Efficacy and safety of sacubitril/valsartan in the treatment of middle-aged and elderly patients with hypertension: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: With the increase of hypertensive patients worldwide, the need for better antihypertensive drugs to achieve blood pressure standards and reduce complications is of great clinical significance. As an angiotensin receptor-neprilysin inhibitor, sacubitril/valsartan has been widely used in the treatment of heart failure, but its efficacy and safety in the treatment of middle-aged and elderly hypertensive patients are still controversial. Therefore, we performed a meta-analysis to compare the efficacy and safety of sacubitril/valsartan and other antihypertensive drugs in the treatment of middle-aged and elderly patients with hypertension. METHODS: The databases of PubMed, Embase, and Web of Science were systematically searched from their establishment to February 2022 to collect the randomized controlled trials (RCTs) of sacubitril/valsartan and other antihypertensive drugs in the treatment of middle-aged and elderly hypertensive patients. The Cochrane Collaboration's tool was used to assess risk of bias for included studies, and the meta-analysis was performed by using RevMan 5.3. RESULTS: In all, 7 studies which met the criteria were included, with a total sample size of 3,323 patients, including 1,899 patients treated with sacubitril/valsartan, and 1,424 patients treated with angiotensin II receptor blockers (ARBs). The meta-analysis showed that compared with other antihypertensive drugs, sacubitril/valsartan can significantly reduce mean reductions in sitting systolic blood pressure [mean difference (MD) =-4.70, 95% confidence interval (CI): -5.79 to -3.61, P<0.001], mean reductions in sitting diastolic blood pressure (MD =-2.29, 95% CI: -2.53 to -2.04, P<0.001), 24-hour mean reductions in ambulatory systolic blood pressure (MD =-3.36, 95% CI: -4.08 to -2.64, P<0.001), and 24-hour mean reductions in ambulatory diastolic blood pressure (MD =-1.49, 95% CI: -1.99 to -0.99, P<0.001), while there was no significant difference in the incidence of adverse events [odds ratio (OR) =1.14, 95% CI: 1.00 to 1.31, P=0.06], serious adverse events (OR =1.06, 95% CI: 0.64 to 1.76, P=0.81), and discontinuations due to adverse events (OR =0.86, 95% CI: 0.51 to 1.46, P=0.58). DISCUSSION: Compared with other antihypertensive drugs, sacubitril/valsartan may be more effective in lowering blood pressure, and its safety may be comparable to that of ARBs. However, these results have to be confirmed by future RCTs with larger sample sizes and higher quality, and the long-term benefits of sacubitril/valsartan require further observation.

Registration errors among patients receiving blood transfusions: a national analysis from 2008 to 2017.

BACKGROUND AND OBJECTIVES: The key first step for a safe blood transfusion is patient registration for identification and linking to past medical and transfusion history. In Canada, any deviation from standard operating procedures in transfusion is an error voluntarily reportable to a national database (Transfusion Error Surveillance System [TESS]). We used this database to characterize the subset of registration-related errors impacting transfusion care, including where, when and why the errors occurred, and to identify frequent high-risk errors. MATERIALS AND METHODS: A retrospective analysis was conducted on transfusion errors reported to TESS by sentinel reporting sites relating to patient registration and patient armbands, between 2008 and 2017. Free-text comments describing the error were coded to further categorize into common error types. The number of specimens received in the transfusion laboratory was used as the denominator for rates to allow for comparison between hospital sites. RESULTS: Five hundred and fifty-four registration errors were reported from 10 hospitals, for a global error rate of 5·4/10 000 samples (median 5·0 [interquartile range 3·7-7·0]). The potential severity was high in 85·7% of errors (n = 475). The patient experienced a consequence in 10·8% of errors (n = 60), but none resulted in patient harm. Rates varied widely and differed by nature across sites. Errors most commonly occurred in outpatient clinics or procedure units (n = 160, 28·8%) and in emergency departments (n = 130, 23·5%). CONCLUSION: Registration errors affect transfusion at every step and location in the hospital and are commonly high risk. Further research into common root causes is warranted to identify preventative strategies.

Efficacy and safety of endovascular coiling vs surgical clipping for patients with ruptured carotid-ophthalmic aneurysm: A protocol for systematic review and meta-analysis.

BACKGROUND: Carotid-ophthalmic aneurysms are relatively rare, and represent 1% of all intracranial aneurysms. Generally, endovascular coiling and surgical clipping are the 2 most commonly used methods to treat ruptured carotid-ophthalmic aneurysms, it provides the most favorable outcome for a patient. This study aims to assess the efficiency and safety of endovascular coiling vs surgical clipping for patients with a ruptured carotid-ophthalmic aneurysm. METHODS: A comprehensive systematic literature review was done in PubMed, EMBASE, Cochrane Library, Web of Science, Scopus, China National Knowledge Infrastructure (CNKI), and WanFang databases. Only randomized trials that compared endovascular coiling with surgical clipping in patients with ruptured carotid-ophthalmic aneurysm was included. Data was extracted independently by 2 review authors. Moreover, the quality of study and bias risk was evaluated by utilizing an appropriate method. Triallists will be contacted to acquire missing information. The data is presented as risk ratio and mean difference, or standardized mean difference with 95% confidence intervals. RESULTS: The results from the present research shall be published in a peer-reviewed journal. CONCLUSION: The present study summarizes the direct and in-direct evidence to judge the efficiency and safety of these 2 methodologies to treat ruptured carotid-ophthalmic aneurysms and attempt to find the most efficiency and safety therapeutical method. ETHICS AND DISSEMINATION: The present study is a meta-analysis based on published evidence. As a result, ethics approval and patient consent are not needed.

Cardio-Metabolic Disease Risks and Their Associations with Circulating 25-Hydroxyvitamin D and Omega-3 Levels in South Asian and White Canadians.

OBJECTIVES: This study compared cardio-metabolic disease risk factors and their associations with serum vitamin D and omega-3 status in South Asian (SAC) and White Canadians (WC) living in Canada's capital region. METHODS: Fasting blood samples were taken from 235 SAC and 279 WC aged 20 to 79 years in Ottawa, and 22 risk factors were measured. RESULTS: SAC men and women had significantly higher fasting glucose, insulin, homeostasis model assessment for insulin resistance (HOMA-IR), apolipoprotein B (ApoB), ratios of total (TC) to HDL cholesterol (HDLC) and ApoB to ApoA1, leptin, E-selectin, P-selectin, ICAM-1 and omega-3 (p < 0.05), but lower HDLC, ApoA1, vitamin D levels than WC (p < 0.05). SAC women had higher CRP and VEGF than WC women. Adequate (50-74.9 nmol/L) or optimal (≥ 75 nmol/L) levels of 25(OH)D were associated with lower BMI, glucose, insulin, HOMA-IR, TG, TC, low density lipoprotein cholesterol (LDLC), ApoB/ApoA1 ratio, CRP, leptin, and higher HDLC, ApoA1, omega-3 index, L-selectin levels in WC, but not in SAC. Intermediate (>4%-<8%) or high (≥ 8%) levels of omega-3 indices were related to lower E-selectin, P-selectin, ICAM-1 and higher HDLC, 25(OH)D levels in WC, but not in SAC. The BMIs of ≤ 25 kg/m2 were related to lower LDLC, ApoB, VEGF, creatinine and higher 25(OH)D in WC, but not in SAC. CONCLUSIONS: The associations of vitamin D, omega-3 status, BMI and risk factors were more profound in the WC than SAC. Compared to WC, vitamin D status and omega-3 index may not be good predictive risk factors for the prevalence of CVD and diabetes in SAC.

[Application of endovascular embolization for brain arteriovenous malformation].

Endovascular embolization has increasingly been applied for brain arteriovenous malformation (BAVM). With our better understanding of BAVM and the continuous improvement of micro-catheter technology and embolic materials, the therapeutic effectiveness has constantly increased. This paper reviews recent advances in research on BAVM and the application of endovascular embolization.

The replicative activity of human endogenous retrovirus K102 (HERV-K102) with HIV viremia.

OBJECTIVE: To address the activation and replicative activity of HERV-K102 in vivo associated with HIV viremia. DESIGN AND METHODS: Initially serology was performed on HERV-K102 specific envelope peptides to determine if HERV-K102 may become activated with HIV viremia. Before developing a quantitative PCR (qPCR) assay, we first determined whether plasma associated particles contained DNA or RNA genomes in a pilot study which surprisingly revealed predominantly DNA genomes. A relative, ddCt qPCR ratio method was then devised to detect excess levels of HERV-K102 pol DNA templates over genomic levels which served as a surrogate marker to reliably index the level of particles found in plasma. RESULTS: Both the peptide serology and ddCt qPCR excess ratio methods suggested the activation of HERV-K102 in about 70-80% of HIV viremic cases whereas only 2-3% of normal healthy adults had marginally activated HERV-K102 (P < 0.0001). Moreover, by digestion with dUTPase we were able to confirm that the vast majority of excess DNA template in plasma related to cDNA production rather than representing genomic copies. CONCLUSIONS: Our work uniquely suggests the common activation of HERV-K102 with HIV viremia and may be first to directly demonstrate HERV-K102 cDNA production in vivo. The potential implications of the induction of HERV-K102 activation and replication for the prevention and control of HIV are discussed.

Age differences in the prevalence of physical aggression among 5-11-year-old Canadian boys and girls.

It has been proven extremely difficult in the past to estimate the prevalence of physical aggression in children for two main reasons: (a) a heterogeneous sampling of behaviors (i.e., mix between physically aggressive and non-physically aggressive antisocial behaviors), and (b) a lack of a "gold standard" to identify children who exhibit physically aggressive behaviors on a frequent basis. The goal of this study was to test for age differences in the prevalence of physical aggression in the Canadian population of school-aged boys and girls, using cross-sectional data from the National Longitudinal Survey of Children and Youth (NLSCY). The first wave of the NLSCY included a representative sample of 12,292 Canadian children aged 5-11 years. We used latent class analysis to identify children whose propensity to exhibit physically aggressive behaviors was much higher than that of other children of the same age and sex in the population. The prevalence of physical aggression was estimated at 3.7% in 5-11-year-old boys and ranged from .5% to 2.3% in 11 and 5-year-old girls, respectively. Hence, the results show a decreasing trend in the prevalence of physical aggression with age for girls, but not for boys. These findings suggest the importance of considering the developmental pathways of physical aggression for boys and girls separately.

Gender differences in physical aggression: A prospective population-based survey of children before and after 2 years of age.

There has been much controversy over the past decades on the origins of gender differences in children's aggressive behavior. A widely held view is that gender differences emerge sometime after 2 years of age and increase in magnitude thereafter because of gender-differentiated socialization practices. The objective of this study was to test for (a) gender differences in the prevalence of physical aggression in the general population of 17-month-old children and (b) change in the magnitude of these differences between 17 and 29 months of age. Contrary to the differential socialization hypothesis, the results showed substantial gender differences in the prevalence of physical aggression at 17 months of age, with 5% of boys but only 1% of girls manifesting physically aggressive behaviors on a frequent basis. The results suggest that there is no change in the magnitude of these differences between 17 and 29 months of age.

The evolution of problem and social competence behaviors during toddlerhood: A prospective population-based cohort survey.

Research in developmental psychopathology has long been preoccupied with rather broad categories of behavior, but we know little about the specific behaviors that comprise these categories. The objective of this study was to: (a) estimate the prevalence of problem and social competence behaviors in the general population of children at 17 months of age, and (b) describe the continuity and discontinuity in the degree to which children exhibit these behaviors between 17 and 29 months of age. The results show that frequent problem behaviors are not typical of children under two years of age. Further, the results suggest that it is possible to distinguish between different types of problem behaviors before two years of age. In addition, the results show that gender differences in some problem behaviors are already present before two years of age, and increase in magnitude during toddlerhood. Finally, the results show that interindividual differences in problem behaviors observed before two years of age are stable. The predictive accuracy of frequent problem behaviors in children at 17 months of age was limited, however, with often a majority of toddlers not behaving this way a year later. Overall, our results suggest that toddlerhood represents a critical period when behavioral and emotional problems of potentially clinical significance emerge. Pediatricians should routinely ask parents to report the frequency of their young children's problem behaviors during child health supervision visits so that children whose frequent problem behaviors persist over time can be identified and possibly referred for treatment.

Hepatitis C virus infection among First Nation and non-First Nation people in Manitoba, Canada: a public health laboratory study.

Demographic information and laboratory test results on 136 169 clinical serum specimens submitted to the public health laboratory in Manitoba, Canada, for hepatitis C virus (HCV) testing between January 1995 and December 2003 were analyzed. The difference in the clearance rates of HCV infection, without therapeutic intervention, and the HCV genotypes infecting First Nation and non-First Nation people were studied. The rates of co-infection of HCV-positive individuals with other hepatitis viruses were also compared between the two study groups. The results of the analyses of the data indicated that there was a 4.4-fold increase in the number of specimens tested and a 4.9-fold decrease in HCV antibody (anti-HCV) positive cases during the study period. The proportion of specimens submitted for testing from First Nation individuals was lower than their proportion in the Manitoba population. Our study also indicated that there was a significantly higher proportion of First Nation patients who had self-limiting infection (patients cleared the infection and became HCV RNA negative without anti-HCV treatment) in comparison to non-First Nation patients. The proportion of First Nation females who had self-limiting infection was significantly higher than non-First Nation females. HCV genotype 1 infection represented more than 60% of HCV infection in Manitoba. The rate of individuals positive for the hepatitis A virus antibody in the HCV-positive population was higher among First Nation than non-First Nation individuals. On the other hand, there were more HCV-infected First Nation patients than non-First Nation patients who were not immune to the hepatitis B virus. The data indicate that fewer First Nation patients seek anti-HCV therapy in comparison to non-First Nation. In conclusion, the differences in the rates of HCV self-limiting infection between First Nation and non-First Nation individuals in Manitoba may reflect the genetic differences between the two cohorts, which may consequently affect the immune response to the HCV infection.

A cross-sectional analysis of acute hepatitis B virus reported to the Vancouver Coastal Health Authority from 2000 to 2003.

BACKGROUND: Acute hepatitis B virus (HBV) transmission remains a significant public health problem despite effective vaccination and prophylaxis strategies. Vancouver, British Columbia, has a large ethnic community from endemic areas, which may further impact on the epidemiology of acute HBV. A cross-sectional study of factors associated with acute HBV cases reported to the Vancouver Coastal Health Authority (Vancouver, British Columbia) from 2000 to 2003 is reported. METHODS: New seropositive cases of hepatitis B surface antigen were reported to the Vancouver Coastal Health Authority Office of Communicable Disease Control. Patients meeting both clinical and laboratory criteria for acute HBV were interviewed by telephone for demographic and risk behaviour information. Risk behaviours within the last six months before disease onset were ranked on efficiency of transmission in a mutually exclusive risk category. RESULTS: There were 78 patients of identified acute HBV in Vancouver from 2000 to 2003. The overall incidence rate was 3.38 per 100,000 person years. Outside of Canada, Asia was the most common place of birth (29.5%). The three most frequently identified risk factors were men who have sex with men (21.9%), heterosexual activity with two or more partners (14.0%) and intravenous drug use (14.0%). Sexual contact with an HBV carrier was identified in 9.4% of patients. CONCLUSIONS: Sexual transmission is a major mode in the spread of HBV in Vancouver. Existing public education, surveillance and vaccination strategies for HBV need to be strengthened to address those engaging in risky behaviours.

Enhanced surveillance of newly acquired hepatitis C virus infection in Canada, 1998 to 2004.

The purpose of this study was to determine trends in disease incidence and recent patterns of hepatitis C virus (HCV) transmission in Canada, using the Enhanced Hepatitis Strain Surveillance System (EHSSS). Demographic, clinical, and potential risk factor information on newly acquired HCV infection, from 1998 to 2004, was collected using standardized questionnaires. During this time period, the reported incidence of newly acquired HCV infection declined by 36.4% from 3.3 cases per 100,000 in 1998, to 2.1 cases per 100,000 in 2004. The disease incidence peaked at 15 to 39 y of age, confirming injecting drug use as the most frequently reported route of transmission. The proportion of cases attributed to health care-acquired HCV infection decreased over this time period. Although the incidence of newly acquired HCV infection in the EHSSS was found to be declining, hepatitis C remains an important public health threat to Canadians. Prevention efforts for HCV should focus on injection drug use, especially for people aged 15 to 39 y.

Synthesis, characterization and biological activity of lanthanum(III) complexes containing 2-methylene-1,10-phenanthroline units bridged by aliphatic diamines.

Two novel lanthanum(III) complexes containing 2-methylene-1,10-phenanthroline units bridged by aliphatic diamines were synthesized and characterized by elemental analysis, IR, NMR, thermal analysis and conductance measurements. They have been assayed for anticancer activity in vitro against HL-60 (human leukocytoma) cells, PC-3MIE8 (human prostate carcinoma) cells, BGC-823 (human stomach carcinoma) cells, MDA-MB-435 (human galactophore carcinoma) cells, Bel-7402 (human liver carcinoma) cells, and Hela (human cervix carcinoma) cells. The results show that the two complexes exhibit good cytotoxic activities against different cell lines in general, especially more effective than cisplatin against Bel-7402, BGC-823 and MDA-MB-435 cell lines. DNA-binding studies indicate that, besides the intercalation, the complexes bind to DNA by the other interaction(s), which might be responsible for the production of more compact DNA, coinciding with more A-like feature of DNA as suggested by CD spectra.

Individual change in methylphenidate use in a national sample of children aged 2 to 11 years.

OBJECTIVES: To determine methylphenidate use in children aged 2 to 13 years. To provide age- and sex-specific estimates of methylphenidate initiation and cessation during a 2-year period. METHOD: Data from 2 cycles of a Canadian household survey yielded a sample of over 10 000 children aged 2 to 11 years at Cycle 1 who continued to participate at Cycle 2. We used logit modelling to estimate Cycle 2 methylphenidate use, methylphenidate use over a 2-year period, and methylphenidate initiation and cessation from Cycles 1 to 2. RESULTS: In 1996 and 1997, methylphenidate use ranged from 0.32% to 6.31% among children aged 4 to 13 years. School-aged boys were more likely than girls to use methylphenidate. Odds were greater for boys aged 6 to 7 years than for boys aged 4 to 5 years; they were also greater for boys aged 10 to 11 years than for boys aged 12 to 13 years. Almost 1% of children used methylphenidate at both data cycles. Odds of Cycle 2 methylphenidate use were 135 times greater for children using methylphenidate at Cycle 1, compared with nonusers. Methylphenidate initiation ranged from 0.20% to 3.34%, and school-aged boys had higher initiation rates than girls. Cessation rates ranged from 18% to78%, and there were no statistically significant differences by age and sex. CONCLUSIONS: Methylphenidate prevalence findings are consistent with past studies. We found an age-by-sex interaction on methylphenidate use. We also found both continuity and discontinuity in methylphenidate use.

A new look at inter-informant agreement on conduct disorder using a latent class approach.

This study examined agreement on aggressive and nonaggressive conduct disorder in a general population sample of 14- to 17-year-old adolescents (n=1165) and their mothers. We collected diagnostic interview data and applied latent class analyses to estimate inter-informant agreement. The preferred model for aggressive conduct disorder for both males and females was a one-latent-variable/two-class model specifying no inter-informant disagreement beyond chance expectations. This model estimated the prevalence of aggressive conduct disorder to be 13% for males and 0.4% for females. For nonaggressive conduct disorder, a one-latent-variable/three-class model specifying asymmetric agreement was preferred for both males and females. This model estimated the prevalence of nonaggressive conduct disorder in adolescents to be 18% according to males and 13% according to mothers. Prevalence estimates were 12% according to females and 7% according to mothers. Symptom sensitivity estimates for all models were poor whereas specificity estimates were near perfect to perfect. Males had higher rates of aggressive and nonaggressive conduct disorder across informants. There was a high level of adolescent-mother agreement on both types of conduct disorder. However, there were some differences, suggesting that aggressive and nonaggressive are two valid subtypes of conduct disorder with different prevalence estimates and agreement levels.

Prevalence of methylphenidate use and change over a two-year period: a nationwide study of 2- to 11-year-old Canadian children.

OBJECTIVE: To provide age- and sex-specific estimates of methylphenidate use and to determine use changes over a 2-year period. STUDY DESIGN: We examined the first and second data collection cycles of the National Longitudinal Survey of Children and Youth, a Canadian household survey of children. Participants were children aged 2 years to 11 years at both the first and second cycles whose mothers responded; thus, 16,798 (13,059) children were assessed for the first (second) cycle. Logit modeling was used to estimate prevalence of methylphenidate use, to determine sex and age effects on prevalence, and to examine use changes from cycle 1 to 2. RESULTS: Methylphenidate prevalence ranged from 0.09% to 3.89% across 2- to 11-year old children from the first cycle. Boys were 4.6 times more likely than girls to consume methylphenidate. Use was >4 times greater among 6- to 7-year-old children compared with 4- to 5-year-old children and almost 2 times greater among 8- to 9-year-old children compared with 6- to 7-year-old children. Methylphenidate prevalence increased by 36% from cycle 1 to 2. CONCLUSIONS: Methylphenidate prevalence was relatively low. Boys and school-age children had higher rates of methylphenidate use, and use among 2- to 11-year-old children appeared to be increasing over time.