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Item Ambulatory Blood Pressure Reduction With SGLT-2 Inhibitors: Dose-Response Meta-analysis and Comparative Evaluation With Low-Dose Hydrochlorothiazide(American Diabetes Association, 2019-04) Georgianos, Panagiotis I.; Agarwal, Rajiv; Medicine, School of MedicineObjective: Sodium-glucose cotransporter (SGLT)-2 inhibitors lower clinic and ambulatory blood pressure (BP), possibly through their natriuretic action. However, it remains unclear whether this BP-lowering effect is dose dependent and different from that of low-dose hydrochlorothiazide. The purpose of this meta-analysis was to quantify the association of the dose with response of ambulatory BP to SGLT-2 inhibition and to provide comparative evaluation with low-dose hydrochlorothiazide. Research design and methods: PubMed/MEDLINE, Embase, and Cochrane database of clinical trials from inception of each database through 22 August 2018. Randomized controlled trials (RCTs) reporting treatment effects of SGLT-2 inhibitors on ambulatory BP. We extracted data on the mean difference between the active treatment and placebo groups in change from baseline (CFB) of ambulatory systolic and diastolic BP. Results: We identified seven RCTs (involving 2,381 participants) comparing SGLT-2 inhibitors with placebo. Of these, two RCTs included low-dose hydrochlorothiazide as active comparator. CFB in 24-h systolic BP between SGLT-2 inhibitor and placebo groups was -3.62 mmHg (95% CI -4.29, -2.94) and in diastolic BP was -1.70 mmHg (95% CI -2.13, -1.26). BP lowering with SGLT-2 inhibition was more potent during daytime than during nighttime. The CFB in ambulatory BP was comparable between low-dose and high-dose subgroups and was similar to that for low-dose hydrochlorothiazide. Eligible RCTs did not evaluate cardiovascular outcomes/mortality. Conclusions: This meta-analysis shows that SGLT-2 inhibitors provoke an average reduction of systolic/diastolic BP 3.62/1.70 mmHg in 24-h ambulatory BP. This BP-lowering effect remains unmodified regardless of the dose of SGLT-2 inhibitor and is comparable with BP-lowering efficacy of low-dose hydrochlorothiazide.Item Body mass index is negatively associated with telomere length: a collaborative cross-sectional meta-analysis of 87 observational studies(Oxford University Press, 2018-09) Gielen, Marij; Hageman, Geja J.; Antoniou, Evangelia E.; Nordfjall, Katarina; Mangino, Massimo; Balasubramanyam, Muthuswamy; de Meyer, Tim; Hendricks, Audrey E.; Giltay, Erik J.; Hunt, Steven C.; Nettleton, Jennifer A.; Salpea, Klelia D.; Diaz, Vanessa A.; Farzaneh-Far, Ramin; Atzmon, Gil; Harris, Sarah E.; Hou, Lifang; Gilley, David; Hovatta, Iiris; Kark, Jeremy D.; Nassar, Hisham; Kurz, David J.; Mather, Karen A.; Willeit, Peter; Zheng, Yun-Ling; Pavanello, Sofia; Demerath, Ellen W.; Rode, Line; Bunout, Daniel; Steptoe, Andrew; Boardman, Lisa; Marti, Amelia; Needham, Belinda; Zheng, Wei; Ramsey-Goldman, Rosalind; Pellatt, Andrew J.; Kaprio, Jaakko; Hofmann, Jonathan N.; Gieger, Christian; Paolisso, Giuseppe; Hjelmborg, Jacob B. H.; Mirabello, Lisa; Seeman, Teresa; Wong, Jason; van der Harst, Pim; Broer, Linda; Kronenberg, Florian; Kollerits, Barbara; Strandberg, Timo; Eisenberg, Dan T. A.; Duggan, Catherine; Verhoeven, Josine E.; Schaakxs, Roxanne; Zannolli, Raffaela; dos Reis, Rosana M. R.; Charchar, Fadi J.; Tomaszewski, Maciej; Mons, Ute; Demuth, Ilja; Iglesias Molli, Andrea Elena; Cheng, Guo; Krasnienkov, Dmytro; D'Antono, Bianca; Kasielski, Marek; McDonnell, Barry J.; Ebstein, Richard Paul; Sundquist, Kristina; Pare, Guillaume; Chong, Michael; Zeegers, Maurice P.; Medical and Molecular Genetics, School of MedicineBackground: Even before the onset of age-related diseases, obesity might be a contributing factor to the cumulative burden of oxidative stress and chronic inflammation throughout the life course. Obesity may therefore contribute to accelerated shortening of telomeres. Consequently, obese persons are more likely to have shorter telomeres, but the association between body mass index (BMI) and leukocyte telomere length (TL) might differ across the life span and between ethnicities and sexes. Objective: A collaborative cross-sectional meta-analysis of observational studies was conducted to investigate the associations between BMI and TL across the life span. Design: Eighty-seven distinct study samples were included in the meta-analysis capturing data from 146,114 individuals. Study-specific age- and sex-adjusted regression coefficients were combined by using a random-effects model in which absolute [base pairs (bp)] and relative telomere to single-copy gene ratio (T/S ratio) TLs were regressed against BMI. Stratified analysis was performed by 3 age categories ("young": 18-60 y; "middle": 61-75 y; and "old": >75 y), sex, and ethnicity. Results: Each unit increase in BMI corresponded to a -3.99 bp (95% CI: -5.17, -2.81 bp) difference in TL in the total pooled sample; among young adults, each unit increase in BMI corresponded to a -7.67 bp (95% CI: -10.03, -5.31 bp) difference. Each unit increase in BMI corresponded to a -1.58 × 10(-3) unit T/S ratio (0.16% decrease; 95% CI: -2.14 × 10(-3), -1.01 × 10(-3)) difference in age- and sex-adjusted relative TL in the total pooled sample; among young adults, each unit increase in BMI corresponded to a -2.58 × 10(-3) unit T/S ratio (0.26% decrease; 95% CI: -3.92 × 10(-3), -1.25 × 10(-3)). The associations were predominantly for the white pooled population. No sex differences were observed. Conclusions: A higher BMI is associated with shorter telomeres, especially in younger individuals. The presently observed difference is not negligible. Meta-analyses of longitudinal studies evaluating change in body weight alongside change in TL are warranted.Item Caregiver Engagement Enhances Outcomes among Randomized Control Trials of Transitional Care Interventions: A Systematic Review and Meta-Analysis(Wolters Kluwer, 2022) Levoy, Kristin; Rivera, Eleanor; McHugh, Molly; Hanlon, Alexandra; Hirschman, Karen B.; Naylor, Mary D.; School of NursingBackground: Fluctuations in health among chronically ill adults result in frequent health care transitions. Some interventions to improve patient outcomes after hospitalization include caregiver engagement as a core component, yet there is unclear evidence of the effects of this component on outcomes. Objective: The objective of this study was to synthesize evidence regarding the attention given to caregiver engagement in randomized control trials of transitional care interventions (TCIs), estimate the overall intervention effects, and assess caregiver engagement as a moderator of intervention effects. Methods: Three databases were systematically searched for randomized control trials of TCIs targeting adults living with physical or emotional chronic diseases. For the meta-analysis, overall effects were computed using the relative risk (RR) effect size and inverse variance weighting. Results: Fifty-four studies met criteria, representing 31,291 participants and 66 rehospitalizations effect sizes. Half (51%) the interventions lacked focus on caregiver engagement. The overall effect of TCIs on all-cause rehospitalizations was nonsignificant at 1 month (P=0.107, k=29), but significant at ≥2 months [RR=0.89; 95% confidence interval (CI): 0.82, 0.97; P=0.007, k=27]. Caregiver engagement moderated intervention effects (P=0.05), where interventions with caregiver engagement reduced rehospitalizations (RR=0.83; 95% CI: 0.75, 0.92; P=0.001), and those without, did not (RR=0.97; 95% CI: 0.87, 1.08; P=0.550). Interventions with and without caregiver engagement did not differ in the average number of components utilized, however, interventions with caregiver engagement more commonly employed baseline needs assessments (P=0.032), discharge planning (P=0.006), and service coordination (P=0.035). Discussion: Future TCIs must consistently incorporate the active participation of caregivers in design, delivery, and evaluation.Item Colorectal cancer in patients with SARS-CoV-2: a systematic review and meta-analysis(BMC, 2022-09-12) Alhumaid, Saad; Al Mutair, Abbas; Busubaih, Jawad S.; Al Dossary, Nourah; Alsuliman, Murtadha; Baltyour, Sarah A.; Alissa, Ibrahim; Al Hassar, Hassan I.; Al Aithan, Noor A.; Albassri, Hani A.; AlOmran, Suliman A.; ALGhazal, Raed M.; Busbaih, Ahmed; Alsalem, Nasser A.; Alagnam, Waseem; Alyousef, Mohammed Y.; Alseffay, Abdulaziz U.; Al Aish, Hussain A.; Aldiaram, Ali; Al Eissa, Hisham A.; Alhumaid, Murtadha A.; Bukhamseen, Ali N.; Al Mutared, Koblan M.; Aljwisim, Abdullah H.; Twibah, Abdullah M.; AlSaeed, Meteab M.; Alkhalaf, Hussien A.; ALShakhs, Fatemah M.; Koritala, Thoyaja; Al-Tawfiq, Jaffar A.; Dhama, Kuldeep; Rabaan, Ali A.; Al-Omari, Awad; Medicine, School of MedicineBackground: Patients with colorectal cancer (CRC) are more likely to develop severe course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and experience increased risk of mortality compared to SARS-CoV-2 patients without CRC. Objectives: To estimate the prevalence of SARS-CoV-2 infection in CRC patients and analyse the demographic parameters, clinical characteristics and treatment outcomes in CRC patients with COVID-19 illness. Methods: For this systematic review and meta-analysis, we searched Proquest, Medline, Embase, Pubmed, CINAHL, Wiley online library, Scopus and Nature for studies on the incidence of SARS-CoV-2 infection in CRC patients, published from December 1, 2019 to December 31, 2021, with English language restriction. Effect sizes of prevalence were pooled with 95% confidence intervals (CIs). Sub-group analyses were performed to minimize heterogeneity. Binary logistic regression model was used to explore the effect of various demographic and clinical characteristics on patient's final treatment outcome (survival or death). Results: Of the 472 papers that were identified, 69 articles were included in the systematic review and meta-analysis (41 cohort, 16 case-report, 9 case-series, 2 cross-sectional, and 1 case-control studies). Studies involving 3362 CRC patients with confirmed SARS-CoV-2 (all patients were adults) were analyzed. The overall pooled proportions of CRC patients who had laboratory-confirmed community-acquired and hospital-acquired SARS-CoV-2 infections were 8.1% (95% CI 6.1 to 10.1, n = 1308, 24 studies, I2 98%, p = 0.66), and 1.5% (95% CI 1.1 to 1.9, n = 472, 27 studies, I2 94%, p < 0.01). The median patient age ranged from 51.6 years to 80 years across studies. The majority of the patients were male (n = 2243, 66.7%) and belonged to White (Caucasian) (n = 262, 7.8%), Hispanic (n = 156, 4.6%) and Asian (n = 153, 4.4%) ethnicity. The main source of SARS-CoV-2 infection in CRC patients was community-acquired (n = 2882, 85.7%; p = 0.014). Most of those SARS-CoV-2 patients had stage III CRC (n = 725, 21.6%; p = 0.036) and were treated mainly with surgical resections (n = 304, 9%) and chemotherapies (n = 187, 5.6%), p = 0.008. The odd ratios of death were significantly high in patients with old age (≥ 60 years) (OR 1.96, 95% CI 0.94-0.96; p < 0.001), male gender (OR 1.44, 95% CI 0.41-0.47; p < 0.001) CRC stage III (OR 1.54, 95% CI 0.02-1.05; p = 0.041), CRC stage IV (OR 1.69, 95% CI 0.17-1.2; p = 0.009), recent active treatment with chemotherapies (OR 1.35, 95% CI 0.5-0.66; p = 0.023) or surgical resections (OR 1.4, 95% CI 0.8-0.73; p = 0.016) and admission to ICU (OR 1.88, 95% CI 0.85-1.12; p < 0.001) compared to those who survived. Conclusion: SARS-CoV-2 infection in CRC patient is not uncommon and results in a mortality rate of 26.2%. Key determinants that lead to increased mortality in CRC patients infected with COVID-19 include older age (≥ 60 years old); male gender; Asian and Hispanic ethnicity; if SARS-CoV-2 was acquired from hospital source; advanced CRC (stage III and IV); if patient received chemotherapies or surgical treatment; and if patient was admitted to ICU, ventilated or experienced ARDS.Item Comparative Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Serum Electrolyte Levels in Patients with Type 2 Diabetes: A Pairwise and Network Meta-Analysis of Randomized Controlled Trials(Wolters Kluwer, 2022-01-19) Zhang, Jingjing; Huan, Yonghong; Leibensperger, Mark; Seo, Bojung; Song, Yiqing; Epidemiology, School of Public HealthBackground: Previous studies have reported that sodium-glucose co-transporter 2 (SGLT2) inhibitors (SGLT2is) affect levels of serum electrolytes, especially magnesium. This study aimed to integrate direct and indirect trial evidence to maximize statistical power to clarify their overall and comparative effects in patients with type 2 diabetes (T2D). Methods: We systematically searched PubMed, EMBASE, CENTRAL, and ClinicalTrials.gov up to January 2021 to identify eligible randomized controlled trials (RCTs) of SGLT2is that reported mean changes in serum electrolytes, including magnesium, sodium, potassium, phosphate, and calcium. We performed both random-effects pairwise and network meta-analyses to calculate the weighted mean difference (WMD) and 95% confidence intervals (CI). Results: In total, we included 25 RCTs involving 28,269 patients with T2D and 6 SGLT2is. Compared with placebo, SGLT2is were significantly associated with elevations in serum magnesium by 0.07 mmol/L (95% CI, 0.06 to 0.08 mmol/L) and serum phosphate by 0.03 mmol/L (95% CI, 0.02 to 0.04 mmol/L). Our network meta-analysis showed no evidence of significantly superior efficacy of any specific SGLT2 inhibitor over the others, although dapagliflozin was associated with a larger increment in serum magnesium (WMD=0.16 mmol/L) compared with other SGLT2is. Similarly, no statistically detectable differences among the effects of SGLT2is on serum levels of other electrolytes were detected. Conclusions: SGLT2is significantly increased serum magnesium and phosphate levels, consistent with a class effect of SGLT2 inhibition. However, further investigations of long-term efficacy and safety in patients with T2D with different clinical phenotypes are needed.Item Concentrations of HMGB1 and Hsp70 of healthy subjects in upper and lower airway: Literature Review and Meta-analysis(Ivyspring International, 2021-02-18) Min, Hyun Jin; Kim, Kyung Soo; Choi, Geun Joo; Kang, Hyun; White, Fletcher A.; Anesthesia, School of MedicineAlthough high-mobility group box 1 and heat-shock protein 70 are implicated in airway diseases and suggested as relevant diagnostic biomarkers, their control concentrations in the airways have not yet been determined. This study aimed to evaluate concentration of healthy subjects for both these proteins in the upper and lower airways via meta-analysis. We searched MEDLINE, EMBASE, and Google Scholar for articles describing concentration of healthy subjects for these proteins. Data from healthy populations were combined using a random-effects model, and subgroup and sensitivity analyses were performed to determine between-study heterogeneity. We analyzed 22 studies involving 485 patients. Concentration of healthy subjects of high-mobility group box 1 and heat-shock protein 70 varied from "not detected" to 326.13 ng/mL and from 0.20 pg/mL to 9240.00 pg/mL, respectively, with the values showing significant heterogeneity. Subgroup analysis for high-mobility group box 1 revealed 13.63 ng/mL (95% CI 12.13-15.14), 100.31 ng/mL (95% CI -31.28-231.91), 9.54 ng/mL (95% CI 8.91-10.17), and 65.82 ng/mL (95% CI 55.51-76.14) for the lower airway, upper airway, pediatric populations, and adults, respectively, whereas that for heat-shock protein 70 revealed 20.58 pg/mL (95% CI 7.87-33.29) for the lower airway and 9240.00 ±11820 pg/mL for the upper airway. Although concentrations of healthy subjects of these proteins varied in the upper and lower airways, the levels of both these proteins were higher in the upper airway than in the lower airway, and these concentrations differed according to the age and sampling procedure. Our findings support the further evaluation of these proteins as biomarkers for airway-related diseases.Item Correlating Spatial Ability With Anatomy Assessment Performance: A Meta-Analysis(Wiley, 2021) Roach, Victoria A.; Mi, Misa; Mussell, Jason; Van Nuland, Sonya E.; Lufler, Rebecca S.; DeVeau, Kathryn M.; Dunham, Stacey M.; Husmann, Polly; Herriott, Hannah L.; Edwards, Danielle N.; Doubleday, Alison F.; Wilson, Brittany M.; Wilson, Adam B.; Anatomy, Cell Biology and Physiology, School of MedicineInterest in spatial ability has grown over the past few decades following the emergence of correlational evidence associating spatial aptitude with educational performance in the fields of science, technology, engineering, and mathematics. The research field at large and the anatomy education literature on this topic are mixed. In an attempt to generate consensus, a meta-analysis was performed to objectively summarize the effects of spatial ability on anatomy assessment performance across multiple studies and populations. Relevant studies published within the past 50 years (1969-2019) were retrieved from eight databases. Study eligibility screening was followed by a full-text review and data extraction. Use of the Mental Rotations Test (MRT) was required for study inclusion. Out of 2,450 screened records, 15 studies were meta-analyzed. Seventy-three percent of studies (11 of 15) were from the United States and Canada, and the majority (9 of 15) studied professional students. Across 15 studies and 1,245 participants, spatial ability was weakly associated with anatomy performance (rpooled = 0.240; CI at 95% = 0.09, 0.38; P = 0.002). Performance on spatial and relationship-based assessments (i.e., practical assessments and drawing tasks) was correlated with spatial ability, while performance on assessments utilizing non-spatial multiple-choice items was not correlated with spatial ability. A significant sex difference was also observed, wherein males outperformed females on spatial ability tasks. Given the role of spatial reasoning in learning anatomy, educators are encouraged to consider curriculum delivery modifications and a comprehensive assessment strategy so as not to disadvantage individuals with low spatial ability.Item Do childhood externalizing disorders predict adult depression? A meta-analysis(Springer, 2014-10) Loth, Annemarie K.; Drabick, Deborah A. G.; Leibenluft, Ellen; Hulvershorn, Leslie A.; Department of Psychiatry, IU School of MedicineChildhood externalizing disorders have been linked to adult affective disorders, although some studies fail to substantiate this finding. Multiple longitudinal cohort studies identifying childhood psychopathology and their association with adult psychiatric illness have been published. To examine the association between childhood externalizing symptoms or disorders and the development of adult depression across cohorts, a meta-analysis was performed. Potential studies were identified using a PubMed search through November 2013. All published, prospective, longitudinal, community-sampled cohort studies of children (≤ 13 years) with externalizing symptoms or disorders (aggression, conduct problems, oppositional defiant disorder, conduct disorder), reassessed in adulthood (≥ 18 years) for depressive disorders (major depressive disorder, depressive disorder NOS, or dysthymic disorder) were included. A random effects model was used to summarize the pooled effect sizes. Ancillary analyses considered covariates that could account for variance among studies. Ten studies representing eight cohorts of children initially assessed at age 13 or younger (N = 17,712) were included in the meta-analysis. Childhood externalizing behavior was associated with adult depressive disorders (OR = 1.52, 95% confidence interval = 1.27-1.80, p < 0.0001). Utilizing Orwin's Fail-safe N approach, 263 studies with a mean odds ratio of 1.0 would have to be added to the analysis before the cumulative effect would become trivial. Externalizing psychopathology in childhood is associated with the development of unipolar depressive disorders in adulthood.Item Don’t Throw the Baby Out with the Bathwater: Meta-Analysis of Advance Care Planning and End-of-life Cancer Care(Elsevier, 2023) Levoy, Kristin; Sullivan, Suzanne S.; Chittams, Jesse; Myers, Ruth L.; Hickman, Susan E.; Meghani, Salimah H.; School of NursingContext: There is ongoing discourse about the impact of advance care planning (ACP) on end-of-life (EOL) care. No meta-analysis exists to clarify ACP's impact on patients with cancer. Objective: To investigate the association between, and moderators of, ACP and aggressive vs. comfort-focused EOL care outcomes among patients with cancer. Methods: Five databases were searched for peer-reviewed observational/experimental ACP-specific studies that were published between 1990-2022 that focused on samples of patients with cancer. Odds ratios were pooled to estimate overall effects using inverse variance weighting. Results: Of 8,673 articles, 21 met criteria, representing 33,541 participants and 68 effect sizes (54 aggressive, 14 comfort-focused). ACP was associated with significantly lower odds of chemotherapy, intensive care, hospital admissions, hospice use fewer than seven days, hospital death, and aggressive care composite measures. ACP was associated with 1.51 times greater odds of do-not-resuscitate orders. Other outcomes-cardiopulmonary resuscitation, emergency department admissions, mechanical ventilation, and hospice use-were not impacted. Tests of moderation revealed that the communication components of ACP produced greater reductions in the odds of hospital admissions compared to other components of ACP (e.g., documents); and, observational studies, not experimental, produced greater odds of hospice use. Conclusion: This meta-analysis demonstrated mixed evidence of the association between ACP and EOL cancer care, where tests of moderation suggested that the communication components of ACP carry more weight in influencing outcomes. Further disease-specific efforts to clarify models and components of ACP that work and matter to patients and caregivers will advance the field.Item Economic Inequality and Prosocial Behavior: A Multidimensional Analysis(2022-06) Yang, Yongzheng; Wiepking, Pamala; Badertscher, Katherine; Konrath, Sara; Ottoni-Wilhelm, Mark; Rooney, PatrickRising economic inequality has become a widespread trend and concern in recent decades. Economic inequality is often associated with pernicious consequences such as a decrease in individual health and social cohesion and an increase in political conflicts. Does economic inequality have a negative association with prosocial behavior, like many other aspects of inequality? To answer this question, this dissertation investigates the relationship between economic inequality and prosocial behavior, particularly charitable giving, by conducting three empirical studies. The first study is a meta-analysis on the overall relationship between economic inequality and prosocial behavior. Results from 192 effect sizes in 100 studies show that there is a general small, negative relationship between economic inequality and different forms of prosocial behavior. Moderator tests demonstrate that social context, the operationalization of prosocial behavior, the operationalization of economic inequality, and average age of participants significantly moderate the relationship between economic inequality and prosocial behavior. The second study differentiates between redistributive and non-redistributive charitable causes and examines how income inequality is associated with charitable giving to these two causes in China. Using synthesized data from the China Labor-force Dynamics Survey (CLDS) and official data, this study shows that income inequality has no significant relationship with charitable giving to redistributive causes, but it has a negative association with charitable giving to non-redistributive causes. Of the four moderators, only education significantly moderates the relationship between income inequality and redistributive giving. The third study tests whether and how government social spending mediates the relationship between income inequality and charitable giving. Using the US county level panel data, this study finds there is no significant relationship between income inequality and government social spending as well as between government social spending and charitable giving. Thus, government social spending does not significantly mediate the relationship between income inequality and charitable giving. However, income inequality has a robustly and significantly negative relationship with charitable giving. In sum, this dissertation furthers our understanding of the relationship between economic inequality and prosocial behavior, especially charitable giving. Given the higher economic inequality facing many countries, it is a timely dissertation and has important practical implications.
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