Renal Hyperfiltration as a New Mechanism of Smoking-Related Mortality.

INTRODUCTION: Renal hyperfiltration (RHF), an established risk factor for mortality, is prevalent among tobacco smokers. The aim of this study was to assess the mediating role of RHF in the association between smoking and mortality. AIMS AND METHODS: Data of this study were retrieved from the cohort of the Kuopio Ischemic Heart Disease Risk Factor Study (KIHD), including 2064 males from Finland. Study participants were followed over a 35-year period. Using classic and counterfactual mediation analysis approaches, we estimated the mediative effect of RHF in the association between smoking and each of the following outcomes: All-cause mortality, cardiovascular disease (CVD) mortality, and non-CVD mortality. RESULTS: The risk of all-cause mortality in smokers was twice that in nonsmokers (hazard ratio [HR], 2.06; 95% confidence interval [CI]: 1.84 to 2.31). Under the counterfactual framework the direct effect of smoking on all-cause mortality, controlled for RHF, corresponded to an HR of 2.00 (95% CI: 1.78 to 2.30). Of the effect of smoking on mortality, 5% (p-value = .016) was mediated by RHF. This finding concerned particularly non-CVD mortality. CONCLUSIONS: RHF mediated the effect of smoking on non-CVD and all-cause mortality, but not on CVD mortality. The generalizability of our study results is however limited by its focus on a Finnish male cohort, underscoring the need for further investigation into RHF's broader implications across diverse populations. IMPLICATIONS: This study elucidates the complex interplay between smoking, renal hyperfiltration (RHF), and mortality, offering novel insights into the mediating role of RHF. Our findings demonstrate that RHF significantly mediates the relationship between smoking and non-cardiovascular disease (non-CVD), but not CVD mortality. This distinction underscores the multifaceted role of RHF beyond its established association with cardiovascular events. By highlighting the specific pathways through which RHF mediates some of the smoking-attributed mortality, this research contributes to our understanding of the mechanisms linking smoking to mortality.

An observational post-authorization safety study (PASS) of naloxegol drug utilization in four European countries.

PURPOSE: Naloxegol has been shown to be an efficient alternative to treat opioid-induced constipation (OIC). This study aimed at describing the characteristics of naloxegol users and assessing patterns of naloxegol use and associated factors. METHODS: This drug utilization cohort study used observational registry data on patients newly prescribed naloxegol in four European countries. Patient characteristics and patterns of naloxegol use and associated factors were described. RESULTS: A total of 17 254 naloxegol users were identified across the countries. Their median age was 56-71 years, and each country had a majority of women (ranging 57.5%-62.9%). Multiple comorbidities, including cancer, were common. Natural opium alkaloids and osmotically acting laxatives (excluding saline) were the most frequently used opioids and laxatives. Overall prior use of opioids ranged from 91.9% to 99.6% and overall prior use of laxatives ranged from 69.9% to 92.4%. Up to 77.7% had prior use of medications with interaction potential, and up to 44.5% used them concurrently with naloxegol. Naloxegol was discontinued by 55.1%-90.9% of users, typically during the first 30 days. Approximately 10%-30% switched to or augmented the treatment with another constipation medication or restarted naloxegol after discontinuation. Augmentation with another constipation medication was relatively common, suggesting that naloxegol was used for multifactorial constipation. CONCLUSION: The present study reflects real-world clinical use of naloxegol, including in vulnerable patient groups. Some naloxegol users lacked laxative or regular opioid use within six months before index date or used naloxegol concomitantly with medications presenting an interaction potential.

Synergic Interaction of Vitamin D Deficiency and Renal Hyperfiltration on Mortality in Middle-Aged Men.

OBJECTIVE: Vitamin D deficiency and renal hyperfiltration (RHF) are prevalent conditions both recently linked with mortality. The two conditions are interrelated, but their combined effect and interaction on mortality have not been studied. The objective of this study was to assess the combined effect and interaction of vitamin D deficiency and RHF on all-cause, cardiovascular (CV), and non-CV mortality in nondiabetic middle-aged men. METHODS: Middle-aged nondiabetic men (n = 1,959) were followed up for a median of 28 years. With adjustment for age, body mass index (BMI), smoking, BMI-smoking interaction, healthy Nordic diet (HND), alcohol consumption, and hypertension, we fitted Cox proportional hazard models to estimate the hazard ratios (HRs) of all-cause-, CV-, and non-CV mortality with respect to vitamin D deficiency and RHF. We evaluated the effect of interaction between RHF and vitamin D on the outcomes on the additive and multiplicative scales. RESULTS: Vitamin D deficiency and RHF, both individually and combined, are associated with a high hazard of mortality. The HRs for all-cause- and non-CV mortality were highest among men with coexisting vitamin D deficiency and RHF (HR, 3.02; 95% CI, 1.90 to 4.79; and HR, 3.63; 95% CI, 2.07 to 6.36; respectively). We found a synergic interaction between vitamin D deficiency and RHF in respect to all-cause (RERI, 1.47; 95% CI, 0.03 to 2.9) and non-CV mortality (RERI, 2.09; 95% CI, 0.02 to 4.16) of type positive multiplicative, positive additive. CONCLUSION: The synergic interaction of vitamin D deficiency and RHF on mortality might have importance in the global burden of the two conditions. Further studies investigating cause-specific mortality are needed to highlight underlying mechanisms by which vitamin D deficiency and RHF interact.

Negative interaction of fatty liver and hypertension on cardiovascular mortality in non-diabetic men: 34 years of follow-up.

BACKGROUND AND OBJECTIVES: Fatty liver disease (FLD) and hypertension are separately associated with cardiovascular (CV) mortality. The two conditions are related in multiple ways. This work aimed to study the joint effect and interaction of FLD and hypertension in respect to overall and CV mortality. METHODS: The population-based cohort, Kuopio Ischaemic Disease Risk Factor Study, followed 1569 middle-aged non-diabetic Finnish men for 34 years. Considering adjustment for age, body mass index, smoking and alcohol consumption, separate and combined effects of FLD and hypertension and their interaction at the multiplicative and additive scales regarding all-cause and CV death were assessed using Cox proportional hazards models. RESULTS: FLD and hypertension coexisted in 8.54% of the men (n = 134). FLD and hypertension associated, independently and combined, with an increased hazard of all-cause and CV deaths. Non-CV mortality associated with FLD, but not with hypertension. We found a negative interaction between FLD and hypertension regarding the hazard of all-cause (relative excess risk due to interaction (RERI), -0.97; 95% confidence interval (CI), -1.65 to -0.28) and CV mortality (RERI, -1.74; 95% CI, -2.98 to -0.5). The interaction was also found on a multiplicative scale. CONCLUSIONS: We found evidence of a negative interaction between FLD and hypertension in respect to CV mortality. We thus recommend adjusting for FLD or hypertension when studying the effect of the other condition on mortality or CV diseases in middle-aged men.

The association between renal hyperfiltration and mortality is not mediated by diabetes mellitus.

BACKGROUND: Renal hyperfiltration (RHF), recently established as a risk factor for mortality, is linked to current and subsequent diabetes mellitus (DM). DM could be seen as a mediator in the pathway between RHF and mortality. However, the mediating role of DM in the relationship between RHF and mortality is unclear. METHODS AND RESULTS: Based on a cohort of 2682 Finnish men from the Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) followed-up for 35 years, we evaluated the association between RHF and mortality, with DM as a mediator, following two methods: a classic mediation analysis approach, using Cox regression, and a counterfactual framework for mediation analysis, using g-computation, Cox regression, and logistic regression. RHF is associated with an increased risk of mortality. This association was not mediated by DM. Under a counterfactual framework and on a hazard ratio scale, RHF association with mortality had a total effect of 1.54 (95% confidence interval, 1.26-1.98) and a controlled direct effect of 1.66 (1.34-2.16). CONCLUSION: An association between RHF and mortality risk, independent of DM, was established. RHF should be considered, managed, and followed-up as a mortality-associated condition, regardless of the status of DM. We suggest clinicians to consider including RHF screening in routine clinical care, especially diabetic care.

In-depth Correlation Analysis of SARS-CoV-2 Effective Reproduction Number and Mobility Patterns: Three Groups of Countries.

OBJECTIVES: Many governments have imposed-and are still imposing-mobility restrictions to contain the coronavirus disease 2019 (COVID-19) pandemic. However, there is no consensus on whether policy-induced reductions of human mobility effectively reduce the effective reproduction number (Rt) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several studies based on country-restricted data reported conflicting trends in the change of the SARS-CoV-2 Rt following mobility restrictions. The objective of this study was to examine, at the global scale, the existence of regional specificities in the correlations between Rt and human mobility. METHODS: We computed the Rt of SARS-CoV-2 using data on worldwide infection cases reported by the Johns Hopkins University, and analyzed the correlation between Rt and mobility indicators from the Google COVID-19 Community Mobility Reports in 125 countries, as well as states/regions within the United States, using the Pearson correlation test, linear modeling, and quadratic modeling. RESULTS: The correlation analysis identified countries where Rt negatively correlated with residential mobility, as expected by policymakers, but also countries where Rt positively correlated with residential mobility and countries with more complex correlation patterns. The correlations between Rt and residential mobility were non-linear in many countries, indicating an optimal level above which increasing residential mobility is counterproductive. CONCLUSIONS: Our results indicate that, in order to effectively reduce viral circulation, mobility restriction measures must be tailored by region, considering local cultural determinants and social behaviors. We believe that our results have the potential to guide differential refinement of mobility restriction policies at a country/regional resolution.

Ramadan favors first blood donation, but not frequent donation: Results of 10,145 blood donors from Algeria.

CONTEXT: Frequent blood donors contribute to an important share of blood donations in many countries. In Algeria, frequent donation and its determinants, notably the place of the month of Ramadan, which plays an important role in blood donation in Muslim countries, have not been studied. METHODS: This was a retrospective cohort study of n = 10145 Algerians who donated blood to the blood transfusion post (BTP) of Boufarik between January 2, 2008, and December 31, 2019. Donors were assessed at each donation for general clinical information, demographic information, and dates and times of donation. Donor return, defined as two or more donations to Boufarik BTP, and frequent donation, defined as three or more blood donations to Boufarik BTP, were the outcomes of interest and were analyzed using groups comparison and logistic and Cox regression analyses. RESULTS: 2.2% of donors were frequent donors and donated 9.6% of all donated blood. The volume of donated blood during Ramadan was twice the monthly volume during the rest of the year, but donation in Ramadan was associated with lower odds of return (odds ratio [OR]: 0.54, 95% confidence interval [CI]: 0.40-0.71) and frequent donation (OR: 0.41, 95% CI: 0.24-0.73). Women were underrepresented (10.9%), but they were more likely to be frequent donors (male vs. female OR: 0.55, 95% CI: 0.31-0.96; hazard ratio: 0.64, 95% CI: 0.41-0.98). CONCLUSIONS: Reducing the gender gap and promoting return could significantly improve the volume of blood donations in Algeria.

Mortality-based definition of renal hyperfiltration in middle-aged men: a 35-year cohort from Finland.

BACKGROUND: While the impact of low glomerular filtration rate (eGFR) on various outcomes has been extensively studied, the other adverse occurrence, renal hyperfiltration (RHF), remains understudied, poorly defined, and, therefore, its impact on mortality unestablished. METHODS: Using a population-based subcohort from the Kuopio Ischaemic Disease Risk Factor Study restricted to non-diabetic Finnish men aged 54 or 55 years, we followed up n = 1179 study participants for up to 35 years. We evaluated the hazard of all-cause mortality associated to RHF at different cutoff points defining eGFR. Based on models' accuracy we suggested an optimal eGFR cutoff point for the definition of RHF. We divided the RHF category to three subgroups and evaluated them in terms of baseline characteristics and mortality hazard. RESULTS: The eGFR value of 97 mL/min/1.73 m2 corresponded to the models with the highest accuracy. Overall RHF associated with an increased risk of mortality (hazard ratio [HR] 1.42; 95% confidence interval [CI] 1.21 to 1.67). Moderate RHF associated with a decreased HR of mortality when compared to mild (0.64; 95% CI 0.46 to 0.9) or to extreme RHF (0.61; 95% CI 0.43 to 0.85), suggesting a rather U-shaped relationship between RHF's eGFR values and mortality hazard. CONCLUSION: The burden of increased eGFR within what is still considered normal eGFR category was highly underestimated. RHF's eGFR values had a U-shaped association with the risk of overall mortality. A more uniform consensual definition of RHF is needed, as higher to normal eGFR values that are not without consequences.

Infodemic and the fear of monkeypox: call for action.

Monkeypox (MPX) was declared a public health emergency of international concern by the World Health Organization (WHO), as of July 23rd, 2022. Fake news spread on social media has already surfaced and contributed to worsening of this concerning situation, making it difficult for the health care experts' voices to be heard. Therefore, we recommend some solutions to overcome this situation, including raising public awareness and preventing stigma through sharing engagement with civil society organizations, and better cooperation between policymakers, the medical community, and social media platforms regarding providing accurate official news about MPX. WHO-one health approach should be established and prioritized.

Prior Tonsillectomy and the Risk of Breast Cancer in Females: A Systematic Review and Meta-analysis.

Background: Exposure to recurrent infections in childhood was linked to an increased risk of cancer in adulthood. There is also evidence that a history of tonsillectomy, a procedure often performed in children with recurrent infections, is linked to an increased risk of leukemia and Hodgkin lymphoma. Tonsillectomy could be directly associated with cancer risk, or it could be a proxy for another risk factor such as recurrent infections and chronic inflammation. Nevertheless, the role of recurrent childhood infections and tonsillectomy on the one hand, and the risk of breast cancer (BC) in adulthood remain understudied. Our study aims to verify whether a history of tonsillectomy increases the risk of BC in women. Methods: A systematic review was performed using PubMed, Google Scholar, Scopus, Embase, and Web of Science databases from inception to January 25, 2022, to identify the studies which assessed the association between the history of tonsillectomy and BC in females. Odds ratio (OR) was calculated using the random/fixed-effects models to synthesize the associations between tonsillectomy and BC risk based on heterogeneity. Results: Eight studies included 2252 patients with breast cancer of which 1151 underwent tonsillectomy and 5314 controls of which 1725 had their tonsils removed. Patients with a history of tonsillectomy showed a higher subsequent risk of developing BC (OR, 1.24; 95% CI: 1.11-1.39) as compared to patients without a history of tonsillectomy. Influence analyses showed that no single study had a significant effect on the overall estimate or the heterogeneity. Conclusions: Our study revealed that a history of tonsillectomy is associated with an increased risk of breast cancer. These findings underscore the need for frequent follow-ups and screening of tonsillectomy patients to assess for the risk of BC.

Renal hyperfiltration, fatty liver index, and the hazards of all-cause and cardiovascular mortality in Finnish men.

OBJECTIVES: Renal hyperfiltration (RHF) and fatty liver are separately associated with adverse health outcomes. In this study, we investigated the mortality hazard of coexisting RHF and fatty liver. METHODS: Middle-aged men from the Kuopio Ischaemic Disease Risk Factor Study (n=1,552) were followed up for a median of 29 years. Associations among RHF, fatty liver index (FLI) score, age, body mass index, smoking status, alcohol consumption, and hypertension status were assessed using logistic regression. Cox proportional hazards models were used to determine the hazard ratios (HRs) for all-cause and cardiovascular disease (CVD) mortality with respect to RHF and fatty liver. RESULTS: Of the men, 5% had RHF (n=73), whereas a majority had fatty liver (n=848). RHF was associated specifically with smoking, and fatty liver was associated specifically with overweight. The all-cause mortality hazard was highest (HR, 1.96; 95% confidence interval [CI], 1.27 to 3.01) among men with RHF and fatty liver (n=33). Among men with RHF but normal FLI (n=40), the HR of all-cause mortality was 1.67 (95% CI, 1.15 to 2.42). Among men with fatty liver but a normal estimated glomerular filtration rate (n=527), the HR of all-cause mortality was 1.35 (95% CI, 1.09 to 1.66). CVD mortality hazard was associated with RHF, but not fatty liver. We detected no interaction effect between RHF and fatty liver for all-cause (synergy index, 0.74; 95% CI, 0.21 to 2.67) or CVD (synergy index, 0.94; 95% CI, 0.34 to 2.60) mortality. CONCLUSIONS: RHF and fatty liver are independently associated with all-cause and CVD mortality.