33 research outputs found
HEALTHY LIFESTYLE AND RISK OF MULTIMORBIDITY
No full textBackground Life expectancy has increased worldwide going from 45.7 years in 1950 to 72.6 years in 2019. A subgroup of these, chronic diseases (i.e., health problems requiring ongoing management over a period of years or decades), may lead to challenges in patient care when they present concomitantly (i.e., as multimorbidity). Because clinical trials often exclude patients with multimorbidity and most guidelines do not provide recommendations for multimorbid patients, these challenges persist. Moreover, multimorbidity negatively affects quality of life and functional ability and accelerates mortality. Many studies have been published on the role of modifiable lifestyle factors on multimorbidity, i.e., of tobacco and alcohol consumption, being overweight or obese, having a poor diet, and a low physical activity level. To our knowledge, only one study combined them in a comprehensive total lifestyle score. Therefore, a gap remains regarding the role of multiple lifestyle habits combined on multimorbidity.
Aim Our aim was: i) to determine the patterns of multimorbidity of selected groups of diseases or conditions, chosen among the major causes of death. and ii) to estimate the effect of five important modifiable lifestyle behaviors on the morbidity and multimorbidity of the selected diseases or conditions.
Methods To define multimorbidity we considered all chronic causes of death among the 369 diseases, injuries, and impairments recorded in the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) publicly available databases. We ranked the causes of death by decreasing yearly rates and grouped them as follows: 1) Cardiovascular diseases, i.e., ischemic heart disease, stroke, and hypertensive heart disease; 2) Gastrointestinal tract (GIT) cancers (i.e., colorectal, gastric, liver, pancreatic, and esophageal cancers) and respiratory tract (RT) cancers (i.e., trachea, bronchus, and lung cancers); 3) Alzheimer disease and other dementias; 4) Chronic obstructive pulmonary disease. These four macro-groups of chronic diseases are together responsible for an average cause-specific crude mortality rate of 827 deaths per thousand inhabitants. Multimorbidity was defined as the occurrence of diseases from two different groups.
We used data from the Swedish National March Cohort (SNMC) to study the association of five lifestyle factors with multimorbidity. We developed a partial healthy lifestyle index (HLI) score for each of the lifestyle exposures and a total HLI score ranging from 0 (worst habits) to 20 (best habits). Four states (i.e., baseline, morbidity, multimorbidity, and death) were used to define a multi-state framework, and each transition was modelled individually with a parametric multi-state model. We estimated transition probability between states and hazard ratios (HRs) and 95% confidence intervals (CIs) for the exposures of interest.
Results During an average follow-up time of 18.2 years we observed 6,458 morbidity cases, 946 transitions to multimorbidity, and 4,441 deaths. For values of the five partial HLI scores corresponding to healthier lifestyles we observed a reduction in the risk of morbidity, multimorbidity, and mortality, and we found that, e.g., over 15 years of follow-up, a man aged 65 years at baseline with an excellent lifestyle (all partial scores 4) would have a 33% reduction in the cumulative probability of morbidity, multimorbidity, and death combined compared to another man with same characteristics but a poor lifestyle (all partial scores 0-1). In case of women, the cumulative probability would be reduced by 29%. One unit increase in the total HLI score corresponded to 4% reduction in the risk of morbidity (HR [95% CI]: 0.96 [0.95-0.97]) and 6% in the risk of multimorbidity (0.94 [0.92-0.96]), similarly for both males and females. Having an HLI score of 16-20 halved the risk of morbidity compared to an HLI of 0-4 (HR [95% CI]: 0.47 [0.36-0.61] in men, and 0.46 [0.33-0.64] in women) with a stronger effect for women (p-value for heterogeneity 0.01), and reduced the risk of multimorbidity by two thirds (0.35 [0.20-0.63] in men and 0.30 [0.16-0.56] in women; p-value for heterogeneity <0.01).
Conclusions We found that healthy lifestyle habits, summarized by the HLI score, were inversely associated with morbidity and multimorbidity of selected cardiovascular diseases, gastrointestinal and respiratory cancers, dementia, and COPD. We determined that being a never smoker or quitting smoking, having a low alcohol consumption, high physical activity levels, and a low BMI, and following the Mediterranean Diet recommendations can lower the probability of morbidity, multimorbidity and death. This effect is particularly evident when all the healthy lifestyles are combined
Satisfaction with online teaching of medical statistics during the COVID-19 pandemic: A survey by the Education Committee of the Italian Society of Medical Statistics and Clinical Epidemiology
No full textOn May 2020, after 2 months of online teaching with no face-to-face lectures, the Education Committee of the Italian scientific Society of Medical Statistics and Clinical Epidemiology conceived an online survey to assess satisfaction of Italian academics of medical statistics with online teaching and remote exams.
This survey highlighted teachers' perceptions as well as opportunities and limitations of online teaching of medical statistics, biostatistics, and epidemiology.
Although 61% of Italian academics of medical statistics declared to be favorable to provide online teaching of medical statistics, biostatistics, and epidemiology
in the future, we recognize that distance education cannot substitute the unique value of teaching and knowledge exchange that could only be transmitted through a personal interaction between students and teachers. These indications may be useful to improve the quality of the teaching process in the future
Strong excess risk of pancreatic cancer for low frequency and duration of cigarette smoking: A comprehensive review and meta-analysis
No full textDose-risk relationships between cigarette smoking and ovarian cancer histotypes: a comprehensive meta-analysis
No full textAlthough smoking has not been associated with overall ovarian cancer risk, a different impact on various histotypes has been reported. Our aim is to provide an accurate, up-to-date estimate of the dose-risk relationships between cigarette smoking and epithelial ovarian cancer, overall and by histotypes
Correlators on the Wilson Line Defect CFT
No full textConformal field theory (CFT) plays a key role in modern theoretical physics.
Through CFT we describe real physical systems at criticality and fixed points
of the renormalization group flow. It is also central in the study of quantum
gravity, thanks to the AdS/CFT correspondence. This thesis originates in the
context of the N=4 supersymmetric Yang-Mills (SYM) theory, which represents the
CFT side of this correspondence. This work mainly revolves around the
supersymmetric Wilson line and its interpretation as a conformal defect in N=4
SYM. Particularly, we focus on excitations localized on the defect called
insertions, whose correlators are described by a one-dimensional CFT. The first
main result of this work is an efficient algorithm for computing multipoint
correlation functions of scalar insertions on the Wilson line, consisting of
recursion relations up to next-to-leading order at weak coupling. We show
various computations of such four-, five- and six-point correlators, and
discuss their properties. Moreover, we use the four-point function case to
illustrate the power of the Ward identities, which are crucial in deriving a
next-to-next-to-leading order result. Thanks to these perturbative results, we
find a family of differential operators annihilating our correlation functions,
which we conjecture to be a multipoint extension of the Ward identities
satisfied by the four-point functions. These non-perturbative constraints are
shown to be fundamental ingredients in the bootstrap of a five-point function
at strong coupling. To conclude, we define an inherently one-dimensional Mellin
amplitude at the non-perturbative level with appropriate subtractions and
analytical continuations. The efficiency of the 1d Mellin formalism is manifest
at the perturbative level. We find a closed-form expression for the Mellin
transform of leading order contact interactions and use it to extract CFT data.Comment: 162 pages, PhD thesis; v
Correlators on the Wilson Line Defect CFT
No full textKonforme Feldtheorien (CFT) spielen eine Schlüsselrolle in der modernen theoretischen Physik. Mit CFT beschreibt man reale physikalische Systeme bei Kritikalität. Dank der AdS/CFT-Korrespondenz spielt sie auch bei der Untersuchung der Quantengravitation eine zentrale Rolle. Auf der Seite der CFT steht die N=4 supersymmetrische Yang-Mills (SYM) Theorie. Diese Arbeit dreht sich hauptsächlich um die supersymmetrische Wilson-Linie und ihre Interpretation als konformer Defekt in N=4 SYM. Insbesondere konzentrieren wir uns auf Anregungen, die auf dem Defekt lokalisiert sind, sogenannte Einfügungen, deren Korrelatoren durch eine eindimensionale CFT beschrieben werden.
Das erste Hauptergebnis dieser Arbeit ist ein effizienter Algorithmus zur Berechnung von Mehrpunkt Korrelationsfunktionen von Skalareinfügungen auf der Wilson-Linie bis zur nächsten Ordnung bei schwacher Kopplung kodieren. Es werden verschiedene Berechnungen solcher Vier-, Fünf- und Sechspunkt-Korrelatoren gezeigt und ihre Eigenschaften diskutiert. Darüber hinaus wird am Beispiel der Vierpunkt-Funktion die Leistungsfähigkeit der Ward-Identitäten veranschaulicht, die für die Ableitung eines Ergebnisses nächster, vorletzter und führender Ordnung entscheidend sind.
Dank dieser perturbativen Ergebnisse vermuten wir eine Mehrpunkt-Erweiterung der Ward-Identitäten, die von den Vier-Punkt-Funktionen erfüllt werden. Diese nichtperturbativen Beschränkungen erweisen sich als fundamentale Bestandteile des Bootstraps einer Fünfpunkt-Funktion bei starker Kopplung.
Zum Abschluss dieser Arbeit definieren wir eine inhärent eindimensionale Mellin-Amplitude auf der nichtperturbativen Ebene mit geeigneten Subtraktionen und analytischen Fortsetzungen. Die Effizienz des 1d-Mellin-Formalismus zeigt sich auf der perturbativen Ebene. Man findet einen Ausdruck in geschlossener Form für die Mellin-Transformation von Kontaktwechselwirkungen führender Ordnung, den man verwendet, um CFT-Daten zu extrahieren.Conformal field theory (CFT) plays a key role in modern theoretical physics. Through CFT we describe real physical systems at criticality and fixed points of the renormalization group flow. It is also central in the study of quantum gravity, thanks to the AdS/CFT correspondence. This thesis originates in the context of the N=4 supersymmetric Yang-Mills (SYM) theory, which represents the CFT side of this correspondence. This work mainly revolves around the supersymmetric Wilson line and its interpretation as a conformal defect in N=4 SYM. Particularly, we focus on excitations localized on the defect called insertions, whose correlators are described by a one-dimensional CFT.
The first main result of this work is an efficient algorithm for computing multipoint correlation functions of scalar insertions on the Wilson line, consisting of recursion relations encoding the possible interactions up to next-to-leading order at weak coupling. We show various computations of such four-, five- and six-point correlators, and discuss their properties. Moreover, we use the four-point function case to illustrate the power of the Ward identities, which are crucial in deriving a next-to-next-to-leading order result.
Thanks to these perturbative results, we find a family of differential operators annihilating our correlation functions, which we conjecture to be a multipoint extension of the Ward identities satisfied by the four-point functions. These non-perturbative constraints are shown to be fundamental ingredients in the bootstrap of a five-point function at strong coupling.
To conclude this thesis, we define an inherently one-dimensional Mellin amplitude at the non-perturbative level with appropriate subtractions and analytical continuations. The efficiency of the 1d Mellin formalism is manifest at the perturbative level. We find a closed-form expression for the Mellin transform of leading order contact interactions and use it to extract CFT data
Utility of Restricted Mean Survival Time Analysis for Heart Failure Clinical Trial Evaluation and Interpretation
No full textOBJECTIVES This study sought to demonstrate the statistical and utilitarian properties of restricted mean survival time (RMST) and restricted mean time lost (RMTL) for assessing treatments for heart failure (HF) with reduced ejection fraction.BACKGROUND Although the hazard ratio (HR) is the most commonly used measure to quantify treatment effects in HF clinical trials, HRs may be difficult to interpret and require the proportional hazards assumption to be valid. RMST and RMTL are intuitive summaries of groupwise survival that measure treatment effects without model assumptions.METHODS Patient time-to-event data were reconstructed from published landmark HF clinical trial Kaplan-Meier curves. We estimated RMST differences (Delta RMSTs) and RMTL ratios between treatment groups for primary and secondary outcomes, and compared test statistics and effect sizes with proportional hazards models. We fit Weibull estimations to extrapolate trial data to 5 years of treatment.RESULTS Using RMSTs and RMTLs yielded similar statistical conclusions as HR analysis for a compendium of 16 HF clinical trials including 48,581 patients. RMTL ratios approximated HRs for each trial, but Delta RMSTs provided absolute effect sizes unavailable with HRs. For instance, spironolactone added 2.2 months of life over 34 months of treatment, and dapagliflozin added 0.3 months of life over 24 months of treatment. When normalized to 5-years follow-up with Weibull estimation, spironolactone and dapagliflozin added 6.0 months and 1.8 months of life for patients, respectively.CONCLUSIONS Statistically, RMST and RMTL perform similarly to proportional hazards modeling but may help patients by providing clinically relevant intuitive estimates of treatment effects without prohibitive assumptions
Adherence and optimization of angiotensin converting enzyme inhibitor/angiotensin II receptors blockers and beta‐blockers in patients hospitalized for acute heart failure
No full textAbstract Aims Treatment with angiotensin converting enzyme inhibitor (ACEi)/angiotensin II receptors blockers (ARBs) and beta‐blockers is frequently suboptimal at discharge in patients hospitalized for acute heart failure (AHF). We investigated the prognostic significance of medical treatment at discharge and its changes during hospitalization. Methods and results In a retrospective analysis, we included 623 patients hospitalized for AHF with reduced left ventricular ejection fraction (<40%). The primary endpoint was all‐cause mortality and heart failure rehospitalization to Day 180 since hospital discharge. A total of 249 (42.4%) of patients received no ACEi/ARBs/BB or <50% target dose (TD) of these drugs, 249 (42.4%) had either ACEi/ARBs or BB ≥ 50% of TD, and 89 (15.2%) ACEi/ARBs and BB ≥ 50% of TD at discharge. The primary endpoint was significantly lower in patients receiving at least one drug ≥50% of TD compared with no or low‐dose treatment (ACEi/ARBs or BB ≥ 50% TD: adjusted hazard ratio (HR) 0.69, 95% confidence interval (CI) [0.49–0.98], P = 0.04; ACEi/ARBs and BB ≥ 50% TD: adjusted HR 0.54, 95% CI [0.30–0.96], P = 0.03). With regard to treatment changes from admission to discharge, therapy was decreased in 258 (44.6%) patients, stable in 194 (33.6%), and increased in 126 (21.8%). Compared with patients with stable therapy, treatment intensification was associated with a lower rate of the primary endpoint (adjusted HR 0.49, 95% CI [0.29–0.83]; P = 0.01). Conclusions In patients with AHF, prescription of ACEi/ARBs/BB ≥ 50% TD at the time of discharge, whether achieved or not through treatment intensification during the hospitalization, is associated with better post‐discharge outcomes
Prognostic significance of serum potassium in patients hospitalized for acute heart failure
No full textWe investigated the prognostic significance of serum potassium abnormalities at discharge in patients hospitalized for acute heart failure (AHF)
Smoking and Colorectal Cancer Risk, Overall and by Molecular Subtypes: A Meta-Analysis
No full textINTRODUCTION: The aim of this study was to provide the most comprehensive and up-to-date evidence on the association
between cigarette smoking and colorectal cancer (CRC) risk.
METHODS: We conducted a systematic review and meta-analysis of epidemiological studies on the association
between cigarette smoking and CRC risk published up to September 2018. We calculated relative risk
(RR) of CRC according to smoking status, intensity, duration, pack-years, and time since quitting, with a
focus on molecular subtypes of CRC.
RESULTS: The meta-analysis summarizes the evidence from 188 original studies. Compared with never smokers,
the pooled RR for CRC was 1.14 (95% confidence interval [CI] 1.10–1.18) for current smokers and
1.17 (95% CI 1.15–1.20) for former smokers. CRC risk increased linearly with smoking intensity and
duration. Former smokers who had quit smoking for more than 25 years had significantly decreased risk
of CRC compared with current smokers. Smoking was strongly associated with the risk of CRC,
characterized by high CpG island methylator phenotype (RR 1.42; 95% CI 1.20–1.67; number of
studies [n]=4), BRAF mutation (RR 1.63;95%CI 1.23–2.16; n=4), or high microsatellite instability
(RR 1.56; 95% CI 1.32–1.85; n = 8), but not characterized by KRAS (RR 1.04; 95% CI 0.90–1.20;
n = 5) or TP53 (RR 1.13; 95% CI 0.99–1.29; n = 5) mutations.
DISCUSSION: Cigarette smoking increases the risk of CRC in a dose-dependent manner with intensity and duration,
and quitting smoking reduces CRC risk. Smoking greatly increases the risk of CRC that develops through
the microsatellite instability pathway, characterized by microsatellite instability-high, CpG island
methylator phenotype positive, and BRAF mutation
