-
Journal of Medical Virology Jan 2023Bladder cancer (BCa) is the 10th most common type of cancer worldwide, and human papillomavirus (HPV) is the most common sexually transmitted infection. However, the... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Bladder cancer (BCa) is the 10th most common type of cancer worldwide, and human papillomavirus (HPV) is the most common sexually transmitted infection. However, the relationship between HPV infection and the risk of BCa is still controversial and inconclusive.
METHODS
This systematic review and meta-analysis were conducted following the PRISMA 2020 reporting guideline. This study searched four bibliographic databases with no language limitation. The databases included PubMed (Medline), EMBASE, Cochrane Library, and Web of Science. Studies evaluating the interaction between HPV infection and the risk of BCa from inception through May 21, 2022, were identified and used in this study. This study estimated the overall and type-specific HPV prevalence and 95% confidence intervals (95% CI) using Random Effects models and Fixed Effects models. In addition, this study also calculated the pooled odds ratio and pooled risk ratio with 95% CI to assess the effect of HPV infection on the risk and prognosis of bladder cancer. Two-sample mendelian randomization (MR) study using genetic variants associated with HPV E7 protein as instrumental variables were also conducted.
RESULTS
This study retrieved 80 articles from the four bibliographic databases. Of the total, 27 were case-control studies, and 53 were cross-sectional studies. The results showed that the prevalence of HPV was 16% (95% CI: 11%-21%) among the BCa patients, most of which were HPV-16 (5.99% [95% CI: 3.03%-9.69%]) and HPV-18 (3.68% [95% CI: 1.72%-6.16%]) subtypes. However, the study found that the prevalence varied by region, detection method, BCa histological type, and sample source. A significantly increased risk of BCa was shown for the positivity of overall HPV (odds ratio [OR], 3.35 [95% CI: 1.75-6.43]), which was also influenced by study region, detection method, histological type, and sample source. In addition, the study found that HPV infection was significantly associated with the progression of BCa (RR, 1.73 [95% CI: 1.39-2.15]). The two-sample MR analysis found that both HPV 16 and 18 E7 protein exposure increased the risk of BCa (HPV 16 E7 protein: IVW OR per unit increase in protein level = 1.0004 [95% CI: 1.0002-1.0006]; p = 0.0011; HPV 18 E7 protein: IVW OR per unit increase in protein level = 1.0003 [95% CI: 1.0001-1.0005]; p = 0.0089).
CONCLUSION
In conclusion, HPV may play a role in bladder carcinogenesis and contribute to a worse prognosis for patients with BCa. Therefore, it is necessary for people, especially men, to get vaccinated for HPV vaccination to prevent bladder cancer.
Topics: Male; Humans; Papillomavirus Infections; Human Papillomavirus Viruses; Mendelian Randomization Analysis; Papillomaviridae; Human papillomavirus 18; Urinary Bladder Neoplasms
PubMed: 36226344
DOI: 10.1002/jmv.28208 -
Nutrients Sep 2023Both 25-autoimmunity and(25(OH)D: calcifediol) and its active form, 1,25-dihydroxyvitamin D (1,25(OH)D: calcitriol), play critical roles in protecting humans from... (Review)
Review
Both 25-autoimmunity and(25(OH)D: calcifediol) and its active form, 1,25-dihydroxyvitamin D (1,25(OH)D: calcitriol), play critical roles in protecting humans from invasive pathogens, reducing risks of autoimmunity, and maintaining health. Conversely, low 25(OH)D status increases susceptibility to infections and developing autoimmunity. This systematic review examines vitamin D's mechanisms and effects on enhancing innate and acquired immunity against microbes and preventing autoimmunity. The study evaluated the quality of evidence regarding biology, physiology, and aspects of human health on vitamin D related to infections and autoimmunity in peer-reviewed journal articles published in English. The search and analyses followed PRISMA guidelines. Data strongly suggested that maintaining serum 25(OH)D concentrations of more than 50 ng/mL is associated with significant risk reduction from viral and bacterial infections, sepsis, and autoimmunity. Most adequately powered, well-designed, randomized controlled trials with sufficient duration supported substantial benefits of vitamin D. Virtually all studies that failed to conclude benefits or were ambiguous had major study design errors. Treatment of vitamin D deficiency costs less than 0.01% of the cost of investigation of worsening comorbidities associated with hypovitaminosis D. Despite cost-benefits, the prevalence of vitamin D deficiency remains high worldwide. This was clear among those who died from COVID-19 in 2020/21-most had severe vitamin D deficiency. Yet, the lack of direction from health agencies and insurance companies on using vitamin D as an adjunct therapy is astonishing. Data confirmed that keeping an individual's serum 25(OH)D concentrations above 50 ng/mL (125 nmol/L) (and above 40 ng/mL in the population) reduces risks from community outbreaks, sepsis, and autoimmune disorders. Maintaining such concentrations in 97.5% of people is achievable through daily safe sun exposure (except in countries far from the equator during winter) or taking between 5000 and 8000 IU vitamin D supplements daily (average dose, for non-obese adults, ~70 to 90 IU/kg body weight). Those with gastrointestinal malabsorption, obesity, or on medications that increase the catabolism of vitamin D and a few other specific disorders require much higher intake. This systematic review evaluates non-classical actions of vitamin D, with particular emphasis on infection and autoimmunity related to the immune system.
Topics: Adult; Humans; Vitamin D; Autoimmunity; COVID-19; Immune System; Autoimmune Diseases; Vitamins; Vitamin D Deficiency
PubMed: 37686873
DOI: 10.3390/nu15173842 -
Comprehensive Psychiatry Apr 2021Cognitive behavioural therapy (CBT), incorporating exposure and response prevention (ERP) is widely recognised as the psychological treatment of choice for... (Meta-Analysis)
Meta-Analysis Review
Cognitive behavioural therapy with exposure and response prevention in the treatment of obsessive-compulsive disorder: A systematic review and meta-analysis of randomised controlled trials.
BACKGROUND
Cognitive behavioural therapy (CBT), incorporating exposure and response prevention (ERP) is widely recognised as the psychological treatment of choice for obsessive-compulsive disorder (OCD). Uncertainty remains however about the magnitude of the effect of CBT with ERP and the impact of moderating factors in patients with OCD.
METHOD
This systematic review and meta-analysis assessed randomised-controlled trials of CBT with ERP in patients of all ages with OCD. The study was preregistered in PROSPERO (CRD42019122311). The primary outcome was end-of-trial OCD symptom scores. The moderating effects of patient-related and study-related factors including type of control intervention and risk of bias were examined. Additional exploratory analyses assessed the effects of treatment fidelity and impact of researcher allegiance.
RESULTS
Thirty-six studies were included, involving 2020 patients (537 children/adolescents and 1483 adults) with 1005 assigned to CBT with ERP and 1015 to control conditions. When compared against all control conditions, a large pooled effect size (ES) emerged in favour of CBT with ERP (g = 0.74: 95% CI = 0.51 to 0.97 k = 36), which appeared to diminish with increasing age. While CBT with ERP was more effective than psychological placebo (g = 1.13 95% CI 0.71 to 1.55, k = 10), it was no more effective than other active forms of psychological therapy (g = -0.05: 95% CI -0.27 to 0.16, k = 8). Similarly, whereas CBT with ERP was significantly superior when compared to all forms of pharmacological treatment (g = 0.36: 95% CI 0.7 to 0.64, k = 7), the effect became marginal when compared with adequate dosages of pharmacotherapy for OCD (g = 0.32: 95% CI -0.00 to 0.64, k = 6).A minority of studies (k = 8) were deemed to be at low risk of bias. Moreover, three quarters of studies (k = 28) demonstrated suspected researcher allegiance and these studies reported a large ES (g = 0.95: 95% CI 0.69 to 1.2), while those without suspected researcher allegiance (k = 8) indicated that CBT with ERP was not efficacious (g = 0.02: 95% CI -0.29 to 0.33).
CONCLUSIONS
A large effect size was found for CBT with ERP in reducing the symptoms of OCD, but depends upon the choice of comparator control. This meta-analysis also highlights concerns about the methodological rigor and reporting of published studies of CBT with ERP in OCD. In particular, efficacy was strongly linked to researcher allegiance and this requires further future investigation.
Topics: Adolescent; Adult; Child; Cognitive Behavioral Therapy; Humans; Obsessive-Compulsive Disorder; Randomized Controlled Trials as Topic; Treatment Outcome; Uncertainty
PubMed: 33618297
DOI: 10.1016/j.comppsych.2021.152223 -
The Lancet. Digital Health Dec 2021Excessive use of digital smart devices, including smartphones and tablet computers, could be a risk factor for myopia. We aimed to review the literature on the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Excessive use of digital smart devices, including smartphones and tablet computers, could be a risk factor for myopia. We aimed to review the literature on the association between digital smart device use and myopia.
METHODS
In this systematic review and meta-analysis we searched MEDLINE and Embase, and manually searched reference lists for primary research articles investigating smart device (ie, smartphones and tablets) exposure and myopia in children and young adults (aged 3 months to 33 years) from database inception to June 2 (MEDLINE) and June 3 (Embase), 2020. We included studies that investigated myopia-related outcomes of prevalent or incident myopia, myopia progression rate, axial length, or spherical equivalent. Studies were excluded if they were reviews or case reports, did not investigate myopia-related outcomes, or did not investigate risk factors for myopia. Bias was assessed with the Joanna Briggs Institute Critical Appraisal Checklists for analytical cross-sectional and cohort studies. We categorised studies as follows: category one studies investigated smart device use independently; category two studies investigated smart device use in combination with computer use; and category three studies investigated smart device use with other near-vision tasks that were not screen-based. We extracted unadjusted and adjusted odds ratios (ORs), β coefficients, prevalence ratios, Spearman's correlation coefficients, and p values for associations between screen time and incident or prevalent myopia. We did a meta-analysis of the association between screen time and prevalent or incident myopia for category one articles alone and for category one and two articles combined. Random-effects models were used when study heterogeneity was high (I>50%) and fixed-effects models were used when heterogeneity was low (I≤50%).
FINDINGS
3325 articles were identified, of which 33 were included in the systematic review and 11 were included in the meta-analysis. Four (40%) of ten category one articles, eight (80%) of ten category two articles, and all 13 category three articles used objective measures to identify myopia (refraction), whereas the remaining studies used questionnaires to identify myopia. Screen exposure was measured by use of questionnaires in all studies, with one also measuring device-recorded network data consumption. Associations between screen exposure and prevalent or incident myopia, an increased myopic spherical equivalent, and longer axial length were reported in five (50%) category one and six (60%) category two articles. Smart device screen time alone (OR 1·26 [95% CI 1·00-1·60]; I=77%) or in combination with computer use (1·77 [1·28-2·45]; I=87%) was significantly associated with myopia. The most common sources of risk of bias were that all 33 studies did not include reliable measures of screen time, seven (21%) did not objectively measure myopia, and nine (27%) did not identify or adjust for confounders in the analysis. The high heterogeneity between studies included in the meta-analysis resulted from variability in sample size (range 155-19 934 participants), the mean age of participants (3-16 years), the standard error of the estimated odds of prevalent or incident myopia (0·02-2·21), and the use of continuous (six [55%] of 11) versus categorical (five [46%]) screen time variables INTERPRETATION: Smart device exposure might be associated with an increased risk of myopia. Research with objective measures of screen time and myopia-related outcomes that investigates smart device exposure as an independent risk factor is required.
FUNDING
None.
Topics: Adolescent; Adult; Cell Phone Use; Child; Child, Preschool; Computers; Female; Humans; Infant; Infant, Newborn; Male; Myopia; Risk Factors; Screen Time; Smartphone; Social Media; Vision, Ocular; Young Adult
PubMed: 34625399
DOI: 10.1016/S2589-7500(21)00135-7 -
Journal of the International AIDS... Mar 2022Integrated knowledge regarding pre-exposure prophylaxis (PrEP) awareness and willingness to use PrEP can be useful for HIV prevention in high incidence groups. This... (Meta-Analysis)
Meta-Analysis Review
Increasing awareness of HIV pre-exposure prophylaxis (PrEP) and willingness to use HIV PrEP among men who have sex with men: a systematic review and meta-analysis of global data.
INTRODUCTION
Integrated knowledge regarding pre-exposure prophylaxis (PrEP) awareness and willingness to use PrEP can be useful for HIV prevention in high incidence groups. This review summarizes the awareness of PrEP and willingness to use PrEP among men who have sex with men (MSM).
METHODS
Online electronic databases were searched before 31 August 2021. A meta-analysis was conducted to pool studies analysing PrEP awareness and willingness to use PrEP. LOESS regression and linear regression were applied to fit the trends over time for the proportion of MSM aware of PrEP and willing to use PrEP. Dose-response meta-analysis (DRMA) was conducted by a restricted cubic spline model to explore the relationship between willingness to use PrEP and selected factors.
RESULTS AND DISCUSSION
A total of 156 articles involving 228,403 MSM were included. The pooled proportions of MSM aware of PrEP and willing to use PrEP were 50.0 (95% CI: 44.8-55.2) and 58.6% (95% CI: 54.8-62.4), respectively. PrEP awareness varied among countries with different economic status and different WHO regions, among different publication and research years, PrEP types and support policies. PrEP willingness differed among countries with different economic status and groups with different risks of HIV. The awareness of PrEP increased from 2007 to 2019 with a slope of 0.040260 (p<0.0001), while the proportion of MSM willing to use PrEP decreased from 2007 to 2014 (slope = -0.03647, p = 0.00390) but increased after 2014 (slope = 0.04187, p = 0.03895). The main facilitators of willingness to use PrEP were PrEP awareness, condomless sexual behaviours, high perceived risk of HIV infection and influence of social network. The main barriers were doubts about the efficacy and side effects of PrEP. DRMA results indicated that MSM with more sexual partners and lower level of education were more willing to use PrEP. No publication bias was observed.
CONCLUSIONS
The proportions of PrEP awareness and willingness to use PrEP among MSM have increased since 2014, although the awareness was low and the willingness was moderate. Improving awareness of PrEP through increasing access to PrEP-related health education and enhancing risk perceptions of HIV infection could have positive effects on the willingness to use PrEP among MSM.
Topics: Female; HIV Infections; Health Knowledge, Attitudes, Practice; Homosexuality, Male; Humans; Male; Patient Acceptance of Health Care; Pre-Exposure Prophylaxis; Sexual Partners; Sexual and Gender Minorities
PubMed: 35255193
DOI: 10.1002/jia2.25883 -
Scientific Reports Nov 2021Skin aging has been defined to encompass both intrinsic and extrinsic aging, with extrinsic aging effected by environmental influences and overlaying the effects of... (Meta-Analysis)
Meta-Analysis
Skin aging has been defined to encompass both intrinsic and extrinsic aging, with extrinsic aging effected by environmental influences and overlaying the effects of chronological aging. The risk factors of skin aging have been studied previously, using methods of quantifying skin aging. However, these studies have yet to be reviewed. To better understand skin aging risk factors and collate the available data, we aimed to conduct a systematic review and meta-analysis. We conducted our systematic review in compliance with Preferred Reporting Item for Systematic Review and Meta-Analyses (PRISMA) guidelines. Embase, PubMed and Web of Science databases were searched in October 2020 using specific search strategies. Where odds ratios were reported, meta-analyses were conducted using the random effects model. Otherwise, significant factors were reported in this review. We identified seven notable risk factors for various skin aging phenotypes: age, gender, ethnicity, air pollution, nutrition, smoking, sun exposure. This review's results will guide future works, such as those aiming to examine the interaction between genetic and environmental influences.
Topics: Age Factors; Air Pollutants; Air Pollution; Humans; Risk Factors; Sex Factors; Skin; Skin Aging; Smoking; Ultraviolet Rays
PubMed: 34764376
DOI: 10.1038/s41598-021-01573-z -
Nutrients Feb 2023There has been an emerging concern that non-nutritive sweeteners (NNS) can increase the risk of cardiometabolic disease. Much of the attention has focused on acute... (Meta-Analysis)
Meta-Analysis
There has been an emerging concern that non-nutritive sweeteners (NNS) can increase the risk of cardiometabolic disease. Much of the attention has focused on acute metabolic and endocrine responses to NNS. To examine whether these mechanisms are operational under real-world scenarios, we conducted a systematic review and network meta-analysis of acute trials comparing the effects of non-nutritive sweetened beverages (NNS beverages) with water and sugar-sweetened beverages (SSBs) in humans. MEDLINE, EMBASE, and The Cochrane Library were searched through to January 15, 2022. We included acute, single-exposure, randomized, and non-randomized, clinical trials in humans, regardless of health status. Three patterns of intake were examined: (1) uncoupling interventions, where NNS beverages were consumed alone without added energy or nutrients; (2) coupling interventions, where NNS beverages were consumed together with added energy and nutrients as carbohydrates; and (3) delayed coupling interventions, where NNS beverages were consumed as a preload prior to added energy and nutrients as carbohydrates. The primary outcome was a 2 h incremental area under the curve (iAUC) for blood glucose concentration. Secondary outcomes included 2 h iAUC for insulin, glucagon-like peptide 1 (GLP-1), gastric inhibitory polypeptide (GIP), peptide YY (PYY), ghrelin, leptin, and glucagon concentrations. Network meta-analysis and confidence in the network meta-analysis (CINeMA) were conducted in R-studio and CINeMA, respectively. Thirty-six trials involving 472 predominantly healthy participants were included. Trials examined a variety of single NNS (acesulfame potassium, aspartame, cyclamate, saccharin, stevia, and sucralose) and NNS blends (acesulfame potassium + aspartame, acesulfame potassium + sucralose, acesulfame potassium + aspartame + cyclamate, and acesulfame potassium + aspartame + sucralose), along with matched water/unsweetened controls and SSBs sweetened with various caloric sugars (glucose, sucrose, and fructose). In uncoupling interventions, NNS beverages (single or blends) had no effect on postprandial glucose, insulin, GLP-1, GIP, PYY, ghrelin, and glucagon responses similar to water controls (generally, low to moderate confidence), whereas SSBs sweetened with caloric sugars (glucose and sucrose) increased postprandial glucose, insulin, GLP-1, and GIP responses with no differences in postprandial ghrelin and glucagon responses (generally, low to moderate confidence). In coupling and delayed coupling interventions, NNS beverages had no postprandial glucose and endocrine effects similar to controls (generally, low to moderate confidence). The available evidence suggests that NNS beverages sweetened with single or blends of NNS have no acute metabolic and endocrine effects, similar to water. These findings provide support for NNS beverages as an alternative replacement strategy for SSBs in the acute postprandial setting.
Topics: Humans; Sugar-Sweetened Beverages; Aspartame; Ghrelin; Glucagon; Cyclamates; Network Meta-Analysis; Blood Glucose; Glucose; Non-Nutritive Sweeteners; Beverages; Sucrose; Insulin; Sugars; Glucagon-Like Peptide 1; Water
PubMed: 36839408
DOI: 10.3390/nu15041050 -
Evidence Report/technology Assessment Aug 2007To review and synthesize the literature in the following areas: the association of specific circulating 25(OH)D concentrations with bone health outcomes in children,... (Review)
Review
OBJECTIVES
To review and synthesize the literature in the following areas: the association of specific circulating 25(OH)D concentrations with bone health outcomes in children, women of reproductive age, postmenopausal women and elderly men; the effect of dietary intakes (foods fortified with vitamin D and/or vitamin D supplementation) and sun exposure on serum 25(OH)D; the effect of vitamin D on bone mineral density (BMD) and fracture or fall risk; and the identification of potential harms of vitamin D above current reference intakes.
DATA SOURCES
MEDLINE(R) (1966-June Week 3 2006); Embase (2002-2006 Week 25); CINAHL (1982-June Week 4, 2006); AMED (1985 to June 2006); Biological Abstracts (1990-February 2005); and the Cochrane Central Register of Controlled Trials (2nd Quarter 2006).
REVIEW METHODS
Two independent reviewers completed a multi-level process of screening the literature to identify eligible studies (title and abstract, followed by full text review, and categorization of study design per key question). To minimize bias, study design was limited to randomized controlled trials (RCTs) wherever possible. Study criteria for question one were broadened to include observational studies due to a paucity of available RCTs, and question four was restricted to systematic reviews to limit scope. Data were abstracted in duplicate and study quality assessed. Differences in opinion were resolved through consensus or adjudication. If clinically relevant and statistically feasible, meta-analyses of RCTs on vitamin D supplementation and bone health outcomes were conducted, with exploration of heterogeneity. When meta-analysis was not feasible, a qualitative systematic review of eligible studies was conducted.
RESULTS
167 studies met our eligibility criteria (112 RCTs, 19 prospective cohorts, 30 case-controls and six before-after studies). The largest body of evidence on vitamin D status and bone health was in older adults with a lack of studies in premenopausal women and infants, children and adolescents. The quality of RCTs was highest in the vitamin D efficacy trials for prevention of falls and/or fractures in older adults. There was fair evidence of an association between low circulating 25(OH)D concentrations and established rickets. However, the specific 25(OH)D concentrations associated with rickets is uncertain, given the lack of studies in populations with dietary calcium intakes similar to North American diets and the different methods used to determine 25(OH)D concentrations. There was inconsistent evidence of an association of circulating 25(OH)D with bone mineral content in infants, and fair evidence that serum 25(OH)D is inversely associated with serum PTH. In adolescents, there was fair evidence for an association between 25(OH)D levels and changes in BMD. There were very few studies in pregnant and lactating women, and insufficient evidence for an association between serum 25(OH)D and changes in BMD during lactation, and fair evidence of an inverse correlation with PTH. In older adults, there was fair evidence that serum 25(OH)D is inversely associated with falls, fair evidence for a positive association with BMD, and inconsistent evidence for an association with fractures. The imprecision of 25(OH)D assays may have contributed to the variable thresholds of 25(OH)D below which the risk of fractures, falls or bone loss was increased. There was good evidence that intakes from vitamin D-fortified foods (11 RCTs) consistently increased serum 25(OH)D in both young and older adults. Eight randomized trials of ultraviolet (UV)-B radiation (artificial and solar exposure) were small and heterogeneous with respect to determination of the exact UV-B dose and 25(OH)D assay but there was a positive effect on serum 25(OH)D concentrations. It was not possible to determine how 25(OH)D levels varied by ethnicity, sunscreen use or latitude. Seventy-four trials examined the effect of vitamin D(3) or D(2) on 25(OH)D concentrations. Most trials used vitamin D(3), and the majority enrolled older adults. In three trials, there was a greater response of serum 25(OH)D concentrations to vitamin D(3) compared to vitamin D(2), which may have been due to more rapid clearance of vitamin D(2) in addition to other mechanisms. Meta-analysis of 16 trials of vitamin D(3) was consistent with a dose-response effect on serum 25(OH)D when comparing daily doses of <400 IU to doses >/= 400 IU. An exploratory analysis of the heterogeneity demonstrated a significant positive association comparable to an increase of 1 - 2 nmol/L in serum 25(OH)D for every 100 additional units of vitamin D although heterogeneity remained after adjusting for dose. Vitamin D(3) in combination with calcium results in small increases in BMD compared to placebo in older adults although quantitative synthesis was limited due to variable treatment durations and BMD sites. The evidence for fracture reduction with vitamin D supplementation was inconsistent across 15 trials. The combined results of trials using vitamin D(3) (700 - 800 IU daily) with calcium (500 - 1,200 mg) was consistent with a benefit on fractures although in a subgroup analysis by setting, benefit was primarily in elderly institutionalized women (fair evidence from two trials). There was inconsistent evidence across 14 RCTs of a benefit on fall risk. However, a subgroup analysis showed a benefit of vitamin D in postmenopausal women, and in trials that used vitamin D(3) plus calcium. In addition, there was a reduction in fall risk with vitamin D when six trials that adequately ascertained falls were combined. Limitations of the fall and fracture trials included poor compliance with vitamin D supplementation, incomplete assessment of vitamin D status and large losses to follow-up. We did not find any systematic reviews that addressed the question on the level of sunlight exposure that is sufficient to maintain serum 25(OH)D concentrations but minimizes risk of melanoma and non-melanoma skin cancer. There is little evidence from existing trials that vitamin D above current reference intakes is harmful. In most trials, reports of hypercalcemia and hypercalciuria were not associated with clinically relevant events. The Women's Health Initiative study did report a small increase in kidney stones in postmenopausal women aged 50 to 79 years whose daily vitamin D(3) intake was 400 IU (the reference intake for 50 to 70 years, and below the reference intake for > 70 years) combined with 1000 mg calcium. The increase in renal stones corresponded to 5.7 events per 10,000 person-years of exposure. The women in this trial had higher calcium intakes than is seen in most post-menopausal women.
CONCLUSIONS
The results highlight the need for additional high quality studies in infants, children, premenopausal women, and diverse racial or ethnic groups. There was fair evidence from studies of an association between circulating 25(OH)D concentrations with some bone health outcomes (established rickets, PTH, falls, BMD). However, the evidence for an association was inconsistent for other outcomes (e.g., BMC in infants and fractures in adults). It was difficult to define specific thresholds of circulating 25(OH)D for optimal bone health due to the imprecision of different 25(OH)D assays. Standard reference preparations are needed so that serum 25(OH)D can be accurately and reliably measured, and validated. In most trials, the effects of vitamin D and calcium could not be separated. Vitamin D(3) (>700 IU/day) with calcium supplementation compared to placebo has a small beneficial effect on BMD, and reduces the risk of fractures and falls although benefit may be confined to specific subgroups. Vitamin D intake above current dietary reference intakes was not reported to be associated with an increased risk of adverse events. However, most trials of higher doses of vitamin D were not adequately designed to assess long-term harms.
Topics: Adolescent; Aged; Bone Density; Bone Density Conservation Agents; Bone and Bones; Child; Child, Preschool; Dietary Supplements; Female; Fractures, Bone; Humans; Infant; Lactation; Male; Osteoporosis, Postmenopausal; Pregnancy; Rickets; Sunlight; Ultraviolet Rays; Vitamin D; Vitamin D Deficiency
PubMed: 18088161
DOI: No ID Found -
Health Technology Assessment... Jul 2014It is unclear whether or not the current evidence base allows definite conclusions to be made regarding the optimal maternal circulating concentration of... (Review)
Review
BACKGROUND
It is unclear whether or not the current evidence base allows definite conclusions to be made regarding the optimal maternal circulating concentration of 25-hydroxyvitamin D [25(OH)D] during pregnancy, and how this might best be achieved.
OBJECTIVES
To answer the following questions: (1) What are the clinical criteria for vitamin D deficiency in pregnant women? (2) What adverse maternal and neonatal health outcomes are associated with low maternal circulating 25(OH)D? (3) Does maternal supplementation with vitamin D in pregnancy lead to an improvement in these outcomes (including assessment of compliance and effectiveness)? (4) What is the optimal type (D2 or D3), dose, regimen and route for vitamin D supplementation in pregnancy? (5) Is supplementation with vitamin D in pregnancy likely to be cost-effective?
METHODS
We performed a systematic review and where possible combined study results using meta-analysis to estimate the combined effect size. Major electronic databases [including Database of Abstracts of Reviews of Effects (DARE), Centre for Reviews and Dissemination (CRD), Cochrane Database of Systematic Reviews (CDSR) and the Health Technology Assessment (HTA) database] were searched from inception up to June 2012 covering both published and grey literature. Bibliographies of selected papers were hand-searched for additional references. Relevant authors were contacted for any unpublished findings and additional data if necessary. Abstracts were reviewed by two reviewers.
SUBJECTS
pregnant women or pregnant women and their offspring.
EXPOSURE
either assessment of vitamin D status [dietary intake, sunlight exposure, circulating 25(OH)D concentration] or supplementation of participants with vitamin D or food containing vitamin D (e.g. oily fish).
OUTCOMES
offspring - birthweight, birth length, head circumference, bone mass, anthropometry and body composition, risk of asthma and atopy, small for gestational dates, preterm birth, type 1 diabetes mellitus, low birthweight, serum calcium concentration, blood pressure and rickets; mother - pre-eclampsia, gestational diabetes mellitus, risk of caesarean section and bacterial vaginosis.
RESULTS
Seventy-six studies were included. There was considerable heterogeneity between the studies and for most outcomes there was conflicting evidence. The evidence base was insufficient to reliably answer question 1 in relation to biochemical or disease outcomes. For questions 2 and 3, modest positive relationships were identified between maternal 25(OH)D and (1) offspring birthweight in meta-analysis of three observational studies using log-transformed 25(OH)D concentrations after adjustment for potential confounding factors [pooled regression coefficient 5.63 g/10% change maternal 25(OH)D, 95% confidence interval (CI) 1.11 to 10.16 g], but not in those four studies using natural units, or across intervention studies; (2) offspring cord blood or postnatal calcium concentrations in a meta-analysis of six intervention studies (all found to be at high risk of bias; mean difference 0.05 mmol/l, 95% CI 0.02 to 0.05 mmol/l); and (3) offspring bone mass in observational studies judged to be of good quality, but which did not permit meta-analysis. The evidence base was insufficient to reliably answer questions 4 and 5.
LIMITATIONS
Study methodology varied widely in terms of study design, population used, vitamin D status assessment, exposure measured and outcome definition.
CONCLUSIONS
The evidence base is currently insufficient to support definite clinical recommendations regarding vitamin D supplementation in pregnancy. Although there is modest evidence to support a relationship between maternal 25(OH)D status and offspring birthweight, bone mass and serum calcium concentrations, these findings were limited by their observational nature (birthweight, bone mass) or risk of bias and low quality (calcium concentrations). High-quality randomised trials are now required.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42011001426.
FUNDING
The National Institute for Health Research Health Technology Assessment programme.
Topics: Birth Weight; Dietary Supplements; Female; Humans; Infant, Newborn; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Vitamin D; Vitamin D Deficiency; Vitamins
PubMed: 25025896
DOI: 10.3310/hta18450 -
JAMA Oncology Dec 2020The treatment landscape for advanced hepatocellular carcinoma (HCC) has recently changed and become relatively confusing. Head-to-head comparisons between most of the... (Comparative Study)
Comparative Study
IMPORTANCE
The treatment landscape for advanced hepatocellular carcinoma (HCC) has recently changed and become relatively confusing. Head-to-head comparisons between most of the available agents have not been performed and are less likely to be examined in a prospective fashion in the future. Therefore, a network meta-analysis (NMA) is helpful to compare different agents from across different trials.
OBJECTIVE
To evaluate comparative effectiveness of different systemic treatments in advanced patients with HCC across lines of therapy.
DATA SOURCES
We searched various databases for abstracts and full-text articles published from database inception through March 2020.
STUDY SELECTION
We included phase 3 trials evaluating different vascular endothelial growth factor inhibitors (VEGFis), checkpoint inhibitors (CPIs), or their combinations in advanced HCC, in the first-line or refractory setting.
DATA EXTRACTION AND SYNTHESIS
The reporting of this systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. The overall effect was pooled using the random effects model.
MAIN OUTCOMES AND MEASURES
Outcomes of interest included overall (OS) and progression-free survival (PFS).
FINDINGS
Fourteen trials (8 in the first-line setting and 6 in the second-line setting) at low risk of bias were included. The 8 trials in the first-line setting encompassed a total of 6290 patients, with an age range of 18 to 89 years. The 5 trials included in the second-line analysis encompassed a total of 2653 patients, with an age range of 18 to 91 years. Network meta-analysis showed the combination of atezolizumab and bevacizumab was superior in patients with HCC treated in the first-line setting compared with lenvatinib (HR, 0.63; 95% CI, 0.44-0.89), sorafenib (HR, 0.58; 95% CI, 0.42-0.80), and nivolumab (HR, 0.68; 95% CI, 0.48-0.98). In the refractory setting, NMA showed that all studied drugs had PFS benefit compared with placebo. However, this only translated into OS benefit with regorafenib (HR, 0.62; 95% CI, 0.51-0.75) and cabozantinib (HR, 0.76; 95% CI, 0.63-0.92) compared with placebo. In the NMA of patients with α-fetoprotein (AFP) levels of 400 ng/mL or greater, regorafenib, cabozantinib, and ramucirumab showed PFS and OS benefit compared with placebo with no superiority of an active drug compared with any others.
CONCLUSIONS AND RELEVANCE
This systematic review and NMA of 14 trials found that atezolizumab and bevacizumab in combination is now considered the standard of care in the first-line setting in patients with advanced HCC. Regorafenib and cabozantinib are preferred options in refractory patients, with ramucirumab as an additional option in those with levels of AFP of 400 ng/mL or higher. Future trials should focus on other potential combinations and best treatment strategy in patients with prior VEGFi/CPI exposure.
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Clinical Trials, Phase III as Topic; Female; Humans; Immune Checkpoint Inhibitors; Liver Neoplasms; Male; Middle Aged; Network Meta-Analysis; Protein Kinase Inhibitors; Randomized Controlled Trials as Topic; Survival Analysis; Treatment Outcome; Young Adult
PubMed: 33090186
DOI: 10.1001/jamaoncol.2020.4930