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Journal of Clinical Medicine Aug 2023Despite preventive measures, stroke rates remain high in the primary and secondary prevention settings. Factor XIa inhibition may offer a novel, safe and effective... (Review)
Review
INTRODUCTION
Despite preventive measures, stroke rates remain high in the primary and secondary prevention settings. Factor XIa inhibition may offer a novel, safe and effective antithrombotic option for stroke prevention.
METHODS
We conducted a systematic review and meta-analysis including all available randomized controlled clinical trials (RCTs) that investigated the efficacy and safety of factor XIa inhibitors versus controls in primary or secondary stroke prevention. The primary efficacy and safety outcomes of interest were symptomatic ischemic stroke (IS) and the composite of major bleeding and clinically relevant non-major bleeding.
RESULTS
Four phase II dose-finding RCTs were included, comprising a total of 4732 patients treated with factor XIa inhibitors versus 1798 controls. Treatment with factor XIa inhibitors did not reduce the risk of IS compared to controls (RR: 0.89; 95% CI: 0.67-1.17). The composite of symptomatic IS and covert infarcts on brain MRI (RR: 1.01; 95% CI: 0.87-1.18), the composite of symptomatic IS and transient ischemic attack (TIA; RR: 0.78; 95% CI: 0.61-1.01), and the composite of major adverse cardiovascular events (RR: 1.07; 95% CI: 0.87-1.31) did not differ between the treatment groups. Treatment with factor XIa inhibitors did not increase the risk of the composite of major bleeding and clinically relevant non-major bleeding (RR: 1.19; 95% CI: 0.65-2.16), major bleeding alone (RR: 1.19; 95% CI: 0.64-2.22), intracranial bleeding (RR: 0.91; 95% CI: 0.26-3.19) or all-cause mortality (RR: 1.21; 95% CI: 0.77-1.90).
CONCLUSION
This meta-analysis provides reassuring evidence regarding the safety of factor XIa inhibitors. These findings, coupled with potential signals of efficacy in reducing IS (and TIA), underscore the importance of ongoing phase III RCTs for providing definitive data regarding the effect of factor XIa inhibition on stroke prevention.
PubMed: 37685629
DOI: 10.3390/jcm12175562 -
The Cochrane Database of Systematic... Apr 2024Osteoporosis is an abnormal reduction in bone mass and bone deterioration, leading to increased fracture risk. Etidronate belongs to the bisphosphonate class of drugs... (Review)
Review
BACKGROUND
Osteoporosis is an abnormal reduction in bone mass and bone deterioration, leading to increased fracture risk. Etidronate belongs to the bisphosphonate class of drugs which act to inhibit bone resorption by interfering with the activity of osteoclasts - bone cells that break down bone tissue. This is an update of a Cochrane review first published in 2008. For clinical relevance, we investigated etidronate's effects on postmenopausal women stratified by fracture risk (low versus high).
OBJECTIVES
To assess the benefits and harms of intermittent/cyclic etidronate in the primary and secondary prevention of osteoporotic fractures in postmenopausal women at lower and higher risk of fracture, respectively.
SEARCH METHODS
We searched the Cochrane Central Register of Control Trials (CENTRAL), MEDLINE, Embase, two clinical trial registers, the websites of drug approval agencies, and the bibliographies of relevant systematic reviews. We identified eligible trials published between 1966 and February 2023.
SELECTION CRITERIA
We included randomized controlled trials that assessed the benefits and harms of etidronate in the prevention of fractures for postmenopausal women. Women in the experimental arms must have received at least one year of etidronate, with or without other anti-osteoporotic drugs and concurrent calcium/vitamin D. Eligible comparators were placebo (i.e. no treatment; or calcium, vitamin D, or both) or another anti-osteoporotic drug. Major outcomes were clinical vertebral, non-vertebral, hip, and wrist fractures, withdrawals due to adverse events, and serious adverse events. We classified a study as secondary prevention if its population fulfilled one or more of the following hierarchical criteria: a diagnosis of osteoporosis, a history of vertebral fractures, a low bone mineral density T-score (≤ -2.5), or aged 75 years or older. If none of these criteria were met, we considered the study to be primary prevention.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. The review has three main comparisons: (1) etidronate 400 mg/day versus placebo; (2) etidronate 200 mg/day versus placebo; (3) etidronate at any dosage versus another anti-osteoporotic agent. We stratified the analyses for each comparison into primary and secondary prevention studies. For major outcomes in the placebo-controlled studies of etidronate 400 mg/day, we followed our original review by defining a greater than 15% relative change as clinically important. For all outcomes of interest, we extracted outcome measurements at the longest time point in the study.
MAIN RESULTS
Thirty studies met the review's eligibility criteria. Of these, 26 studies, with a total of 2770 women, reported data that we could extract and quantitatively synthesize. There were nine primary and 17 secondary prevention studies. We had concerns about at least one risk of bias domain in each study. None of the studies described appropriate methods for allocation concealment, although 27% described adequate methods of random sequence generation. We judged that only 8% of the studies avoided performance bias, and provided adequate descriptions of appropriate blinding methods. One-quarter of studies that reported efficacy outcomes were at high risk of attrition bias, whilst 23% of studies reporting safety outcomes were at high risk in this domain. The 30 included studies compared (1) etidronate 400 mg/day to placebo (13 studies: nine primary and four secondary prevention); (2) etidronate 200 mg/day to placebo (three studies, all secondary prevention); or (3) etidronate (both dosing regimens) to another anti-osteoporotic agent (14 studies: one primary and 13 secondary prevention). We discuss only the etidronate 400 mg/day versus placebo comparison here. For primary prevention, we collected moderate- to very low-certainty evidence from nine studies (one to four years in length) including 740 postmenopausal women at lower risk of fractures. Compared to placebo, etidronate 400 mg/day probably results in little to no difference in non-vertebral fractures (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.20 to 1.61); absolute risk reduction (ARR) 4.8% fewer, 95% CI 8.9% fewer to 6.1% more) and serious adverse events (RR 0.90, 95% CI 0.52 to 1.54; ARR 1.1% fewer, 95% CI 4.9% fewer to 5.3% more), based on moderate-certainty evidence. Etidronate 400 mg/day may result in little to no difference in clinical vertebral fractures (RR 3.03, 95% CI 0.32 to 28.44; ARR 0.02% more, 95% CI 0% fewer to 0% more) and withdrawals due to adverse events (RR 1.41, 95% CI 0.81 to 2.47; ARR 2.3% more, 95% CI 1.1% fewer to 8.4% more), based on low-certainty evidence. We do not know the effect of etidronate on hip fractures because the evidence is very uncertain (RR not estimable based on very low-certainty evidence). Wrist fractures were not reported in the included studies. For secondary prevention, four studies (two to four years in length) including 667 postmenopausal women at higher risk of fractures provided the evidence. Compared to placebo, etidronate 400 mg/day may make little or no difference to non-vertebral fractures (RR 1.07, 95% CI 0.72 to 1.58; ARR 0.9% more, 95% CI 3.8% fewer to 8.1% more), based on low-certainty evidence. The evidence is very uncertain about etidronate's effects on hip fractures (RR 0.93, 95% CI 0.17 to 5.19; ARR 0.0% fewer, 95% CI 1.2% fewer to 6.3% more), wrist fractures (RR 0.90, 95% CI 0.13 to 6.04; ARR 0.0% fewer, 95% CI 2.5% fewer to 15.9% more), withdrawals due to adverse events (RR 1.09, 95% CI 0.54 to 2.18; ARR 0.4% more, 95% CI 1.9% fewer to 4.9% more), and serious adverse events (RR not estimable), compared to placebo. Clinical vertebral fractures were not reported in the included studies.
AUTHORS' CONCLUSIONS
This update echoes the key findings of our previous review that etidronate probably makes or may make little to no difference to vertebral and non-vertebral fractures for both primary and secondary prevention.
Topics: Humans; Female; Osteoporotic Fractures; Etidronic Acid; Wrist Fractures; Secondary Prevention; Calcium; Postmenopause; Osteoporosis; Spinal Fractures; Hip Fractures; Vitamin D; Wrist Injuries
PubMed: 38591743
DOI: 10.1002/14651858.CD003376.pub4 -
BMC Cancer Sep 2023Global annual cancer incidence is forecast to rise to 27.5 M by 2040, a 62% increase from 2018. For most cancers, prevention and early detection are the most effective...
BACKGROUND
Global annual cancer incidence is forecast to rise to 27.5 M by 2040, a 62% increase from 2018. For most cancers, prevention and early detection are the most effective ways of reducing mortality. This study maps trials in cancer screening, prevention, and early diagnosis (SPED) to identify areas of unmet need and highlight research priorities.
METHODS
A systematic mapping review was conducted to evaluate all clinical trials focused on cancer SPED, irrespective of tumour type. The National Cancer Research Institute (NCRI) portfolio, EMBASE, PubMed and Medline were searched for relevant papers published between 01/01/2007 and 01/04/2020. References were exported into Covidence software and double-screened. Data were extracted and mapped according to tumour site, geographical location, and intervention type.
RESULTS
One hundred seventeen thousand seven hundred one abstracts were screened, 5157 full texts reviewed, and 2888 studies included. 1184 (52%) trials focussed on screening, 554 (24%) prevention, 442 (20%) early diagnosis, and 85 (4%) a combination. Colorectal, breast, and cervical cancer comprised 61% of all studies compared with 6.4% in lung and 1.8% in liver cancer. The latter two are responsible for 26.3% of global cancer deaths compared with 19.3% for the former three. Number of studies varied markedly according to geographical location; 88% were based in North America, Europe, or Asia.
CONCLUSIONS
This study shows clear disparities in the volume of research conducted across different tumour types and according to geographical location. These findings will help drive future research effort so that resources can be directed towards major challenges in cancer SPED.
Topics: Female; Humans; Early Detection of Cancer; Uterine Cervical Neoplasms; Liver Neoplasms; Asia; Breast
PubMed: 37667231
DOI: 10.1186/s12885-023-11300-8 -
Italian Journal of Pediatrics Jul 2023Robust routine immunization schedules for pertussis-containing vaccines have been applied for years, but pertussis outbreaks remain a worldwide problem. This study aimed... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Robust routine immunization schedules for pertussis-containing vaccines have been applied for years, but pertussis outbreaks remain a worldwide problem. This study aimed to investigate the association between vaccine hesitancy and pertussis in infants and children.
METHODS
We searched PubMed, Cochrane, Web of Science, Embase, and China National Knowledge Internet for studies published between January 2012 and June 2022. This study included case-control and cohort studies that assessed the association between childhood/maternal vaccine hesitancy and odds ratios (ORs), risk ratios (RRs), and vaccine effectiveness (VE) related to pertussis in infants and children [Formula: see text] 9 years old. ORs/VEs with a 95% confidence interval (CI) were calculated. Random-effects meta-analysis models were used for appropriate pooled estimates, and heterogeneity was assessed using [Formula: see text]. Cumulative meta-analysis and subgroup analyses stratified by study characteristics were performed.
RESULTS
Twenty-two studies were included, with a mean quality score of 7.0 (range 6.0-9.0). Infants and children with pertussis were associated with higher vaccine hesitancy to all doses (OR = 4.12 [95% CI: 3.09-5.50]). The highest OR was between children who were unvaccinated over four doses and children who were fully vaccinated (OR = 14.26 [95%CI: 7.62-26.70]); childhood vaccine delay was not statistically significantly associated with pertussis risk (OR = 1.18 [95% CI: 0.74-1.89]). Maternal vaccine hesitancy was associated with significantly higher pertussis risk in infants aged 2 and 3 months old, with higher pertussis ORs in infants [Formula: see text] 2 months old (OR = 6.02 [95%CI: 4.31-8.50], OR = 5.14 [95%CI: 1.95-13.52] for infants [Formula: see text] 2 and [Formula: see text] 3 months old, respectively). Maternal and childhood VEs were high in reducing pertussis infection in infants and children. The administration time of maternal vaccination had little effect on VE.
CONCLUSION
Vaccine hesitancy increased pertussis risks in infants and children. Ensuring that children receive up-to-date pertussis vaccines is essential; short delays in receiving childhood vaccinations may be unimportant. Maternal vaccinations for pertussis should be encouraged.
Topics: Child; Infant; Humans; Whooping Cough; Vaccination Hesitancy; Vaccination; Immunization Schedule; Vaccines
PubMed: 37443026
DOI: 10.1186/s13052-023-01495-8 -
Prevention Science : the Official... May 2024Exposure to certain chemicals prenatally and in childhood can impact development and may increase risk for attention-deficit/hyperactivity disorder (ADHD). Leveraging a... (Meta-Analysis)
Meta-Analysis Review
Exposure to certain chemicals prenatally and in childhood can impact development and may increase risk for attention-deficit/hyperactivity disorder (ADHD). Leveraging a larger set of literature searches conducted to synthesize results from longitudinal studies of potentially modifiable risk factors for childhood ADHD, we present meta-analytic results from 66 studies that examined the associations between early chemical exposures and later ADHD diagnosis or symptoms. Studies were eligible for inclusion if the chemical exposure occurred at least 6 months prior to measurement of ADHD diagnosis or symptomatology. Included papers were published between 1975 and 2019 on exposure to anesthetics (n = 5), cadmium (n = 3), hexachlorobenzene (n = 4), lead (n = 22), mercury (n = 12), organophosphates (n = 7), and polychlorinated biphenyls (n = 13). Analyses are presented for each chemical exposure by type of ADHD outcome reported (categorical vs. continuous), type of ADHD measurement (overall measures of ADHD, ADHD symptoms only, ADHD diagnosis only, inattention only, hyperactivity/impulsivity only), and timing of exposure (prenatal vs. childhood vs. cumulative), whenever at least 3 relevant effect sizes were available. Childhood lead exposure was positively associated with ADHD diagnosis and symptoms in all analyses except for the prenatal analyses (odds ratios (ORs) ranging from 1.60 to 2.62, correlation coefficients (CCs) ranging from 0.14 to 0.16). Other statistically significant associations were limited to organophosphates (CC = 0.11, 95% confidence interval (CI): 0.03-0.19 for continuous measures of ADHD outcomes overall), polychlorinated biphenyls (CC = 0.08, 95% CI: 0.02-0.14 for continuous measures of inattention as the outcome), and both prenatal and childhood mercury exposure (CC = 0.02, 95% CI: 0.00-0.04 for continuous measures of ADHD outcomes overall for either exposure window). Our findings provide further support for negative impacts of prenatal and/or childhood exposure to certain chemicals and raise the possibility that primary prevention and targeted screening could prevent or mitigate ADHD symptomatology. Furthermore, these findings support the need for regular review of regulations as our scientific understanding of the risks posed by these chemicals evolves.
Topics: Attention Deficit Disorder with Hyperactivity; Humans; Child; Environmental Exposure; Female; Prenatal Exposure Delayed Effects; Pregnancy
PubMed: 38108946
DOI: 10.1007/s11121-023-01601-6 -
BMC Public Health Sep 2023Social determinants of health are drivers of vaccine inequity and lead to higher risks of complications from infectious diseases in under vaccinated communities. In many... (Review)
Review
CONTEXT
Social determinants of health are drivers of vaccine inequity and lead to higher risks of complications from infectious diseases in under vaccinated communities. In many countries, pharmacists have gained the rights to prescribe and administer vaccines, which contributes to improving vaccination rates. However, little is known on how they define and target vulnerable communities.
OBJECTIVE
The purpose of this study is to describe how vulnerable communities are targeted in community pharmacies.
METHODS
We performed a systematic search of the Embase and MEDLINE database in August 2021 inspired by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocols (PRISMA ScR). Articles in English, French or Spanish addressing any vaccine in a community pharmacy context and that target a population defined as vulnerable were screened for inclusion.
RESULTS
A total of 1039 articles were identified through the initial search, and 63 articles met the inclusion criteria. Most of the literature originated from North America (n = 54, 86%) and addressed influenza (n = 29, 46%), pneumococcal (n = 14, 22%), herpes zoster (n = 14, 22%) or human papilloma virus vaccination (n = 14, 22%). Lifecycle vulnerabilities (n = 48, 76%) such as age and pregnancy were most often used to target vulnerable patients followed by clinical factors (n = 18, 29%), socio-economical determinants (n = 16, 25%) and geographical vulnerabilities (n = 7, 11%). The most frequently listed strategy was providing a strong recommendation for vaccination, promotional posters in pharmacy, distributing leaflet/bag stuffers and providing staff training. A total of 24 barriers and 25 facilitators were identified. The main barriers associated to each vulnerable category were associated to effective promotional strategies to overcome them.
CONCLUSION
Pharmacists prioritize lifecycle and clinical vulnerability at the expense of narrowing down the definition of vulnerability. Some vulnerable groups are also under targeted in pharmacies. A wide variety of promotional strategies are available to pharmacies to overcome the specific barriers experienced by various groups.
Topics: Female; Pregnancy; Humans; Pharmacies; Vaccination; Pneumococcal Vaccines; Influenza Vaccines; Databases, Factual
PubMed: 37741997
DOI: 10.1186/s12889-023-16601-y -
Heart, Lung & Circulation Aug 2023Statins are well-established for their treatment of cardiovascular disease (CVD) due to their cholesterol-lowering effects and potential anti-inflammatory properties.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Statins are well-established for their treatment of cardiovascular disease (CVD) due to their cholesterol-lowering effects and potential anti-inflammatory properties. Although previous systematic reviews demonstrate that statins reduce inflammatory biomarkers in the secondary prevention of CVD, none examine their effects on cardiac and inflammatory biomarkers in a primary prevention setting.
METHODS
We conducted a systematic review and meta-analysis to examine the effects of statins on cardiovascular and inflammatory biomarkers among individuals without established CVD. The biomarkers included are: cardiac troponin, N-terminal pro B-type natriuretic peptide (NT-proBNP), C-reactive protein (CRP), tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), soluble vascular cell adhesion molecule (sVCAM), soluble intercellular adhesion molecule (sICAM), soluble E-selectin (sE-selectin) and endothelin-1 (ET-1). A literature search was performed through Ovid MEDLINE, Embase and CINAHL Plus for randomised controlled trials (RCTs) published up to June 2021.
RESULTS
Overall, 35 RCTs with 26,521 participants were included in our meta-analysis. Data was pooled using random effects models presented as standardised mean differences (SMD) with 95% confidence intervals (CI). Combining 36 effect sizes from 29 RCTs, statin use resulted in a significant reduction in CRP levels (SMD -0.61; 95% CI -0.91, -0.32; P<0.001). This reduction was observed for both hydrophilic (SMD -0.39; 95% CI -0.62, -0.16; P<0.001) and lipophilic statins (SMD -0.65; 95% CI -1.01, -0.29; P<0.001). There were no significant changes in serum concentrations of cardiac troponin, NT-proBNP, TNF-α, IL-6, sVCAM, sICAM, sE-selectin and ET-1.
CONCLUSION
This meta-analysis demonstrates that statin use reduces serum CRP levels in a primary prevention setting for CVD, with no clear effect on the other eight biomarkers studied.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Interleukin-6; Tumor Necrosis Factor-alpha; Biomarkers; Cardiovascular Diseases; Troponin
PubMed: 37291001
DOI: 10.1016/j.hlc.2023.04.300 -
Human Vaccines & Immunotherapeutics Dec 2023Patients received kidney transplantation (KTR) have a low seroconversion rate after vaccination. Our objective was to compare the seroconversion rates and adverse... (Meta-Analysis)
Meta-Analysis
A systematic review and meta-analysis of the seroconversion rates and adverse effects of COVID-19 mRNA vaccine and COVID-19 viral vector vaccine in kidney transplant recipient patients.
Patients received kidney transplantation (KTR) have a low seroconversion rate after vaccination. Our objective was to compare the seroconversion rates and adverse effects of additional different vaccinations in KTR patients in existing studies. Databases such as PubMed, Cochrane Library, Web of Science, Embase, ClinicalTrials.gov and others. Three high-quality RCT were included and showed no statistical difference in seroconversion rates between the two vaccines (RR = 0.93[0.76,1.13]). There was no statistical difference in seroconversion rates between the sexes, for men (RR = 0.93[0.69,1.25]) and women (RR = 0.91[0.62,1.33]). Among the adverse effects there was no statistically significant difference in fever (RR = 1.06[0.44,2.57]), while for injection site pain there was a statistically significant difference (RR = 1.14[1.18,1.84]). There was no significant difference in seroconversion rates in patients with KTR who received the two additional vaccines. Patients injected with the viral vector vaccine were less painful than those injected with the mRNA vaccine.
Topics: Female; Humans; Male; Antibodies, Viral; COVID-19; COVID-19 Vaccines; Kidney Transplantation; Seroconversion; Vaccination
PubMed: 37057765
DOI: 10.1080/21645515.2023.2196893 -
Pharmaceuticals (Basel, Switzerland) Jul 2023There are significant considerations about the prevention of cardiotoxicity caused by trastuzumab therapy in patients with breast cancer, leading to discontinuation.... (Review)
Review
There are significant considerations about the prevention of cardiotoxicity caused by trastuzumab therapy in patients with breast cancer, leading to discontinuation. Recently, randomized controlled trials (RCTs) have evaluated the effects of early commitment of beta-blockers (BBs), angiotensin receptor blockers (ARBs) and angiotensin converting enzyme inhibitors (ACEIs) during trastuzumab chemotherapy in order to prevent the related cardiotoxicity. The present systematic review and meta-analysis of six RCTs included patients who have predominantly non-metastatic, HER2-positive, breast cancer and received trastuzumab as primary or adjuvant therapy. Those patients did not have any obvious cardiac dysfunction or any previous therapy with cardioprotective agent. We evaluated the efficacy of the aforementioned medications for primary prevention of cardiotoxicity, using random effects models. Any preventive treatment did not reduce cardiotoxicity occurrence compared to controls (Odds ratios (OR) = 0.92, 95% CI 0.54-1.56, = 0.75). Results were similar for ACEIs/ARBs and beta-blockers. Treatment with ACEIs/ARBs led to a slight, but significant, increase in LVEF in patients compared to the placebo group. Only two studies reported less likelihood of discontinuation of trastuzumab treatment. More adequately powered RCTs are needed to determine the efficacy of routine prophylactic therapy.
PubMed: 37513895
DOI: 10.3390/ph16070983 -
BMC Endocrine Disorders Sep 2023Concerning ascending trend in the prevalence of chronic type II diabetes, prevention and the development of an effective approach after the recognition of at-risk... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Concerning ascending trend in the prevalence of chronic type II diabetes, prevention and the development of an effective approach after the recognition of at-risk individuals is crucial. This study aims to investigate comparing the influence of lifestyle modification and metformin interventions in the prevention of type II diabetes developments.
METHOD
The search was conducted using PubMed, Google Scholar, Scopus and Web of Science databases. The inclusion criteria include randomized controlled trials (RCT) which studied both lifestyle modification and metformin interventions in the population above 18 years old without a history of any type of diabetes. After excluding studies with intervention time of fewer than 6 months, a systematic review and meta-analysis were performed to evaluate relative risk (RR) with a confidence interval (CI) of 95% of type II diabetes development.
RESULTS
Data from 5 studies were included in the meta-analysis. The population also consists of individuals with a mean age of 50 years old with BMI and FBS of 35.5 and 104.7 mg/dl respectively. Participants range of prevention years was between 2-3 years with a mean of 2.8 years. Lifestyle modification decreases the probability of the incidence of type II diabetes by 25.3% (RR: 0.747, 95% CI, 0.6-0.92) compared to the metformin intervention (p-value = 0.007). Our results indicate that long-term lifestyle modifications can prevent diabetes type II and decrease diabetes mellitus incidence down to one-quarter in comparison to metformin.
CONCLUSION
Lifestyle modification can be more efficacious than metformin in diminishing the incidence of type II diabetes. Therefore, lifestyle modification can be a therapeutic strategy for controlling type II diabetes incidence, especially in high-risk individuals.
Topics: Humans; Middle Aged; Adolescent; Metformin; Diabetes Mellitus, Type 2; Behavior Therapy; Life Style; Primary Prevention
PubMed: 37723440
DOI: 10.1186/s12902-023-01445-9