Does cardiometabolic risk profile differ among individuals with traumatic and non-traumatic spinal cord injury (SCI): the evidence from the multicenter SCI cohort in Switzerland (SwiSCI).

STUDY DESIGN: Longitudinal study. OBJECTIVE: To explore whether individuals with traumatic spinal cord injury (TSCI) and non-traumatic SCI (NTSCI) experience different trajectories in changes of cardiometabolic disease (CMD) factors during initial rehabilitation stay. SETTING: Multicenter Swiss Spinal Cord Injury Cohort (SwiSCI) study. METHODS: Individuals without history of cardiovascular diseases were included. CMD factors and Framingham risk score (FRS) were compared between TSCI and NTSCI. Linear mixed models' analysis was employed to explore the trajectory in CMD factors changes over rehabilitation period and a multivariate linear regression analysis was used at discharge from inpatient rehabilitation to explore factors associated with CMD risk profile in TSCI and NTSCI. We performed age and sex-stratified analyses. RESULTS: We analyzed 530 individuals with SCI (64% with TSCI and 36% NTSCI). The median age was 53 years (IQR:39-64) with 67.9% (n = 363) of the study cohort being male. The median rehabilitation duration was 4.4 months (IQR 2.4-6.4). At admission to rehabilitation, FRS (9.61 vs. 5.89) and prevalence of hypertension (33.16% vs. 13.62%), diabetes (13.68% vs. 4.06%), and obesity (79.05% vs. 66.67%) were higher in NTSCI as compared to TSCI, No difference was observed in cardiometabolic syndrome between the groups (around 40% in both groups). Overall, we observed longitudinal increases in total cholesterol, HDL-C and HDL/total cholesterol ratio, and a decrease in fasting glucose over the rehabilitation period. No differences in longitudinal changes in cardiovascular risk factors were observed between TSCI and NTSCI. CONCLUSIONS: There was no deterioration in cardiometabolic risk factors over rehabilitation period, at discharge from initial rehabilitation stay. Both TSCI and NTSCI experienced high burden of cardiometabolic syndrome components with NTSCI experiencing more disadvantageous risk profile. The effectiveness of therapeutic and lifestyle/behavioral strategies to decrease burden of cardiometabolic disease and its components in early phase should be explored in future studies.

Cross-sectional and longitudinal associations of Iron biomarkers and cardiovascular risk factors in pre- and postmenopausal women: leveraging repeated measurements to address natural variability.

BACKGROUND: The association between iron biomarkers and cardiovascular disease risk factors (CVD-RFs) remains unclear. We aimed to (1) evaluate the cross-sectional and longitudinal associations between iron biomarkers (serum ferritin, transferrin saturation (TSAT), transferrin) and CVD-RFs among women, and (2) explore if these associations were modified by menopausal status. METHOD: Cross-sectional and longitudinal analyses including 2542 and 1482 women from CoLaus cohort, respectively. Multiple linear regression and multilevel mixed models were used to analyse the associations between Iron biomarkers and CVD-RFs. Variability of outcomes and iron markers between surveys was accessed using intraclass correlation (ICC). RESULTS: After multivariable adjustment, elevated serum ferritin levels were associated with increased insulin and glucose levels, while higher transferrin levels were linked to elevated glucose, insulin and total cholesterol, and systolic and diastolic blood pressure (p < 0.05). No association was observed between CVD-RFs and TSAT (p > 0.05). Iron biomarkers demonstrated low reliability across reproductive stages but exhibited stronger associations in the perimenopausal group. In longitudinal analysis, we found association only for transferrin with lower glucose levels [ß = - 0.59, 95% CI (- 1.10, - 0.08), p = 0.02] and lower diastolic blood pressure [ß = - 7.81, 95% CI (- 15.9, - 0.56), p = 0.04]. CONCLUSION: In cross-sectional analysis, transferrin was associated with several CVD-RFs, and the associations did not change according to menopausal status. Conversely, in the longitudinal analyses, changes in transferrin were associated only with lower glucose and diastolic blood pressure levels. These differences might stem from the substantial longitudinal variation of iron biomarkers, underscoring the need for multiple iron measurements in longitudinal analyses.

Effectiveness of combined approach to recurrent respiratory papillomatosis (RRP).

PURPOSE: Recent approaches for recurrent respiratory papillomatosis including local injection of bevacizumab and HPV vaccination show promise in reducing the need for frequent surgeries. In this study we propose a new combined approach of surgery, intralesional injection of 25 mg bevacizumab and HPV vaccine that can lead to resolution of RRP. MATERIAL AND METHODS: Our study involved 5 patients treated with a combination of transoral microsurgery, intralesional injection of 25 mg bevacizumab, and HPV vaccination with Gardasil 9 between April 2020 and May 2023. Standard video laryngoscopy was performed to assess the presence of papilloma and Derkay score was used to assess the severity of disease. RESULTS: All 5 patients completed the study successfully and a complete response was achieved by all. The follow-up ranged from 8 to 45 months. The mean total Derkay score before treatment was 41 (range 25 to 52) and after the combined approach was 0 both anatomically and clinically in all patients. CONCLUSIONS: This study demonstrates the effectiveness of a combined treatment approach for RRP involving surgical intervention, intralesional injection of bevacizumab, and HPV vaccination.

The complementary roles of iron and estrogen in menopausal differences in cardiometabolic outcomes.

Biological hormonal changes are frequently cited as an explanatory factor of sex and menopause differences in cardiometabolic diseases (CMD) and its associated risk factors. However, iron metabolism which varies between sexes and among women of different reproductive stages could also play a role. Recent evidence suggest that iron may contribute to CMD risk by modulating oxidative stress pathways and inflammatory responses, offering insights into the mechanistic interplay between iron and CMD development. In the current review, we provide a critical appraisal of the existing evidence on sex and menopausal differences in CMD, discuss the pitfall of current estrogen hypothesis as sole explanation, and the emerging role of iron in CMD as complementary pathway. Prior to menopause, body iron stores are lower in females as compared to males, but the increase during and after menopause, is tandem with an increased CMD risk. Importantly, basic science experiments show that an increased iron status is related to the development of type 2 diabetes (T2D), and different cardiovascular diseases (CVD). While epidemiological studies have consistently reported associations between heme iron intake and some iron biomarkers such as ferritin and transferrin saturation with the risk of T2D, the evidence regarding their connection to CVD remains controversial. We delve into the factors contributing to this inconsistency, and the limitation of relying on observational evidence, as it does not necessarily imply causation. In conclusion, we provide recommendations for future studies on evaluating the potential role of iron in elucidating the sex and menopausal differences observed in CMD.

Development and external validation of a home-based risk predicTion modEl of natUral onseT of menopAuse -TEUTA.

OBJECTIVE: To develop and externally validate a 10-year risk prediction model of natural onset of menopause using ready-to-use predictors. DESIGN: Population-based prospective cohort study. PARTICIPANTS: Community-dwelling, premenopausal women aged 28 years and older enrolled in the Swiss (CoLaus) and Dutch (PREVEND) study. MAIN OUTCOME MEASURE: Incidence of self-reported natural menopause. MODEL DEVELOPMENT: Based on existing literature, 11 predictors were tested in this study. The CoLaus cohort was used to develop the model by applying the backward-elimination approach and Bayesian Model Averaging. Internal validation was performed by bootstrapping. External validation was performed using data from the PREVEND cohort and recalibrating the baseline survival estimate. C-statistic, calibration slopes, and expected/observed probabilities were calculated as measures of model internal and/or external performances. RESULTS: The final analysis included 750 and 1032 premenopausal women from the CoLaus and the PREVEND cohort, respectively. Among them, 445 (59%) from CoLaus and 387 (38%) from PREVEND experienced menopause over a median follow-up of 10.7 and 9 years, respectively. The final model included age, alcohol consumption, smoking status, education level, and systolic blood pressure. Upon external calibration in the PREVEND cohort, the model exhibited good discrimination, with a C-statistic of 0.888 and an expected/observed probability of 0.82. CONCLUSIONS: We present the first internally and externally validated prediction model of natural menopause onset using readily available predictors. Validation of our model to other populations is needed.

Calcium Hydroxylapatite (CaHA) and Aesthetic Outcomes: A Systematic Review of Controlled Clinical Trials.

Background: This study aimed to systematically review and summarize the available controlled clinical trials on the effectiveness of calcium hydroxylapatite (CaHA) in terms of aesthetic outcomes, skin-aging-related outcomes, and patient/investigator satisfaction. Methods: We included controlled clinical trials involving at least 10 human adults that examined the effects of CaHA on aesthetic and skin-aging-related outcomes and satisfaction. Due to the high heterogeneity among the included studies, only a qualitative analysis is provided. Results: Out of 2935 relevant references, 13 studies were included, of which 8 studies focused on facial areas and 5 on dorsum of hand. CaHA injection was associated with enhancements in global aesthetic improvement scale, whether applied in facial regions or on the dorsum of hands. The findings suggested high patients' satisfaction following CaHA when applied to facial areas. Studies highlighted improvements in hand grading scales and a reduction in facial wrinkles. Conclusions: Current evidence suggests that CaHA injections improve aesthetic results, including facial areas, such as nasolabial folds and jawline, and hands, with high levels of satisfaction. Considering the methodological limitations and heterogeneous comparisons groups, additional controlled clinical trials would contribute to a better understanding of the applications and advantages offered by CaHA.

Two cosmoses, one universe: a narrative review exploring the gut microbiome's role in the effect of urban risk factors on vascular ageing.

In the face of rising global urbanisation, understanding how the associated environment and lifestyle impact public health is a cornerstone for prevention, research, and clinical practice. Cardiovascular disease is the leading cause of morbidity and mortality worldwide, with urban risk factors contributing greatly to its burden. The current narrative review adopts an exposome approach to explore the effect of urban-associated physical-chemical factors (such as air pollution) and lifestyle on cardiovascular health and ageing. In addition, we provide new insights into how these urban-related factors alter the gut microbiome, which has been associated with an increased risk of cardiovascular disease. We focus on vascular ageing, before disease onset, to promote preventative research and practice. We also discuss how urban ecosystems and social factors may interact with these pathways and provide suggestions for future research, precision prevention and management of vascular ageing. Most importantly, future research and decision-making would benefit from adopting an exposome approach and acknowledging the diverse and boundless universe of the microbiome.

Utility of iron biomarkers in differentiating menopausal status: Findings from CoLaus and PREVEND.

AIM: To examine the association of iron biomarkers with menopausal status and assess whether these biomarkers can help differentiate menopausal status beyond age. METHODS: In this cross-sectional study we included 1679 women from the CoLaus and 2133 from the PREVEND cohorts, with CoLaus used as primary cohort and PREVEND for replication. Ferritin, transferrin, iron, and transferrin saturation (TSAT) were used to assess iron status. Hepcidin and soluble transferrin receptor were assessed only in PREVEND. Menopausal status was self-reported and defined as menopausal or non-menopausal. Logistic regressions were used to explore the association of these iron biomarkers with menopause status. Sensitivity, specificity, area under the receiver operating characteristic curves (AUC), positive and negative predictive values as well as cut-off points for the iron biomarkers were calculated. The model with the highest AUC was defined as the best. RESULTS: In the CoLaus and PREVEND cohorts, respectively, 513 (30.6 %) and 988 (46.3 %) women were postmenopausal. Ferritin (OR, 2.20; 95 % CI 1.72-2.90), transferrin (OR, 0.03; 95 % CI 0.01-0.10), and TSAT (OR, 1.28; 95 % CI 1.06-1.54) were significantly associated with menopausal status in CoLaus, with the findings replicated in PREVEND. AUC of age alone was 0.971. The best model resulted from combining age, ferritin, and transferrin, with an AUC of 0.976, and sensitivity and specificity of 87.1 % and 96.5 %, respectively. Adding transferrin and ferritin to a model with age improved menopause classification by up to 7.5 %. In PREVEND, a model with age and hepcidin outperformed a model with age, ferritin, and transferrin. CONCLUSION: Iron biomarkers were consistently associated with menopausal status in both cohorts, and modestly improved a model with age alone for differentiating menopause status. Our findings on hepcidin need replication.

Association between Total Dietary Phytochemical Intake and Cardiometabolic Health Outcomes-Results from a 10-Year Follow-Up on a Middle-Aged Cohort Population.

Dietary phytochemical intake associations with cardiovascular health and mortality remain unknown. We studied the relations between total dietary phytochemical intake and cardiovascular health outcomes in a middle-aged Swiss population. We analyzed data spanning 2009 to 2021 from a prospective cohort study in Lausanne, Switzerland, including 3721 participants (54.8% women, 57.2 ± 10.3 years) without cardiovascular disease (CVD) history. Dietary intake was assessed using a validated self-reported food frequency questionnaire. The Dietary Phytochemical Index (DPI) and the healthy Dietary Phytochemical Index (hDPI) were calculated as the total energy intake percentage obtained from phytochemical-rich food consumption. The Healthy Plant-Based Diet Index (hPBD) was estimated by scoring healthy plant foods positively and less-healthy plant foods negatively. Indices tertiles and cardiometabolic outcome associations were determined using Cox proportional hazard models. Over 30,217 person-years of follow-up, 262 CVD events, and 178 deaths occurred. Unadjusted analyses found 36%, 33%, and 32% lower CVD risk for the highest hDPI, DPI, and hPBD tertiles, respectively. After adjustment, only the second hDPI tertile showed a 30% lower CVD risk (HR 0.70, 95% CI 0.51-0.95; P for trend 0.362). No other associations emerged. In this middle-aged Swiss cohort, no associations between dietary indices reflecting a phytochemical-rich dietary pattern and incident CVD, all-cause, or CVD mortality were observed.

Changes in fasting plasma glucose and subclinical atherosclerosis: A cohort study from VIPVIZA trial.

BACKGROUND AND AIMS: Studies on the influence of fasting plasma glucose (FPG) on the development of carotid plaque (CP) and intima media thickness (CIMT) mainly focused on single FPG measures. We investigated whether changes in FPG (ΔFPG) are associated with incident CP and CIMT change (ΔCIMT) over time. METHODS: Analyses were based on information from 1896 participants from the VIPVIZA trial (Visualization of asymptomatic atherosclerotic disease for optimum cardiovascular prevention), with baseline and 3-year follow-up data on FPG, ultrasonographic CP (none or ≥1 lesion/s) and CIMT assessments. We studied the association between baseline FPG (prior to intervention) or 3-year ΔFPG (mmol/L) and incident CP (logistic regression) or ΔCIMT (linear regression). Analyses were adjusted for multiple potential confounders. RESULTS: 1896 and 873 individuals, respectively, were included in the analysis on incident CP and ΔCIMT. Participants were 60 years old at baseline and 61% and 54% were females, in the CP and CIMT analyses, respectively. Every mmol/L increase in FPG was associated with an increased odds of incident CP (odds ratio: 1.42, 95% confidence interval [CI]: 1.17, 1.73), but there was no association with ΔCIMT (mean difference: 0.002 mm, 95% CI: -0.003, 0.008) after 3 years. Baseline FPG was not associated with incident CP nor ΔCIMT progression. CONCLUSIONS: In middle-aged individuals with low to moderate risk for cardiovascular diseases, 3-year ΔFPG was positively associated with the risk of incident CP, but not with ΔCIMT. Single measures of FPG may not be sufficient in estimating cardiovascular risk among individuals with low to moderate risk.

Eating out intensity, ultra-processed foods and BMI among Albanian youth.

OBJECTIVE: Ultra-processed foods (UPF) and eating out of home (OH) are changing nutrition, particularly among youth in constrained settings. We aimed to assess the role of eating OH intensity on the associations of UPF and unprocessed or minimally processed foods (UMPF) with BMI among Albanian youth. DESIGN: Cross-sectional. SETTING: Albania, a south-eastern European country. PARTICIPANTS: 281 youth, predominantly females. METHODS: UPF and UMPF were defined based on NOVA, while eating OH intensity based on energy percentage from OH foods. Multivariable models tested associations of UPF and UMPF with BMI stratified by eating OH intensity, controlled for relevant covariates including diet quality, portion size and costs. RESULTS: The respondents age ranged between 18 and 23 years with a female predominance (87·5 %). Mean energy from UPF and UMPF was 846 (sd: 573·0) and 802·9 (422·5) kcals, respectively. Among substantial at home eaters UPF intake was not associated (ß = −0·07, 95 % CI (−0·13, 0·267)) with BMI; however, UMPF negatively associated with BMI (ß = −0·24, 95 % CI (−0·43, −0·06)). Among those defined as substantial OH eaters, UPF (ß = 0·24, 95 % CI (0·08, 0·40)) and UMPF (ß = 0·18, 95 % CI (0·04, 0·33)) were positively associated with BMI. CONCLUSIONS: Our findings provide evidence for the hypothesis that eating OH plays an important role in the association of UPF and UMPF with BMI in youth. While causality cannot be established due to cross-sectional design, to the best of our knowledge, we provide the first assessment of UPF and UMPF intake in a south-eastern European setting, while highlighting the need for establishing and integrating youth nutrition into national nutritional surveillance systems for key dietary risk factors in Albania.

Policies on children and schools during the SARS-CoV-2 pandemic in Western Europe.

During the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), mitigation policies for children have been a topic of considerable uncertainty and debate. Although some children have co-morbidities which increase their risk for severe coronavirus disease (COVID-19), and complications such as multisystem inflammatory syndrome and long COVID, most children only get mild COVID-19. On the other hand, consistent evidence shows that mass mitigation measures had enormous adverse impacts on children. A central question can thus be posed: What amount of mitigation should children bear, in response to a disease that is disproportionally affecting older people? In this review, we analyze the distinct child versus adult epidemiology, policies, mitigation trade-offs and outcomes in children in Western Europe. The highly heterogenous European policies applied to children compared to adults did not lead to significant measurable differences in outcomes. Remarkably, the relative epidemiological importance of transmission from school-age children to other age groups remains uncertain, with current evidence suggesting that schools often follow, rather than lead, community transmission. Important learning points for future pandemics are summarized.

Association between dietary phytochemical index, cardiometabolic risk factors and metabolic syndrome in Switzerland. The CoLaus study.

BACKGROUND AND AIMS: Plant-based diets are associated with reduced cardiometabolic risk factors (CRFs) and lower risk of metabolic syndrome (MetS), probably via phytochemicals acting synergistically. However, dietary phytochemical content estimation is challenging; therefore, the dietary phytochemical index (DPI) was proposed as a practical way to assess total dietary phytochemical content from phytochemical-rich foods (PRFs). We evaluated the association between DPI with CRFs and MetS and its components. METHODS AND RESULTS: Cross-sectional analysis of 2009-2012 data of Colaus cohort study (Lausanne, Switzerland), including 3879 participants (mean age 57.6 ± 10.4 years, 53.5% women). Dietary intake was assessed via a validated food frequency questionnaire. DPI was calculated as the total energy intake percentage obtained from PRFs consumption and assessed as quartiles. Associations were determined using multivariable linear and logistic regression for CRFs and MetS, respectively. Median DPI value was 25.5 (interquartile range: 17.7-34.6). After multivariable-adjusted analyses, significant inverse associations were observed between the last two highest DPI quartiles and waist circumference (WC), body mass index (BMI), insulin, leptin, and hs-CRP. No significant associations were observed for MetS or its components except for central obesity, as subjects in the highest DPI quartile had lower odds (OR: 0.78; 95% CI: 0.62, 0.97) than those in lowest quartile. CONCLUSION: A diet high in PRFs assessed via DPI is associated with lower WC, BMI, insulin, leptin, hs-CRP values, and lower odds of central obesity, indicating a potential protective effect of phytochemical intake on these CRFs and highlighting the importance of high PRFs intake in promoting cardiometabolic health.

Changes in Iron Status Biomarkers with Advancing Age According to Sex and Menopause: A Population-Based Study.

BACKGROUND: The risk of chronic diseases increases markedly with age and after menopause. An increase in bodily iron following menopause could contribute to this phenomenon of increased risk of chronic diseases. We aimed to investigate how various iron biomarkers change with advancing age, according to sex and menopausal status. METHODS: We enrolled community-dwelling individuals with available information on ferritin, transferrin, iron, hepcidin, and soluble transferrin receptor levels from the Prevention of Renal and Vascular Endstage Disease study. The association of the iron biomarkers with age, sex, and menopausal status was investigated with linear regression models. RESULTS: Mean (SD) age of the 5222 individuals (2680 women [51.3%], among whom 907 [33.8%] were premenopausal, 529 [19.7%] perimenopausal, and 785 [29.3%] postmenopausal), was 53.4 (12.0) years. Iron biomarkers showed a constant increase in women throughout their life course, in some cases at older ages surpassing values in men who, in turn, showed consistently higher levels of iron status compared to women in most age categories. Ferritin, hepcidin, and transferrin saturation levels were 3.03, 2.92, and 1.08-fold (all p < 0.001) higher in postmenopausal women compared to premenopausal. CONCLUSIONS: We found that iron accumulates differently depending on sex, age, and menopausal status. An increased iron status was identified in women, especially during and after menopause.

Effect of aerobic exercise, slow deep breathing and mindfulness meditation on cortisol and glucose levels in women with type 2 diabetes mellitus: a randomized controlled trial.

Background: Aerobic exercise combined with breathing exercise can be an integral part of diabetes mellitus treatment. This single-center, randomized, parallel-group study investigated the effect of the combination of aerobic exercise with slow deep breathing and mindfulness meditation on the glucose and cortisol levels of women with type 2 diabetes mellitus (T2DM). Materials and Methods: Fifty-eight middle-aged women with T2DM (mean age: 45.67 ± 2.92 years) were randomly assigned to either the aerobic training group (AT: n = 29; mean age [46.1 ± 2.7 years]) or the aerobic exercise combined with slow deep breathing and mindfulness meditation (AT + DMM: n = 29; mean age [45.24 ± 3.14 years]). Aerobic exercise was performed at 60%-75% of the maximum heart rate. The women in each group were asked to perform the training three times weekly over a 6-week period. The duration of each session was 40 min for the AT group and 60 min for the AT + DMM group. The two groups were asked to perform aerobic exercise at 60%-75% of the maximum heart rate. Their fasting blood glucose (FBG) and serum cortisol levels were measured at the baseline and after the 6 weeks. Results: Compared with the AT group, the group undertaking 6 weeks of aerobic training combined with slow, deep breathing exercises and mindfulness meditation showed significantly lower levels of FBG (p = 0.001) and cortisol levels (p = 0.01) than the AT group. Conclusion: The addition of slow deep breathing and mindfulness meditation to aerobic exercise can better control the glucose and cortisol levels of women with T2DM and thereby improve their outcomes and decrease their cardiometabolic risk.

Impact of type 2 diabetes on life expectancy and role of kidney disease among inpatients with heart failure in Switzerland: an ambispective cohort study.

BACKGROUND: Type 2 diabetes (T2D) is expected to worsen the prognosis of inpatients with heart failure (HF) but the evidence from observational studies is inconsistent. We aimed to compare mortality outcomes and life expectancy among inpatients with HF with or without T2D and explored whether chronic kidney disease (CKD) influenced these associations. METHODS: We collected hospital and civil registry records of consecutive inpatients from a tertiary hospital in Switzerland with a diagnosis of HF from the year 2015 to 2019. We evaluated the association of T2D with mortality risk using Cox regression and adjusted for confounders. RESULTS: Our final cohort consisted of 10,532 patients with HF of whom 27% had T2D. The median age (interquartile range [IQR]) was 75 [68 to 82] and 78 [68 to 86] for the diabetes and non-diabetes groups, respectively. Over a median follow-up [IQR] of 4.5 years [3.3 to 5.6], 5,347 (51%) of patients died. T2D patients had higher risk of all-cause mortality (hazard ratio [HR] 1.21, 95% confidence interval [CI] 1.14 to 1.29). Compared to control (i.e. no T2D nor CKD), average life expectancy (95% CI) among T2D patients, CKD, or both was shorter by 5.4 months (95% CI 1.1 to 9.7), 9.0 months (95% CI 8.4 to 9.6), or 14.8 months (95% CI 12.4 to 17.2), respectively. No difference by sex or ejection fraction category was observed. CONCLUSIONS: T2D is associated with a significantly higher risk of all-cause mortality and shorter life expectancy compared to those without among middle-aged and elderly inpatients with HF; presence of CKD may further increase these risks.

A 7-Step Guideline for Qualitative Synthesis and Meta-Analysis of Observational Studies in Health Sciences.

Objectives: To provide a step-by-step, easy-to-understand, practical guide for systematic review and meta-analysis of observational studies. Methods: A multidisciplinary team of researchers with extensive experience in observational studies and systematic review and meta-analysis was established. Previous guidelines in evidence synthesis were considered. Results: There is inherent variability in observational study design, population, and analysis, making evidence synthesis challenging. We provided a framework and discussed basic meta-analysis concepts to assist reviewers in making informed decisions. We also explained several statistical tools for dealing with heterogeneity, probing for bias, and interpreting findings. Finally, we briefly discussed issues and caveats for translating results into clinical and public health recommendations. Our guideline complements "A 24-step guide on how to design, conduct, and successfully publish a systematic review and meta-analysis in medical research" and addresses peculiarities for observational studies previously unexplored. Conclusion: We provided 7 steps to synthesize evidence from observational studies. We encourage medical and public health practitioners who answer important questions to systematically integrate evidence from observational studies and contribute evidence-based decision-making in health sciences.

Skin regeneration-related mechanisms of Calcium Hydroxylapatite (CaHA): a systematic review.

Introduction: Calcium Hydroxylapatite (CaHA) is a common dermal filler used in aesthetic medicine for volumizing and contouring. Understanding mechanisms of actions of CaHA can help improve our understanding of its clinical applications. Methods: We performed a systematic review to summarize the skin-regeneration related mechanisms of CaHA. Five bibliographic databases were searched for English-language publications that evaluated CaHA in skin regeneration outcomes including neocollagenesis, cell proliferation and growth factors, angiogenesis, vascular dynamic and inflammatory markers, among others. Methodological rigor of included studies was assessed. Results: Of 2,935 identified citations, 12 studies were included for final analysis. Collagen production was reported by nine studies, cell proliferation by four, elastic fibers and/or elastin by four, and three studies on angiogenesis, while limited studies were available on the other outcomes. Six were clinical/observational studies. Only seven studies had a control group. Overall, studies showed CaHA resulted in increased cell proliferation, increased collagen production and angiogenesis, as well as in higher elastic fiber and elastin formation. Limited and inconclusive evidence was available on the other mechanisms. The majority of the studies had methodological limitations. Discussion: Current evidence is limited but indicates several mechanisms through which CaHA could lead to skin regeneration, volume enhancement, and contouring. Systematic review registration: https://doi.org/10.17605/OSF.IO/WY49V.

Prognostic Role of Polyvascular Involvement in Patients with Symptomatic Peripheral Artery Disease.

Background: Statin therapy is recommended for patients with peripheral artery disease (PAD). However, PAD patients with polyvascular (PV) extent remain threatened by an increased residual cardiovascular (CV) risk. Purpose: To investigate the association of prescribed statin therapy and mortality in PAD patients with or without PV extent. Methods: A single-center retrospective longitudinal observational study originating from a consecutive registry with 1380 symptomatic PAD patients over a mean observational time of 60 ± 32 months. The association of atherosclerotic extent and statin use (PAD, plus one additional region (CAD or CeVD, [+1 V]), +2 vascular regions (+CAD and CeVD [+2 V]) with the risk of all-cause mortality was evaluated using Cox proportional hazard models adjusted for potential confounding factors. Results: The mean age of the study's participants was 72.0 ± 11.7 years, with 36% being female. PAD patients with PV extent [+1 V] and [+2 V] were older and suffered from diabetes, hypertension, or dyslipidemia more often; they, too, had more severely impaired kidney function (all p < 0.0001) compared to patients with PAD only. PAD patients with PV [+1 V] and [+2 V] received better statin medication and reached the recommended LDL-C target compared to PAD-only patients (p < 0.001). Despite better statin treatment, the rate of all-cause mortality was higher in PV patients than in PAD-only patients (PAD only: 13%; [+1 V]: 22%; [+2 V]: 35%; p < 0.0001). Conclusion: PV patients receive better statin therapy than PAD-only patients but nevertheless still have higher mortality rates. Future studies are needed to explore whether more aggressive LDL-lowering treatment for PAD patients may be translated into better prognosis.

Early menopause and cardiovascular risk factors: a cross-sectional and longitudinal study.

OBJECTIVE: The aim of the study is to evaluate the cross-sectional and longitudinal association of early natural menopause with changes in cardiovascular risk factors (CVRFs). METHODS: Postmenopausal women from the Swiss CoLaus study, reporting age at natural menopause (ANM) and having CVRFs measurements (blood lipids, blood pressure, glucose, homeostatic model assessment for insulin resistance [HOMA-IR], and inflammatory markers) at baseline (2003-2006) and first follow-up (2009-2012) were eligible for analysis. Age at natural menopause was analyzed as a continuous variable and in categories (ANM <45 and ≥45 y old). Linear regression analysis and linear mixed models were used to assess whether ANM is associated cross-sectionally and longitudinally with changes in CVRFs. Models were adjusted for demographic characteristics, lifestyle-related factors, time since menopause, medication, and clinical conditions. RESULTS: We analyzed 981 postmenopausal women. The cross-sectional analysis showed that women with ANM younger than 45 years had lower diastolic blood pressure (ß = -3.76 mm Hg; 95% confidence interval [CI] = -5.86 to -1.65) compared with women whose ANM was 45 years or older. In the longitudinal analysis, ANM younger than 45 years was associated with changes in log insulin (ß = 0.26; 95% CI = 0.08 to 0.45) and log homeostatic model assessment for insulin resistance levels (ß = 0.28; 95% CI = 0.08 to 0.48). No associations were found between ANM and other CVRFs. CONCLUSIONS: Early menopause may be associated with changes in glucose metabolism, while it may have little to no impact on other CVRFs. Larger longitudinal studies are needed to replicate our findings.