Does fluoride exposure affect thyroid function? A systematic review and dose-response meta-analysis.

INTRODUCTION: Fluoride exposure may have various adverse health effects, including affecting thyroid function and disease risk, but the pattern of such relation is still uncertain. METHODS: We systematically searched human studies assessing the relation between fluoride exposure and thyroid function and disease. We compared the highest versus the lowest fluoride category across these studies, and we performed a one-stage dose-response meta-analysis for aggregated data to explore the shape of the association. RESULTS: Most retrieved studies (27 of which with a cross-sectional design) were conducted in Asia and in children, assessing fluoride exposure through its concentrations in drinking water, urine, serum, or dietary intake. Twenty-four studies reported data on thyroid function by measuring thyroid-related hormones in blood (mainly thyroid-stimulating-hormone - TSH), 9 reported data on thyroid disease, and 4 on thyroid volume. By comparing the highest versus the lowest fluoride categories, overall mean TSH difference was 1.05 µIU/mL. Dose-response curve showed no change in TSH concentrations in the lowest water fluoride exposure range, while the hormone levels started to linearly increase around 2.5 mg/L, also dependending on the risk of bias of the included studies. The association between biomarkers of fluoride exposure and TSH was also positive, with little evidence of a threshold. Evidence for an association between fluoride exposure and blood concentrations of thyroid hormones was less evident, though there was an indication of inverse association with triiodothyronine. For thyroid disease, the few available studies suggested a positive association with goiter and with hypothyroidism in both children and adults. CONCLUSIONS: Overall, exposure to high-fluoride drinking water appears to non-linearly affect thyroid function and increase TSH release in children, starting above a threshold of exposure, and to increase the risk of some thyroid diseases.

Fluoride exposure and cognitive neurodevelopment: Systematic review and dose-response meta-analysis.

Many uncertainties still surround the possible harmful effect of fluoride exposure on cognitive neurodevelopment in children. The aim of this systematic review and meta-analysis was to characterize this relation through a dose-response approach, by comparing the intelligence quotient (IQ) scores in the highest versus the lowest fluoride exposure category with a random-effects model, within a one-stage dose-response meta-analysis based on a cubic spline random-effects model. Out of 1996 potentially relevant literature records, 33 studies were eligible for this review, 30 of which were also suitable for meta-analysis. The summary mean difference of IQ score, comparing highest versus lowest fluoride categories and considering all types of exposure, was -4.68 (95% confidence interval-CI -6.45; -2.92), with a value of -5.60 (95% CI -7.76; -3.44) for drinking water fluoride and -3.84 (95% CI -7.93; 0.24) for urinary fluoride. Dose-response analysis showed a substantially linear IQ decrease for increasing water fluoride above 1 mg/L, with -3.05 (95% CI -4.06; -2.04) IQ points per 1 mg/L up to 2 mg/L, becoming steeper above such level. A weaker and substantially linear decrease of -2.15 (95% CI -4.48; 0.18) IQ points with increasing urinary fluoride emerged above 0.28 mg/L (approximately reflecting a water fluoride content of 0.7 mg/L). The inverse association between fluoride exposure and IQ was particularly strong in the studies at high risk of bias, while no adverse effect emerged in the only study judged at low risk of bias. Overall, most studies suggested an adverse effect of fluoride exposure on children's IQ, starting at low levels of exposure. However, a major role of residual confounding could not be ruled out, thus indicating the need of additional prospective studies at low risk of bias to conclusively assess the relation between fluoride exposure and cognitive neurodevelopment.

Atrial Fibrillation and the Risk of Early-Onset Dementia: A Systematic Review and Meta-Analysis.

Background Recent studies have identified an increased risk of dementia in patients with atrial fibrillation (AF). However, both AF and dementia usually manifest late in life. Few studies have investigated this association in adults with early-onset dementia. The aim of this study was to investigate the relationship between AF and early-onset dementia. Methods and Results We searched the PubMed/MEDLINE, Embase, and Scopus databases through April 15, 2022, for studies reporting on the association between AF and dementia in adults aged <70 years, without language restrictions. Two reviewers independently performed the study selection, assessed the risk of bias, and extracted the study data. We performed a meta-analysis of early-onset dementia risk according to occurrence of AF using a random-effects model. We retrieved and screened 1006 potentially eligible studies. We examined the full text of 33 studies and selected the 6 studies that met our inclusion criteria. The pooled analysis of their results showed an increased risk of developing dementia in individuals with AF, with a summary relative risk of 1.50 (95% CI, 1.00-2.26) in patients aged <70 years, and 1.06 (95% CI, 0.55-2.06) in those aged <65 years. Conclusions In this systematic review and meta-analysis, AF was a risk factor for dementia in adults aged <70 years, with an indication of a slight and statistically imprecise excess risk already at ages <65 years. Further research is needed to assess which characteristics of the arrhythmia and which mechanisms play a role in this relationship.

An assessment of case-fatality and infection-fatality rates of first and second COVID-19 waves in Italy.

BACKGROUND AND AIM: The exact COVID-19 severity is still not well defined and it is hotly debated due to the a few methodological issues such as the uncertainties about the spread of the SARS-CoV-2 infection. METHODS: We investigated COVID-19 case-fatality rate and infection-fatality rate in 2020 in Italy, a country severely affected by the pandemic, basing our assessment on publicly available data, and calculating such measures during the first and second waves. RESULTS: We found that province-specific crude case-fatality rate in the first wave (February-July 2020) had a median value of 12.0%. Data about infection-fatality rate was more difficult to compute, due to large underestimation of SARS-CoV-2 infection during the first wave when asymptomatic individuals were very rarely tested. However, when using as a reference population-based seroprevalence data for anti-SARS-CoV-2 antibodies collected in May-July 2020, we computed an infection-fatality rate of 2.2%. During the second wave (Sep-Dec 2020), when SARS-CoV-2 testing was greatly increased and extended to many asymptomatic individuals, we could only compute a 'hybrid' case/infection-fatality rate with a value of 2.2%, similar to the infection-fatality rate of the first wave. CONCLUSIONS: Overall, this study allowed to assess the COVID-19 case- and infection-fatality rates in Italy before of variant spread and vaccine availability, confirming their high values compared with other airborne infections like influenza. Our findings for Italy were similar to those characterizing other Western European countries.