Risk factors and comorbidities associated with magnesium deficiency in pregnant women and women with hormone-related conditions: analysis of a large real-world dataset.

BACKGROUND: An accumulating body of literature indicates that magnesium deficiency is associated with a number of hormone-related conditions (HRC) in women, and epidemiological studies are needed to assess its prevalence and risk factors. Here, we present a secondary analysis of data pooled from four large observational studies that assessed magnesium deficiency among pregnant women and women with HRC across the Russian Federation. METHODS: The main objective of this analysis was to estimate the prevalence of magnesium deficiency in this population and to describe risk factors and comorbidities associated with low serum magnesium. Univariate logistic regression analysis was performed to identify the risk factors and comorbid conditions associated with an increased risk of low serum magnesium level. RESULTS: A total of 983 pregnant women and 9444 women with HRC were eligible for analysis. Prevalence of hypomagnesemia (magnesium serum level cut-off < 0.66 mmol/L/< 0.8 mmol/L) was 34.0%/78.9% in pregnant women and 21.4%/54.8% in women with HRC. The highest prevalence of magnesium deficiency was observed for osteoporosis and climacteric syndrome. Risk factors included diastolic blood pressure, previous pregnancy complications, infections and edema for pregnant women, and age, body mass index, and various comorbidities for women with HRC. CONCLUSIONS: These results confirm the high prevalence of hypomagnesemia in pregnant women and women with HRC and underline the importance of routine screening, since risk factors are mostly non-specific.

Magnesium level correlation with clinical status and quality of life in women with hormone related conditions and pregnancy based on real world data.

This study was aimed to assess the effectiveness of magnesium (Mg)-vitamin B 6 replenishment and its correlation with clinical status in pregnant women (PW), and quality of life in women with hormone-related conditions (HRCW) and hypomagnesemia (HME). Data collected in four observational studies were pooled and analysed. All women received Mg supplementation for 4 weeks. The proportion of women with normalized Mg level, and the correlation between serum Mg dynamics and number of symptoms/complaints (PW) or changes in World Health Organization quality of life questionnaire scores (WHOQOL; HRCW) were evaluated. 869 PW and 957 HRCW were included in the study. Normalization of serum Mg level to ≥ 0.66 mmol/L occurred in 92.1% of PW and 78.4% of HRCW, and to ≥ 0.8 mmol/L in 73.8% and 58.9%, respectively. Mg normalization was accompanied by a median decrease of 1 symptom and 1 complaint in PW. Serum Mg level increase by 0.1 mmol/L was associated to significant changes in the WHOQOL scores in HRCW. Treatment of HME with the Mg for approximately 4 weeks provided a high response rate of Mg serum level, was associated with an improvement in symptom severity and complaints in PW, and WHOQOL score in HRCW. A 0.8 mmol/L cut-off appeared to be more relevant in terms of patient-reported outcomes.

Safety and Effectiveness of Essential Phospholipids Paste in Patients with Non-alcoholic Fatty Liver Disease or Viral Hepatitis.

BACKGROUND: Essential phospholipids (EPL) are used as adjuvant treatment in people with fatty liver disease and other chronic liver diseases. A new formulation of EPL paste was developed to improve patient compliance. The study was aimed to assess the safety, patient-reported outcomes, and impact on compliance of the new EPL paste formulation in patients with non-alcoholic fatty liver disease (NAFLD) or viral hepatitis. METHODS: The study enrolled 147 patients (48.3% male; mean ± standard deviation (SD) age 44.8 ± 10.5 years) in the intention-to-treat population; 72.8% had NAFLD and 27.9% had viral hepatitis B (HBV) or hepatitis C (HCV). Patients received EPL paste (one 600 mg sachet 3 times daily) for 12 weeks, with 4-, 8-, and 12-week scheduled visits and a 13-week follow-up visit. Patient-reported outcomes were evaluated at 4, 8, and 12 weeks compared with baseline using dedicated Likert scales. Compliance was assessed by comparing actual versus prescribed dosing of the EPL. RESULTS: After 12-week treatment with EPL paste, statistically significant improvements were observed in mean ± SD Global Overall Symptom scores (from 4.21 ± 1.09 to 1.87 ± 0.91; P < .01) and overall Gastrointestinal Symptom scores (from 19.91 ± 5.74 to 11.17 ± 3.57; P < .01), compared to baseline scores. Compliance with prescribed essential phospholipid treatment was 99% throughout the 12-week treatment period. CONCLUSION: Essential phospholipids paste had a favorable safety profile associated with improved gastrointestinal symptoms and with high levels of compliance in patients with NAFLD and viral hepatitis.

Correlation of Objective Endpoints and Subjective Patient-Reported Outcomes in NAFLD Treatment with Essential Phospholipids: Real-World Data Based on Pooled Analysis of Observational Studies.

BACKGROUND: While no "gold-standard" pharmacotherapy for nonalcoholic fatty liver disease (NAFLD) is yet established, essential phospholipids (EPLs) are reported to decrease steatosis and improve laboratory parameters. OBJECTIVE: This analysis evaluated adherence and satisfaction with EPL treatment as patient-reported outcomes and their relationship with changes in laboratory and ultrasound parameters among Russian patients with NAFLD. METHODS: Data were pooled from three observational Russian studies-MANPOWER (2015-2016), LIDER 1 (2012-2013), and LIDER 2 (2013)-in which EPLs were used for at least 12 weeks in the treatment of liver diseases and which measured both subjective and objective endpoints. Only patients who had NAFLD were included in this analysis. The main endpoints were to determine treatment adherence and satisfaction with 12 weeks of EPL therapy, relationship between adherence/satisfaction and changes in the laboratory and ultrasound parameters. A secondary subgroup analysis was performed to identify patients with NAFLD who responded better (or worse) to 24 weeks of adjunctive EPL treatment. RESULTS: Overall, 3384 patients were included. A total of 82.2% of patients were adherent to 12 weeks of EPL treatment; high/very high satisfaction was reported by 15.3%/65.9% of clinicians and 15.9%/64.4% of patients. There was positive correlation between patients' adherence and satisfaction and significant improvement in laboratory (transaminases, lipid profile; p < 0.001) and ultrasound (steatosis, p < 0.001) parameters, and improvement in symptoms (p < 0.001) after 24 weeks of EPL. Male patients, patients with unhealthy lifestyles, and those with more comorbidities showed a better response in laboratory and ultrasound parameters. CONCLUSIONS: Patients with NAFLD treated with adjunctive EPL therapy in real-world clinical practice in Russia showed good treatment adherence and treatment satisfaction. Improvements in laboratory and ultrasound parameters, as well as dynamics of patient symptoms, were positively correlated with adherence and satisfaction.

Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver disease, and patients have a risk of liver cancer and needing transplantation. Patients with advanced NAFLD are usually recommended to use medication. Clinical trials in patients with NAFLD showed that essential phospholipids (EPLs) comprising phosphatidylcholine improved liver fat accumulation (known as steatosis), so treatment guidelines in several countries recommend they be added to the usual therapy. EPLs have been associated with both objective and subjective improvements. This real-world study evaluated three observational studies to assess how patient adherence and satisfaction with EPL treatment were related to changes in clinical parameters in 3384 Russian patients with NAFLD. Overall, 82.2% of patients were adherent with 12 weeks of EPL therapy, and almost two-thirds of patients (64.4%) and clinicians (65.9%) reported very high satisfaction with treatment. Patients' adherence and satisfaction increased alongside significant improvements in liver enzymes, lipid levels, liver fat content (steatosis), and fewer symptoms after 24 weeks of EPL therapy. Male patients, those with an unhealthy lifestyle, and those with other comorbid conditions had the best response to EPL therapy. This study shows that Russian patients with NAFLD have good adherence and satisfaction with EPL therapy in routine clinical practice and highlights the importance of adherence to EPL therapy in these patients.

Magnesium Deficiency Questionnaire: A New Non-Invasive Magnesium Deficiency Screening Tool Developed Using Real-World Data from Four Observational Studies.

Due to the high estimated prevalence of magnesium deficiency, there is a need for a rapid, non-invasive assessment tool that could be used by patients and clinicians to confirm suspected hypomagnesemia and substantiate laboratory testing. This study analyzed data from four large observational studies of hypomagnesemia in pregnant women and women with hormone-related conditions across Russia. Hypomagnesemia was assessed using a 62-item magnesium deficiency questionnaire (MDQ-62) and a serum test. The diagnostic utility (sensitivity/specificity) of MDQ-62 was analyzed using area under the receiver operating characteristic curve (AUROC). A logistic regression model was applied to develop a shorter, optimized version of MDQ-62. A total of 765 pregnant women and 8836 women with hormone-related conditions were included in the analysis. The diagnostic performance of MDQ-62 was "fair" (AUROC = 0.7-0.8) for women with hormone-related conditions and "poor" for pregnant women (AUROC = 0.6-0.7). The optimized MDQ-23 (23 questions) and MDQ-10 (10 questions) had similar AUROC values; for all versions of the questionnaire, there was a significant negative correlation between score and changes in total serum magnesium levels (p < 0.0001 for all comparisons; correlation coefficients ranged from -0.1667 to -0.2716). This analysis confirmed the value of MDQ in identifying women at risk of hypomagnesemia.

Effectiveness of phosphatidylcholine as adjunctive therapy in improving liver function tests in patients with non-alcoholic fatty liver disease and metabolic comorbidities: real-life observational study from Russia.

Objective: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of abnormal results of liver function tests. Earlier research showed that polyenylphosphatidylcholine (PPC) has hepatoprotective effects and thus can be used for the treatment of NAFLD and the prevention of its progression. Accordingly, the aim of this observational study was to evaluate if PPC administered as adjunctive therapy in routine clinical practice can effectively improve liver function tests of NAFLD in Russian patients with associated metabolic comorbidities. Design: A total of 2843 adult patients with newly diagnosed NAFLD, who had a least one of four comorbidities, namely, overweight/obesity, hypertension, type 2 diabetes mellitus, and hypercholesterolaemia, and who were prescribed 1.8 g/day of PPC as an adjunctive treatment to standard care, were enrolled during 2015-2016. Laboratory data were collected at baseline and 12 and 24 weeks of the study, and included liver function tests (aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT)), fasting plasma glucose, and lipid profile. Results: Overall, 2263 patients (79.6%) had at least two metabolic comorbidities associated with NAFLD, and overweight/obesity was the most common comorbidity reported in 2298 (80.8%) patients. At 24 weeks, there was a significant decrease in liver enzyme levels (all p<0.001 compared with baseline). Across the four comorbidity subgroups, there was a mean drop of ALT levels ranging from 19.7 to 22.0 U/L, AST from 16.9 to 18.4 U/L, and GGT from 17.2 to 18.7 U/L. Similar findings were reported in subgroups with either one, two, three, or four comorbidities, with a significant decrease in liver enzyme levels ranging from 18.4 to 22.4 U/L for ALT, 14.8 to 18.7 U/L for AST, and 15.5 to 19.5 U/L for GGT. Conclusions: Adjuvant treatment with PPC resulted in consistent improvements in liver enzymes in patients with newly diagnosed NAFLD and associated metabolic comorbidities. Trial registration number: NCT00063622.

Comparative Safety of Bevacizumab, Ranibizumab, and Aflibercept for Treatment of Neovascular Age-Related Macular Degeneration (AMD): A Systematic Review and Network Meta-Analysis of Direct Comparative Studies.

BACKGROUND: Since the efficacy of ranibizumab (RBZ), bevacizumab (BVZ) and aflibercept (AFB) is comparable in neovascular age-related macular degeneration (AMD), we conducted a systematic review and meta-analysis to evaluate the long-term safety profiles of these agents, including ocular safety. METHODS: Systematic review identifying randomized controlled trials (RCTs) comparing RBZ, BVZ and AFB directly published before March 2019. Serious ocular adverse events (SOAE) of special interest were endophthalmitis, pseudo-endophthalmitis, retinal pigment epithelium tear and newly identified macular atrophy. RESULTS: Thirteen RCTs selected for meta-analysis (4952 patients, 8723 people-years follow-up): 10 compared RBZ vs. BVZ and three RBZ vs. AFB. There were no significant differences in almost all adverse events (systemic and ocular) between BVZ, RBZ and AFB in up to two years' follow-up. Macular atrophy was reported heterogeneously and not reported as SOAE in most trials. CONCLUSIONS: Direct comparison of RBZ, BVZ and AFB safety profiles in the RCT network meta-analytical setting have not revealed a consistent benefit of these three commonly used anti-vascular endothelial growth factor (anti-VEGF) agents in AMD. Network model ranking highlighted potential benefits of RBZ in terms of a systemic safety profile; however, this appears a hypothesis rather than a conclusion. Newly identified macular atrophy is underestimated in RCTs-future real-world data should be focused on SOAE.

Effectiveness of phosphatidylcholine in alleviating steatosis in patients with non-alcoholic fatty liver disease and cardiometabolic comorbidities (MANPOWER study).

Objective: The concept of using naturally occurring compounds such as polyenylphosphatidylcholine (PPC) as an adjunctive therapy to treat non-alcoholic fatty liver disease (NAFLD) and alleviate or reverse hepatic steatosis appears a very attractive option for liver protection. We aim to evaluate if PPC adjunctive therapy can effectively improve the ultrasonographic features of NAFLD in routine clinical practice in Russian patients with cardiometabolic comorbidities. Design: This 24-week, observational, prospective study was carried out in 174 medical sites across 6 federal districts of Russia. A total of 2843 adult patients with newly diagnosed NAFLD, who had a least one of four comorbidities, namely overweight/obesity, hypertension, type 2 diabetes mellitus and hypercholesterolaemia, and who received PPC as an adjunctive treatment to standard care, were enrolled. The assessment of liver ultrasonography was qualitative. Results: Overall, 2263 (79.6%) patients had at least two metabolic comorbidities associated with NAFLD, and overweight/obesity was the most common comorbidity reported in 2298 (80.8%) patients. Almost all study participants (2837/2843; 99.8%) were prescribed 1.8 g of PPC administered three times daily. At baseline, the most frequently identified abnormalities on ultrasound were liver hyperechogenicity (84.0% of patients) and heterogeneous liver structure (62.9%). At 24 weeks, a significant (p<0.05) improvement in liver echogenicity and in liver structure was observed in 1932/2827 (68.3%) patients (95% CI 66.6% to 70.1%) and in 1207/2827 (42.7%) patients (95% CI 40.9% to 44.5%), respectively. The analysis of ultrasonographic signs by number of comorbidities revealed similar findings-liver echogenicity improved in 67.2%-69.3% and liver structure in 35.6%-45.3% of patients depending on the number of comorbidities. Conclusion: This study showed that PPC adjunctive therapy may be useful in improving the ultrasonographic features of NAFLD in patients with associated cardiometabolic comorbidities. It also supports evidence regarding the role of PPC in the complex management of NAFLD.

A New, Non-Invasive Scale for Steatosis Developed Using Real-World Data From Russian Outpatients to Aid in the Diagnosis of Non-Alcoholic Fatty Liver Disease.

INTRODUCTION: The current non-invasive tools for the diagnosis of non-alcoholic fatty liver disease (NAFLD) have methodological limitations. We aimed to develop a non-invasive scale to assist in the diagnosis of NAFLD. To achieve our aim, we conducted a secondary analysis of data from a large observational study conducted in Russia. METHODS: This retrospective analysis assessed the frequency of NAFLD in the population of patients in the DIREG_L_06725 study, an epidemiological, observational, cross-sectional, multicenter study performed in 50,145 outpatients from 16 Russian cities. Among the cohort of patients diagnosed with NAFLD, we identified factors associated with the risk of NAFLD. To develop a non-invasive tool for diagnosing NAFLD, we also determined the frequency of steatohepatitis. RESULTS: Our analysis included 48,297 patients; NAFLD was present in 20,281 patients (42.0%). The majority (64.1%) were women (80.3% post-menopause), and 87% had a body mass index (BMI) > 27.0 kg/m2. We developed a fully non-invasive scale (St-index) that showed a specificity of 91.4% for ruling in steatosis, and a sensitivity of 93.8% for ruling out steatosis. Multivariate regression analyses conducted in the subgroups of patients aged ≥ 12 and < 18 years and those with BMI < 25.0 kg/m2 produced area under the receiver operating characteristic (AUROC) curve values of 0.8243 and 0.7054, respectively. The factors most strongly associated with the development of NAFLD were age > 35 years, presence of type 2 diabetes mellitus, and a waist circumference/height ratio > 0.54. CONCLUSION: Our non-invasive steatosis scale, St-index, can help physicians diagnose NAFLD in high-risk patients in the absence of ultrasound data.

Real-world comorbidities and treatment patterns among patients with non-alcoholic fatty liver disease receiving phosphatidylcholine as adjunctive therapy in Russia.

OBJECTIVE: Previous research conducted in Russia showed that the number of patients with non-alcoholic fatty liver disease (NAFLD) and associated metabolic comorbidities is large. We conducted an observational study to describe the management of NAFLD in patients with metabolic syndrome in Russia. DESIGN: A total of 2843 adult patients from 174 medical sites across 6 federal districts of Russia with newly diagnosed NAFLD, who had at least one of four comorbidities, namely overweight/obesity, hypertension, type 2 diabetes mellitus, and hypercholesterolaemia, and who received phosphatidylcholine (PPC) as an adjunctive treatment to standard care, were enrolled during 2015-2016. RESULTS: Overall, 2263 patients (79.6%) had at least two metabolic comorbidities associated with NAFLD; overweight/obesity was the most common comorbidity reported in 2298 patients (80.8%). Simple steatosis was the most frequently identified clinical form of NAFLD, diagnosed in 2128 patients (74.9%). Among hypertensive patients, ACE inhibitors, statins, and sartans were most commonly prescribed. Biguanides were administered in more than half of diabetic patients. In patients with overweight/obesity and hypercholesterolaemia, statins were the most frequently prescribed medications. Almost all patients (2837/2843; 99.8%) were treated with 1.8 g of PPC three times per day. PPC therapy was associated with a 90.5% 6-month compliance rate, high treatment satisfaction, and a favourable safety profile. However, almost 15% of diabetic patients and 40% of overweight/obese patients received no further treatment. CONCLUSIONS: In Russia, patients with newly diagnosed NAFLD represent a population heavily burdened by comorbidities, mainly overweight/obesity and hypercholesterolaemia. A significant part of these patients did not receive a comprehensive pharmacotherapy, highlighting the existing unmet need in the current management of NAFLD patients with metabolic syndrome in Russia.