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The Cochrane Database of Systematic... Oct 2021Endocrine therapy is effective at preventing or treating breast cancer. Some forms of endocrine therapy have been shown to reduce mammographic density. Reduced... (Review)
Review
BACKGROUND
Endocrine therapy is effective at preventing or treating breast cancer. Some forms of endocrine therapy have been shown to reduce mammographic density. Reduced mammographic density for women receiving endocrine therapy could be used to estimate the chance of breast cancer returning or developing breast cancer in the first instance (a prognostic biomarker). In addition, changes in mammographic density might be able to predict how well a woman responds to endocrine therapy (a predictive biomarker). The role of breast density as a prognostic or predictive biomarker could help improve the management of breast cancer.
OBJECTIVES
To assess the evidence that a reduction in mammographic density following endocrine therapy for breast cancer prevention in women without previous breast cancer, or for treatment in women with early-stage hormone receptor-positive breast cancer, is a prognostic or predictive biomarker.
SEARCH METHODS
We searched the Cochrane Breast Cancer Group Specialised Register, CENTRAL, MEDLINE, Embase, and two trials registers on 3 August 2020 along with reference checking, bibliographic searching, and contact with study authors to obtain further data.
SELECTION CRITERIA
We included randomised, cohort and case-control studies of adult women with or without breast cancer receiving endocrine therapy. Endocrine therapy agents included were selective oestrogen receptor modulators and aromatase inhibitors. We required breast density before start of endocrine therapy and at follow-up. We included studies published in English.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Two review authors independently extracted data and assessed risk of bias using adapted Quality in Prognostic Studies (QUIPS) and Risk Of Bias In Non-randomised Studies - of Interventions (ROBINS-I) tools. We used the GRADE approach to evaluate the certainty of the evidence. We did not perform a quantitative meta-analysis due to substantial heterogeneity across studies.
MAIN RESULTS
Eight studies met our inclusion criteria, of which seven provided data on outcomes listed in the protocol (5786 women). There was substantial heterogeneity across studies in design, sample size (349 to 1066 women), participant characteristics, follow-up (5 to 14 years), and endocrine therapy agent. There were five breast density measures and six density change definitions. All studies had at least one domain as at moderate or high risk of bias. Common concerns were whether the study sample reflected the review target population, and likely post hoc definitions of breast density change. Most studies on prognosis for women receiving endocrine therapy reported a reduced risk associated with breast density reduction. Across endpoints, settings, and agents, risk ratio point estimates (most likely value) were between 0.1 and 1.5, but with substantial uncertainty. There was greatest consistency in the direction and magnitude of the effect for tamoxifen (across endpoints and settings, risk ratio point estimates were between 0.3 and 0.7). The findings are summarised as follows. Prognostic biomarker findings: Treatment Breast cancer mortality Two studies of 823 women on tamoxifen (172 breast cancer deaths) reported risk ratio point estimates of ~0.4 and ~0.5 associated with a density reduction. The certainty of the evidence was low. Recurrence Two studies of 1956 women on tamoxifen reported risk ratio point estimates of ~0.4 and ~0.7 associated with a density reduction. There was risk of bias in methodology for design and analysis of the studies and considerable uncertainty over the size of the effect. One study of 175 women receiving an aromatase inhibitor reported a risk ratio point estimate of ~0.1 associated with a density reduction. There was considerable uncertainty about the effect size and a moderate or high risk of bias in all domains. One study of 284 women receiving exemestane or tamoxifen as part of a randomised controlled trial reported risk ratio point estimates of ~1.5 (loco-regional recurrence) and ~1.3 (distance recurrence) associated with a density reduction. There was risk of bias in reporting and study confounding, and uncertainty over the size of the effects. The certainty of the evidence for all recurrence endpoints was very low. Incidence of a secondary primary breast cancer Two studies of 451 women on exemestane, tamoxifen, or unknown endocrine therapy reported risk ratio point estimates of ~0.5 and ~0.6 associated with a density reduction. There was risk of bias in reporting and study confounding, and uncertainty over the effect size. The certainty of the evidence was very low. We were unable to find data regarding the remaining nine outcomes prespecified in the review protocol. Prevention Incidence of invasive breast cancer and ductal carcinoma in situ (DCIS) One study of 507 women without breast cancer who were receiving preventive tamoxifen as part of a randomised controlled trial (51 subsequent breast cancers) reported a risk ratio point estimate of ~0.3 associated with a density reduction. The certainty of the evidence was low. Predictive biomarker findings: One study of a subset of 1065 women from a randomised controlled trial assessed how much the effect of endocrine therapy could be explained by breast density declines in those receiving endocrine therapy. This study evaluated the prevention of invasive breast cancer and DCIS. We found some evidence to support the hypothesis, with a risk ratio interaction point estimate ~0.5. However, the 95% confidence interval included unity, and data were based on 51 women with subsequent breast cancer in the tamoxifen group. The certainty of the evidence was low.
AUTHORS' CONCLUSIONS
There is low-/very low-certainty evidence to support the hypothesis that breast density change following endocrine therapy is a prognostic biomarker for treatment or prevention. Studies suggested a potentially large effect size with tamoxifen, but the evidence was limited. There was less evidence that breast density change following tamoxifen preventive therapy is a predictive biomarker than prognostic biomarker. Evidence for breast density change as a prognostic treatment biomarker was stronger for tamoxifen than aromatase inhibitors. There were no studies reporting mammographic density change following endocrine therapy as a predictive biomarker in the treatment setting, nor aromatase inhibitor therapy as a prognostic or predictive biomarker in the preventive setting. Further research is warranted to assess mammographic density as a biomarker for all classes of endocrine therapy and review endpoints.
Topics: Biomarkers; Breast Density; Breast Neoplasms; Female; Humans; Prognosis; Randomized Controlled Trials as Topic; Tamoxifen
PubMed: 34697802
DOI: 10.1002/14651858.CD013091.pub2 -
PLoS Neglected Tropical Diseases Jun 2023Dengue has historically been considered an urban disease associated with dense human populations and the built environment. Recently, studies suggest increasing dengue... (Review)
Review
Dengue has historically been considered an urban disease associated with dense human populations and the built environment. Recently, studies suggest increasing dengue virus (DENV) transmission in rural populations. It is unclear whether these reports reflect recent spread into rural areas or ongoing transmission that was previously unnoticed, and what mechanisms are driving this rural transmission. We conducted a systematic review to synthesize research on dengue in rural areas and apply this knowledge to summarize aspects of rurality used in current epidemiological studies of DENV transmission given changing and mixed environments. We described how authors defined rurality and how they defined mechanisms for rural dengue transmission. We systematically searched PubMed, Web of Science, and Embase for articles evaluating dengue prevalence or cumulative incidence in rural areas. A total of 106 articles published between 1958 and 2021 met our inclusion criteria. Overall, 56% (n = 22) of the 48 estimates that compared urban and rural settings reported rural dengue incidence as being as high or higher than in urban locations. In some rural areas, the force of infection appears to be increasing over time, as measured by increasing seroprevalence in children and thus likely decreasing age of first infection, suggesting that rural dengue transmission may be a relatively recent phenomenon. Authors characterized rural locations by many different factors, including population density and size, environmental and land use characteristics, and by comparing their context to urban areas. Hypothesized mechanisms for rural dengue transmission included travel, population size, urban infrastructure, vector and environmental factors, among other mechanisms. Strengthening our understanding of the relationship between rurality and dengue will require a more nuanced definition of rurality from the perspective of DENV transmission. Future studies should focus on characterizing details of study locations based on their environmental features, exposure histories, and movement dynamics to identify characteristics that may influence dengue transmission.
Topics: Child; Humans; Dengue; Dengue Virus; Seroepidemiologic Studies; Longitudinal Studies; Rural Population
PubMed: 37289678
DOI: 10.1371/journal.pntd.0011333 -
Frontiers in Pediatrics 2021Technological advances over the last 2 decades have led to an increase in the time spent by children and youth engaged in screen-based activities, and growing...
Technological advances over the last 2 decades have led to an increase in the time spent by children and youth engaged in screen-based activities, and growing recognition of deleterious effects on health. In this systematic review of cohort and cross-sectional studies, we assess current data on the relationship between screen time and bone status in children and teenagers. We searched PUBMED and SCOPUS databases for studies of children and adolescents that assessed screen time and bone status, determined by measuring bone mineral content or density, bone stiffness index, bone speed of sound, bone broadband ultrasound attenuation, or frame index. Searches were limited to studies published between 1900 and 2020, and performed in accordance with Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. The studies included were evaluated using the Newcastle-Ottawa quality assessment scale. Ten cohort and cross-sectional studies including pediatric population were selected. The combined study population was 20,420 children/adolescents, of whom 18,444 participated in cross-sectional studies. Four studies assessed the effects of total screen time, seven the consequences of TV viewing time, and six the effects of recreational computer use on bone health. Our findings indicate an inverse association between total and weekly screen time and bone health in children and adolescents. In 57% of the studies included also a negative correlation between television viewing time and bone status was observed, while recreational computer time did not have a significant impact on bone health. According to the only four studies that included dietetic factors, no relevant differences were found between calcium intake and screen time or bone broadband ultrasound attenuation and bone speed of sound. Review of the literature of the past three decades provides strong support for comprehensive education of screen time on bone status. The findings of this systematic review support a negative association between screen time and bone status in children and adolescents, with a different impact when considering the different technological devices. As peak bone mass in adolescents is the strongest predictor of osteoporosis risk, strategies aimed at improving bone health should incorporate conscious use of digital technology.
PubMed: 34926335
DOI: 10.3389/fped.2021.675214 -
Clinical Therapeutics Mar 2024The aging of the population increases the incidence of postmenopausal osteoporosis, which threatens the health of elderly women. Abaloparatide is a synthetic peptide... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
The aging of the population increases the incidence of postmenopausal osteoporosis, which threatens the health of elderly women. Abaloparatide is a synthetic peptide analogue of the human parathyroid hormone-related protein that has recently been approved for the treatment of postmenopausal osteoporosis. Its efficacy and safety have not been systematically evaluated. Therefore, studies on the efficacy and safety of abaloparatide could be of assistance in the clinical medication of postmenopausal osteoporosis. The aim of this study was to evaluate the clinical efficacy and safety of abaloparatide in postmenopausal osteoporosis.
METHODS
PubMed, Cochrane Library, EMBASE, and Web of Science databases were electronically searched from inception to July 6, 2023, for relevant randomized controlled trials. Two review authors independently conducted the study screening, quality assessment (based on the Risk of Bias Assessment Tool recommended in the Cochrane handbook), and data extraction. Outcome measures included bone mineral density (BMD), bone turnover and metabolic markers, incidence of fractures, and adverse events. Data analyses were processed by using Stata SE15.
FINDINGS
Ultimately, 8 randomized controlled trials, involving a total of 3705 postmenopausal women, were included. Meta-analysis showed that abaloparatide administration significantly increased the BMD of the lumbar vertebrae (standardized mean difference [SMD], 1.28 [95% CI, 0.81-1.76); I = 78.5%]), femoral neck (SMD, 0.70 [95% CI, 0.17-1.23; I = 75.7%]), and hip bone (SMD, 0.86 [95% CI, 0.53-1.20; I = 60.4%]) in postmenopausal women compared with the control group. Type I procollagen N-terminal propeptide, a bone formation marker, was also elevated after abaloparatide administration. The incidence of vertebral fracture was lower in the abaloparatide group than in the control group (risk ratio, 0.13; 95% CI, 0.06-0.26; I = 0%). There was no significant difference in the incidence of adverse events between the abaloparatide and the placebo groups (risk ratio, 1.03; 95% CI, 0.99-1.06; I = 0%).
IMPLICATIONS
Abaloparatide has a protective effect on women with postmenopausal osteoporosis. It could reduce their risk for vertebral fracture; increase their BMD of the lumbar spine, femoral neck, and hip; and alleviate symptoms and complications of postmenopausal osteoporosis with considerable safety. Limitations of this study include not searching the gray literature and not performing a subgroup analysis. PROSPERO Registration No.: CRD42022370944.
Topics: Female; Humans; Aged; Osteoporosis, Postmenopausal; Parathyroid Hormone-Related Protein; Spinal Fractures; Bone Density Conservation Agents; Bone Density
PubMed: 38307725
DOI: 10.1016/j.clinthera.2023.12.010 -
The American Journal of Cardiology Jan 2023In the much older population (≥80 years), the management of cardiovascular diseases requires specific research to avoid a plain transposition of medical practice from... (Review)
Review
In the much older population (≥80 years), the management of cardiovascular diseases requires specific research to avoid a plain transposition of medical practice from younger populations. Whether statins are useful in primary prevention in this population is not clear. The 3 intricate issues requiring attention are (1) the impact of hypercholesterolemia on mortality and major adverse cardiovascular events in subjects >80 years, (2) the efficacy of statins to prevent cardiovascular events at this age, and (3) the safety and tolerance of statins in this population. Three systematic reviews were performed using a search on EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials, and Web of Science databases including publication until January 2021. Among the 7,617 references identified, 29 were finally retained. Regarding the first objective (16 studies, 121,250 participants), 7 studies (10,241 participants) did not find total cholesterol and low-density lipoprotein levels associated with an increased rate of major cardiovascular events in octogenarians. A total of 6 studies (14,493 participants) found increased levels associated with events, whereas 3 studies (96,516 participants) found the opposite, with increased risk of major adverse cardiovascular events with lower levels of cholesterol. In 8 studies (436,005 participants) addressing the efficacy of statins, most did not indicate a significant decrease in the rate of major cardiovascular events in these subjects. Finally, regarding tolerance (9 studies, 217,088 participants), the most important side effects in this population were muscular, hepatic, and gastrointestinal disorders. These events were more frequent than in the younger population. In conclusion, in the absence of convincing evidence, the benefit of statins in primary prevention for much older patients is not certain. Their prescription in this setting should only be considered case by case, taking into consideration physiological status, co-morbidities, level of risk, and expected life expectancy. Specific trials are mandatory.
Topics: Aged, 80 and over; Humans; Cardiovascular Diseases; Cause of Death; Cholesterol; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Primary Prevention
PubMed: 36459749
DOI: 10.1016/j.amjcard.2022.10.015 -
The Journal of Foot and Ankle Surgery :... 2020Ankle fractures are becoming increasingly more common in the elderly population and present a significant burden to the United States health care system. Many factors... (Meta-Analysis)
Meta-Analysis Review
Ankle fractures are becoming increasingly more common in the elderly population and present a significant burden to the United States health care system. Many factors have been associated with fragility ankle fractures including age, gender, body mass index, diabetes, tobacco use, and osteoporosis. However, the literature is inconsistent regarding the relationship between ankle fractures and osteoporosis. The primary aim of this meta-analysis was to quantify the relationship between bone mineral density (BMD) in elderly patients with ankle fractures compared with BMD in elderly patients without ankle fractures. A literature search was undertaken using relevant search terms. Articles were screened for suitability and data extracted where studies met inclusion criteria and were of sufficient quality. Data were combined using standard meta-analysis methods. Seven studies were used in the final analysis. A small-pooled effect size was found indicating the control group had increased BMD regardless of measurement used (95% confidence interval 0.09-0.58; I = 98.39%). Lower femoral neck BMD showed a small-pooled effect size (femoral neck 0.36; 95% confidence interval 0.00-0.73; I = 94.91%) with the ankle fracture cohort. This is the first meta-analysis to quantify the relationship between BMD and ankle fractures in the elderly population. Elderly ankle fractures showed a significant association with femoral neck BMD. The current data can be used in orthopedic clinics and Fracture Liaison Service programs to assign the appropriate subgroup of ankle fracture patients to investigative and treatment groups, assess fracture risk, and serve as an indication for secondary fracture prevention by stimulating an osteoporosis prevention workup. There may be a role for a team approach to fracture care including metabolic optimization.
Topics: Aged; Ankle Fractures; Body Mass Index; Bone Density; Fractures, Bone; Humans; Osteoporosis
PubMed: 32386919
DOI: 10.1053/j.jfas.2020.03.012 -
Journal of Pharmaceutical Policy and... Mar 2021Measuring access to medicines has often been limited to assessing availability and affordability, while little is known regarding other dimensions of access including... (Review)
Review
BACKGROUND
Measuring access to medicines has often been limited to assessing availability and affordability, while little is known regarding other dimensions of access including geographical accessibility. Our study aims to provide a systematic review of literature on the accessibility of medicines by studying the geographical distribution of pharmacies using Spatial Analytical methods.
METHODS
As systematic review of scientific peer-reviewed literature between 2000 and 2018 was carried out using PubMed, Web of Science, Google Scholar, Google and the Preferred Reporting items for Systematic Reviews and Meta-Analyses (PRISMA). Data regarding pharmacy density, distance to pharmacies in relation of pharmacy to sociodemographic factors and pharmacy characteristics were extracted from studies that meet the inclusion criteria.
FINDINGS
Twenty papers fulfilled our inclusion criteria, of which only three were from middle income countries and rest from high-income economies. Pharmacy density per population was reported in 15 studies. Although geographical information was utilized in all studies, only 14 studies reported distance to pharmacies represented as Euclidean (straight line) distance. Disparities in accessibility was reported according to population income and rural or urban location. Seven studies described additional pharmacy characteristics including opening hours, presence of a pharmacist and delivery services.
CONCLUSIONS
Geographical accessibility is a key dimension of access to medicines. Pharmacy density per population is a relevant indicator to assess geographical accessibility which should be complemented by an equity analysis using socio-demographic information and population perception of accessibility.
PubMed: 33663583
DOI: 10.1186/s40545-020-00291-7 -
Changes in bone mineral density in Down syndrome individuals: a systematic review and meta-analysis.Osteoporosis International : a Journal... Jan 2022Data evaluating changes in bone mineral density (BMD) in Down syndrome (DS) individuals remains controversial. Therefore, we conducted a systematic review and... (Meta-Analysis)
Meta-Analysis Review
Data evaluating changes in bone mineral density (BMD) in Down syndrome (DS) individuals remains controversial. Therefore, we conducted a systematic review and meta-analysis to better understand associations between BMD and DS. A systematic literature search of PubMed, EMBASE, Web of Science, and the Cochrane Library up until 1st January 2021 was conducted. We used the keywords "bone mineral density" and "Down Syndrome." Fifteen studies were included. Overall, our results showed a significant decrease in BMD of total body (TB BMD) [MD = - 0.18; 95% CI (- 0.23 and - 0.12), P < 0.00001, I = 89%], total hip (TH BMD) [MD = - 0.12; 95% CI (- 0.15 and - 0.10), P < 0.00001, I = 0%], lumbar spine (LS BMD) [MD = - 0.12; 95% CI (- 0.14 and - 0.09), P < 0.00001, I = 18%], and femoral neck (FN BMD) [MD = - 0.08; 95% CI (- 0.10 and - 0.06), P < 0.00001, I = 0%] in DS individuals when compared with controls. Moreover, the volumetric BMD of lumbar spine (LS vBMD) [MD = - 0.01; 95% CI (- 0.02 and - 0.01), P = 0.0004, I = 19%] also showed a decreasing tendency while the volumetric BMD of the femoral neck (FN vBMD) [MD = 0.01; 95% CI (0.00 and 0.02), P = 0.02, I = 0%] was elevated in DS individuals versus controls. These findings demonstrated that individuals with DS had a decreased total and regional (TH, LS, and FN) BMD when compared with the general population. Additionally, when BMD was adjusted for skeletal volume, LS vBMD was also lower, while FN vBMD was elevated in DS individuals versus controls.
Topics: Absorptiometry, Photon; Bone Density; Down Syndrome; Femur Neck; Humans; Lumbar Vertebrae
PubMed: 34383099
DOI: 10.1007/s00198-021-06070-7 -
International Journal of Environmental... Dec 2022In the United States, a significant amount of the population is affected by hyperlipidemia, which is associated with increased levels of serum low-density lipoprotein... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
In the United States, a significant amount of the population is affected by hyperlipidemia, which is associated with increased levels of serum low-density lipoprotein (LDL-C) and risk of cardiovascular disease. As of 2019, the guidelines set by the American College of Cardiology/American Heart Association advocate for the use of statins as the major contributor to lowering serum LDL-C. While proven to be effective, side effects, including muscle-related symptoms and new-onset diabetes mellitus, can make patients unable to tolerate statin therapy. Additionally, there is a subset of the population which does not approach a recommended LDL-C goal on statin treatment. Due to these findings, it was deemed necessary to review the literature of current statin-alternative lipid-lowering therapies.
METHODS
A systematic review of preclinical and clinical papers, and a current meta-analysis, was performed using PubMed and Google Scholar. Following the literature review, a meta-analysis was conducted using ProMeta 3.
RESULTS
Through systematic review and meta-analysis of the current literature, it is suggested that newer lipid-lowering therapies such as proprotein convertase subtilsin-kixen type 9 (PCSK9) inhibitors are a safe and effective statin alternative for the population with statin intolerance. PCSK9 inhibitors were shown to have no significant effect in causing myalgia in patients and showed no increase in adverse cardiovascular outcomes compared to a control of a current antilipemic medication regimen.
DISCUSSION
There are many statin-alternative therapies that should be investigated further as a potential replacement for patients with statin intolerance or as an addition for patients with statin resistance.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Proprotein Convertase 9; PCSK9 Inhibitors; Cholesterol, LDL; Cardiovascular Diseases; Anticholesteremic Agents
PubMed: 36554779
DOI: 10.3390/ijerph192416899 -
Seminars in Arthritis and Rheumatism Jun 2023This systematic review and meta-analysis aimed to summarize current evidence on vitamin D status in patients with psoriatic arthritis (PsA) with a particular focus on... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This systematic review and meta-analysis aimed to summarize current evidence on vitamin D status in patients with psoriatic arthritis (PsA) with a particular focus on disease activity.
METHODS
PubMed, Web of Science, Scopus and Cochrane Library databases were searched for studies that investigated vitamin D levels in PsA. The search was conducted on 12 October 2022. Included studies were cohorts, RCTs or observational studies, those assessing the level of 25(OH)D with control group consisting of healthy or psoriasis (Pso) patients. Nottingham-Ottawa Quality Scale was used to assess methodological quality. Random effects meta-analysis model was applied with inverse variance weighting and mean difference with 95% CI was calculated.
RESULTS
Of 356 retrieved studies, 76 duplicates and 270 studies were excluded according to the exclusion criteria with one study unavailable. Four studies including 264 PsA patients and 287 healthy controls and five studies including 225 PsA patients and 391 Pso patients assessing vitamin D levels were eligible for meta-analysis. Vitamin D levels were lower in PsA patients compared to the healthy group (MD = -6.42; 95 % CI -8.31, -4.53; P < 0.01), while higher compared to Pso patients (MD = 2.37; 95 % CI 0.97, 3.78; P < 0.01). Included studies had moderate to low risk of bias.
CONCLUSION
In conclusion, PsA patients have lower vitamin D levels than the general population. However, further studies are essential to understand the role of vitamin D in the development and treatment of PsA and the differences in vitamin D metabolism in PsA and Pso.
Topics: Humans; Vitamin D; Arthritis, Psoriatic; Psoriasis; Risk
PubMed: 37062151
DOI: 10.1016/j.semarthrit.2023.152200