Impact of the COVID-19 pandemic and corresponding control measures on long-term care facilities: a systematic review and meta-analysis.

BACKGROUND: Long-term care facilities (LTCFs) were high-risk settings for COVID-19 outbreaks. OBJECTIVE: To assess the impacts of the COVID-19 pandemic on LTCFs, including rates of infection, hospitalisation, case fatality, and mortality, and to determine the association between control measures and SARS-CoV-2 infection rates in residents and staff. METHOD: We conducted a systematic search of six databases for articles published between December 2019 and 5 November 2021, and performed meta-analyses and subgroup analyses to identify the impact of COVID-19 on LTCFs and the association between control measures and infection rate. RESULTS: We included 108 studies from 19 countries. These studies included 1,902,044 residents and 255,498 staff from 81,572 LTCFs, among whom 296,024 residents and 36,807 staff were confirmed SARS-CoV-2 positive. The pooled infection rate was 32.63% (95%CI: 30.29 ~ 34.96%) for residents, whereas it was 10.33% (95%CI: 9.46 ~ 11.21%) for staff. In LTCFs that cancelled visits, new patient admissions, communal dining and group activities, and vaccinations, infection rates in residents and staff were lower than the global rate. We reported the residents' hospitalisation rate to be 29.09% (95%CI: 25.73 ~ 32.46%), with a case-fatality rate of 22.71% (95%CI: 21.31 ~ 24.11%) and mortality rate of 15.81% (95%CI: 14.32 ~ 17.30%). Significant publication biases were observed in the residents' case-fatality rate and the staff infection rate, but not in the infection, hospitalisation, or mortality rate of residents. CONCLUSION: SARS-CoV-2 infection rates would be very high among LTCF residents and staff without appropriate control measures. Cancelling visits, communal dining and group activities, restricting new admissions, and increasing vaccination would significantly reduce the infection rates.

Safety of SGLT2 Inhibitors in Three Chronic Diseases.

This study aimed to assess the safety of SGLT2 inhibitors in type 2 diabetes, chronic kidney disease, and chronic heart failure considering the number needed to treat (NNT).Methods: Data were obtained from 10 morbidity-mortality trials and were pooled to calculate the NNTs. The number needed to treat to benefit (NNTB) is used to express beneficial outcomes, whereas the number needed to treat to be harmed (NNTH) is used for harmful outcomes. The eight safety outcomes of interest were fracture, diabetic ketoacidosis, amputation, urinary tract infection, genital infection, acute kidney injury, severe hypoglycemia, and volume depletion.A total of 10 trials involving 76319 patients were included in this meta-analysis. The mean follow-up was 2.35 years. SGLT2 inhibitors play a positive role in acute kidney injury and severe hypoglycemia, with the corresponding mean NNTBs being 157 and 561, respectively. SGLT2 inhibitors significantly increased the risk of diabetic ketoacidosis, genital infection, and volume depletion, with the corresponding mean NNTHs being 1014, 41, and 139. It was found that the safety of SGLT2 inhibitors was the same in three diseases and five SGLT2 inhibitors.SGLT2 inhibitors have a positive impact on acute kidney injury and severe hypoglycemia, but they increase the incidence of diabetic ketoacidosis, genital infection, and volume depletion.

Incidence and risk factors associated with surgical site infection after surgically treated hip fractures in older adults: a retrospective cohort study.

BACKGROUND: Surgical site infection (SSI) is one of the most common complications in the traumatic orthopedics field, but remains not adequately studied after hip fractures. AIMS: This study aims to investigate the incidence and risk factors associated with SSI after surgically treated hip fractures in older adults. METHODS: A retrospective cohort study including 2932 older adult patients (1416 with femoral neck fracture and 1516 with intertrochanteric fracture) surgically treated from Jan 2015 to Dec 2019 due to hip fractures was performed. Their data on demographics, injury-related data, surgery-related data, and preoperative laboratory test results were collected from hospitalization medical records. Univariate analyses were used to compare between the patients with and without SSI, and multivariate logistic regression analyses were used to identify the risk factors. RESULTS: A total of 89 patients developed SSI, with an accumulated incidence rate of 3.04% (95%CI 2.41-3.66). Staphylococcus aureus was the most common source of infection. In univariate analysis, 11 items were found to be significant in femoral neck fractures and 5 items were found to be significant in intertrochanteric fracture. In the multivariable logistic regression model, cerebrovascular disease (OR 2.17, 95%CI 1.14-4.15) and hematocrit (HCT) (< Lower limit) (OR 3.46, 95%CI 1.13-10.56) were independent risk factors for SSI in femoral neck fracture. Heart disease (OR 2.13, 95%CI 1.18-3.85) was a risk factor for SSI, while LDH (> 250 U/L) (OR 0.44, 95%CI 0.20-0.95) was a protective factor for SSI in intertrochanteric fracture. DISCUSSION: We observed 89 cases (3.04%) of SSI in 2932 older adult patients with hip fractures in this study. Cerebrovascular disease and lower HCT were two independent risk factors for SSI in femoral neck fracture, whereas heart disease was a risk factor and LDH was a protective factor for SSI in intertrochanteric fracture. CONCLUSIONS: Targeted preoperative management, such as predicting the probability of SSI and taking appropriate measures accordingly is essential and highly regarded. Future multicentric studies with more patients evaluated are expected to better address the risk factors for SSI in older hip fracture patients.

The Impact of Hypertension Definition Based on Two-visit Strategy on Estimate of Hypertension Burden: Results From the China Health and Nutrition Survey 1989-2011.

BACKGROUND: The diagnosis of hypertension should be based on the mean of two or more properly measured BP readings on each of two visits for clinical practice, but a one-visit strategy was applied in most epidemiological surveys. The impact of hypertension definition based on two visits on estimates of hypertension burden is unknown. This study aims to assess the impact of hypertension diagnosis based on a two-visit strategy for estimating hypertension burden in China. METHODS: The one-visit and two-visit strategies were applied to investigate the incidence of hypertension in a cohort study based on the China Health and Nutrition Survey (CHNS) 1989-2011. Additionally the prevalence of hypertension was investigated in a cross-sectional study based on the CHNS 2006-2009/2011 and the hypertension burden in China was estimated with data from the 2012-2015 China hypertension survey. RESULTS: Overall, the age-adjusted incidence of hypertension based on the two-visit strategy (1.82%; 95% confidence interval [CI], 1.74-1.90%) was 62.1% lower than estimation based on the one-visit strategy (4.80%; 95% CI, 4.68-4.93%). Similar results were found in the prevalence of hypertension (one-visit: 18.13% [95% CI, 17.34-18.92%]; two-visit: 9.47% [95% CI, 8.87-10.07%]). When the two-visit strategy was applied to the 2012-2015 China hypertension survey, the hypertension burden was predicted to be overestimated by 25.5-47.8% (based on JNC 7) and 23.5-48.2% (based on the 2017 ACC/AHA). CONCLUSION: The hypertension burden would decrease from 244.5 million persons to 127.5-182.3 million persons in China if the two-visit strategy was applied.

Associations of fat and carbohydrate intake with becoming overweight and obese: an 11-year longitudinal cohort study.

The effects of macronutrient intake on obesity are controversial. This research aims to investigate the associations between macronutrient intake and new-onset overweight/obesity. The relationship between the consumption of carbohydrate and total fat and obesity was assessed by the multivariable Cox model in this 11-year cohort, which included 6612 adults (3291 men and 3321 women) who were free of overweight and obesity at baseline. The dietary intake was recorded using a 24-h recall method for three consecutive days. Moreover, substitution models were developed to distinguish the effects of macronutrient composition alteration from energy intake modification. During 7·5 person years (interquartile range 4·3, 10·8) of follow-up, 1807 participants became overweight or obese. After adjusting for risk factors, the hazard ratio (HR) of overweight/obesity in extreme quintiles of fat was 1·48 (quintile 5 v. quintile 1, 95 % CI 1·16, 1·89; Ptrend = 0·02) in women. Additionally, replacing 5 % of energy from carbohydrate with equivalent energy from fat was associated with an estimated 4·3 % (HR 1·043, 95 % CI 1·007, 1·081) increase in overweight/obesity in women. Moreover, dietary carbohydrate was inversely associated with overweight/obesity (quintile 5 v. quintile 1, HR 0·70, 95 % CI 0·55, 0·89; Ptrend = 0·02) in women. Total fat was related to a higher risk of overweight/obesity, whereas high carbohydrate intake was related to a lower risk of overweight/obesity in women, which was not observed in men.

Plain Water Intake and Association With the Risk of Overweight in the Chinese Adult Population: China Health and Nutrition Survey 2006-2011.

BACKGROUND: The prevalence of overweight is increasing dramatically worldwide. The aim of our study was to investigate the association of plain water intake (PWI) with the risk of new-onset overweight risk among Chinese adults. METHODS: A total of 3,200 adults aged 18-65 who were free of overweight at baseline were enrolled from China Health and Nutrition Survey (CHNS) cohort study in 2006-2011. The risk of new-onset overweight with different amounts of PWI per day was analyzed in this 5-year cohort. A multiple logistic regression model was used to assess the association of PWI and the risk of new-onset overweight and adjust for potential confounders. Moreover, dose-response models were developed to estimate the linear relationship. RESULTS: During 5 years of follow-up, 1,018 incident cases were identified. Our analysis indicated an inverse association of more than 4 cups of PWI per day and the risk of new-onset overweight among normal weight individuals. Compared with participants who drank 2 to 3 cups PWI, the adjusted odds ratios (OR) of overweight were 0.741 (95% confidence interval [CI], 0.599-0.916) in participants who drank 4 to 5 cups PWI, and 0.547 (95% CI, 0.435-0.687) in participants who drank more than 6 cups PWI. The dose-response analysis showed that every cup of PWI was associated with a 6.5% and 8.4% decrease in the risk of new-onset overweight among men and women, respectively. The interactions of PWI and covariates on the risk of overweight were not found. CONCLUSION: Drinking more than 4 cups (≈1 liter) per day of plain water is associated with decrease in the risk of new-onset overweight among normal-weight individuals.

Prevalence of abdominal obesity among Chinese adults in 2011.

BACKGROUND: The prevalence of abdominal obesity is increasing dramatically worldwide. This study aimed to estimate the current prevalence of abdominal obesity from the 2011 China Health and Nutrition Survey (CHNS) and compare the data with other countries. METHODS: Waist circumference (WC) of 12,326 Chinese adults (aged 20 years or older) from the 2011 CHNS were analyzed by age group and region. Abdominal obesity was defined as a WC ≥90 cm for men and WC ≥80 cm for women based on World Health Organization (WHO) recommendations for Asians. RESULTS: In 2011, the age-adjusted mean WC was 85.9 cm (95% confidence interval [CI], 85.6-86.2 cm) for men and 80.7 cm (95% CI, 80.4-80.9 cm) for women. Based on the WHO recommendations, the age-adjusted prevalence of abdominal obesity was 44.0% (95% CI, 43.1%-44.8%) overall, 35.3% (95% CI, 34.1%-36.6%) in men, and 51.7% (95% CI, 50.5%-52.9%) in women. Moreover, the age-adjusted prevalence was 44.0% (95% CI, 42.7%-45.2%) in rural populations, 42.5% (95% CI, 40.7%-44.2%) in urban populations, and 45.2% (95% CI, 43.5%-46.9%) in megacity populations. The prevalence in China (35.3% for men and 51.7% for women) was lower than in Japan (50.8% for men) and the United States (43.5% for men and 64.7% for women). Similar results were observed when applying the criteria suggested by the Working Group on Obesity in China. CONCLUSIONS: In 2011, the age-adjusted prevalence of abdominal obesity in China was 35.3% in men and 51.7% in women.

Excess Body Weight during Childhood and Adolescence Is Associated with the Risk of Multiple Sclerosis: A Meta-Analysis.

BACKGROUND AND AIM: Several epidemiological studies have reported the association between obesity and multiple sclerosis (MS). METHODS: A literature search of the observational studies, published as original articles in English before December 2015, was performed using electronic databases. RESULTS: Five observational studies were included, of which 3 were case-control studies and 2 were cohort studies. The pooled relative risk (RR) for overweight and obesity during childhood and adolescence compared with normal weight (body mass index = 18.5-24.9 kg/m2) was 1.44 (95% CI 1.22-1.70) and 2.01 (95% CI 1.63-2.48), respectively. In subgroup analyses, we found that excess body weight during childhood and adolescence increased the risk of MS in the female group (overweight: pooled RR = 1.62, 95% CI 1.35-1.94; obesity: pooled RR = 2.25, 95% CI 1.77-2.85), but not in the male group (overweight: pooled RR = 1.19, 95% CI 0.91-1.55; obesity: pooled RR = 1.22, 95% CI 0.79-1.90). CONCLUSIONS: Excess body weight during childhood and adolescence was associated with an increased risk of MS; severe obesity demonstrated a stronger risk. A statistically significant association was found in the female group, but not in the male group.

Joint effects of age and body mass index on the incidence of hypertension subtypes in the China Health and Nutrition Survey: A cohort study over 22years.

OBJECTIVES: We seek to investigate the joint effects of age and body mass index (BMI) on the incident hypertension subtypes among Chinese adults during 1989-2011. METHODS: We investigated the Incidence rates (IRs, per 100person-years) of hypertension subtypes, adjusted relative risks (RRs) and population attributable risk percent (PAR%) of BMI for hypertension, and clarified the age-specific effect of BMI on incident hypertension utilizing a dynamic cohort study from the China Health and Nutrition Survey (CHNS) 1989-2011. RESULTS: Normotensive participants (n=53,028) at baseline were included, with mean age was 41.7 (95% CI, 41.6-41.7)years old. During a total of 118,694person years (average was 6.38years) of follow-up, a total of 5208 incident cases of hypertension were documented. The IRs of hypertension were 4.4 (95% CI, 4.3-4.5), which increased gradually by age and BMI (Ptrend<0.001). Compared with those with BMI<22kg/m(2), the RR of hypertension was 3.13 (95% CI, 2.84-3.45) in the group with BMI≥28kg/m(2). The PAR% (BMI>22 vs. BMI<22) for hypertension in Chinese population was 32% (95% CI, 29-34%). Similar trends were observed in all age and BMI groups for both isolated systolic hypertension and systolic-diastolic hypertension, which were mainly affected by age. In contrast, the peak IR of isolated diastolic hypertension was observed in participants aged 30-49years with higher BMIs. CONCLUSIONS: The PAR% (IR of BP≥140/90 or treatment for BMI>22 vs. IR for BMI<22) of elevated body weight for hypertension was 32% in Chinese population.

The association between overweight, obesity and ovarian cancer: a meta-analysis.

OBJECTIVE: Epidemiological studies have reported an inconsistent association between obesity and ovarian cancer. To update the current knowledge of and further qualify the association between overweight, obesity and ovarian cancer risk, we conducted a meta-analysis of published observational studies. METHODS: Using the PubMed, MEDLINE and EMBASE databases, we performed a literature search of all of the case-control and cohort studies published as original articles in English before March 2015. We included 26 observational studies, of which 13 were case-control studies (7782 cases and 21 854 controls) and 13 were cohort studies (5181 cases). Fixed- and random-effects models were used to compute summary estimates and the corresponding 95% confidence intervals. Subgroup analyses were also performed. RESULTS: The pooled relative risk for overweight and obesity compared with normal weight (body mass index = 18.5-24.9 kg/m(2)) was 1.07 (95% confidence interval: 1.02-1.12) and 1.28 (95% confidence interval: 1.16-1.41), respectively. In subgroup analyses, we found that overweight/obesity increased the risk of ovarian cancer in most groups, except for the postmenopausal group (overweight: pooled relative risk = 0.97, 95% confidence interval: 0.76-1.24; obesity: pooled relative risk = 0.93, 95% confidence interval: 0.61-1.42). There was no evidence of publication bias. CONCLUSIONS: Increased body weight was associated with an increased risk of ovarian cancer; in particular, severe obesity demonstrated a stronger risk effect. No statistically significant association was observed in the postmenopausal period, but was in the premenopausal period.

Benefits and Risks of Antihyperlipidemic Medication in Adults with Different Low-Density Lipoprotein Cholesterol Based on the Number Needed to Treat.

PURPOSE: The objective of this investigation is to examine the benefits and potential risks of these drugs in individuals by varying baseline low-density lipoprotein cholesterol (LDL-C) values, utilizing the concept of the number needed to treat (NNT). METHODS: We extensively searched electronic databases, such as PubMed, EMBASE, Cochrane, and Web of Science, up to 6 August 2023. Baseline LDL-C values were stratified into four categories: < 100, 100-129, 130-159, and ≥ 160 mg/dL. Risk ratios (RRs) and NNT values were computed. RESULTS: This analysis incorporated data from 46 randomized controlled trials (RCTs), encompassing a total of 237,870 participants. The meta-regression analysis demonstrated an incremental diminishing risk of major adverse cardiovascular events (MACE) with increasing baseline LDL-C values. Statins exhibited a significant reduction in MACE [number needed to treat to benefit (NNTB) 31, 95% confidence interval (CI) 25-37], but this effect was observed only in individuals with baseline LDL-C values of 100 mg/dL or higher. Ezetimibe and PCSK9 inhibitors also were effective in reducing MACE (NNTB 18, 95% CI 11-41, and NNTB 18, 95% CI 16-24). Notably, the safety outcomes of statins and ezetimibe did not reach statistical significance, while the incidence of injection-site reactions with PCSK9 inhibitors was statistically significant [number needed to treat to harm (NNTH) 41, 95% CI 80-26]. CONCLUSION: Statins, ezetimibe, and PCSK9 inhibitors demonstrated a substantial capacity to reduce MACE, particularly among individuals whose baseline LDL-C values were relatively higher. The NNT visually demonstrates the gradient between baseline LDL-C and cardiovascular disease (CVD) risk. SYSTEMATIC REVIEW REGISTRATION: Registration: PROSPERO identifier number: CRD42023458630.

Functional variants in NBS1 and cancer risk: evidence from a meta-analysis of 60 publications with 111 individual studies.

Several potentially functional variants of Nijmegen breakage syndrome 1 (NBS1) have been implicated in cancer risk, but individually studies showed inconclusive results. In this study, a meta-analysis based on 60 publications with a total of 39 731 cancer cases and 64 957 controls was performed. The multivariate method and the model-free method were adopted to determine the best genetic model. It was found that rs2735383 variant genotypes were associated with significantly increased overall risk of cancer under the recessive genetic model [odds ratio (OR) =1.12, 95% confidence interval (CI): 1.02-1.22, P = 0.013]. Similar results were found for rs1063054 under the dominant model effect (OR = 1.12, 95% CI: 1.01-1.23, P = 0.024). The I171V mutation, 657del5 mutation and R215W mutation also contribute to the development of cancer (for I171V, OR = 3.93, 95% CI: 1.68-9.20, P = 0.002; for 657del5, OR = 2.79, 95% CI: 2.17-3.68, P < 0.001; for R215W, OR = 1.77, 95% CI: 1.07-2.91, P = 0.025). From stratification analyses, an effect modification of cancer risks was found in the subgroups of tumour site and ethnicity for rs2735383, whereas the I171V, 657del5 and R215W showed a deleterious effect of cancer susceptibility in the subgroups of tumour site. However, rs1805794, D95N and P266L did not appear to have an effect on cancer risk. These results suggest that rs2735383, rs1063054, I171V, 657del5 and R215W are low-penetrance risk factors for cancer development.

Mineralocorticoid receptor antagonists for chronic heart failure: a meta-analysis focusing on the number needed to treat.

Aims: Recent studies have shown that mineralocorticoid receptor antagonists (MRAs) can decrease mortality in patients with heart failure; however, the application of MRAs in current clinical practice is limited because of adverse effects such as hyperkalemia that occur with treatment. Therefore, this meta-analysis used the number needed to treat (NNT) to assess the efficacy and safety of MRAs in patients with chronic heart failure. Methods: We meta-analysed randomized controlled trials (RCTs) which contrasted the impacts of MRAs with placebo. As of March 2023, all articles are published in English. The primary outcome was major adverse cardiovascular events (MACE), and secondary outcomes included all-cause mortality, cardiovascular death, myocardial infarction (MI), stroke, and adverse events. Results: We incorporated seven studies with a total of 9,056 patients, 4,512 of whom received MRAs and 4,544 of whom received a placebo, with a mean follow-up period of 2.1 years. MACE, all-cause mortality, and cardiovascular mortality were all reduced by MRAs, with corresponding numbers needed to treat for benefit (NNTB) of 37, 28, and 34; as well as no impact on MI or stroke. MRAs increased the incidence of hyperkalemia and gynecomastia, with the corresponding mean number needed to treat for harm (NNTH) of 18 and 52. Conclusions: This study showed that enabling one patient with HF to avoid MACE required treating 37 patients with MRAs for 2.1 years. MRAs reduce MACE, all-cause mortality, and cardiovascular death; however, they increase the risk of hyperkalemia and gynecomastia.

Benefits and risks of antihypertensive medication in adults with different systolic blood pressure: A meta-analysis from the perspective of the number needed to treat.

Background: The blood pressure (BP) threshold for initial pharmacological treatment remains controversial. The number needed to treat (NNT) is a significant indicator. This study aimed to explore the benefits and risks of antihypertensive medications in participants with different systolic BPs (SBPs), and cardiovascular disease status from the perspective of the NNT. Methods: We conducted a meta-analysis of 52 randomized placebo-controlled trials. The data were extracted from published articles and pooled to calculate NNTs. The participants were divided into five groups, based on the mean SBP at entry (120-129.9, 130-139.9, 140-159.9, 160-179.9, and ≥180 mmHg). Furthermore, we stratified patients into those with and without cardiovascular disease. The primary outcomes were the major adverse cardiovascular events (MACEs), and adverse events (AEs) leading to discontinuation. Results: Antihypertensive medications were not associated with MACEs, however, it increased AEs, when the SBP was <140 mmHg. For participants with cardiovascular disease or at a high risk of heart failure and stroke, antihypertensive treatment reduced MACEs when SBP was ≥130 mmHg. Despite this, only 2-4 subjects had reduced MACEs per 100 patients receiving antihypertensive medications for 3.50 years. The number of individuals who needed to treat to avoid MACEs declined with an increased cardiovascular risk. Conclusion: Pharmacological treatment could be activated when SBP reaches 140 mmHg. For people with cardiovascular disease or at a higher risk of stroke and heart failure, 130 mmHg may be a better therapeutic threshold. It could be more cost-effective to prioritize antihypertensive medications for people with a high risk of developing cardiovascular disease.

Corrigendum: Benefits and risks of antihypertensive medication in adults with different systolic blood pressure: A meta-analysis from the perspective of the number needed to treat.

[This corrects the article DOI: 10.3389/fcvm.2022.986502.].

Association of leisure activity changes and reversion from mild cognitive impairment to normal cognitive function among older adults: A prospective cohort study.

Background: Older adults with mild cognitive impairment (MCI) have the possibility of reverting to normal cognitive function. Leisure activity engagement (LAE) plays a critical role in the progress of the cognitive function. A better understanding of the dynamic relationship between LAE and MCI reversion would inform the implementation of preclinical dementia interventions. This study aimed to investigate the association between change patterns of LAE and MCI reversion among older adults using the Chinese Longitudinal Healthy Longevity Survey (CLHLS) database. Study design: Longitudinal population-based study. Methods: Older adults with MCI at the baseline were enrolled in this study. Information about cognitive function, overall, cognitively stimulating, physically active/demanding, and socially engaged LAE was collected at baseline and follow-up. Adjusted hazard ratios (HRs) for reversion and 95% confidence intervals (CIs) were calculated by Cox hazard models with time as the underlying time metric. We also assessed potential effect modifications by creating a cross-product of the stratifying variable with LAE change patterns in the fully adjusted model. Results: The restricted cubic spline showed that the association between LAE change scores and MCI reversion rate was statistically significant and nonlinear (p<0.01). Taking participants in the low-low group as a reference, participants in the low-medium, low-high, medium-medium, medium-high, high-medium, and high-high groups had increased possibilities of MCI reversion with HRs (95% CI) of 2.19 (1.57-3.06), 2.97 (2.13-4.13), 0.87 (0.64-1.19), 2.28 (1.71-3.03), 2.78 (2.10-3.69), 1.93 (1.43-2.59), and 2.74 (2.09-3.60), respectively. Further stratified models showed that the impact of LAE change patterns on MCI reversion varied in different ages (nonagenarian, octogenarian, and younger elderly) and gender. Conclusions: Participants who maintained the highest LAE had the greatest possibility of MCI reversion. Meanwhile, a higher level of LAE maintenance was associated with the increased possibility of MCI reversion. These results provide a practical message to older adults about how dynamic changes in LAE are associated with improved cognitive function.

Effect of alirocumab and evolocumab on all-cause mortality and major cardiovascular events: A meta-analysis focusing on the number needed to treat.

Aims: The efficacy of anti-proprotein convertase subtilisin/Kexin type 9 (PCSK9) monoclonal antibodies in patients with atherosclerotic cardiovascular disease (ASCVD) remains unclear. Therefore, this study aims to assess the effect of PCSK9 inhibitors (alirocumab and evolocumab) on ASCVD patients considering the number needed to treat (NNT). Methods: We reviewed randomized controlled trials (RCTs) which compared the effects of alirocumab or evolocumab and placebo or standards of care. All articles were published in English up to May 2022. Using random effect models, we estimated risk ratios (RRs), NNT, and 95% confidence intervals (CI). Results: We incorporated 12 RCTs with 53 486 patients total, of which 27 674 received PCSK9 inhibitors and 25 812 received placebos. The mean follow-up duration was 1.56 years. The effect of PCSK9 inhibitors on major adverse cardiovascular events (MACE) was statistically significant, and the corresponding mean NNT was 36. Alirocumab reduced the risk of MACE, stroke, and coronary revascularization; the corresponding mean NNT were 37, 319, and 107, respectively. Evolocumab positively affected MACE, myocardial infarction, stroke, and coronary revascularization; the corresponding mean NNT were 32, 78, 267, and 65, respectively. The effects of alirocumab or evolocumab on all-cause mortality and cardiovascular mortality were not statistically significant. Conclusion: This study suggests that preventing one patient from MACE needed to treat 36 patients with ASCVD with PCSK9 inhibitors for 1.56 years. Both alirocumab and evolocumab reduced MACE, stroke, and coronary revascularization. Evolocumab had a positive effect on myocardial infarction, but no effects were noted for alirocumab. In addition, alirocumab may not be as effective as evolocumab. NNT visualizes the magnitude of efficacy to assist in clinical decisions. Systematic review registration: [https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=344908], identifier [CRD42022344908].

Associations of Carbohydrate Intake With New-Onset Hypertension Subtypes: Results From the China Health and Nutrition Survey (2000-2011).

Background: The effects of carbohydrate intake on hypertension (HTN) subtypes are scarce. We examined the association of carbohydrate intake with new-onset HTN subtypes in Chinese adults. Methods: Chinese Health and Nutrition Survey (CHNS) 2000-2011, 22,418 individuals were recorded using a 24-h recall method over three consecutive days. We excluded those who were pregnant women, lactating mothers, age <18 years, baseline age, blood pressure, and energy intake deficiency, extreme energy intake (male > 6,000 kcal or < 800 kcal; female > 4,000 kcal or < 600 kcal), and pulse pressure difference (Systolic Blood Pressure [SBP] - Diastolic Blood Pressure [DBP]) <10 mm Hg, HTN at baseline and data from only one survey. The total number of subjects who participated in at least two surveys was 7,930. The main outcome was new-onset HTN subtypes over 6.9 person years of follow-up. Results: 2,521 participants were found to be HTN, which included 1,318 males (52.3%), 1,203 females (47.7%), 721 had systolic-diastolic hypertension (SDH, 28.6%), 655 had isolated systolic hypertension (ISH, 26.0%), and 993 had isolated diastolic hypertension (IDH, 39.4%). Compared with extreme quintiles of carbohydrate, multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI) for new-onset HTN, SDH, ISH and IDH associated with carbohydrate intake were 1.12 (0.97-1.30), 1.54 (1.18-2.00), 0.89 (0.67-1.19) and 1.15 (0.91-1.45), respectively. The HR of SDH compared with extreme quintiles of carbohydrates was 1.56 (95% CI, 1.08-2.25; P trend = 0.04) in men and 1.52 (95% CI, 1.02-2.26; P trend = 0.02) in women. Conclusion: Carbohydrates were related to a higher risk of SDH, which were not observed with HTN, ISH, and IDH.

Effect of renin-angiotensin-aldosterone system inhibitors on all-cause mortality and major cardiovascular events in patients with diabetes: A meta-analysis focusing on the number needed to treat and minimal clinical effect.

AIMS: To assess the effectiveness of renin-angiotensin-aldosterone system (RAAS) inhibitors, angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) separately to prevent all-cause mortality, myocardial infarction (MI), stroke and heart failure (HF) in patients with diabetes considering the number needed to treat (NNT) and minimal clinical effect (MCE). METHODS: Data from 17 morbidity-mortality trials in patients with diabetes were used to calculate NNTs and evaluate MCE to prevent all-cause mortality, myocardial infarction, stroke, and heart failure. RESULTS: A total of 17 trials involving 42,037 patients were included in this meta-analysis. Mean follow-up was 3.7 years. ACEIs significantly reduced the risk of all-cause mortality, MI and HF; the corresponding mean NNTBs were 48, 62 and 78, respectively, but ARBs were only associated with a reduction in heart failure. The clinical significance assessment of the included trials indicated that most of the statistically significant trial results had no definitive clinical significance, and only some of them had possible clinical significance. CONCLUSIONS: Among patients with diabetes, ACEIs reduced all-cause mortality, MI and HF, whereas ARBs could only prevent HF. However, none of the results of these trials had clear clinical significance, and most had only possible clinical significance.

Ca2+/calmodulin-dependent protein kinase IIalpha clusters are associated with stable lipid rafts and their formation traps PSD-95.

Relatively large number of post-synaptic density (PSD) proteins, including Ca2+/calmodulin-dependent protein kinase II (CaMKII), have the potential to associate with lipid rafts. We in this study demonstrate that the CaMKIIalpha clusters induced by ionomycin in human embryonic kidney 293 cells, as well as unclustered CaMKIIalpha (Du F., Saitoh F., Tian Q. B., Miyazawa S., Endo S. and Suzuki T, 2006, Biochem. Biophys. Res. Commun 347, 814-820), were associated with lipid rafts. The CaMKIIalpha clusters associated with lipid raft fraction became resistant to treatment with methyl-beta-cyclodextrin and subsequent cold Triton X-100, which suggests the stabilization of CaMKIIalpha cluster-associated lipid rafts. Next, we found that PSD-95, which is also a component of lipid raft fraction and does not interact directly with CaMKII, was trapped by stable CaMKIIalpha cluster-containing structure. Association of PSD-95 with CaMKIIalpha clusters was also observed in cultured neuronal cells. These results suggest the CaMKIIalpha clusters associated with the lipid rafts in the cytoplasmic region play a role in the assembly and stabilization of certain PSD proteins that have the potential to associate with lipid rafts.