Publications by authors named "Taulant Muka"

104 Publications

Body Composition According to Spinal Cord Injury Level: A Systematic Review and Meta-Analysis.

J Clin Med 2021 Aug 30;10(17). Epub 2021 Aug 30.

Institute of Social and Preventive Medicine, University of Bern, Mittelstrasse 43, 3012 Bern, Switzerland.

The level of injury is linked with biochemical alterations and limitations in physical activity among individuals with spinal cord injury (SCI), which are crucial determinants of body composition. We searched five electronic databases from inception until 22 July 2021. The pooled effect estimates were computed using random-effects models, and heterogeneity was calculated using I statistics and the chi-squared test. Study quality was assessed using the Newcastle-Ottawa Scale. We pooled 40 studies comprising 4872 individuals with SCI (3991 males, 825 females, and 56 sex-unknown) in addition to chronic SCI (median injury duration 12.3 y, IQR 8.03-14.8). Individuals with tetraplegia had a higher fat percentage (weighted mean difference (WMD) 1.9%, 95% CI 0.6, 3.1) and lower lean mass (WMD -3.0 kg, 95% CI -5.9, -0.2) compared to those with paraplegia. Those with tetraplegia also had higher indicators of central adiposity (WMD, visceral adipose tissue area 0.24 dm 95% CI 0.05, 0.43 and volume 1.05 L 95% CI 0.14, 1.95), whereas body mass index was lower in individuals with tetraplegia than paraplegia (WMD -0.9 kg/mg, 95% CI -1.4, -0.5). Sex, age, and injury characteristics were observed to be sources of heterogeneity. Thus, individuals with tetraplegia have higher fat composition compared to paraplegia. Anthropometric measures, such as body mass index, may be inaccurate in describing adiposity in SCI individuals.
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http://dx.doi.org/10.3390/jcm10173911DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8432215PMC
August 2021

Systematic Review of the Effects of Oat Intake on Gastrointestinal Health.

J Nutr 2021 Sep 6. Epub 2021 Sep 6.

Swiss Paraplegic Research, Nottwil, Switzerland.

Background: Oats are a food source with multiple health benefits that could support beneficial bacterial groups and provide important bioactive compounds for the gut.

Objectives: This review explores the association between oat intake, gastrointestinal (GI) symptoms, and microbial community changes in individuals with celiac disease (CeD), irritable bowel syndrome (IBS), and inflammatory bowel disease (IBD) and without GI disease.

Methods: Four databases and Google Scholar were systematically searched from inception until April 29, 2021. Clinical trials, observational studies, and in vitro studies with human gut-derived samples were included.

Results: There were 84 articles [23 randomized controlled trials (RCTs), 21 nonrandomized trials, 8 observational studies, and 32 in vitro studies] included. Oat intake increased total bacterial count, Lactobacilli spp., and Bifidobacterium spp. in healthy individuals and those with CeD. There was an increased concentration of short-chain fatty acids and improved gut permeability with oat intake but with no significant quality-of-life difference. In some individuals with CeD, consumption of certain oat types was associated with worsening of GI symptoms. We found no studies reporting on IBS and only 3 for IBD. The quality of RCTs showed some concerns mostly in domains of randomization (73.9%), whereas the quality of evidence of non-RCTs, observational studies, and in vitro studies was satisfactory.

Conclusions: Oat intake was associated with the increase of beneficial bacterial groups in individuals without GI disease and those with CeD. Most studies showed no changes in GI symptoms with oat consumption. In vitro studies in CeD provide insight to oat-sensitive individuals and their GI mucosa, but the clinical studies remain limited, precluding our ability to draw firm conclusions. The prevalence of oat sensitivity in individuals with CeD should be further explored as this could improve clinical management and facilitate inclusion of oat in the diet for this population.
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http://dx.doi.org/10.1093/jn/nxab245DOI Listing
September 2021

Oat Intake and Risk of Type 2 Diabetes, Cardiovascular Disease and All-Cause Mortality: A Systematic Review and Meta-Analysis.

Nutrients 2021 Jul 26;13(8). Epub 2021 Jul 26.

Standard Process Nutrition Innovation Center, Kannapolis, NC 28018, USA.

Cardiovascular disease (CVD) and type 2 diabetes (T2D) remain the top disease and mortality burdens worldwide. Oats have been shown to benefit cardiovascular health and improve insulin resistance. However, the evidence linking oat consumption with CVD, T2D and all-cause mortality remains inconclusive. We conducted a comprehensive systematic review and meta-analysis of prospective cohort studies to evaluate the associations between oat consumption and risks of T2D, CVD and all-cause mortality in the general population. Five electronic databases were searched until September, 2020. Study specific relative risks (RR) were meta-analyzed using random effect models. Of 4686 relevant references, we included 9 articles, based on 8 unique studies and 471,157 participants. Comparing oat consumers versus non-consumers, RRs were 0.86 (95% CI 0.72-1.03) for T2D incidence and 0.73 (95% CI 0.5-1.07) for combined CVD incidence. Comparing participants with highest versus lowest oat intake, RRs were 0.78 (95% CI 0.74-0.82) for T2D incidence, 0.81 (95% CI 0.61-1.08) for CHD incidence and 0.79 (95% CI 0.59-1.07) for stroke. For all-cause mortality one study based on three cohorts found RR for men and women were 0.76 (95% CI 0.69-0.85) and 0.78 (95% CI 0.70-0.87), respectively. Most studies ( = 6) were of fair to good quality. This meta-analysis suggests that consumption of oat could reduce the risk for T2D and all-cause mortality, while no significant association was found for CVD. Future studies should address a lack of standardized methods in assessing overall oat intake and type of oat products, and investigate a dose-dependent response of oat products on cardiometabolic outcomes in order to introduce oat as preventive and treatment options for the public.
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http://dx.doi.org/10.3390/nu13082560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8398256PMC
July 2021

The neurological level of spinal cord injury and cardiovascular risk factors: a systematic review and meta-analysis.

Spinal Cord 2021 Aug 20. Epub 2021 Aug 20.

Swiss Paraplegic Research, Nottwil, Switzerland.

Study Design: Systematic review and meta-analysis.

Objective: To determine the difference in cardiovascular risk factors (blood pressure, lipid profile, and markers of glucose metabolism and inflammation) according to the neurological level of spinal cord injury (SCI).

Methods: We searched 5 electronic databases from inception until July 4, 2020. Data were extracted by two independent reviewers using a pre-defined data collection form. The pooled effect estimate was computed using random-effects models, and heterogeneity was calculated using I statistic and chi-squared test (CRD42020166162).

Results: We screened 4863 abstracts, of which 47 studies with 3878 participants (3280 males, 526 females, 72 sex unknown) were included in the meta-analysis. Compared to paraplegia, individuals with tetraplegia had lower systolic and diastolic blood pressure (unadjusted weighted mean difference, -14.5 mmHg, 95% CI -19.2, -9.9; -7.0 mmHg 95% CI -9.2, -4.8, respectively), lower triglycerides (-10.9 mg/dL, 95% CI -19.7, -2.1), total cholesterol (-9.9 mg/dL, 95% CI -14.5, -5.4), high-density lipoprotein (-1.7 mg/dL, 95% CI -3.3, -0.2) and low-density lipoprotein (-5.8 mg/dL, 95% CI -9.0, -2.5). Comparing individuals with high- vs. low-thoracic SCI, persons with higher injury had lower systolic and diastolic blood pressure (-10.3 mmHg, 95% CI -13.4, -7.1; -5.3 mmHg 95% CI -7.5, -3.2, respectively), while no differences were found for low-density lipoprotein, serum glucose, insulin, and inflammation markers. High heterogeneity was partially explained by age, prevalent cardiovascular diseases and medication use, body mass index, sample size, and quality of studies.

Conclusion: In SCI individuals, the level of injury may be an additional non-modifiable cardiovascular risk factor. Future well-designed longitudinal studies with sufficient follow-up and providing sex-stratified analyses should confirm our findings and explore the role of SCI level in cardiovascular health and overall prognosis and survival.
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http://dx.doi.org/10.1038/s41393-021-00678-6DOI Listing
August 2021

A systematic review of the safety and efficacy of currently used treatment modalities in the treatment of patients with PIK3CA-related overgrowth spectrum.

J Vasc Surg Venous Lymphat Disord 2021 Aug 3. Epub 2021 Aug 3.

Division of Angiology, Swiss Cardiovascular Center, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. Electronic address:

Background: PIK3CA (activating mutations of the p110α subunit of phosphatidylinositol 3-kinases)-related overgrowth spectrums (PROS) include a variety of clinical presentations that are associated with hypertrophy of different parts of the body. We performed a systematic literature review to assess the current treatment options and their efficacy and safety for PROS.

Methods: A literature search was performed in Embase, MEDLINE (Ovid), Web of Science Core Collection, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and Google Scholar to retrieve studies on the treatment of hypertrophy in PROS. Randomized controlled trials, cohort studies, and case series with ≥10 patients were included in the present review. The titles, abstracts, and full text were assessed by two reviewers independently. The risk of bias was assessed using the Newcastle-Ottawa scale.

Results: We included 16 studies of the treatment of hypertrophy in PROS patients, 13 (81.3%) from clinical retrospective studies and 3 (13.7%) from prospective cohort studies. The risk of bias grade was low for 2, medium for 12, and high for 2 studies. Of the 16 studies, 13 reported on surgical treatment and 3 reported pharmacologic treatment using phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway inhibitors in PROS patients. In 3 studies, PROS was defined by a mutation in the PIK3CA gene, and 13 studies relied on a clinical definition of PROS. Surgical therapy was beneficial for a specific subgroup of PROS (macrodactyly). However, little has been reported concerning surgery and the potential benefits for other PROS entities. The reported side effects after surgical therapy were mostly prolonged wound healing or scarring. PI3K/mTOR pathway inhibition was beneficial in patients with PROS by reducing hypertrophy and systemic symptoms. The adverse effects reported included infection, changes in blood count, liver enzymes, and metabolic measures.

Conclusions: Surgery is a locally limited treatment option for specific types of PROS. A promising treatment option for PROS is pharmacologic PIK3CA inhibition. However, the level of evidence on the treatment of overgrowth in PROS patients is limited.
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http://dx.doi.org/10.1016/j.jvsv.2021.07.008DOI Listing
August 2021

Sex and gender gap in spinal cord injury research: Focus on cardiometabolic diseases. A mini review.

Maturitas 2021 May 4;147:14-18. Epub 2021 Mar 4.

Swiss Paraplegic Research, Nottwil, Switzerland; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland. Electronic address:

Cardiometabolic disease (CMD) is among the leading causes of morbidity and mortality in people with a spinal cord injury (SCI). Despite well-acknowledged sex and gender differences in CMD in the general population, they remain insufficiently studied in persons with SCI. To describe the landscape of sex and gender in SCI research, we searched the literature for systematic reviews on cardiometabolic health in this population. Out of 15 systematic reviews identified, only 9 provided meaningful information on sex. Although one-quarter to one-fifth of the SCI population is female, women comprised only one-eighth to a quarter of study participants. A number of clinical studies purposively excluded women, to make the study population more homogenous. For those studies which included both sexes, in general, no sex-specific analyses were performed due to small sample sizes. All these reasons have contributed to the underrepresentation of females in the current body of evidence. Therefore, future studies should adopt a more sex- and gender-sensitive research framework to address cardiometabolic risk in SCI. Novel and advanced epidemiological methods should also be used, considering small sample sizes. Finally, collaborative research (through consortia and multi-center studies) should be encouraged to include more females. More inclusive research will ensure that everyone will benefit from scientific advancements, regardless of sex and gender.
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http://dx.doi.org/10.1016/j.maturitas.2021.03.004DOI Listing
May 2021

Menopausal Transition Is Not Associated with Dietary Change in Swiss Women.

J Nutr 2021 05;151(5):1269-1276

Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland.

Background: Adherence to a healthy diet could contribute to maintaining adequate health throughout the menopausal transition, but data are scarce.

Objective: We evaluated the association between menopausal status and changes in dietary intake in Swiss adult women.

Methods: Cross-sectional (n = 2439) and prospective analyses (n = 1656) were conducted between 2009 and 2012 (first follow-up) among women (mean age ± SD, 58.2 ± 10.5 y) living in Lausanne, Switzerland. In both visits, dietary intake was assessed using a validated FFQ, and menopausal status was classified based on the presence or absence of menstruations. Multivariable linear and logistic regression models were used to investigate the cross-sectional association of menopausal status (postmenopausal compared with premenopausal) at the first follow-up with food intake and dietary recommendations. To examine whether menopausal status (premenopausal as reference group, menopausal transition, and postmenopausal) during 5 y of follow-up was associated with longitudinal changes in diet, including adherence to dietary Swiss recommendations, we applied multivariable linear and logistic mixed models adjusted for several covariates.

Results: At the first follow-up, postmenopausal women consumed less (P < 0.002) meat [median (IQR) 57.2 (35-86.2) compared with 62.5 (41.2-95.2) g/d], pasta [61.8 (37.5-89.2) compared with 85 (57.8-128) g/d], and added sugar [0.1 (0-4) compared with 0.7 (0-8) g/d] and more dairy products [126 (65.4-214) compared with 109 (64.5-182) g/d] and fruit [217 (115-390) compared with 174 (83.2-319) g/d] than premenopausal women. However, linear regression analysis adjusted for potential confounding factors showed no independent (cross-sectional) associations of menopausal status with total energy intake (TEI) and individual macro- or micronutrient intakes. In the prospective analysis, compared with women who remained premenopausal during follow-up (n = 244), no differences were found in changes in TEI, dietary intakes, or adherence to the Swiss dietary recommendations in women transitioning from premenopausal to postmenopausal (n = 229) and who remained postmenopausal (n = 1168).

Conclusion: The menopausal transition is not associated with changes in dietary habits among Swiss women.
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http://dx.doi.org/10.1093/jn/nxab003DOI Listing
May 2021

Phytochemical characterization of turnip greens (Brassica rapa ssp. rapa): A systematic review.

PLoS One 2021 17;16(2):e0247032. Epub 2021 Feb 17.

Nutrition Innovation Center, Standard Process Inc., Kannapolis, NC, United States of America.

Objective: The Turnip (Brassica rapa L. ssp. rapa) is a leaf and root vegetable grown and consumed worldwide. The consumption of Turnip has been associated with beneficial effects on human health due to their phytochemicals that may control a variety of physiological functions, including antioxidant activity, enzyme regulation, and apoptotic control and the cell cycle. The current systematic review of the literature aims to evaluate both the profile and quantity of phytochemicals commonly found in Turnip greens and to provide perspectives for further investigation.

Methods: This review was conducted following the PRISMA guidelines. Four bibliographic databases (PubMed, Embase, Web-of-Science and Cochrane Central Register of Controlled Trials) were searched to identify published studies until April 8th, 2020 (date last searched) without data and language restriction. Studies were included if they used samples of Turnip greens (the leaves), and evaluated its phytochemical content. Two reviewers independently evaluated the titles and abstracts according to the selection criteria. For each potentially eligible study, two reviewers assessed the full-texts and independently extracted the data using a predesigned data extraction form.

Results: Based on the search strategy 5,077 potentially relevant citations were identified and full texts of 37 studies were evaluated, among which 18 studies were eligible to be included in the current review. The majority of included studies were focused on identification of glucosinolates and isothiocyanates (n = 14, 82%), four studies focused on organic acids, and five studies reported phenolic component profile in Turnip greens. Among included studies nine studies (50%) provided information on phytochemical's content. We found 129 phytochemicals (19 glucosinolates, 33 glucosinolate-breakdown products, 10 organic acids and 59 polyphenolic compounds) reported in Turnip greens. Flavonoids were mainly present as quercetin, kaempferol and isorhamnetin derivatives; while aliphatic forms were the predominant glucosinolate (gluconapin was the most common across five studies, followed by glucobrassicanapin). In general, the phytochemical content varied among the leaves, tops and Turnip roots.

Conclusions: Emerging evidence suggests the Turnip as a substantial source of diverse bioactive compounds. However, detailed investigation on the pure compounds derived from Turnip green, their bioavailability, transport and metabolism after consumption is further needed. Additional studies on their biological activity are crucial to develop dietary recommendations on the effective dosage and dietary recommendation of Turnip greens for nutrition and health.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247032PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7888597PMC
August 2021

Meta-analysis on facemask use in community settings to prevent respiratory infection transmission shows no effect.

Int J Infect Dis 2021 02 17;103:257-259. Epub 2020 Nov 17.

Institute of Social and Preventive Medicine (ISPM), University of Bern, Mittelstrasse 43, 3012, Bern, Switzerland. Electronic address:

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http://dx.doi.org/10.1016/j.ijid.2020.11.139DOI Listing
February 2021

A systematic review of phytochemicals in oat and buckwheat.

Food Chem 2021 Feb 5;338:127982. Epub 2020 Sep 5.

Standard Process Nutrition Innovation Center, Kannapolis, NC 28018, USA.

Consumption of oat and buckwheat have been associated with various health benefits that may be attributed to their nutritional composition. We performed a systematic review to evaluate the profile and quantity of bioactive compounds present in oat and buckwheat. Among 154 studies included in final analysis, 113 and 178 bioactive compounds were reported in oat and buckwheat, respectively. Total phytosterols, tocols, flavonoids and rutin content were generally higher in buckwheat, β-glucans were significantly higher in oat, while avenanthramides and saponins were characteristically present in oat. The majority of studies included in current review were published before 2010s. The heterogeneous methodological procedures used across the studies precluded our possibility to meta-analyse the evidence and raises the need for harmonization of separation and extraction methods in future studies. Our findings should further stimulate the exploration of metabolites related to identified phytochemicals and their roles in human health.
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http://dx.doi.org/10.1016/j.foodchem.2020.127982DOI Listing
February 2021

COVID-19 in Health-Care Workers: A Living Systematic Review and Meta-Analysis of Prevalence, Risk Factors, Clinical Characteristics, and Outcomes.

Am J Epidemiol 2021 01;190(1):161-175

Health-care workers (HCWs) are at the frontline of response to coronavirus disease 2019 (COVID-19), being at a higher risk of acquiring the disease and, subsequently, exposing patients and others. Searches of 8 bibliographic databases were performed to systematically review the evidence on the prevalence, risk factors, clinical characteristics, and prognosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among HCWs. A total of 97 studies (all published in 2020) met the inclusion criteria. The estimated prevalence of SARS-CoV-2 infection from HCWs' samples, using reverse transcription-polymerase chain reaction and the presence of antibodies, was 11% (95% confidence interval (CI): 7, 15) and 7% (95% CI: 4, 11), respectively. The most frequently affected personnel were nurses (48%, 95% CI: 41, 56), whereas most of the COVID-19-positive medical personnel were working in hospital nonemergency wards during screening (43%, 95% CI: 28, 59). Anosmia, fever, and myalgia were the only symptoms associated with HCW SARS-CoV-2 positivity. Among HCWs positive for COVID-19 by reverse transcription-polymerase chain reaction, 40% (95% CI: 17, 65) were asymptomatic at time of diagnosis. Finally, severe clinical complications developed in 5% (95% CI: 3, 8) of the COVID-19-positive HCWs, and 0.5% (95% CI: 0.02, 1.3) died. Health-care workers suffer a significant burden from COVID-19, with those working in hospital nonemergency wards and nurses being the most commonly infected personnel.
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http://dx.doi.org/10.1093/aje/kwaa191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7499478PMC
January 2021

Effects of phytoestrogen supplementation on intermediate cardiovascular disease risk factors among postmenopausal women: a meta-analysis of randomized controlled trials.

Menopause 2020 09;27(9):1081-1092

Leibniz Institute for Prevention Research and Epidemiology - BIPS, Bremen, Germany.

Importance: Phytoestrogens are becoming popular constituents of human diets and are increasingly used by postmenopausal women.

Objective: Our study aims to determine the effects of phytoestrogen supplementation on intermediate cardiovascular disease (CVD) risk factors in postmenopausal women.

Evidence Review: Five electronic databases (Medline, EMBASE, Web of Science, Cochrane CENTRAL, Google Scholar) were systematically searched to identify eligible studies, that is, randomized controlled trials (RCTs) that assessed the association of phytoestrogen supplementation with CVD risk factors (serum lipids, homocysteine, fibrinogen, markers of inflammation, oxidative stress and endothelial function, carotid intima-media thickness [CIMT]) in postmenopausal women. Data were extracted by two independent reviewers using a predefined data collection form.

Findings: In total, 56 RCTs were identified, including 4,039 individual postmenopausal women. There was substantial heterogeneity in quality across studies. Twenty-six (46%) RCTs showed poor quality and there was an indication of publication bias presence for some of the biomarkers. Results are reported in pooled mean difference (95% CI) of changes. Use of phytoestrogens was associated with a decrease in serum total cholesterol (-0.27 mmol/L [-0.41 to -0.13]), low-density lipoprotein (-0.25 mmol/L [-0.37 to -0.13]), triglycerides (-0.20 mmol/L [-0.28 to -0.11]), and apolipoprotein B (-0.13 g/L [-0.23 to -0.03]) and with an increase in serum apolipoprotein A-1 (0.04 g/L [0.02-0.07]. Also, phytoestrogen supplementation was associated with a decrease in serum intercellular adhesion molecule 1 (-18.86 ng/mL [-30.06 to -7.65]) and E-selectin (-2.32 ng/mL [-4.05 to -0.59]). There was no association observed between phytoestrogen supplementation and inflammatory markers, fibrinogen, homocysteine, or other endothelial function markers. In contrast, use of phytoestrogens was associated with an increase in CIMT (9.34 μm [95% CI, 0.39-18.29]). Effect estimates of phytoestrogen supplementation on oxidative stress could not be pooled.

Conclusions And Relevance: Phytoestrogen supplementation seems to modestly improve the CVD risk profile of postmenopausal women by influencing blood lipids and parameters of endothelial function. In women with an increased risk of atherosclerosis, although modest, a harmful effect on CIMT progression may be present. Because of limited quality and the heterogeneous nature of the current evidence, additional rigorous studies are needed to explore the role of phytoestrogens in menopausal cardiovascular health. : Video Summary: http://links.lww.com/MENO/A593.
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http://dx.doi.org/10.1097/GME.0000000000001566DOI Listing
September 2020

Anemia and iron metabolism in COVID-19: a systematic review and meta-analysis.

Eur J Epidemiol 2020 Aug 20;35(8):763-773. Epub 2020 Aug 20.

Institute of Social and Preventive Medicine (ISPM), University of Bern, Mittelstrasse 43, 3012, Bern, Switzerland.

Iron metabolism and anemia may play an important role in multiple organ dysfunction syndrome in Coronavirus disease 2019 (COVID-19). We conducted a systematic review and meta-analysis to evaluate biomarkers of anemia and iron metabolism (hemoglobin, ferritin, transferrin, soluble transferrin receptor, hepcidin, haptoglobin, unsaturated iron-binding capacity, erythropoietin, free erythrocyte protoporphyrine, and erythrocyte indices) in patients diagnosed with COVID-19, and explored their prognostic value. Six bibliographic databases were searched up to August 3rd 2020. We included 189 unique studies, with data from 57,563 COVID-19 patients. Pooled mean hemoglobin and ferritin levels in COVID-19 patients across all ages were 129.7 g/L (95% Confidence Interval (CI), 128.51; 130.88) and 777.33 ng/mL (95% CI, 701.33; 852.77), respectively. Hemoglobin levels were lower with older age, higher percentage of subjects with diabetes, hypertension and overall comorbidities, and admitted to intensive care. Ferritin level increased with older age, increasing proportion of hypertensive study participants, and increasing proportion of mortality. Compared to moderate cases, severe COVID-19 cases had lower hemoglobin [weighted mean difference (WMD), - 4.08 g/L (95% CI - 5.12; - 3.05)] and red blood cell count [WMD, - 0.16 × 10 /L (95% CI - 0.31; - 0.014)], and higher ferritin [WMD, - 473.25 ng/mL (95% CI 382.52; 563.98)] and red cell distribution width [WMD, 1.82% (95% CI 0.10; 3.55)]. A significant difference in mean ferritin levels of 606.37 ng/mL (95% CI 461.86; 750.88) was found between survivors and non-survivors, but not in hemoglobin levels. Future studies should explore the impact of iron metabolism and anemia in the pathophysiology, prognosis, and treatment of COVID-19.
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http://dx.doi.org/10.1007/s10654-020-00678-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438401PMC
August 2020

Efficacy of Dietary Supplements to Reduce Liver Fat.

Nutrients 2020 Jul 31;12(8). Epub 2020 Jul 31.

Department of Diabetes, Endocrinology, Nutritional Medicine, and Metabolism, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland.

Liver fat accumulation is an important pathophysiological feature of non-alcoholic fatty liver disease that may be modulated by dietary supplements (DS). A systematic search of the literature was conducted for randomized controlled trials (RCTs) pertaining to the effect of a DS on liver fat as assessed using quantitative tomographic imaging in human adults. Where feasible, data were pooled, and meta-analyses conducted using random-effect model. Quality assessment was done according the Cochrane Collaboration's tool for assessing risk of bias. Twenty RCTs, involving 1171 overweight and obese adults, of which 36% were females, with or without comorbidities, were included. Only RCTs assessing omega-3 fatty acids ( = 4) and resveratrol ( = 4) qualified for meta-analysis. Results did neither favor omega-3 (effect size -1.17; weighted mean difference (WMD) (95% confidence interval (CI)) -3.62, 1.28; < 0.001) nor resveratrol supplementation (0.18; 95% CI -1.08, 1.43; = 0.27). The findings of the qualitatively summarized RCTs suggested that catechins ( = 1), ( = 1), and carnitine ( = 1) may reduce liver fat. All other DS did not show any influence. The current evidence is scarce, of limited quality and does not support DS use to reduce liver fat. Further well-designed trials are warranted.
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http://dx.doi.org/10.3390/nu12082302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7469018PMC
July 2020

Bioactive compounds and nutritional composition of Swiss chard ( L. var. and ): a systematic review.

Crit Rev Food Sci Nutr 2020 Aug 4:1-16. Epub 2020 Aug 4.

Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.

Swiss chard ( L. var. or ) is a green leafy vegetable whose bioactive compounds have been studied due to its effects on health. We systematically reviewed the nutritional profile and bioactive composition of Swiss chard and reported their concentrations. Four main databases were searched for studies analyzing the chemical composition of Swiss chard. Screening, selection of articles, and data extraction were carried out by two independent reviewers. Twenty-eight articles of 1102 records identified by bibliographic search met our inclusion criteria for final analysis. We found a total of 192 chemical compounds categorized into 23 groups. The variety was the most studied, and nutrients and phytochemicals were reported mainly on leaves. Betalains with 20% of the reported data, fats (16%), flavonoids (11%), non-flavonoid phenolics (11%), terpenes and derivatives (8%), carbohydrates (7%), and minerals (6%) were among the most reported categories. Swiss chard leaves have the highest content of fiber, sodium, magnesium, flavonoids, and vitamin C, while stems are high in potassium. Swiss chard should be considered a source of nutrients and phytochemicals, and further research is needed on identifying and quantifying other bioactive compounds and understanding their impact on health.
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http://dx.doi.org/10.1080/10408398.2020.1799326DOI Listing
August 2020

Genomic analysis of diet composition finds novel loci and associations with health and lifestyle.

Mol Psychiatry 2021 Jun 11;26(6):2056-2069. Epub 2020 May 11.

Department of Endocrinology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.

We conducted genome-wide association studies (GWAS) of relative intake from the macronutrients fat, protein, carbohydrates, and sugar in over 235,000 individuals of European ancestries. We identified 21 unique, approximately independent lead SNPs. Fourteen lead SNPs are uniquely associated with one macronutrient at genome-wide significance (P < 5 × 10), while five of the 21 lead SNPs reach suggestive significance (P < 1 × 10) for at least one other macronutrient. While the phenotypes are genetically correlated, each phenotype carries a partially unique genetic architecture. Relative protein intake exhibits the strongest relationships with poor health, including positive genetic associations with obesity, type 2 diabetes, and heart disease (r ≈ 0.15-0.5). In contrast, relative carbohydrate and sugar intake have negative genetic correlations with waist circumference, waist-hip ratio, and neighborhood deprivation (|r| ≈ 0.1-0.3) and positive genetic correlations with physical activity (r ≈ 0.1 and 0.2). Relative fat intake has no consistent pattern of genetic correlations with poor health but has a negative genetic correlation with educational attainment (r ≈-0.1). Although our analyses do not allow us to draw causal conclusions, we find no evidence of negative health consequences associated with relative carbohydrate, sugar, or fat intake. However, our results are consistent with the hypothesis that relative protein intake plays a role in the etiology of metabolic dysfunction.
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http://dx.doi.org/10.1038/s41380-020-0697-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767645PMC
June 2021

Fetal sex and maternal pregnancy outcomes: a systematic review and meta-analysis.

Biol Sex Differ 2020 05 11;11(1):26. Epub 2020 May 11.

Department of Obstetrics and Gynecology, Erasmus Medical Center, Rotterdam, the Netherlands.

Background: Since the placenta also has a sex, fetal sex-specific differences in the occurrence of placenta-mediated complications could exist.

Objective: To determine the association of fetal sex with multiple maternal pregnancy complications.

Search Strategy: Six electronic databases Ovid MEDLINE, EMBASE, Cochrane Central, Web-of-Science, PubMed, and Google Scholar were systematically searched to identify eligible studies. Reference lists of the included studies and contact with experts were also used for identification of studies.

Selection Criteria: Observational studies that assessed fetal sex and the presence of maternal pregnancy complications within singleton pregnancies.

Data Collection And Analyses: Data were extracted by 2 independent reviewers using a predesigned data collection form.

Main Results: From 6522 original references, 74 studies were selected, including over 12,5 million women. Male fetal sex was associated with term pre-eclampsia (pooled OR 1.07 [95%CI 1.06 to 1.09]) and gestational diabetes (pooled OR 1.04 [1.02 to 1.07]). All other pregnancy complications (i.e., gestational hypertension, total pre-eclampsia, eclampsia, placental abruption, and post-partum hemorrhage) tended to be associated with male fetal sex, except for preterm pre-eclampsia, which was more associated with female fetal sex. Overall quality of the included studies was good. Between-study heterogeneity was high due to differences in study population and outcome definition.

Conclusion: This meta-analysis suggests that the occurrence of pregnancy complications differ according to fetal sex with a higher cardiovascular and metabolic load for the mother in the presence of a male fetus.

Funding: None.
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http://dx.doi.org/10.1186/s13293-020-00299-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7216628PMC
May 2020

Meta-analysis of l-carnitine supplementation on lipid profile and glycemic control: Inadequate search strategy and other methodological issues.

Clin Nutr 2020 06 25;39(6):1975-1976. Epub 2020 Apr 25.

Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland. Electronic address:

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http://dx.doi.org/10.1016/j.clnu.2020.04.016DOI Listing
June 2020

Trajectories of BMI Before Diagnosis of Type 2 Diabetes: The Rotterdam Study.

Obesity (Silver Spring) 2020 06 7;28(6):1149-1156. Epub 2020 May 7.

Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.

Objective: People with diabetes show great variability in weight gain and duration of obesity at the time of diagnosis. BMI trajectories and other cardiometabolic risk factors prior to type 2 diabetes were investigated.

Methods: A total of 6,223 participants from the Rotterdam Study cohort were included. BMI patterns before diagnosis of diabetes were identified through latent class trajectories.

Results: During a mean follow-up of 13.7 years, 565 participants developed type 2 diabetes. Three distinct trajectories of BMI were identified, including the "progressive overweight" group (n = 481, 85.1%), "progressive weight loss" group (n = 59, 10.4%), and "persistently high BMI" group (n = 25, 4.4%). The majority, the progressive overweight group, was characterized by a steady increase of BMI in the overweight range 10 years before diabetes diagnosis. The progressive weight loss group had fluctuations of glucose and marked beta cell function loss. The persistently high BMI group was characterized by a slight increase in insulin levels and sharp increase of insulin resistance accompanied by a rapid decrease of beta cell function.

Conclusions: Heterogeneity of BMI changes prior to type 2 diabetes was found in a middle-aged and elderly white population. Prevention strategies should be tailored rather than focusing only on high-risk individuals.
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http://dx.doi.org/10.1002/oby.22802DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7317538PMC
June 2020

Sexually dimorphic DNA-methylation in cardiometabolic health: A systematic review.

Maturitas 2020 May 13;135:6-26. Epub 2020 Feb 13.

Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland; Swiss Paraplegic Research, Nottwil, Switzerland.

Sex is a major determinant of cardiometabolic risk. DNA methylation (DNAm), an important epigenetic mechanism that differs between sexes, has been associated with cardiometabolic diseases. Therefore, we aimed to systematically review studies in adults investigating sex-specific associations of DNAm with intermediate cardiometabolic traits and incident cardiovascular disease including stroke, myocardial infarction (MI) and coronary heart disease (CHD). Five bibliographic databases were searched from inception to 15 July 2019. We selected 35 articles (based on 30 unique studies) from 17,023 references identified, with a total of 14,020 participants of European, North American or Asian ancestry. Four studies reported sex differences between global DNAm and blood lipid levels and stroke risk. In 25 studies that took a genome wide or candidate gene approach, DNAm at 31 gene sites was associated with sex differences in cardiometabolic diseases. The identified genes were PLA2G7, BCL11A, KDM6A, LIPC, ABCG1, PLTP, CETP, ADD1, CNN1B, HOOK2, GFBP-7,PTPN1, GCK, PTX3, ABCG1, GALNT2, CDKN2B, APOE, CTH, GNASAS, INS, PON1, TCN2, CBS, AMT, KDMA6A, FTO, MAP3K13, CCDC8, MMP-2 and ER-α. Prioritized pathway connectivity analysis associated these genes with biological pathways such as vitamin B12 metabolism, statin pathway, plasma lipoprotein, plasma lipoprotein assembly, remodeling and clearance and cholesterol metabolism. Our findings suggest that DNAm might be a promising molecular strategy for understanding sex differences in the pathophysiology of cardiometabolic diseases and that future studies should investigate the effects of sex on epigenetic mechanisms in cardiometabolic risk. In addition, we emphasize the gap between the translational potential and the clinical utilization of cardiometabolic epigenetics.
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http://dx.doi.org/10.1016/j.maturitas.2020.02.005DOI Listing
May 2020

Cardiovascular screening and prevention strategies in women with history of preeclampsia: One size does not fit all.

Eur J Prev Cardiol 2020 09 4;27(13):1386-1388. Epub 2020 Mar 4.

Institute of Social and Preventive Medicine (ISPM), University of Bern, Switzerland.

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http://dx.doi.org/10.1177/2047487320908977DOI Listing
September 2020

Epigenetic Link Between Statin Therapy and Type 2 Diabetes.

Diabetes Care 2020 04 7;43(4):875-884. Epub 2020 Feb 7.

Department of Epidemiology and Biostatistics, Imperial College London, London, U.K.

Objective: To investigate the role of epigenetics in statins' diabetogenic effect comparing DNA methylation (DNAm) between statin users and nonusers in an epigenome-wide association study in blood.

Research Design And Methods: Five cohort studies' participants ( = 8,270) were classified as statin users when they were on statin therapy at the time of DNAm assessment with Illumina 450K or EPIC array or noncurrent users otherwise. Associations of DNAm with various outcomes like incident type 2 diabetes, plasma glucose, insulin, and insulin resistance (HOMA of insulin resistance [HOMA-IR]) as well as with gene expression were investigated.

Results: Discovery ( = 6,820) and replication ( = 1,450) phases associated five DNAm sites with statin use: cg17901584 (1.12 × 10 []), cg10177197 (3.94 × 10 []), cg06500161 (2.67 × 10 []), cg27243685 (6.01 × 10 []), and cg05119988 (7.26 × 10 []). Two sites were associated with at least one glycemic trait or type 2 diabetes. Higher cg06500161 methylation was associated with higher fasting glucose, insulin, HOMA-IR, and type 2 diabetes (odds ratio 1.34 [95% CI 1.22, 1.47]). Mediation analyses suggested that methylation partially mediates the effect of statins on high insulin and HOMA-IR. Gene expression analyses showed that statin exposure and methylation were associated with downregulation, suggesting epigenetic regulation of expression. Further, outcomes insulin and HOMA-IR were significantly associated with expression.

Conclusions: This study sheds light on potential mechanisms linking statins with type 2 diabetes risk, providing evidence on DNAm partially mediating statins' effects on insulin traits. Further efforts shall disentangle the molecular mechanisms through which statins may induce DNAm changes, potentially leading to epigenetic regulation.
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http://dx.doi.org/10.2337/dc19-1828DOI Listing
April 2020

Eating to add years of life and life to these years: what should be in the menu?

Am J Clin Nutr 2020 04;111(4):733-734

Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland.

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http://dx.doi.org/10.1093/ajcn/nqaa017DOI Listing
April 2020

The Role of Atrial Fibrosis Detected by Delayed - Enhancement MRI in Atrial Fibrillation Ablation.

Curr Med Imaging Rev 2020 ;16(2):135-144

Department of Clinical Electrophysiology, Erasmus Medical Center, University Medical Center, Rotterdam, Netherlands.

Introduction: Atrial Fibrillation (AF) is associated with remodeling of the atrial tissue, which leads to fibrosis that can contribute to the initiation and maintenance of AF. Delayed- Enhanced Cardiac Magnetic Resonance (DE-CMR) imaging for atrial wall fibrosis detection was used in several studies to guide AF ablation. The aim of present study was to systematically review the literature on the role of atrial fibrosis detected by DE-CMR imaging on AF ablation outcome.

Methods: Eight bibliographic electronic databases were searched to identify all published relevant studies until 21st of March, 2016. Search of the scientific literature was performed for studies describing DE-CMR imaging on atrial fibrosis in AF patients underwent Pulmonary Vein Isolation (PVI).

Results: Of the 763 citations reviewed for eligibility, 5 articles (enrolling a total of 1040 patients) were included into the final analysis. The overall recurrence of AF ranged from 24.4 - 40.9% with median follow-up of 324 to 540 days after PVI. With less than 5-10% fibrosis in the atrial wall there was a maximum of 10% recurrence of AF after ablation. With more than 35% fibrosis in the atrial wall there was 86% recurrence of AF after ablation.

Conclusion: Our analysis suggests that more extensive left atrial wall fibrosis prior ablation predicts the higher arrhythmia recurrence rate after PVI. The DE-CMR imaging modality seems to be a useful method for identifying the ideal candidate for catheter ablation. Our findings encourage wider usage of DE-CMR in distinct AF patients in a pre-ablation setting.
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http://dx.doi.org/10.2174/1573405614666180806130327DOI Listing
January 2020

Thyroid Function and the Risk of Fibrosis of the Liver, Heart, and Lung in Humans: A Systematic Review and Meta-Analysis.

Thyroid 2020 06 13;30(6):806-820. Epub 2020 Feb 13.

Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.

Fibrotic diseases have an unclear etiology and poor prognosis. Fluctuations in thyroid function may play a role in the development of fibrosis, but evidence is fragmented and inconclusive. This systematic review and meta-analysis aimed to investigate the association of thyroid function with fibrotic diseases of the liver, heart, and lung in humans. We searched PubMed, Medline Ovid, Embase Ovid, and Web-of-Science for studies published from inception to 14 June 2019, to identify observational studies that investigated the association of thyroid function with fibrosis of the liver, heart, and lung in humans. Study quality was evaluated by the Newcastle-Ottawa Scale. The Mantel-Haenszel method was used to pool the odds ratios (ORs) of studies investigating the association of hypothyroidism with liver fibrosis. Of the 2196 identified articles, 18 studies were included in the systematic review, of which 11 studies reported on liver fibrosis, 4 on myocardial fibrosis, and 3 on pulmonary fibrosis. The population sample size ranged from 36 to 7259 subjects, with median mean age 51 years (range, 36-69) and median percentage of women 53 (range, 17-100). The risk of bias of studies was low to moderate to high. Higher serum thyrotropin and lower thyroid hormone levels were generally associated with higher likelihood of fibrosis. Compared with euthyroidism, overt and subclinical hypothyroidism was associated with a higher likelihood of fibrosis in the liver (six of seven studies), heart (three of three studies), and lung (three of three studies). Based on the results of the seven studies included in the meta-analysis, overt and subclinical hypothyroidism was associated with an increased risk of liver fibrosis (pooled OR, 2.81; 95% confidence interval [CI], 1.74-4.53; heterogeneity, 31.4%; pooled OR, 2.12; CI, 1.45-3.12; heterogeneity, 0%; respectively), without evidence of publication bias. This study suggests that low thyroid function is associated with increased likelihood of chronic fibrotic diseases of the liver, heart, and lung. However, the evidence is mainly based on cross-sectional data. Prospective studies and randomized clinical trials are needed to investigate the potential efficacy of thyroid hormone and its analogs on the occurrence and progression of fibrosis.
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http://dx.doi.org/10.1089/thy.2019.0572DOI Listing
June 2020

Sex and gender in cardiovascular medicine: presentation and outcomes of acute coronary syndrome.

Eur Heart J 2020 04;41(13):1328-1336

Department of Nuclear Medicine, University Hospital Zurich, Raemistrasse 100, 8091 Zurich, Switzerland.

Although health disparities in women presenting with acute coronary syndrome (ACS) have received growing attention in recent years, clinical outcomes from ACS are still worse for women than for men. Women continue to experience higher patient and system delays and receive less aggressive invasive treatment and pharmacotherapies. Gender- and sex-specific variables that contribute to ACS vulnerability remain largely unknown. Notwithstanding the sex differences in baseline coronary anatomy and function, women and men are treated the same based on guidelines that were established from experimental and clinical trial data over-representing the male population. Importantly, younger women have a particularly unfavourable prognosis and a plethora of unanswered questions remains in this younger population. The present review summarizes contemporary evidence for gender and sex differences in vascular biology, clinical presentation, and outcomes of ACS. We further discuss potential mechanisms and non-traditional risk conditions modulating the course of disease in women and men, such as unrecognized psychosocial factors, sex-specific vascular and neural stress responses, and the potential impact of epigenetic modifications.
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http://dx.doi.org/10.1093/eurheartj/ehz898DOI Listing
April 2020

A 24-step guide on how to design, conduct, and successfully publish a systematic review and meta-analysis in medical research.

Eur J Epidemiol 2020 Jan 13;35(1):49-60. Epub 2019 Nov 13.

Institute of Social and Preventive Medicine (ISPM), University of Bern, Mittelstrasse 43, 3012, Bern, Switzerland.

To inform evidence-based practice in health care, guidelines and policies require accurate identification, collation, and integration of all available evidence in a comprehensive, meaningful, and time-efficient manner. Approaches to evidence synthesis such as carefully conducted systematic reviews and meta-analyses are essential tools to summarize specific topics. Unfortunately, not all systematic reviews are truly systematic, and their quality can vary substantially. Since well-conducted evidence synthesis typically involves a complex set of steps, we believe formulating a cohesive, step-by-step guide on how to conduct a systemic review and meta-analysis is essential. While most of the guidelines on systematic reviews focus on how to report or appraise systematic reviews, they lack guidance on how to synthesize evidence efficiently. To facilitate the design and development of evidence syntheses, we provide a clear and concise, 24-step guide on how to perform a systematic review and meta-analysis of observational studies and clinical trials. We describe each step, illustrate it with concrete examples, and provide relevant references for further guidance. The 24-step guide (1) simplifies the methodology of conducting a systematic review, (2) provides healthcare professionals and researchers with methodologically sound tools for conducting systematic reviews and meta-analyses, and (3) it can enhance the quality of existing evidence synthesis efforts. This guide will help its readers to better understand the complexity of the process, appraise the quality of published systematic reviews, and better comprehend (and use) evidence from medical literature.
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http://dx.doi.org/10.1007/s10654-019-00576-5DOI Listing
January 2020

Associations of autozygosity with a broad range of human phenotypes.

Nat Commun 2019 10 31;10(1):4957. Epub 2019 Oct 31.

Department of Neurology, Brain Centre Rudolf Magnus, University Medical Centre Utrecht, Utrecht University, Utrecht, 3584 CX, The Netherlands.

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (F) for >1.4 million individuals, we show that F is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: F equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44-66%] in the odds of having children. Finally, the effects of F are confirmed within full-sibling pairs, where the variation in F is independent of all environmental confounding.
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http://dx.doi.org/10.1038/s41467-019-12283-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6823371PMC
October 2019

Vertebral Fractures in Individuals With Type 2 Diabetes: More Than Skeletal Complications Alone.

Diabetes Care 2020 01 28;43(1):137-144. Epub 2019 Oct 28.

Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands

Objective: We aimed to assess whether individuals with type 2 diabetes (T2D) have increased risk of vertebral fractures (VFs) and to estimate nonvertebral fracture and mortality risk among individuals with both prevalent T2D and VFs.

Research Design And Methods: A systematic PubMed search was performed to identify studies that investigated the relationship between T2D and VFs. Cohorts providing individual participant data (IPD) were also included. Estimates from published summary data and IPD cohorts were pooled in a random-effects meta-analysis. Multivariate Cox regression models were used to estimate nonvertebral fracture and mortality risk among individuals with T2D and VFs.

Results: Across 15 studies comprising 852,705 men and women, individuals with T2D had lower risk of prevalent (odds ratio [OR] 0.84 [95% CI 0.74-0.95]; = 0.0%; = 0.54) but increased risk of incident VFs (OR 1.35 [95% CI 1.27-1.44]; = 0.6%; = 0.43). In the IPD cohorts ( = 19,820), risk of nonvertebral fractures was higher in those with both T2D and VFs compared with those without T2D or VFs (hazard ratio [HR] 2.42 [95% CI 1.86-3.15]) or with VFs (HR 1.73 [95% CI 1.32-2.27]) or T2D (HR 1.94 [95% CI 1.46-2.59]) alone. Individuals with both T2D and VFs had increased mortality compared with individuals without T2D and VFs (HR 2.11 [95% CI 1.72-2.59]) or with VFs alone (HR 1.84 [95% CI 1.49-2.28]) and borderline increased compared with individuals with T2D alone (HR 1.23 [95% CI 0.99-1.52]).

Conclusions: Based on our findings, individuals with T2D should be systematically assessed for presence of VFs, and, as in individuals without T2D, their presence constitutes an indication to start osteoporosis treatment for the prevention of future fractures.
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http://dx.doi.org/10.2337/dc19-0925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7411280PMC
January 2020

Correction to: The role of DNA methylation and histone modifications in blood pressure: a systematic review.

J Hum Hypertens 2020 Feb;34(2):193

Department of Epidemiology, Erasmus University Medical Center, Rotterdam, Netherlands.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41371-019-0234-7DOI Listing
February 2020
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