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Article ; Online: Issues with the expected information matrix of linear mixed models provided by popular statistical packages under missingness at random dropout.

Thomadakis, Christos / Pantazis, Nikos / Touloumi, Giota

2023 Volume 42, Issue 16, Page(s) 2873–2885

Abstract: Likelihood-based methods ignoring missingness at random (MAR) produce consistent estimates provided that the whole likelihood model is correct. However, the expected information matrix (EIM) depends on the missingness mechanism. It has been shown that ... ...

Abstract	Likelihood-based methods ignoring missingness at random (MAR) produce consistent estimates provided that the whole likelihood model is correct. However, the expected information matrix (EIM) depends on the missingness mechanism. It has been shown that calculating the EIM by considering the missing data pattern as fixed (naive EIM) is incorrect under MAR, but the observed information matrix (OIM) is valid under any MAR missingness mechanism. In longitudinal studies, linear mixed models (LMMs) are routinely applied, often without any reference to missingness. However, most popular statistical packages currently provide precision measures for the fixed effects by inverting only the corresponding submatrix of the OIM (naive OIM), which is effectively equivalent to the naive EIM. In this paper, we analytically derive the correct form of the EIM of LMMs under MAR dropout to compare its differences with the naive EIM, which clarifies why the naive EIM fails under MAR. The asymptotic coverage rate of the naive EIM is numerically calculated for two parameters (population slope and slope difference between two groups) under various dropout mechanisms. The naive EIM can severely underestimate the true variance, especially when the degree of MAR dropout is high. Similar trends emerge under misspecified covariance structure, where, even the full OIM may lead to incorrect inferences and sandwich/bootstrap estimators are generally required. Results from simulation studies and application to real data led to similar conclusions. In LMMs, the full OIM should be preferred to the naive EIM/OIM, though if misspecified covariance structure is suspected, robust estimators should be used.
MeSH term(s)	Humans ; Models, Statistical ; Likelihood Functions ; Linear Models ; Computer Simulation ; Longitudinal Studies
Language	English
Publishing date	2023-04-24
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	843037-8
ISSN	1097-0258 ; 0277-6715
ISSN (online)	1097-0258
ISSN	0277-6715
DOI	10.1002/sim.9754
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Article: Pet ownership and survival of European older adults.

Christopoulos, Konstantinos / Benetou, Vasiliki / Riza, Elena / Pantazis, Nikos

European journal of ageing

2022 Volume 19, Issue 4, Page(s) 1549–1560

Abstract: With pet ownership on the rise, millions of individuals are exposed to this environmental exposure. Although the subject has been largely studied, more evidence is needed to clarify the potential association of pet ownership with human health. The aim of ...

Abstract	With pet ownership on the rise, millions of individuals are exposed to this environmental exposure. Although the subject has been largely studied, more evidence is needed to clarify the potential association of pet ownership with human health. The aim of this research is to study the potential association of pet exposure (any pet, cat, dog, bird, fish) with all-cause, cardiovascular and cancer mortality of older (
Language	English
Publishing date	2022-11-04
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2190233-1
ISSN	1613-9372
ISSN	1613-9372
DOI	10.1007/s10433-022-00739-6
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Article ; Online: Effectiveness of fissure sealants on initial caries lesions (ICDAS 1-3) of permanent molars: A 4-year follow-up.

Berdouses, E D / Michalaki, M / Tsinidou, K / Vlachou, A / Pantazis, N / Oulis, C J

European journal of paediatric dentistry

2021 Volume 22, Issue 3, Page(s) 180–188

Abstract: Aim: The aim of the present prospective study was to evaluate the retention and effectiveness of two types of sealants (clear vs. opaque) on early pit and fissure occlusal non-cavitated ICDAS II #1-3, caries lesions of permanent posterior teeth of ... ...

Abstract	Aim: The aim of the present prospective study was to evaluate the retention and effectiveness of two types of sealants (clear vs. opaque) on early pit and fissure occlusal non-cavitated ICDAS II #1-3, caries lesions of permanent posterior teeth of children. Materials and methods: Study Design: 6986 pit and fissure occlusal surfaces were randomly sealed with clear or opaque sealants out of which, 5828 sealants were placed on sound and 1158 on questionable surfaces, while 3508 were clear and 3478 opaque sealants. The mean age of the sample at initial sealant placement was 9.5 (±2.9) years and the follow-up time was 12-48 months. The median (IQR, range) follow-up time was 17.9 (8.7-28.6) months. Study inclusion and exclusion criteria applied to the combined database in order to select the study sample. Teethmate™ F-1 natural and opaque sealants (Kuraray, Hattersheim am Main, Germany) were applied following the standard procedure of preparation with moisture control kept by cotton rolls handled Dri-Angles" and a 30 seconds acid-etch with 37% ortho-phosphoric acid gel was used followed by 10 sec air-water spraying washing and polymerization for 20x2 sec. Sealants were applied on sound tooth surfaces (ICDAS #0) with no visible defects or on surfaces with early caries lesions (ICDAS #1-3), randomly and interchangeably on the upper or lower Jaw. Total retention was considered when all pits and fissures were completely sealed, while partial or complete loss was scored as one code, although was registered separately. Statistics: Separate analyses were performed for each type of failure (loss of sealant or restoration). Cumulative probabilities of failure over time after sealant placement, overall or by specific characteristics, were calculated using the Kaplan-Meier method. Association between these characteristics and the hazard of failure were investigated using appropriate Cox proportional hazard models. Results: Sealed surfaces with ICDAS II # 1-3, showed 100% higher probability of having a restoration and 60% higher probability of sealant loss, with both differences being statistically significant (aHR=2.03, p=0.046), adjusted for age, sex, type of sealant and location of surface. Opaque sealants presented statistically significant (p 0.009) higher re-application rate, while fissures had 70% statistically significant (p<0.001) higher probability for resealing with time compared to pits, with gender not affecting sealant retention while the earlier a sealant was placed on children's teeth, the more probable it was to need resealing or restoration (p <0.012). Conclusions: The therapeutic use of sealants on occlusal surfaces of posterior permanent molars with early carious lesions (ICDAS II 1-3) is inferior compared to sound surfaces, showing higher sealant failures and restorations.
MeSH term(s)	Child ; Dental Caries/prevention & control ; Dental Caries Susceptibility ; Follow-Up Studies ; Humans ; Molar ; Pit and Fissure Sealants/therapeutic use ; Prospective Studies
Chemical Substances	Pit and Fissure Sealants
Language	English
Publishing date	2021-09-20
Publishing country	Italy
Document type	Journal Article
ZDB-ID	2035588-9
ISSN	2035-648X ; 1591-996X
ISSN (online)	2035-648X
ISSN	1591-996X
DOI	10.23804/ejpd.2021.22.03.2
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Article ; Online: Validation of NoSAS score for the screening of obstructive sleep apnea.

Georgakopoulou, Vasiliki Epameinondas / Pantazis, Nikos / Tsiafaki, Xanthi / Nena, Evangelia / Amfilochiou, Anastasia / Steiropoulos, Paschalis

Medicine international

2023 Volume 3, Issue 2, Page(s) 14

Abstract: Obstructive sleep apnea (OSA) is the most common sleep-related breathing disorder (SBD) characterized by the repetitive collapse of the upper airway during sleep. The aim of the present study was to validate the Neck circumference, Obesity, Snoring, Age, ...

Abstract	Obstructive sleep apnea (OSA) is the most common sleep-related breathing disorder (SBD) characterized by the repetitive collapse of the upper airway during sleep. The aim of the present study was to validate the Neck circumference, Obesity, Snoring, Age, Sex (NoSAS) score in a sample population and to compare its validity for OSA screening, with that of the Berlin questionnaire, STOP-BANG questionnaire and Epworth Sleepiness Scale (ESS). A retrospective analysis was conducted on individuals, aged 18 to 80 years, who reported symptoms indicating SBD and were examined with full-night polysomnography (PSG) at a sleep center. Demographics, anthropometric parameters, comorbidities, ESS, STOP-BANG questionnaire, Berlin questionnaire and PSG data were obtained from the recorded data of the patients. The NoSAS score was determined using the recorded data. A total of 347 participants were enrolled in the study. The NoSAS scores identified individuals with OSA, with an area under the curve (AUC) of 0.774. The NoSAS score performed significantly better than the Berlin questionnaire (AUC 0.617) and the ESS (AUC 0.642), and similarly to STOP-BANG (AUC 0.777) for OSA screening. Using a NoSAS score >7 to predict OSA, the sensitivity and specificity were 85.6 and 50%, respectively; using the STOP-BANG questionnaire, for a score >2, the values were 98.32 and 22% respectively; using the Berlin questionnaire for >1 positive categories, the values were 93.6 and 20%, and using the ESS, for a score >10, the values were 30.3% and 72%, respectively. On the whole, the present study demonstrates that the NoSAS score is a simple, efficient and easy method for screening OSA in the clinical setting. The NoSAS score performs significantly more efficiently than the Berlin questionnaire and ESS, and similarly to STOP-BANG questionnaire for OSA screening.
Language	English
Publishing date	2023-02-22
Publishing country	England
Document type	Journal Article
ISSN	2754-1304
ISSN (online)	2754-1304
DOI	10.3892/mi.2023.74
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Article ; Online: HIV continuum of care: expanding scope beyond a cross-sectional view to include time analysis: a systematic review.

Vourli, Georgia / Katsarolis, Ioannis / Pantazis, Nikos / Touloumi, Giota

BMC public health

2021 Volume 21, Issue 1, Page(s) 1699

Abstract: Introduction: The continuum of care (CoC) model has been used to describe the main pillars of HIV care. This study aims to systematically review methods and elucidate gaps in the CoC analyses, especially in terms of the timing of the progression through ...

Abstract	Introduction: The continuum of care (CoC) model has been used to describe the main pillars of HIV care. This study aims to systematically review methods and elucidate gaps in the CoC analyses, especially in terms of the timing of the progression through steps, recognized nowadays as a critical parameter for an effective response to the epidemic. Methods: A PubMed and EMBASE databases search up to December 2019 resulted in 1918 articles, of which 209 were included in this review; 84 studies presented in major HIV conferences were also included. Studies that did not provide explicit definitions, modelling studies and those reporting only on metrics for subpopulations or factors affecting a CoC stage were excluded. Included articles reported results on 1 to 6 CoC stages. Results: Percentage treated and virally suppressed was reported in 78%, percentage diagnosed and retained in care in 58%, percentage linked to care in 54% and PLHIV in 36% of the articles. Information for all stages was provided in 23 studies. Only 6 articles use novel CoC estimates: One presents a dynamic CoC based on multistate analysis techniques, two base their time-to-next-stage estimates on a risk estimation method based on the cumulative incidence function, weighted for confounding and censoring and three studies estimated the HIV infection time based on mathematical modelling. Conclusion: A limited number of studies provide elaborated time analyses of the CoC. Although time analyses lack the straightforward interpretation of the cross-sectional CoC, they provide valuable insights for the timely response to the HIV epidemic. A future goal would be to develop a model that retains the simplicity of the cross-sectional CoC but also incorporates timing between stages.
MeSH term(s)	Continuity of Patient Care ; Cross-Sectional Studies ; HIV Infections/drug therapy ; HIV Infections/epidemiology ; Humans
Language	English
Publishing date	2021-09-17
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Systematic Review
ISSN	1471-2458
ISSN (online)	1471-2458
DOI	10.1186/s12889-021-11747-z
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Article ; Online: Rejoinder to "Biased Estimation With Shared Parameter Models in the Presence of Competing Dropout Mechanisms".

Thomadakis, Christos / Meligkotsidou, Loukia / Pantazis, Nikos / Touloumi, Giota

Biometrics

2021 Volume 78, Issue 1, Page(s) 407–408

MeSH term(s)	Data Interpretation, Statistical ; Longitudinal Studies ; Models, Statistical
Language	English
Publishing date	2021-02-16
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	213543-7
ISSN	1541-0420 ; 0099-4987 ; 0006-341X
ISSN (online)	1541-0420
ISSN	0099-4987 ; 0006-341X
DOI	10.1111/biom.13437
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Article ; Online: Misspecifying the covariance structure in a linear mixed model under MAR drop-out.

Thomadakis, Christos / Meligkotsidou, Loukia / Pantazis, Nikos / Touloumi, Giota

Statistics in medicine

2020 Volume 39, Issue 23, Page(s) 3027–3041

Abstract: Misspecification of the covariance structure in a linear mixed model (LMM) can lead to biased population parameters' estimates under MAR drop-out. In our motivating example of modeling CD4 cell counts during untreated HIV infection, random intercept and ... ...

Abstract	Misspecification of the covariance structure in a linear mixed model (LMM) can lead to biased population parameters' estimates under MAR drop-out. In our motivating example of modeling CD4 cell counts during untreated HIV infection, random intercept and slope LMMs are frequently used. In this article, we evaluate the performance of LMMs with specific covariance structures, in terms of bias in the fixed effects estimates, under specific MAR drop-out mechanisms, and adopt a Bayesian model comparison criterion to discriminate between the examined approaches in real-data applications. We analytically show that using a random intercept and slope structure when the true one is more complex can lead to seriously biased estimates, with the degree of bias depending on the magnitude of the MAR drop-out. Under misspecified covariance structure, we compare in terms of induced bias the approach of adding a fractional Brownian motion (BM) process on top of random intercepts and slopes with the approach of using splines for the random effects. In general, the performance of both approaches was satisfactory, with the BM model leading to smaller bias in most cases. A simulation study is carried out to evaluate the performance of the proposed Bayesian criterion in identifying the model with the correct covariance structure. Overall, the proposed method performs better than the AIC and BIC criteria under our specific simulation setting. The models under consideration are applied to real data from the CASCADE study; the most plausible model is identified by all examined criteria.
MeSH term(s)	Bayes Theorem ; CD4 Lymphocyte Count ; HIV Infections/drug therapy ; Humans ; Linear Models ; Longitudinal Studies
Language	English
Publishing date	2020-05-25
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	843037-8
ISSN	1097-0258 ; 0277-6715
ISSN (online)	1097-0258
ISSN	0277-6715
DOI	10.1002/sim.8589
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Article ; Online: What do the changing patterns of comorbidity burden in people living with HIV mean for long-term management? Perspectives from European HIV cohorts.

d'Arminio Monforte, A / Bonnet, F / Bucher, H C / Pourcher, V / Pantazis, N / Pelchen-Matthews, A / Touloumi, G / Wolf, E

HIV medicine

2021 Volume 21 Suppl 2, Page(s) 3–16

Abstract: Undoubtedly, comorbidities complicate long-term HIV management and have significant cost implications for healthcare systems. A better understanding of these comorbidities and underlying causes would allow for a more considered and proactive approach to ... ...

Abstract	Undoubtedly, comorbidities complicate long-term HIV management and have significant cost implications for healthcare systems. A better understanding of these comorbidities and underlying causes would allow for a more considered and proactive approach to the long-term management of HIV. This review examines cross-sectional analyses of six European cohort studies (Athens Multicenter AIDS Cohort Study, Aquitaine Cohort, EuroSIDA Cohort study, French claims EGB, German InGef Cohort and the Italian Cohort of Individuals, Naïve for Antiretrovirals), which included individuals with HIV followed over a certain period of time. Based on these cohorts, we examined how comorbidities have changed over time; how they compromise HIV management; and how much of a financial burden they impart. These data also provided a framework to explore the major issues of ageing and HIV and the practical implications of managing such issues in real-life practice.
MeSH term(s)	Aging ; Anti-Retroviral Agents/therapeutic use ; Comorbidity ; Cross-Sectional Studies ; Disease Management ; Europe ; Female ; HIV Infections/drug therapy ; Health Expenditures ; Humans ; Male
Chemical Substances	Anti-Retroviral Agents
Language	English
Publishing date	2021-08-31
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2001932-4
ISSN	1468-1293 ; 1464-2662
ISSN (online)	1468-1293
ISSN	1464-2662
DOI	10.1111/hiv.12935
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Article: The impact of meteorological factors on involuntary admission in Attica, Greece.

Rizavas, Ioannis / Gournellis, Rossetos / Pantazis, Nikos / Chatzinikolaou, Fotios / Douzenis, Phoebe / Efstathiou, Vasiliki / Lagouvardos, Kostas / Douzenis, Athanasios

Psychiatrike = Psychiatriki

2023 Volume 34, Issue 4, Page(s) 289–300

Abstract: Few studies in the literature have examined the effect of meteorological factors, especially temperature, on psychiatric hospitalization and even less on their association with involuntary admission. This study aimed to investigate the potential ... ...

Abstract	Few studies in the literature have examined the effect of meteorological factors, especially temperature, on psychiatric hospitalization and even less on their association with involuntary admission. This study aimed to investigate the potential association of meteorological factors with the involuntary psychiatric hospitalization in the region of Attica, Greece. The research was conducted at the Psychiatric Hospital of Attica "Dafni". This was a retrospective time series study of 8 consecutive years of data (2010 to 2017) and included 6887 involuntarily hospitalized patients. Data on daily meteorological parameters were provided from the National Observatory of Athens. Statistical analysis was based on Poisson or negative binomial regression models with adjusted standard errors. Analyses were initially based on univariable models for each meteorological factor separately. All meteorological factors were taken into account through factor analysis and then, through cluster analysis, an objective grouping of days with similar weather type was performed. The resulting types of days were examined for their effect on the daily number of involuntary hospitalizations. Increases in maximum temperature, in average wind speed and in minimum atmospheric pressure values were associated with an increase in the average number of involuntary hospitalizations per day. Increase of the maximum temperature above 23 °C at lag 6 days before admission did not affect significantly the frequency of involuntary hospitalizations. Low temperature and average relative humidity above 60% levels had a protective effect. The predominant day type at lag 1 to 5 days before admission showed the strongest correlation with the daily number of involuntary hospitalizations. The cold season day type, with lower temperatures and a small diurnal temperature range, northerly winds of moderate speed, high atmospheric pressure and almost no precipitation, was associated with the lowest frequency of involuntary hospitalizations, whereas the warm season day type, with low daily temperature and small daily temperature range during the warm season, high values of relative humidity and daily precipitation, moderate wind speed/gust and atmospheric pressure, was associated with the highest. As climate change increases the frequency of extreme weather events, it is necessary to develop a different organizational and administrative culture of mental health services.
MeSH term(s)	Humans ; Retrospective Studies ; Greece/epidemiology ; Weather ; Meteorological Concepts ; Seasons
Language	English
Publishing date	2023-05-12
Publishing country	Greece
Document type	Journal Article
ZDB-ID	2653266-9
ISSN	1105-2333
ISSN	1105-2333
DOI	10.22365/jpsych.2023.011
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Article: HIV RNA/DNA Levels at Diagnosis Can Predict Immune Reconstitution: A Longitudinal Analysis.

Basoulis, Dimitrios / Pantazis, Nikos / Paraskevis, Dimitrios / Iliopoulos, Panos / Papadopoulou, Martha / Akinosoglou, Karolina / Hatzakis, Angelos / Daikos, George L / Psichogiou, Mina

Microorganisms

2023 Volume 11, Issue 6

Abstract: Background: HIV DNA mirrors the number of infected cells and the size of the HIV viral reservoir. The aim of this study was to evaluate the effect of pre-cART HIV DNA levels as a predictive marker of immune reconstitution and on the post-cART CD4 counts ...

Abstract	Background: HIV DNA mirrors the number of infected cells and the size of the HIV viral reservoir. The aim of this study was to evaluate the effect of pre-cART HIV DNA levels as a predictive marker of immune reconstitution and on the post-cART CD4 counts trends. Methods: HIV DNA was isolated from PBMCs and quantified by real-time PCR. Immune reconstitution was assessed up to four years. Piecewise-linear mixed models were used to describe CD4 count changes. Results: 148 people living with HIV (PLWH) were included. The highest rate of immune reconstitution was observed during the first trimester. There was a trend showing that high HIV RNA level resulted in greater increase in CD4 count, especially during the first trimester of cART (difference above vs. below median 15.1 cells/μL/month; 95% CI -1.4-31.5; Conclusions: In successfully treated PLWH, pre-cART HIV DNA and HIV RNA levels are predictors of immune reconstitution.
Language	English
Publishing date	2023-06-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720891-6
ISSN	2076-2607
ISSN	2076-2607
DOI	10.3390/microorganisms11061510
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