Use of GLP1 receptor agonists in early pregnancy and reproductive safety: a multicentre, observational, prospective cohort study based on the databases of six Teratology Information Services.

OBJECTIVES: Glucagon-like peptide 1 receptor agonists (GLP1-RA) are indicated for the treatment of type 2 diabetes and more recently for weight loss. The aim of this study was to assess the risks associated with GLP1-RA exposure during early pregnancy. DESIGN: This multicentre, observational prospective cohort study compared pregnancy outcomes in women exposed to GLP1-RA in early pregnancy either for diabetes or obesity treatment with those in two reference groups: (1) women with diabetes exposed to at least one non-GLP1-RA antidiabetic drug during the first trimester and (2) a reference group of overweight/obese women without diabetes, between 2009 and 2022. SETTING: Data were collected from the databases of six Teratology Information Services. PARTICIPANTS: This study included 168 pregnancies of women exposed to GLP1-RA during the first trimester, alongside a reference group of 156 pregnancies of women with diabetes and 163 pregnancies of overweight/obese women. RESULTS: Exposure to GLP1-RA in the first trimester was not associated with a risk of major birth defects when compared with diabetes (2.6% vs 2.3%; adjusted OR, 0.98 (95% CI, 0.16 to 5.82)) or to overweight/obese (2.6% vs 3.9%; adjusted OR 0.54 (0.11 to 2.75)). For the GLP1-RA group, cumulative incidence for live births, pregnancy losses and pregnancy terminations was 59%, 23% and 18%, respectively. In the diabetes reference group, corresponding estimates were 69%, 26% and 6%, while in the overweight/obese reference group, they were 63%, 29% and 8%, respectively. Cox proportional cause-specific hazard models indicated no increased risk of pregnancy losses in the GLP1-RA versus the diabetes and the overweight/obese reference groups, in both crude and adjusted analyses. CONCLUSIONS: This study offers reassurance in cases of inadvertent exposure to GLP1-RA during the first trimester of pregnancy. Due to the limited sample size, larger studies are required to validate these findings.

Reference values for plasma and urine trace elements in a Swiss population-based cohort.

OBJECTIVES: Trace elements (TEs) are ubiquitous. TE concentrations vary among individuals and countries, depending on factors such as living area, workplaces and diet. Deficit or excessive TEs concentrations have consequences on the proper functioning of human organism so their biomonitoring is important. The aim of this project was to provide reference values for TEs concentrations in the Swiss population. METHODS: The 1,078 participants to the SKiPOGH cohort included in this study were aged 18-90 years. Their 24-h urine and/or plasma samples were analyzed by inductively coupled plasma mass spectrometry (ICP-MS) to determine 24 TEs concentrations: Ag, Al, As, Be, Bi, Cd, Co, Cr, Cu, Hg, I, Li, Mn, Mo, Ni, Pb, Pd, Pt, Sb, Se, Sn, Tl, V and Zn. Statistical tests were performed to evaluate the influence of covariates (sex, age, BMI, smoking) on these results. Reference intervals for the Swiss adult population were also defined. RESULTS: TEs concentrations were obtained for respectively 994 and 903 persons in plasma and urine matrices. It was possible to define percentiles of interest (P50 and P95) for almost all the TEs. Differences in TEs distribution between men and women were noticed in both matrices; age was also a cofactor. CONCLUSIONS: This first Swiss biomonitoring of a large TEs-panel offers reference values in plasma and in urine for the Swiss population. The results obtained in this study were generally in line with clinical recommendations and comparable to levels reported in other population-based surveys.

HOPE survival probability cutoff for ECLS rewarming in hypothermic cardiac arrest.

The HOPE score (https://www.hypothermiascore.org) is a validated instrument for estimating the survival probability of patients in hypothermic cardiac arrest with ECLS rewarming. It is based on six patient characteristics: sex, age, mechanism of hypothermia, duration of cardiopulmonary resuscitation, serum potassium and temperature. The HOPE score provides a reliable estimate of survival probability that can be used to decide whether to rewarm a patient. In the initial publication of the HOPE score, a cutoff of 10% was proposed, below which a patient would not be rewarmed. This choice was tentative and subject to debate. In this paper, we examine the implications of this choice on the proportions of false positives (i.e., rewarmed patient who ends up dying) and false negatives (i.e., non-rewarmed patients who would have survived if rewarmed), and we provide approximate formulas to obtain upper bounds for these proportions as a function of the cutoff chosen. In particular, the choice of a 10% cutoff will result in a proportion of FP of less than 40% and a proportion of FN of less than 0.5% in many practical situations.

Stress Markers, Executive Functioning, and Resilience Among Early Adolescents With Complex Congenital Heart Disease.

Importance: Infants with complex congenital heart disease (cCHD) may experience prolonged and severe stress when undergoing open heart surgery. However, little is known about long-term stress and its role in neurodevelopmental impairments in this population. Objective: To investigate potential differences between early adolescents aged 10 to 15 years with cCHD and healthy controls in physiological stress markers by hair analysis, executive function (EF) performance, and resilience. Design, Setting, and Participants: This single-center, population-based case-control study was conducted at the University Children's Hospital Zurich, Switzerland. Patients with different types of cCHD who underwent cardiopulmonary bypass surgery during the first year of life and who did not have a genetic disorder were included in a prospective cohort study between 2004 and 2012. A total of 178 patients were eligible for assessment at ages 10 to 15 years. A control group of healthy term-born individuals was cross-sectionally recruited. Data assessment was between 2019 and 2021. Statistical analysis was performed from January to April 2023. Exposure: Patients with cCHD who underwent infant open heart surgery. Main Outcomes and Measures: Physiological stress markers were quantified by summing cortisol and cortisone concentrations measured with liquid chromatography with tandem mass spectrometry in a 3-centimeter hair strand. EFs were assessed with a neuropsychological test battery to produce an age-adjusted EF summary score. Resilience was assessed with a standardized self-report questionnaire. Results: The study included 100 patients with cCHD and 104 controls between 10 and 15 years of age (mean [SD] age, 13.3 [1.3] years); 110 (53.9%) were male and 94 (46.1%) were female. When adjusting for age, sex, and parental education, patients had significantly higher sums of hair cortisol and cortisone concentrations (ß, 0.28 [95% CI, 0.12 to 0.43]; P < .001) and lower EF scores (ß, -0.36 [95% CI, -0.49 to -0.23]; P < .001) than controls. There was no group difference in self-reported resilience (ß, -0.04 [95% CI, -0.23 to 0.12]; P = .63). A significant interaction effect between stress markers and EFs was found, indicating a stronger negative association in patients than controls (ß, -0.65 [95% CI, -1.15 to -0.15]; P = .01). The contrast effects were not significant in patients (ß, -0.21 [95% CI, -0.43 to -0.00]; P = .06) and controls (ß, 0.09 [95% CI, -0.11 to 0.30]; P = .38). Conclusions and Relevance: This case-control study provides evidence for altered physiological stress levels in adolescents with cCHD and an association with poorer EF. These results suggest that future studies are needed to better understand the neurobiological mechanisms and timing of alterations in the stress system and its role in neurodevelopment.

Evaluating the cost of simplicity in score building: An example from alcohol research.

Building a score from a questionnaire to predict a binary gold standard is a common research question in psychology and health sciences. When building this score, researchers may have to choose between statistical performance and simplicity. A practical question is to what extent it is worth sacrificing the former to improve the latter. We investigated this research question using real data, in which the aim was to predict an alcohol use disorder (AUD) diagnosis from 20 self-reported binary questions in young Swiss men (n = 233, mean age = 26). We compared the statistical performance using the area under the ROC curve (AUC) of (a) a "refined score" obtained by logistic regression and several simplified versions of it ("simple scores"): with (b) 3, (c) 2, and (d) 1 digit(s), and (e) a "sum score" that did not allow negative coefficients. We used four estimation methods: (a) maximum likelihood, (b) backward selection, (c) LASSO, and (d) ridge penalty. We also used bootstrap procedures to correct for optimism. Simple scores, especially sum scores, performed almost identically or even slightly better than the refined score (respective ranges of corrected AUCs for refined and sum scores: 0.828-0.848, 0.835-0.850), with the best performance been achieved by LASSO. Our example data demonstrated that simplifying a score to predict a binary outcome does not necessarily imply a major loss in statistical performance, while it may improve its implementation, interpretation, and acceptability. Our study thus provides further empirical evidence of the potential benefits of using sum scores in psychology and health sciences.

Organizational interventions and occupational burnout: a meta-analysis with focus on exhaustion.

PURPOSE: To assess whether organizational interventions are effective to prevent or reduce exhaustion, the core dimension of occupational burnout. METHODS: We searched in PubMed, EMBASE, PsycINFO, and Cochrane Library databases randomized and non-randomized controlled trials conducted among active workers and reporting the outcome as exhaustion score. We calculated the effect sizes using the pre-test-post-test control group design's estimate. We used the random effects model in meta-analysis and Cochrane collaboration's tool for interventions to assess the risk of bias. Overall quality of evidence was appraised using the GRADE. RESULTS: From the 2425 identified records, we assessed 228 full texts for eligibility and included 11 original articles describing 13 studies, 11 on organizational interventions, and 2 on combined inventions. The interventions were participatory (n = 9), focused on workload (n = 2), or on work schedule (n = 2). The overall effect size was - 0.30 ((95% CI = - 0.42; - 0.18), I2 = 62.28%), corresponding to a small reduction in exhaustion with a very low quality of evidence. Combined interventions had a larger effect (- 0.54 (95% CI = - 0.76; - 0.32)) than organizational interventions. When split by type of intervention, both participatory interventions and interventions focused on workload had a benefic effect of exhaustion reduction, with an estimated effect size of - 0.34 (95% CI = - 0.47; - 0.20) and - 0.44 (95% CI = - 0.68, - 0.20), respectively. CONCLUSION: Interventions at combined level in workplaces could be helpful in preventing exhaustion. However, the evidence is still limited, due to a high heterogeneity between studies, bias potential, and small number of eligible studies. This calls for further research, using workload interventions at organizational level, especially in sectors with high risk of job stress and exhaustion.

Two complementary approaches to estimate an excess of mortality: The case of Switzerland 2022.

OBJECTIVE: During the COVID-19 pandemic, excess mortality has generally been estimated comparing overall mortality in a given year with either past mortality levels or past mortality trends, with different results. Our objective was to illustrate and compare the two approaches using mortality data for Switzerland in 2022, the third year of the COVID-19 pandemic. METHODS: Using data from the Swiss Federal Statistical Office, standardized mortality rates and life expectancies in 2022 were compared with those of the last pre-pandemic year 2019 (first approach), as well as with those that would be expected if the pre-pandemic downward trend in mortality had continued during the pandemic (second approach). The pre-pandemic trend was estimated via a Poisson log-linear model on age-specific mortality over the period 2010-19. RESULTS: Using the first approach, we estimated in Switzerland in 2022 an excess mortality of 2.6% (95%CI: 1.0%-4.1%) for men and 2.5% (95%CI: 1.0%-4.0%) for women, while the excess mortality rose to 8.4% (95%CI: 6.9%-9.9%) for men and 6.0% (95%CI: 4.6%-7.5%) for women using the second approach. Age classes over 80 were the main responsible for the excess mortality in 2022 for both sexes using the first approach, although a significant excess mortality was also found in most age classes above 30 using the second approach. Life expectancy in 2022 has been reduced by 2.7 months for men and 2.4 months for women according to the first approach, whereas it was reduced by respectively 8.8 and 6.0 months according to the second approach. CONCLUSIONS: The excess mortality and loss of life expectancy in Switzerland in 2022 are around three times greater if the pre-pandemic trend is taken into account than if we simply compare 2022 with 2019. These two different approaches, one being more speculative and the other more factual, can also be applied simultaneously and provide complementary results. In Switzerland, such a dual-approach strategy has shown that the pre-pandemic downward trend in mortality is currently halted, while pre-pandemic mortality levels have largely been recovered by 2022.

Hypothermic cardiac arrest patients admitted to hospital who were not rewarmed with extracorporeal life support: A retrospective study.

Aims: Our goal was to study hypothermic cardiac arrest (CA) patients who were not rewarmed by Extracorporeal Life Support (ECLS) but were admitted to a hospital equipped for it. The focus was on whether the decisions of non-rewarming, meaning termination of resuscitation, were compliant with international guidelines based on serum potassium at hospital admission. Methods: We retrospectively included all hypothermic CA who were not rewarmed, from three Swiss centers between 1st January 2000 and 2nd May 2021. Data were extracted from medical charts and assembled into two groups for analysis according to serum potassium. We identified the criteria used to terminate resuscitation. We also retrospectively calculated the HOPE score, a multivariable tool predicting the survival probability in hypothermic CA undergoing ECLS rewarming. Results: Thirty-eight victims were included in the study. The decision of non-rewarming was compliant with international guidelines for 12 (33%) patients. Among the 36 patients for whom the serum potassium was measured at hospital admission, 24 (67%) had a value that - alone - would have indicated ECLS. For 13 of these 24 (54%) patients, the HOPE score was <10%, meaning that ECLS was not indicated. The HOPE estimation of the survival probabilities, when used with a 10% threshold, supported 23 (68%) of the non-rewarming decisions made by the clinicians. Conclusions: This study showed a low adherence to international guidelines for hypothermic CA patients. In contrast, most of these non-rewarming decisions made by clinicians would have been compliant with current guidelines based on the HOPE score.

Association of plasma zinc levels with anti-SARS-CoV-2 IgG and IgA seropositivity in the general population: A case-control study.

INTRODUCTION: Some micronutrients have key roles in immune defence, including mucosal defence mechanisms and immunoglobulin production. Altered micronutrient status has been linked with COVID-19 infection and disease severity. We assessed the associations of selected circulating micronutrients with anti-SARS-CoV-2 IgG and IgA seropositivity in the Swiss community using early pandemic data. METHODS: Case-control study comparing the first PCR-confirmed COVID-19 symptomatic cases in the Vaud Canton (May to June 2020, n = 199) and controls (random population sample, n = 447), seronegative for IgG and IgA. The replication analysis included seropositive (n = 134) and seronegative (n = 152) close contacts from confirmed COVID-19 cases. Anti-SARS-CoV-2 IgG and IgA levels against the native trimeric spike protein were measured using the Luminex immunoassay. We measured plasma Zn, Se and Cu concentrations by ICP-MS, and 25-hydroxy-vitamin D3 (25(OH)D3) with LC-MS/MS and explored associations using multiple logistic regression. RESULTS: The 932 participants (54.1% women) were aged 48.6 ± 20.2 years (±SD), BMI 25.0 ± 4.7 kg/m2 with median C-Reactive Protein 1 mg/l. In logistic regressions, log2(Zn) plasma levels were negatively associated with IgG seropositivity (OR [95% CI]: 0.196 [0.0831; 0.465], P < 0.001; replication analyses: 0.294 [0.0893; 0.968], P < 0.05). Results were similar for IgA. We found no association of Cu, Se, and 25(OH)D3 with anti-SARS-CoV-2 IgG or IgA seropositivity. CONCLUSION: Low plasma Zn levels were associated with higher anti-SARS-CoV-2 IgG and IgA seropositivity in a Swiss population when the initial viral variant was circulating, and no vaccination available. These results suggest that adequate Zn status may play an important role in protecting the general population against SARS-CoV-2 infection. REGISTRY: CORONA IMMUNITAS:: ISRCTN18181860.

Comparison of statistical models to predict age-standardized cancer incidence in Switzerland.

This study compares the performance of statistical methods for predicting age-standardized cancer incidence, including Poisson generalized linear models, age-period-cohort (APC) and Bayesian age-period-cohort (BAPC) models, autoregressive integrated moving average (ARIMA) time series, and simple linear models. The methods are evaluated via leave-future-out cross-validation, and performance is assessed using the normalized root mean square error, interval score, and coverage of prediction intervals. Methods were applied to cancer incidence from the three Swiss cancer registries of Geneva, Neuchatel, and Vaud combined, considering the five most frequent cancer sites: breast, colorectal, lung, prostate, and skin melanoma and bringing all other sites together in a final group. Best overall performance was achieved by ARIMA models, followed by linear regression models. Prediction methods based on model selection using the Akaike information criterion resulted in overfitting. The widely used APC and BAPC models were found to be suboptimal for prediction, particularly in the case of a trend reversal in incidence, as it was observed for prostate cancer. In general, we do not recommend predicting cancer incidence for periods far into the future but rather updating predictions regularly.

Secular trends in motor performance in Swiss children and adolescents from 1983 to 2018.

Introduction: Environmental changes, including globalization, urbanization, social and cultural changes in society, and exposure to modern digital technology undoubtedly have an impact on children's activity and lifestyle behavior. In fact, marked reductions in children's physical activity levels have been reported over the years and sedentary behavior has increased around the world. The question arises whether these environmental changes had an impact on general motor performance in children and adolescents. The study aimed to investigate secular trends of motor performance in Swiss children and adolescents, aged between 7 and 18 years, over a period of 35 years from 1983 to 2018. Methods: Longitudinal data on the five motor components of the Zurich Neuromotor Assessment (ZNA) - pure motor (PM), fine motor (FM), dynamic balance (DB), static balance (SB), and contralateral associated movements (CAM) - were pooled with cross-sectional data on PM and FM from eight ZNA studies between 1983 and 2018. Regression models were used to estimate the effect of the year of birth on motor performance and body mass index (BMI) measurements. Models were adjusted for age, sex, and socioeconomic status. Results: The secular trend estimates in standard deviation scores (SDS) per 10 years were - 0.06 [-0.33; 0.22, 95% Confidence Interval] for PM, -0.11 [-0.41; 0.20] for FM, -0.38 [-0.66; -0.09] for DB (-0.42 when controlled for BMI), -0.21 [-0.47; 0.06] for SB, and - 0.01 [-0.32; 0.31] for CAM. The mean change in BMI data was positive with 0.30 SDS [0.07; 0.53] over 10 years. Discussion: Despite substantial societal changes since the 1980s, motor performance has remained relatively stable across generations. No secular trend was found in FM, PM, SB, and CAM over a period of 35 years. A secular trend in DB was present independent of the secular trend in body mass index.

Reproductive Safety of Trazodone After Maternal Exposure in Early Pregnancy: A Comparative ENTIS Cohort Study.

PURPOSE/BACKGROUND: Trazodone is indicated for the treatment of major depressive disorder, but more frequently prescribed off-label at lower doses for insomnia in women of childbearing age. The aim of this study was to assess the risks linked to trazodone exposure during pregnancy for which limited safety data are available. METHODS/PROCEDURES: This multicenter, observational prospective cohort study compared pregnancy outcomes in women exposed to trazodone in early pregnancy against those in a reference group of women exposed to a selective serotonin reuptake inhibitors (SSRIs) between 1996 and 2021. FINDINGS/RESULTS: The sample included 221 trazodone and 869 SSRI-exposed pregnancies. Exposure to trazodone in the first trimester was not associated with a significant difference in the risk of major congenital anomalies (trazodone [1/169, 0.6%]; SSRI [19/730, 2.6%]; adjusted odds ratio, 0.2; 95% confidence interval, 0.03-1.77). The cumulative incidences of live birth were 61% and 73% in the trazodone and reference group, respectively (25% vs 18% for pregnancy loss and 14% vs 10% for pregnancy termination). Trazodone exposure was not associated with a significantly increased risk of pregnancy termination and pregnancy loss. The rate of small for gestational age infants did not differ between the groups. IMPLICATIONS/CONCLUSIONS: This study did not reveal a significant difference in the risk of major congenital anomalies after first trimester exposure to trazodone, compared with SSRI exposure. Although this study is the largest so far, these results call for confirmation through further studies.

On the impacts of the COVID-19 pandemic on mortality: Lost years or lost days?

Objective: To quantify the (direct and indirect) impacts of the COVID-19 pandemic on mortality for actual populations of persons living in 12 European countries in 2020. Method: Based on demographic and mortality data, as well as remaining life expectancies found in the Human Mortality Database, we calculated a "population life loss" in 2020 for men and women living in Belgium, Croatia, Denmark, Finland, Hungary, Lithuania, Luxembourg, Norway, Portugal, Spain, Sweden, and Switzerland. This quantity was obtained by dividing the total number of years lost in 2020 (estimated from all-cause mortality data and attributed directly or indirectly to COVID-19) by the size of the population. Results: A significant population life loss was found in 8 countries in 2020, with men losing an average of 8.7, 5.0, 4.4, 4.0, 3.7, 3.4, 3.1, and 2.7 days in Lithuania, Spain, Belgium, Hungary, Croatia, Portugal, Switzerland, and Sweden, respectively. For women, this loss was 5.5, 4.3, 3.7, 3.7, 3.1, 2.4, 1.6, and 1.4 days, respectively. No significant losses were found in Finland, Luxembourg, Denmark and Norway. Life loss was highly dependent on age, reaching 40 days at the age of 90 in some countries, while only a few significant losses occurred under the age of 60. Even in countries with a significant population life loss in 2020, it was on average about 30 times lower than in 1918, at the time of the Spanish flu. Conclusions: Our results based on the concept of population life loss were consistent with those based on the classical concept of life expectancy, confirming the significant impact of COVID-19 on mortality in 8 European countries in 2020. However, while life expectancy losses were typically counted in months or years, population life losses could be counted in days, a potentially useful piece of information from a public health perspective.

Holistic Assessment of Factors Associated with Exhaustion, the Main Symptom of Burnout: A Meta-Analysis of Longitudinal Studies.

BACKGROUND: This meta-analysis summarized longitudinal findings pertaining to exhaustion's predictors. In so doing, our aim was ultimately to identify target factors for the prevention of burnout. METHODS: We searched for studies that (a) examined predictors of exhaustion longitudinally and (b) reported correlation coefficients as an effect estimate. We conducted our literature search in three databases: MEDLINE, PsycINFO, and Embase. We focused on studies published between January 1990 and November 2020. Predictors were grouped into families, subfamilies, and subgroups. A meta-analysis of z-transformed correlation coefficients (rho) was performed. The results were scrutinized in relation to studies' follow-up length. RESULTS: We included 65 studies assessing 242 predictors of different types captured across different occupations. Our findings highlighted mostly weak associations (rho < 0.30). For six predictors-Job control, Job resources, Interactions at work, Communication and leadership, Job attitudes, and Work-family interface-longer length of follow-up involved weaker associations with exhaustion. The quality of the evidence available was generally low. CONCLUSIONS: The evidence available does not point to clear target factors for preventing burnout. The decrease in associations as the follow-up length increases may suggest a relatively short latency period, followed by recovery. Higher-quality cohorts should be conducted to better understand the etiology and course of burnout.

Integration of Speed and Quality in Measuring Graphomotor Skills: The Zurich Graphomotor Test.

IMPORTANCE: In educational settings, children are under pressure to finish their work successfully within required time frames. Existing tools for assessing graphomotor skills measure either quality or speed of performance, and the speed-accuracy trade-off (SAT) in such tools has never been investigated. OBJECTIVE: We aimed to evaluate a newly developed tool for measuring graphomotor skills, the Zurich Graphomotor Test (ZGT), that assesses both speed and quality of performance. We also explored whether graphomotor tests are affected by the SAT and, if so, the effects it has on graphomotor test results. DESIGN: Cross-sectional study. SETTING: Educational institutions in Switzerland. PARTICIPANTS: Children, adolescents, and young adults (N = 547) ages 4-22 yr (50.3% female). OUTCOMES AND MEASURES: Graphomotor performance was measured with the ZGT and the Developmental Test of Visual Perception, Second Edition (DVTP-2). Standard deviation scores were used to quantify performance. We combined ZGT speed and quality measurements into a performance score adjusted for age and sex. RESULTS: ZGT results indicated a marked developmental trend in graphomotor performance; older children were faster than younger children. Girls showed higher overall performance than boys. The pattern of making more mistakes when being faster and making fewer mistakes when being slower was observed for both graphomotor tests, regardless of time pressure, indicating that the SAT affected the children's scores on both tests. CONCLUSIONS AND RELEVANCE: SAT is influential in graphomotor assessment. The ZGT captures this trade-off by combining accuracy and speed measurements into one score that provides a realistic assessment of graphomotor skills. What This Article Adds: The newly developed ZGT provides occupational therapy practitioners with more precise information on graphomotor skills in children, adolescents, and young adults than currently available tools.

Mortality in Switzerland in 2021.

OBJECTIVE: To analyze mortality trends in Switzerland in 2021, the second year of the COVID-19 pandemic. METHODS: Using data from the Swiss Federal Statistical Office, we compared mortality in Switzerland in 2021 with that of previous years in terms of standardized weekly deaths, standardized (annual) mortality rates (overall and stratified by age and sex) and life expectancy. The latter is a well-known demographic concept defining the average lifespan of a hypothetical cohort living and dying according to the mortality rates of a given year. RESULTS: After a favorable first half of the year and a fairly standard second half in terms of mortality in Switzerland, the year 2021 ended with a wave of deaths of moderate intensity related to the 5th wave of COVID-19. Overall, and after a notable increase in mortality in 2020 (+9.2%, 95%CI: +8.0%; +10.3%, compared to 2019, and +5.1%, 95%CI: +4.3%; +6.0%, compared to 2015-19), the pre-pandemic mortality level was approximately recovered in 2021 (+0.8%, 95%CI: -0.3%; +0.8%, compared to 2019, and -2.9%, 95%CI: -3.7%; -2.2%, compared to 2015-19). Life expectancy, after declining by 10 months for men and 6 months for women in 2020 (i.e. men would have lost 10 months and women 6 months had they lived their entire lives with COVID-19 as it was in 2020), returned in 2021 to 2019 levels for women (85.6 years) and regained 2018 levels for men (81.6 years, still -0.3 years from 2019). The age group responsible for the small remaining loss for men was the 50-70 age group, which had similar mortality in 2020 and 2021. CONCLUSIONS: The second year of the COVID-19 pandemic in Switzerland was characterized by an approximate return to pre-pandemic mortality levels, with a faster recovery for women than for men with respect to 2020.

Outcome prediction for hypothermic patients in cardiac arrest.

The 5A score predicts in-hospital mortality of patients suffering from accidental hypothermia, including those not in cardiac arrest. The HOPE score was specifically developed to predict survival for the subgroup of hypothermic patients in cardiac considered for extracorporeal life support rewarming. The C-statistic in the external validation study of the HOPE score was 0.825 (95% CI: 0.753-0.897), confirming its excellent discrimination. In addition, its good calibration allows for a reliable interpretation of the corresponding survival probability after rewarming. The HOPE score should be used for predicting outcome and selecting hypothermic patients in cardiac arrest for rewarming.

Association of growth with neurodevelopment in extremely low gestational age infants: a population-based analysis.

To assess the association between postnatal growth and neurodevelopment at the age of 2 years in extremely low gestational age newborns (ELGAN, < 28 weeks' gestation). Retrospective population-based cohort study including all live born ELGAN in 2006-2012 in Switzerland. Growth parameters (weight, length, head circumference, body mass index) were assessed at birth, at hospital discharge home, and 2-year follow-up (FU2). Unadjusted and adjusted regression models assessed associations between growth (birth to hospital discharge and birth to FU2) and neurodevelopment at FU2. A total of 1244 infants (mean GA 26.5 ± 1.0 weeks, birth weight 853 ± 189 g) survived to hospital discharge and were included in the analyses. FU2 was documented for 1049 (84.3%) infants. The mean (± SD) mental and a psychomotor development index at 2FU were 88.9 (± 18.0) and 86.9 (± 17.7), respectively. Moderate or severe neurodevelopmental impairment was documented in 23.2% of patients. Changes of z-scores between birth and discharge and between birth and FU2 for weight were - 1.06 (± 0.85) and - 0.140 (± 1.15), for length - 1.36 (± 1.34), and - 0.40 (± 1.33), for head circumference - 0.61 (± 1.04) and - 0.76 (± 1.32) as well as for BMI 0.22 (± 3.36) and - 0.006 (± 1.45). Unadjusted and adjusted analyses showed that none of the four growth parameters was significantly associated with any of the three outcome parameters of neurodevelopment. This was consistent for both time intervals. CONCLUSION: In the present population-based cohort of ELGAN, neither growth between birth and hospital discharge nor between birth and FU2 were significantly associated with neurodevelopment at age of 2 years. WHAT IS KNOWN: • Studies assessing the association between growth and neurodevelopment in extremely low gestational age newborns (28 weeks' gestation) show conflicting results. WHAT IS NEW: • Neither growth between birth and hospital discharge nor between birth and corrected age of 2 years were significantly associated with neurodevelopment at age of 2 years. • The role of postnatal growth as a predictor of neurodevelopmental outcome during infancy might be smaller than previously assumed.

Clinical efficacy of resin-based direct posterior restorations and glass-ionomer restorations - An updated meta-analysis of clinical outcome parameters.

OBJECTIVE: The present review is an update of a systematic review that has been published in 2012. Meanwhile, many new clinical trials on resin composites had been published. New materials such as bulk fill resin composites and new glass-ionomer (GIC) based materials had been introduced. The focus of this review was to evaluate the longevity in relation to the material class and adhesive class, while adjusting for a possible study bias effect. MATERIAL AND METHODS: The database PUBMED/SCOPUS were searched for clinical trials on posterior resin composites. The inclusion criteria were: (1) studies published between 2000 and 2019, (2) prospective clinical trial with at least 2 years of observation; (2) minimal number of restorations at last recall = 20; (3) report on drop-out rate; (4) report of operative technique and used materials; (5) utilisation of Ryge, modified Ryge or FDI evaluation criteria. The bias of each study was assessed by two independent reviewers using Cochrane Collaboration's tool for assessing risk of bias in randomised trials. For the statistical analysis, linear mixed models fitted on the individual data recorded along time have been used with random effects to account for study, patients and experiment effects. P-values smaller than 0.05 were considered significant. RESULTS: Of the 423 clinical trials, 62 studies (including 110 experiments) met the inclusion criteria. Material class was divided according to the composite filler in microhybrid (39 experiments/2807 restorations), nanohybrid (24 experiments/1254 restorations), and hybrid (22 experiments/1255 restorations). So-called bulk fill materials were treated as a separate category (9 experiments/506 restorations) as were the GIC (11 experiments/2121 restorations) and the compomer materials (5 experiments/238 restorations). Only one study (1.6%) had low risk of bias, 42 (67.7%) were assessed to have unclear risk of bias and 19 (30.6%) had a high risk of bias. In 52.3% of the studies Class II and Class I restorations had been placed. After 10 years, the survival rate for resin composite restorations dropped to about 85-90% with no significant difference between hybrid, microhybrid and nao-hybrid resin materials. The main reasons for restoration replacement were bulk fractures and wear, which accounted for a about 70% of replacements. Caries at the restorative margins accounted for about 20% of the replacements, and retention loss, inacceptable colour match or marginal integrity, endodontic treatment or cusp fracture for about 10% of the replacements of the resin composite restorations. For compomer and GIC restorations the mean overall survival rate was about 80% after 6 years. For GIC, the main reasons for failure were substantial loss of anatomical contour along with loss of proximal contacts and retention loss. Mainly fractures reduced the longevity of compomers restorations. Also, there was no statistically significant difference between hybrid, micro-hybrid, nano-hybrid and bulk fill resin composites with regard to colour match, surface texture, material fractures, and anatomical form. CONCLUSIONS: Posterior resin composite restorations that were placed with the enamel etch technique showed the best overall performance; the longevity was not significantly influenced by the filler type or viscosity of resin composite material. With regard to colour match, surface texture and anatomical form, nanohybrid resins were not significantly superior to hybrid or microhybrid resin composites. Compomer and GIC restorations demonstrated considerable shortcomings and had a significant shorter longevity.