Greater Risk Reduction Research Articles

Meta-analysis: the prophylactic use of tranexamic acid to reduce blood loss during caesarean delivery.

The 2022 national guideline on The Prevention and Management of Primary Postpartum Haemorrhage (PPH) recommended consideration of prophylactic tranexamic acid (TXA) for women who are at high PPH risk undergoing caesarean section (CS). This meta-analysis reviews the basis for this recommendation. PubMed, OVID Medline, EMBASE, Science Citation Index, Scopus, CENTRAL, and ClinicalTrials.gov were searched (from inception to January 2024) for randomised controlled trials comparing prophylactic intravenous TXA with placebo or no treatment in women undergoing CS who received a uterotonic. Our main outcome was PPH > 1L. Secondary outcomes included estimated mean blood loss, blood transfusion, drop in haemoglobin, the need for additional uterotonics, or surgical intervention. Adverse effects of TXA were also assessed. Sixty-one studies including 25,098 women were identified, and 12,446 received prophylactic TXA. Patients who received prophylactic TXA had significantly reduced likelihood of PPH > 1L (RR, 0.47; 95% CI, 0.38 to 0.59), reduced estimated mean blood loss (MD 185.86 ml, 95% CI 159.14-212.59), and reduced drop in Hb (MD 0.84g/dl, 95% CI 0.72, 0.95). There was a significant reduction in need for additional uterotonics (RR 0.47, 95% CI 0.39-0.57) or surgical intervention (RR 0.54, 95% CI 0.30-0.95). The reduced risk of PPH > 1L was greatest in patients at higher risk of bleeding. The greatest risk reduction was seen in smaller studies and in studies undertaken in developing economies. Prophylactic TXA administration is effective at reducing the incidence of PPH > 1L at CS. The clinical benefit of universal prophylaxis is questionable; women who are high risk of PPH are more likely to derive benefit.

Effects of statins in patients with coronary artery spasm: A nationwide population-based study.

Controversies regarding the benefits of statin treatment on clinical outcomes in coronary artery spasm (CAS) without obstructive coronary artery disease (CAD) persist due to limited data. In this retrospective nationwide population-based cohort study from the Taiwan National Health Insurance Research Database during the period 2000-2012, the matched cohorts consisted of 12,000 patients with CAS. After propensity score matching with 1:1 ratio, 2216 patients were eligible for outcome analysis in either statin or nonstatin group, with the mean follow-up duration of 4.8 and 4.6 years, respectively. Statin users versus nonusers had a significantly reduced risk of major adverse cardiovascular events (MACEs) (6.7% vs. 9.5%, hazard ratio [HR] 0.68; 95% confidence interval [CI] 0.55-0.84) and all-cause mortality (6.0% vs. 7.6%; HR 0.77; 95% CI 0.61-0.96). While the results of MACEs were mainly contributed by cardiovascular death (1.9% vs. 3.2%; HR 0.56; 95% CI 0.38-0.83) and ischemic stroke (3.8% vs. 5.4%; subdistribution HR 0.69; 95% CI 0.52-0.91), they were primarily driven by reductions in ischemic but not hemorrhagic stroke. The benefit of statins was significantly pronounced in patients with hypertension and diabetes. Nevertheless, the effect on MACEs was consistent irrespective of age, sex, dyslipidemia, and mental disorder. Statins significantly reduced the risk of MACEs and all-cause mortality in CAS patients. The benefit of statin therapy in reducing MACEs appeared to be linear, with greater risk reduction with higher doses and longer duration without upper threshold, reflecting the dose-dependent relationship of statins with MACEs in CAS patients.

High intensity statin-ezetimibe combination therapy reduces mortality in patients with ischaemic heart disease and elevated Lipoprotein(a)

Abstract Background Early and prompt reduction of low-density lipoprotein cholesterol concentrations (LDL-C) using combination lipid-lowering therapy (LLT) is recommended to lower cardiovascular risk in patients with ischaemic heart disease (IHD) and elevated LDL-C. Lowering LDL-C is also an important cardiovascular risk mitigation strategy in patients with elevated lipoprotein(a) [Lp(a)]. However, it is unknown if combination LLT reduces mortality in patients with elevated Lp(a). Aim To undertake an observational study to investigate the effect of combination LLT using high intensity statin with ezetimibe on cardiovascular outcomes in patients with and without elevated Lp(a). Methods Serum Lp(a) concentrations were measured in 520 consecutively recruited patients with IHD admitted to hospital, half of whom were admitted for acute myocardial infarction. Patients treated with high intensity statin and ezetimibe within the 1st year from admission to hospital (‘HI statin-ezetimibe group’, n=157) were compared with the rest of patients who had less intensive lipid lowering regimen (‘Others group’, n=363) for cardiovascular outcomes. Results During the 2-year follow-up period, 14.6%, 6.5%, and 53.1% of patients had all-cause mortality, cardiovascular mortality, and major adverse cardiovascular events (MACE) respectively. Median age was 63.5 years and 82.3% were male. Multivariable Cox regression showed that baseline Lp(a) ≥70 nmol/L was associated with increased risk of all-cause mortality (HR 1.97, 95% CI 1.20-3.22, P=0.007). Compared with a less intensive regimen, HI statin-ezetimibe was associated with reduced risk of all-cause mortality (HR 0.44 [0.21-0.89], P=0.023) and MACE (HR 0.71 [0.52-0.95], P=0.027), with no statistically significant effect on cardiovascular mortality (HR 0.43, P=0.142). Notably, the cardiovascular benefits of HI statin-ezetimibe were more pronounced in patients with elevated Lp(a); a greater reduction in risk of MACE was seen for patients with Lp(a) ≥70 nmol/L (HR 0.51, P=0.007) or Lp(a) ≥100 nmol/L (HR 0.36, P=0.009), and in all-cause mortality risk for those with Lp(a) ≥70 nmol/L (HR 0.24, P=0.025). Although LDL-C reduction >50% was associated with reduced risk of all-cause mortality (p=0.027), this could not fully explain the overall cardiovascular benefit of HI statin-ezetimibe use in patients with or without elevated Lp(a). Conclusion Intensification of lipid-lowering therapy with high-intensity statin and ezetimibe improves cardiovascular outcomes in patients at very high cardiovascular risk, particularly those with elevated Lp(a). Larger studies are required to confirm our findings that this cardiovascular benefit is partially independent of LDL-C lowering.

Flavonoid-Rich Foods, Dementia Risk, and Interactions With Genetic Risk, Hypertension, and Depression.

A composite score of flavonoid-rich foods (flavodiet) may provide a clear public health message regarding the range of foods with the potential to lower dementia risk. To examine associations of flavodiet score and intakes of flavonoid subclasses with dementia risk according to genetic risk and presence of depression and hypertension. This prospective, population-based cohort study included dietary data from adults aged 40 to 70 years in the UK Biobank, recruited between 2006 and 2010, with a mean (SD) follow-up of 9.2 (1.5) years. The data analyses were conducted from September 1 to 30, 2023. Flavodiet score adherence and intake of flavonoid subclasses derived from 24-hour computerized dietary assessments. The main outcome was incident all-cause dementia and interactions with genetic risk, hypertension, and depressive symptoms using multivariable Cox proportional hazards regression models. The sample included 121 986 participants (mean [SD] age, 56.1 [7.8] years; 55.6% female; 882 with incident dementia). Comparing the highest with lowest quintile of flavodiet score, consuming 6 additional servings per day of flavonoid-rich foods was associated with a lower risk of dementia among all participants (adjusted hazard ratio [AHR], 0.72; 95% CI, 0.57-0.89), those at high genetic risk (AHR, 0.57; 95% CI, 0.42-0.78), and those with depressive symptoms (AHR, 0.52; 95% CI, 0.33-0.81) after multivariable adjustment. The greatest risk reduction was observed in participants consuming at least 2 of the following per day: 5 servings of tea, 1 serving of red wine, and 0.5 servings of berries, compared with those who did not achieve any of these intakes (AHR, 0.62; 95% CI, 0.46-0.84). Higher intakes of flavonoid subclasses, including anthocyanins, flavan-3-ols, flavonols, and flavones, of which tea, red wine, and berries are the main contributors, supported these findings, showing inverse associations with dementia risk. In this cohort study, high adherence to a flavonoid-rich diet score was associated with a lower risk of dementia, with reductions more pronounced in individuals with a high genetic risk, hypertension, and depressive symptoms. These findings suggest that simple dietary changes of increasing intakes of commonly consumed flavonoid-rich foods and drinks may lower dementia risk.

Apolipoprotein A-I Infusions and Cardiovascular Outcomes in Acute Myocardial Infarction According to Baseline LDL-Cholesterol Levels: The AEGIS-II Trial.

In the AEGIS-II trial (NCT03473223), CSL112, a human apolipoprotein A1 derived from plasma that increases cholesterol efflux capacity, did not significantly reduce the risk of the primary endpoint through 90 days versus placebo after acute myocardial infarction (MI). Nevertheless, given the well-established relationship between higher low-density lipoprotein cholesterol (LDL-C) and plaque burden, as well as greater risk reductions seen with PCSK9 inhibitors in patients with baseline LDL-C ≥100 mg/dL on statin therapy, the efficacy of CSL112 may be influenced by baseline LDL-C. Overall, 18,219 patients with acute MI, multivessel coronary artery disease, and additional risk factors were randomized to either four weekly infusions of 6 g CSL112 or placebo. This exploratory post-hoc analysis evaluated cardiovascular outcomes by baseline LDL-C in patients prescribed guideline-directed statin therapy at the time of randomization (n=15,731). As baseline LDL-C increased, risk of the primary endpoint at 90 days lowered in those treated with CSL112 compared with placebo. In patients with LDL-C ≥100 mg/dL at randomization, there was a significant risk reduction of cardiovascular death, MI, or stroke in the CSL112 vs. placebo group at 90, 180, and 365 days (hazard ratio 0.69 [0.53-0.90], 0.71 [0.57-0.88], and 0.78 [0.65-0.93]). In contrast, there was no difference between treatment groups among those with LDL-C <100 mg/dL at baseline. In this population, treatment with CSL112 compared to placebo was associated with a significantly lower risk of recurrent cardiovascular events among patients with a baseline LDL-C ≥100 mg/dL. Further studies need to confirm that CSL112 efficacy is influenced by baseline LDL-C.

Association between grip strength and walking pace with incidence of degenerative cervical myelopathy: a UK biobank observational study.

This study investigates the association between handgrip strength, walking pace, and the incidence of degenerative cervical myelopathy (DCM) using the UK Biobank dataset. We analyzed data from 364,716 UK Biobank participants without prior neurological conditions. Handgrip strength was measured with a dynamometer, and walking pace was self-reported. Cox proportional hazards models assessed hazard ratios (HRs) and 95% confidence intervals (CIs) for DCM development. The cohort, with an average age of 56.2 years (SD, 8.1) and 47.4% male, was followed for a median of 12.6 years. During this period, 3,993 participants (1.1%) developed DCM. A significant inverse correlation was found between handgrip strength and DCM incidence (P for trend < 0.001), with decreasing HRs for DCM across quartiles of increasing grip strength: HRs were 0.70 (95% CI: 0.64-0.76), 0.62 (95% CI: 0.57-0.68), and 0.59 (95% CI: 0.54-0.66) for the second, third, and fourth quartiles, respectively. Participants with average or brisk walking paces had a lower DCM risk (HR, 0.55; 95% CI: 0.50-0.61 and HR, 0.48; 95% CI: 0.43-0.54) compared to slow walkers. The greatest risk reduction was in those with both higher handgrip strength and faster pace (HR, 0.39; 95% CI: 0.34-0.44). Handgrip strength and walking pace are inversely associated with DCM incidence, suggesting their potential as cost-effective screening tools for identifying individuals at risk for DCM.

Tea consumption and risk of all-cause, cardiovascular disease, and cancer mortality: a meta-analysis of thirty-eight prospective cohort data sets.

Tea consumption has been considered beneficial to human health because tea contains phytochemicals such as polyphenols and theaflavins. We conducted a systematic review and meta-analysis on the association between tea consumption and mortality from all causes, cardiovascular disease (CVD), and cancer to provide a quantitative assessment of current evidence. The PubMed, Web of Science, and Scopus databases were searched through April 2024 to identify eligible studies. Random effects models were used to combine study-specific effect estimates (ESs). A total of 38 prospective cohort data sets (from 27 papers) with 1,956,549 participants were included in this meta-analysis. The pooled ESs of the highest versus lowest categories of tea consumption were 0.90 (95% confidence interval [CI], 0.86 to 0.95) for all-cause mortality, 0.86 (95% CI, 0.79 to 0.94) for CVD mortality, and 0.90 (95% CI, 0.78 to 1.03) for cancer mortality. In the dose-response analysis, a non-linear association was observed. The greatest risk reductions were observed for the consumption of 2.0 cup/day for all-cause mortality (ES, 0.91; 95% CI, 0.88 to 0.94) and 1.5 cup/day for cancer mortality (ES, 0.92; 95% CI, 0.89 to 0.96), whereas additional consumption did not show a further reduction in the risk of death. A plateau was observed for CVD mortality at moderate consumption levels (1.5-3.0 cup/day), but a sustained reduction in mortality risk was observed at higher intake levels. Moderate tea consumption (e.g., 1.5-2.0 cup/day) was associated with lower all-cause, CVD, and cancer mortality compared to no tea consumption. Further well-designed prospective studies are needed for a definitive conclusion.

Epidural analgesia during labour and severe maternal morbidity: population based study

ObjectivesTo determine the effect of labour epidural on severe maternal morbidity (SMM) and to explore whether this effect might be greater in women with a medical indication for epidural analgesia...

Traditional Chinese medicine lowering lipid levels and cardiovascular events across baseline lipid levels among coronary heart disease: a meta-analysis of randomized controlled trials.

Dyslipidemia is a critical driver in the development of coronary heart disease (CHD), which further exacerbates the risk of major adverse cardiovascular events (MACEs). Chinese herbal medicine (CHM) plays an important role in the regulation of lipid levels and improvement of prognosis. However, few systematic reviews report whether the efficacy of CHM therapy for regulating lipid levels and lowering cardiovascular events is associated with baseline lipid levels. Randomized controlled trials assessing efficacy of CHM for lipid profiles and MACEs among patients with CHD were searched in six databases. Two authors independently extracted studies according to a predesigned form. Cochrane risk of bias tool and Grading of Recommendations Assessment, Development, and Evaluation system were used to assess the methodological quality of the included studies. The primary outcomes were blood lipid levels and MACEs including cardiovascular mortality, non-fatal myocardial infarction, revascularization, angina pectoris, heart failure, and non-fatal stroke across baseline lipid levels. The secondary outcomes were individual components of the primary outcomes. A total of 23 trials with 7,316 participants were included in this study. Altogether 377 cardiovascular events occurred in 3,670 patients in the CHM group, while 717 events occurred in 3,646 patients in the Western medicine-alone group. Compared with the Western medicine alone, additional CHM significantly lowered low-density lipoprotein cholesterol (LDL-C) [MD = -0.46, 95% CI (-0.60 to -0.32), P < 0.00001, I 2 = 96%]. The risk reduction in MACEs associated with CHM vs. Western medicine therapy was 0.52 [95% CI (0.47-0.58), P < 0.00001, I 2 = 0%], but varied by baseline LDL-C level (P = 0.03 for interaction). Triglycerides (TG) level was also significantly lowered by additional CHM vs. Western medicine alone [MD = -0.27, 95% CI (-0.34 to -0.20), P < 0.00001, I 2 = 81%], and risk reduction for MACEs also varied with baseline TG, with greater risk reduction in higher baseline TG subgroups (P = 0.03 for interaction). Similar results were observed with total cholesterol and high-density lipoprotein cholesterol. Compared with Western medicine alone, additional CHM was associated with lower risk of cardiovascular events and improvement of lipid profiles. Risk reduction for cardiovascular events was associated with baseline LDL-C and TG levels. https://www.crd.york.ac.uk/PROSPERO, identifier CRD42023425791.

Statin Use and the Risk of Venous Thromboembolism in Women Taking Hormone Therapy

Although hormone therapy (HT) in perimenopausal women is associated with increased risk for venous thromboembolism (VTE), it is unclear to what extent statins may mitigate this HT-associated risk. To estimate VTE risk in women aged 50 to 64 years taking HT with or without statins. This nested case-control study analyzed data from a commercially insured claims database in the US. Eligible participants included women aged 50 to 64 years with at least 1 year of continuous enrollment between 2008 and 2019. Data analysis occurred from January 2022 to August 2023. Filled prescriptions for estrogens, progestogens, and statins were recorded in the 12 months prior to index. Recent HT was defined as any estrogen or progestogen exposure within 60 days before the index date. Current statin exposure was defined as 90 or more days of continuous exposure prior to and including the index date. Statin intensity was defined by the statin exposure 30 days prior to index. Cases were identified with VTE diagnoses (diagnostic codes) preceded by at least 12 months without VTE and followed within 30 days by anticoagulation, an inferior vena cava filter placement, or death. Controls were matched to cases (10:1) on date and age. Conditional logistic regression models estimated risk for HT and statin exposures with odds ratios (OR), adjusted for comorbidities. Conditional logistic regression models were used to estimate VTE risk for HT and statin exposures with odds ratios (ORs), adjusted for comorbidities. Intensity of statin therapy was measured as a subgroup analysis. The total sample of 223 949 individuals (mean [SD] age, 57.5 [4.4] years) included 20 359 cases and 203 590 matched controls. Of the entire sample, 19 558 individuals (8.73%) had recent HT exposure and 36 238 individuals (16.18%) had current statin exposure. In adjusted models, individuals with any recent HT exposure had greater odds of VTE compared with those with no recent HT exposure (OR, 1.51; 95% CI, 1.43-1.60). Individuals receiving current statin therapy had lower odds of VTE compared with those with no current statin exposure (OR, 0.88; 95% CI, 0.84-0.93). When compared with those not recently taking HT or statins, the odds of VTE were greater for those taking HT without statins (OR, 1.53; 95% CI, 1.44-1.63) and for those taking HT with statins (OR, 1.25; 95% CI, 1.10-1.43), but were lower for those taking statins without HT (OR, 0.89; 95% CI, 0.85-0.94). Individuals taking HT with statin therapy had 18% lower odds of VTE than those taking HT without statins (OR, 0.82; 95% CI, 0.71-0.94) and there was greater risk reduction with higher intensity statins. In this case-control study, statin therapy was associated with reduced risk of VTE in women taking HT, with greater risk reduction with high-intensity statins. These findings suggest that statins may reduce risk of VTE in women exposed to HT and that HT may not be contraindicated in women taking statins.

Phytonutrients and outcomes following breast cancer: a systematic review and meta-analysis of observational studies.

Phytonutrient intakes may improve outcomes following breast cancer, but the impact of postdiagnosis introduction vs established prediagnostic exposure as well as optimum doses has not been established. Evidence from observational studies for key exposures was evaluated, including dosage and intake time frames. MEDLINE, EMBASE, CINAHL, Cochrane Library, ClinicalTrials.gov, and the ISRCTN registry were searched for prospective and retrospective observational studies investigating the impact of soybean, lignans, cruciferous (cabbage-family) vegetables, green tea, or their phytonutrients on breast cancer survival outcomes. A random-effects model was used to calculate summary hazard ratios (HRs) and 95% confidence intervals (CIs). Nonlinear dose-response analyses were conducted using restricted cubic splines. Thirty-two articles were included. Soy isoflavones were associated with a 26% reduced risk of recurrence (HR = 0.74, 95% CI = 0.60 to 0.92), particularly among postmenopausal (HR = 0.72, 95% CI = 0.55 to 0.94) and estrogen receptor-positive survivors (HR = 0.82, 95% CI = 0.70 to 0.97), with the greatest risk reduction at 60 mg/day. In mortality outcomes, the reduction was mostly at 20 to 40 mg/day. Soy protein and products were inversely associated with cancer-specific mortality for estrogen receptor-positive disease (HR = 0.75, 95% CI = 0.60 to 0.92). An inverse association was observed for serum or plasma enterolactone, measured prediagnosis and early postdiagnosis, with cancer-specific mortality (HR = 0.72, 95% CI = 0.58 to 0.90) and all-cause mortality (HR = 0.69, 95% CI = 0.57 to 0.83). No effects were observed for cruciferous vegetables. There was a 44% reduced risk of recurrence with prediagnostic green tea for stage I and II breast cancer (HR = 0.56, 95% CI = 0.38 to 0.83). Soy, enterolactone, and green tea demonstrated significant risk reductions in outcomes following breast cancer. Evidence is needed regarding the impact of postdiagnostic introduction or substantial increase of these exposures.

Abstract 17586: Physical Activity Associates With a Greater Reduction in Heart Failure Risk Among Individuals With Depression and/or Anxiety

Introduction: Physical activity (PA) has shown a dose-dependent reduction in the incidence of heart failure (HF) by mitigating stress-related neural activity (SNA). Accordingly, we postulated that the impact of PA on HF incidence may be more pronounced in individuals with chronic stress conditions (e.g., depression and/or anxiety) that associate with heightened baseline SNA. Objective: To test whether PA confers a greater reduction in HF incidence among individuals with (vs. without) pre-existing depression and/or anxiety. Methods: Among 48,673 participants (median age 60 years, 40% male) in the Mass General Brigham Biobank, self-reported PA data were collected through a health survey and converted to metabolic equivalent of task minutes per week. Data on incident HF, its subtypes, depression, anxiety, and cardiovascular risk factors were obtained using the International Classification of Disease Codes. Cox regression was employed to assess the association between PA and ten-year HF risk and to examine potential interactions. Results: PA (per each standard deviation) is independently associated with greater reductions in all HF risk among individuals with depression and/or anxiety (standardized hazard ratio [HR] [95% confidence interval (CI)]: 0.735 [0.648, 0.834], p&lt;0.001) compared to those without depression and/or anxiety (0.821 [0.781, 0.864], p&lt;0.001, p-interaction=0.038*). Similar associations were observed between PA and the risk of HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF) among those in whom HF could be classified, Fig1. Conclusions: PA is associated with greater reductions in risk of incident HF, including HFpEF and HFrEF, with the greatest reductions in those with pre-existing depression and/or anxiety. These findings highlight the potential for improved cardiovascular benefits linked to PA in individuals with elevated baseline SNA.

Market Discipline in the Direct Lending Space

Abstract Using the exclusion of business development companies (BDCs) from stock indexes, this paper studies the effectiveness of market discipline in the direct lending space. Amid share sell-offs by institutional investors, a drop in BDCs’ valuations limits their ability to raise new equity capital. Following this funding shock, BDCs do not adjust their capital structure. At the same time, they are reducing the risk exposure of their portfolios. We document a greater reduction in risk for BDCs subject to stronger market discipline from their debtholders. BDCs pass through the capital shock to their portfolio firms by reducing their investment intensity.

Is Personal Protective Equipment Worth the Hassle? Annual Risk of Cryptosporidiosis to Dairy Farmers and How Personal Protective Equipment and Handwashing Can Mitigate It.

Cows are known carriers of Cryptosporidium parvum (C. parvum), a protozoa that can cause the gastrointestinal illness cryptosporidiosis in humans. Despite this potential exposure, dairy farmers tend to wear personal protective equipment (PPE) to protect the milk from contamination, rather than to protect themselves from zoonotic diseases, such as cryptosporidiosis. In this study, cow feces were collected from individual cattle on dairy farms and analyzed for C. parvum using qPCR. Quantitative microbial risk assessment (QMRA) was used to determine the risk of cryptosporidiosis to the dairy farmer with and without the use of handwashing and PPE (gloves and masks). The annualized risk of cryptosporidiosis to dairy farmers was 29.08% but was reduced significantly in each of the three interventions. Among the individual interventions, glove use provided the greatest reduction in risk, bringing the annual risk of cryptosporidiosis to 4.82%. Implementing regular handwashing, the use of gloves and a mask brought the annual risk of cryptosporidiosis to 1.29%. This study provides evidence that handwashing and PPE use can significantly reduce the risk of cryptosporidiosis to farmers and is worth implementing despite potential barriers such as discomfort and cost.

Modelling population-level and targeted interventions of weight loss on chronic disease prevention in the Canadian population

Obesity is a known risk factor for major chronic diseases. Prevention of chronic disease is a top global priority. The study aimed to model scenarios of population-level and targeted weight loss interventions on 10-year projected risk of chronic disease in Canada using a population-level risk prediction algorithm. The validated Chronic Disease Population Risk Tool (CDPoRT) forecasts 10-year risk of chronic disease in the adult population. We applied CDPoRT to the 2013/14 Canadian Community Health Survey to generate prospective chronic disease estimates for adults 20 years and older in Canada (n = 83,220). CDPoRT was used to model the following scenarios: British Columbia's (BC) and Quebec's (QC) provincial population-level weight reduction targets, a population-level intervention that could achieve weight loss, targeted weight loss interventions for overweight and obese groups, and the combination of a population-level and targeted weight loss intervention. We estimated chronic disease risk reductions and number of cases prevented in each scenario compared with the baseline. At baseline, we predicted an 18.4% risk and 4,151,929 new cases of chronic disease in Canada over the 10-year period. Provincial weight loss targets applied to the Canadian population estimated chronic disease reductions of 0.6% (BC) and 0.1% (QC). The population-level intervention estimated a greater reduction in risk (0.2%), compared to the targeted interventions (0.1%). The combined approach estimated a 0.3% reduction in chronic disease risk. Our modelling predicted that population-level approaches that achieve weight loss in combination with targeted weight loss interventions can substantially decrease the chronic disease burden in Canada.

Does decarbonization policy decrease disease risks from black carbon in Beijing, China? A comparison study

Epidemiology studies evaluating the health effect of the decarbonization policy in Beijing, China are limited. This time series study sought to examine the health effectiveness of BC and PM2.5 in Beijing, a formerly heavily polluted city. Therefore, the objectives of this article were (1) to evaluate the modification effects of temperature on the health effects of black carbon (BC) and fine particles (PM2.5) in Beijing. (2) to compare the health effects of BC and PM2.5 pre- and post-implementation of decarbonization policy. Bivariate Response Surface Model and Generalised Additive Model were used to analyze the modification effects. Comparison analysis was conducted pre- and post-implementation of decarbonization policy. The results indicated that (i) Post-implementation, reductions were noted in non-accidental diseases (RR = 1.064 per 10 μg/m3), circulatory diseases (RR = 1.068 per 10 μg/m3) and respiratory diseases (RR = 1.148 per 10 μg/m3) related to BC; this was especially pronounced on cold days. (ii) Greater reductions in risk of non-accidental, circulatory and respiratory deaths (D-value: 0.134 versus 0.002, 0.180 versus 0.003, 0.176 versus 0.002) were noted for BC than for PM2.5. (iii) Higher risks of the impact of BC on respiratory diseases were observed in females than in males. In conclusion, a stronger correlation existed between BC and mortality on cold days than moderately cold days in Beijing. Furthermore, compared with PM2.5, BC posed a greater disease risk and the effectiveness of the decarbonization policy was more obvious.

Differential effects of sodium-glucose cotransporter 2 inhibitors on cardiovascular and renal outcomes according to renal function: a dose-response meta-analysis involving 10 randomized clinical trials and 71 553 individuals.

The main target of sodium-glucose cotransporter 2 inhibitors (SGLT2i), the sodium-glucose cotransporters 2, is found in the kidneys, and their activity is reduced in patients with chronic kidney disease (CKD). How the efficacy of SGLT2i may vary in patients with different levels of renal impairment has not been fully elucidated. We searched the PubMed databases for relevant studies published through May 25, 2022. Randomized control trials comparing SGLT2i with placebo and reporting cardiovascular or renal outcomes were included. The primary outcome was the composite of major adverse cardiovascular events (MACE), which were defined as cardiovascular death (CV death), nonfatal myocardial infarction (MI), and nonfatal ischemic stroke. Secondary outcomes included the components of MACE, all-cause mortality, hospitalization for heart failure (HHF), the composite of CV death and HHF, and composite renal outcomes. Linear meta-regression analysis was used to assess the effects of estimated glomerular filtration rate (eGFR) on the risks associated with SGLT2i treatment vs placebo for all outcomes. Nonlinear meta-regression analysis was also performed for MACE to investigate the combined influence of reduced drug efficacy in CKD but possible greater risk reduction in a population with higher risk at baseline. Further analyses were performed by including additional study-level covariates, including the prevalence of diabetes mellitus (DM), heart failure (HF), and atherosclerotic cardiovascular disease (ASCVD). Risk ratios for MACE, CV death, nonfatal MI, HHF, and composite renal outcomes associated with SGLT2i treatment were not significantly related to baseline eGFR values. A positive association was observed between eGFR values and the risk of stroke with SGLT2i use (regression coefficient β = .0109, 95% confidence interval [CI] 0.0029-0.0188). A similar positive association was observed between eGFR values and the composite outcome of CV death and HHF (β = .0025, 95% CI 0.0000-0.0051). The results of the meta-regression analyses, including the additional covariates of DM, HF, and ASCVD, were consistent with the results of the primary analyses for most outcomes. The protective effects of SGLT2i for reducing most adverse cardiovascular and renal outcomes persisted in patients with variable degrees of renal impairment. The observed benefits such as preventing CV death, HF worsening, or stroke may be greater for patients with more severe CKD. Considering the cardiovascular and renal benefits associated with SGLT2i treatment, patients with CKD should be treated aggressively to improve outcomes. CRD42021273500.

Impacts of PM2.5 before and after COVID-19 outbreak on emergency mental disorders: A population-based quasi-experimental and case-crossover study

The ongoing COVID-19 pandemic is a great challenge to mental health, but fine particulate matter (PM2.5), an increasingly reported risk factor for mental disorders, has been greatly alleviated during the pandemic in many countries. It remains unknown whether COVID-19 outbreak can affect the association between PM2.5 exposure and the risk of mental disorders. This study aimed to investigate the associations of total and cause-specific mental disorders with PM2.5 exposure before and after the COVID-19 outbreak in China. Data on daily emergency department visits (EDVs) and hospitalizations of mental disorders from 2016 to 2021 were obtained from Anhui Mental Health Center for Hefei city. An interrupted time series analysis was used to quantify the impact of COVID-19 outbreak on EDVs and hospitalizations of mental disorders. A time-stratified case-crossover analysis was employed to evaluate the association of mental disorders with PM2.5 exposure before and after the COVID-19 outbreak, especially in the three months following the COVID-19 outbreak. After COVID-19 outbreak, there was an immediate and significant decrease in total mental disorders, including a reduction of 15% (95% CI: 3%–26%) in EDVs and 44% (95% CI: 36%–51%) in hospitalizations. PM2.5 exposure was associated with increased risk of EDVs and hospitalizations for total and cause-specific mental disorders (schizophrenia, schizotypal and delusional disorders; neurotic, stress-related, and somatoform disorders) before COVID-19 outbreak, but this PM2.5-related risk elevation significantly decreased after COVID-19 outbreak, with greater risk reduction at the first month after the outbreak. However, young people (0–45 years) were still vulnerable to PM2.5 exposure after the COVID-19 outbreak. This study first reveals that the risk of PM2.5-related emergency mental disorders decreased after the COVID-19 outbreak in China. The low concentration of PM2.5 might benefit mental health and greater efforts are required to mitigate air pollution in the post-COVID-19 era.

All-cause mortality and cardiovascular outcomes with sodium-glucose Co-transporter 2 inhibitors, glucagon-like peptide-1 receptor agonists and with combination therapy in people with type 2 diabetes.

To assess the relationship of sodium-glucose cotransporter-2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor analogues (GLP-1RA) and their combination (SGLT2i + GLP-1RA) with 5-year risk of all-cause mortality, hospitalization and cardiovascular/macrovascular disease in people with type 2 diabetes. Retrospective cohort analysis of 2.2 million people with type 2 diabetes receiving insulin across 85 health care organizations using a global federated health research network. Three intervention cohorts (SGLT2i, GLP-1RA and SGLT2i + GLP-1RA) were compared against a control cohort (no SGLT2i/GLP-1RA). Propensity score matching for age, ischaemic heart disease, sex, hypertension, chronic kidney disease, heart failure and glycated haemoglobin was used to balance cohorts 1:1 (SGLT2i, n = 143 600; GLP-1RA, n = 186 841; SGLT-2i + GLP-1RA, n = 108 504). A sub-analysis comparing combination and monotherapy cohorts was also performed. The intervention cohorts showed a reduced hazard ratio (HR, 95% confidence interval) over 5 years compared with the control cohort for all-cause mortality (SGLT2i 0.49, 0.48-0.50; GLP-1RA 0.47, 0.46-0.48; combination 0.25, 0.24-0.26), hospitalization (0.73, 0.72-0.74; 0.69, 0.68-0.69; 0.60, 0.59-0.61) and acute myocardial infarct (0.75, 0.72-0.78; 0.70, 0.68-0.73; 0.63, 0.60-0.66), respectively. All other outcomes showed a significant risk reduction in favour of the intervention cohorts. The sub-analysis showed a significant risk reduction in all-cause mortality for combination therapy versus SGLT2i (0.53, 0.50-0.55) and GLP-1RA (0.56, 0.54-0.59). SGLT2i, GLP-1RAs or combination therapy confers mortality and cardiovascular protection in people with type 2 diabetes over 5 years. Combination therapy was associated with the greatest risk reduction in all-cause mortality versus a propensity matched control cohort. In addition, combination therapy offers a reduction in 5-year all-cause mortality when compared directly against either monotherapy.

Association between resilience promotion factors during childhood and risk of drug use disorder during adulthood.

Few studies have been conducted on the relationship between "outside-residing" resilience characteristics and the risk of developing drug use disorder later in life. These characteristics include responsive and caring parenting, household routines involving regular family meals and bedtime routines, social support from peers, participation in organized activities, and religious service attendance. We quantified the association between these resilience promotion factors during childhood and the risk of developing criteria for drug use disorder during adulthood using data from a retrospective cohort study of 618 adults born in Massachusetts during 1969-1983, including those with adverse childhood experiences (ACEs). Self-administered questionnaires gathered information on criteria for drug use disorder, ACEs, and family and community resilience promotion factors. Compared to individuals with "low" numbers of resilience promotion factors, 30% (95% CI: 0.5-0.9) and 50% reductions (95% CI: 0.4-0.8) in the risk of developing one or more criteria for drug use disorder were observed among those with "moderate" and "high" numbers of resilience factors, respectively (p value for trend=0.003). Overall, family factors were associated with greater risk reductions than comparable numbers of community factors. Among individuals with ACEs, a "high" number of family factors but not community factors were associated with a reduction in risk (RR:0.6, 95% CI:0.4-1.0 for family factors, RR:1.0, 95% CI:0.5-1.8 for community factors). These results suggest that the risk of developing criteria for drug use disorder decreases in a dose-response fashion according to the number of "outside-residing" resilience promotion factors during childhood, and that family factors are associated with greater risk reductions than community factors, particularly among individuals with ACEs. Coordinated prevention efforts at the family and community level are recommended to reduce the risk of this important societal problem.