalence reported in this study is lower than estimates from prior studies, with variation by pregnancy outcomes between programs. Survival was lower when CLP was associated with other congenital anomalies or syndromes compared to isolated CLP
Shared genetic risk between eating disorder- and substance-use-related phenotypes:Evidence from genome-wide association studies
First published: 16 February 202
Finishing the euchromatic sequence of the human genome
The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers âŒ99% of the euchromatic genome and is accurate to an error rate of âŒ1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead