Effect of tomato,lycopene and related products on blood pressure: A systematic review and network meta-analysis

BackgroundA number of randomized controlled trials (RCTs) have been conducted to evaluate the hypotensive effects of tomato, lycopene, and related products. However, the findings were conflicting, partly due to differences in the types of products investigated. Therefore, this study aimed to assess and compare the hypotensive effects of different tomato-related preparations through a network meta-analysis based on randomized controlled trials.Study designA systematic review and network meta-analysis.MethodsA network meta-analysis based on a systematic review of RCTs comparing the effect of various tomato, lycopene and related products versus placebo on blood pressure in adults was performed. PubMed, EMBASE, SCOPUS, and Clinicaltrial.gov databases were searched up to October 2020 without language restrictions. The primary outcomes were systolic and diastolic blood pressure. Mean differences (MDs) along with 95% confidence intervals (CIs) were estimated and pooled using a random-effects model. Heterogeneity was assessed using the global inconsistency test.ResultsA total of 11 studies including six forms of tomato, lycopene and related products met the inclusion criteria. Among these trials, eight (N = 617) and seven trials (N = 501) were included in the analysis of systolic (SBP) and diastolic blood pressure (DBP) outcomes, respectively. The standardized tomato extract (STE) significantly decreased SBP compared to placebo, with a pooled MD (95% CI) of –5.89 (–9.13 to –2.64) mmHg. The effect on DBP was not significant, with a pooled MD (95% CI) of –3.51 (–7.39 to 0.38) mmHg. Subgroup analysis in hypertensive patients showed that STE significantly reduced both SBP and DBP with pooled MDs (95% CIs) of –8.09 (–11.52 to –4.67) and –4.25 (–6.97 to –1.53) mmHg, respectively, compared to placebo. Other forms of tomato, including other dose ranges of standardized tomato extract, tomato-containing diet, lycopene-free preparation, and synthetic lycopene, did not show consistent and significant effects on either SBP or DBP in all analyses.ConclusionStandardized tomato extract (STE) significantly decreased SBP compared to placebo in a mixed population of healthy volunteers and hypertensive patients. The BP-lowering effect was more pronounced among hypertensive patients. No significant BP effects were seen with other forms of tomato, lycopene and related products in the overall population or any subgroup of the population.     

Sumac fruit supplementation improve glycemic parameters in patients with metabolic syndrome and related disorders: A systematic review and meta-analysis

BackgroundMetabolic syndrome (MetS) is the one of the main causes of mortality worldwide. Several randomized controlled trials (RCTs) have revealed the beneficial effects of sumac (Rhus coriaria) on cardiometabolic risk factors. However, the entirety of the evidence has yet to be summarized in a systematic review.ObjectiveThe aim of this systematic review and meta-analysis was to evaluate the effects of sumac on several cardiometabolic risk factors in patients with MetS and related disorders.MethodsWe reviewed Medline, Scopus, Web of Science and Cochrane CENTRAL for RCTs published from inception to December 2020 evaluating the impact of sumac in adults with MetS or related disorders. Outcome measures included anthropometric measures, glycemic indices, blood lipids, blood pressure and liver enzymes. Pooled effect sizes were reported as standard mean differences (SMDs) and 95% confidence intervals (CIs). Trials were pooled using a random effects model.ResultsNine studies enrolling 526 participants met the inclusion criteria for this meta-analysis. Our results indicate that sumac intake significantly decrease fasting blood sugar (FBS) (SMD: −0.28; 95% CI: −0.54, -0.02; I² = 00.0%), insulin (SMD: −0.67; 95% CI: −0.99, -0.36; I² = 03.7%), and insulin resistance (measured through the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)) (SMD: −0.79; 95% CI: −1.24, -0.34; I² = 50.1%). Sumac intake did not have a significant impact on weight, body mass index (BMI), waist circumference (WC), hip circumference (HC), waist to hip ratio (WHR), HbA1c, total cholesterol (TC), triglycerides (TG), high density lipoproteins (HDL), low density lipoprotein (LDL), systolic blood pressure (SBP), diastolic blood pressure (DBP), aspartate transaminase (AST) and alanine transaminase (ALT).ConclusionSumac, as an adjuvant therapy, may decrease serum levels of FBS, insulin and HOMA-IR. However, due to high heterogeneity in the included studies, these findings must be interpreted with great caution. Larger, well-designed placebo-controlled clinical trials are still needed to further evaluate the capacity of sumac as a complementary treatment to control MetS risk factors.     

Effect of dietary nitrate on blood pressure,endothelial function,and insulin sensitivity in type 2 diabetes

Diets rich in green, leafy vegetables have been shown to lower blood pressure (BP) and reduce the risk of cardiovascular disease. Green, leafy vegetables and beetroot are particularly rich in inorganic nitrate. Dietary nitrate supplementation, via sequential reduction to nitrite and NO, has previously been shown to lower BP and improve endothelial function in healthy humans. We sought to determine if supplementing dietary nitrate with beetroot juice, a rich source of nitrate, will lower BP and improve endothelial function and insulin sensitivity in individuals with type 2 diabetes (T2DM). Twenty-seven patients, age 67.2±4.9 years (18 male), were recruited for a double-blind, randomized, placebo-controlled crossover trial. Participants were randomized to begin, in either order, a 2-week period of supplementation with 250 ml beetroot juice daily (active) or 250 ml nitrate-depleted beetroot juice (placebo). At the conclusion of each intervention period 24-h ambulatory blood pressure monitoring, tests of macro- and microvascular endothelial function, and a hyperinsulinemic isoglycemic clamp were performed. After 2 weeks administration of beetroot juice mean ambulatory systolic BP was unchanged: 134.6±8.4 mm Hg versus 135.1±7.8 mm Hg (mean±SD), placebo vs active—mean difference of −0.5 mm Hg (placebo–active), p=0.737 (95% CI −3.9 to 2.8). There were no changes in macrovascular or microvascular endothelial function or insulin sensitivity. Supplementation of the diet with 7.5 mmol of nitrate per day for 2 weeks caused an increase in plasma nitrite and nitrate concentration, but did not lower BP, improve endothelial function, or improve insulin sensitivity in individuals with T2DM.     

Ginkgo biloba extract for essential hypertension: A systemic review

BackgroundGinkgo biloba extract (GBE), a traditional natural herbal product, is often used in the treatment of essential hypertension (EH) as complementary therapy in China and European countries.AimTo critically assess the current clinical evidence of efficacy and safety of GBE for EH.Methods7 electronic databases (Cochrane Library, PubMed, EMBASE, VIP, CBM, Wanfang data, and CNKI) were searched to identify randomized controlled trials (RCTs) of GBE for EH. Methodological quality was assessed independently using the Cochrane Handbook for Systematic Reviews of Interventions.ResultsA total of 9 RCTs with 1012 hypertensive patients were identified and reviewed. Most RCTs were of high risk of bias with flawed study design and poor methodological quality. 6 trials demonstrated potential positive effect of GBE as complementary therapy on BP reduction when compared with antihypertensive drug therapy; however, it was not associated with a statistically significant effect on both SBP and DBP reduction in 3 other trials. Despite the positive findings, there were so many methodological limitations and significant clinical heterogeneity. Most of the trials did not report adverse effects, and the safety of GBE is still uncertain.ConclusionNo confirmative conclusions on the efficacy and safety of GBE for EH could be drawn. More rigorous trials are warranted to support their clinical use.     

Rhodiola rosea versus sertraline for major depressive disorder: A randomized placebo-controlled trial

Background: We performed a proof of concept trial to evaluate relative safety and efficacy of Rhodiola rosea (R. rosea) versus sertraline for mild to moderate major depressive disorder.Hypothesis: We hypothesize that R. rosea would have similar therapeutic effects as sertraline but with less adverse events.Study design: Phase II randomized placebo controlled clinical trial.Methods: 57 subjects were randomized to 12 weeks of standardized R. rosea extract, sertraline, or placebo. Changes over time in Hamilton Depression Rating (HAM-D), Beck Depression Inventory (BDI), and Clinical Global Impression Change (CGI/C) scores among groups were examined using mixed-effects models.Results: Modest, albeit statistically non-significant, reductions were observed for HAM-D, BDI, and CGI/C scores for all treatment conditions with no significant difference between groups (p = 0.79, p = 0.28, and p = 0.17, respectively). The decline in HAM-D scores was greater for sertraline (−8.2, 95% confidence interval [CI], −12.7 to −3.6) versus R. rosea (−5.1, 95% CI: −8.8 to −1.3) and placebo (−4.6, 95% CI: −8.6 to −0.6). While the odds of improving (versus placebo) were greater for sertraline (1.90 [0.44–8.20]; odds ratio [95% CI]) than R. rosea (1.39 [0.38–5.04]), more subjects on sertraline reported adverse events (63.2%) than R. rosea (30.0%) or placebo (16.7%) (p = 0.012).Conclusions: Although R. rosea produced less antidepressant effect versus sertraline, it also resulted in significantly fewer adverse events and was better tolerated. These findings suggest that R. rosea, although less effective than sertraline, may possess a more favorable risk to benefit ratio for individuals with mild to moderate depression.     

Efficacy and Safety of Linagliptin in Black/African American Patients with Type 2 Diabetes: A 6-Month,Randomized, Double-Blind,Placebo-Controlled Study

ObjectiveAlthough black/African American individuals are disproportionately affected by type 2 diabetes, there is scant clinical trial information available on antidiabetes therapies in this group. We compared linagliptin with placebo in black/African American adults who were treatment-naïve or receiving one oral antidiabetes drug.MethodsOf 226 patients randomized to 24 weeks’ linagliptin 5 mg/day or placebo, 208 had baseline and at least one on-treatment glycated hemoglobin (HbA_1c) measurement. Mean baseline HbA_1c was 8.6% in the linagliptin group (n = 98) and 8.68% in the placebo group (n = 110). The primary outcome was change in HbA_1c from baseline to week 24.ResultsBy week 24, mean HbA_1c changes were − 0.84% with linagliptin and − 0.25% with placebo (treatment difference, − 0.58%; P < .001), and more patients in the linagliptin group achieved HbA_1c < 7.0% (26.8% vs. 8.3%; P = .001) or an HbA_1c reduction ≥ 0.5% (54.1% vs. 30.0%; P < .001). Mean weight loss was − 1.1 kg in both groups. During the treatment period, 8 of 98 linagliptingroup patients and 17 of 110 placebo-group patients required rescue therapy (odds ratio, 0.5; P = .14). For postprandial glucose, values were available for few patients (11 placebo, 10 linagliptin), and thus the between-group difference was associated with wide confidence intervals (CIs) (difference, − 1.97 mg/dL; 95% CI, − 53.80 to 49.86; P = .94). In the overall study population, a similar proportion of patients in both groups had adverse events (58.5% vs. 61.7%); most events were mild or moderate and considered unrelated to study drug. Investigator-defined hypoglycemia was rare (3 linagliptin-group patients and 1 placebogroup patient), with no severe events (requiring external assistance).ConclusionThis study confirms that linagliptin is efficacious and well tolerated in black/African American patients with type 2 diabetes. (Endocr Pract. 2014;20: 412-420)     

Risk Factors of Thyroid Eye Disease

ObjectiveTo examine risk factors that might be associated with thyroid eye disease (TED) in patients with Graves’ disease (GD), which may guide physicians in the prevention and management of TED.MethodsMedline and Embase were searched for articles discussing risk factors of TED. Comparisons were made between GD patients with and without TED, and between active and inactive TED GD patients. Weighted mean differences (WMDs) and odds ratios (ORs) were determined for continuous and dichotomous outcomes, respectively. Results were pooled with random effects using the DerSimonian and Laird model.ResultsFifty-six articles were included in the analysis. Smoking, inclusive of current and previous smoking status, was a significant risk factor for TED (OR: 2.401; CI: 1.958-2.945; P < .001). Statistical significance was found upon meta-regression between male sex and the odds of smoking and TED (β = 1.195; SE = 0.436; P = .013). Other risk factors were also examined, and patients with TED were significantly older than those without TED (WMD: 1.350; CI: 0.328-2.372; P = .010). While both age (WMD: 5.546; CI: 3.075-8.017; P < .001) and male sex (OR: 1.819; CI: 1.178-2.808; P = .007) were found to be significant risk factors for active TED patients compared to inactive TED patients, no statistical significance was found for family history, thyroid status, cholesterol levels, or body mass index.ConclusionFactors such as smoking, sex, and age predispose GD patients to TED, and TED patients to active TED. A targeted approach in the management of GD and TED is required to reduce the modifiable risk factor of smoking.     

The Effectiveness of Thyroid Hormone Replacement Therapy on Heart Failure and Low-Triiodothyronine Syndrome: An Updated Systematic Review and Meta-analysis of Randomized Controlled Trials

ObjectiveThe purpose of this study was to conduct a systematic review and meta-analysis evaluating the role of thyroid hormone therapy in patients with heart failure and low-triiodothyronine syndrome.MethodsThe electronic databases PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, China Science and Technology Journal Database, Wanfang Database, and China Biology Medicine disc were systematically searched to identify eligible studies published before November 27, 2021. The mean difference was pooled for randomized controlled trials using a random-effects model.ResultsThe meta-analysis showed that thyroid hormone treatment improved the left ventricular ejection fraction (weighted mean difference [WMD] 5.61, 95% confidence interval [CI]: 4.38 to 6.85, I² = 63.12%, P < 0.01). The cardiac output improved with thyroid hormone therapy (WMD 0.65, 95% CI: 0.42 to 0.89, I² = 84.28%, P < 0.01). The early-to-late diastolic transmitral flow velocity in the thyroid hormone group was also improved compared to the control group (WMD 0.29, 95% CI: 0.15 to 0.42, I² = 95.08%, P < 0.01). The left ventricular diastolic dysfunction was decreased with thyroid hormone treatment (WMD ?5.17, 95% CI: ?7.47 to ?2.88, I² = 90.18%, P < 0.01). The brain natriuretic peptide decreased with thyroid hormone treatment (standardized mean difference ?1.49, 95% CI: ?2.15 to ?0.84, I² = 90.18%, P < 0.01). Noradrenaline decreased with thyroid hormone therapy (WMD ?349.86, 95% CI: ?401.05 to ?298.67, I² = 0%, P < 0.01). Free triiodothyronine increased with thyroid hormone treatment (standardized mean difference 2.18, 95% CI: 0.75 to 2.60, I² = 98.20%, P < 0.01).ConclusionThis meta-analysis showed that thyroid hormone replacement therapy was effective in patients with heart failure and low-triiodothyronine syndrome.     

Suvorexant for Primary Insomnia: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials

Objective

We performed a systematic review and meta-analysis of double-blind, randomized, placebo-controlled trials evaluating suvorexant for primary insomnia.

Methods

Relevant studies were identified through searches of PubMed, databases of the Cochrane Library, and PsycINFO citations through June 27, 2015. We performed a systematic review and meta-analysis of suvorexant trial efficacy and safety outcomes. The primary efficacy outcomes were either subjective total sleep time (sTST) or subjective time-to-sleep onset (sTSO) at 1 month. The secondary outcomes were other efficacy outcomes, discontinuation rate, and individual adverse events. The risk ratio, number-needed-to-treat/harm, and weighted mean difference (WMD) and 95% confidence intervals (CI) based on a random effects model were calculated.

Results

The computerized literature database search initially yielded 48 results, from which 37 articles were excluded following a review of titles and abstracts and another eight review articles after full-text review. Thus, we identified 4 trials that included a total of 3,076 patients. Suvorexant was superior to placebo with regard to the two primary efficacy outcomes (sTST: WMD = −20.16, 95% CI = −25.01 to −15.30, 1889 patients, 3 trials, sTSO: WMD = −7.62, 95% CI = −11.03 to −4.21, 1889 patients, 3 trials) and was not different from placebo in trial discontinuations. Suvorexant caused a higher incidence than placebo of at least one side effects, abnormal dreams, somnolence, excessive daytime sleepiness/sedation, fatigue, dry mouth, and rebound insomnia.

Conclusions

Our analysis of published trial results suggests that suvorexant is effective in treating primary insomnia and is well-tolerated.     

Effects of Fentanyl on Emergence Agitation in Children under Sevoflurane Anesthesia: Meta-Analysis of Randomized Controlled Trials

Background and Objectives

The goal of this meta-analysis study was to assess the effects of fentanyl on emergence agitation (EA) under sevoflurane anesthesia in children.

Subjects and Methods

We searched electronic databases (PubMed, Embase, Web of Science and the Cochrane Central Register of Controlled Trials) for articles published until December 2014. Randomized controlled trials (RCTs) that assessed the effects of fentanyl and placebo on EA under sevoflurane anesthesia in children that the outcome were the incidence of EA, postoperative pain, emergence time or adverse effects were included in this meta-analysis.

Results

A total of 16 studies, including 1362 patients (737 patients for the fentanyl group and 625 for the placebo group), were evaluated in final analysis. We found that administration of fentanyl decreased the incidences of EA (RR = 0.37, 95% CI 0.27~0.49, P<0.00001) and postoperative pain (RR = 0.59, 95% CI 0.41~0.85, P = 0.004) but increased the incidence of postoperative nausea and vomiting (PONV) (RR = 2.23, 95% CI 1.33~3.77, P = 0.003). The extubation time (WMD = 0.71 min, 95% CI 0.12~1.3, P = 0.02), emergence time (WMD = 4.90 min, 95% CI 2.49~7.30, P<0.0001), and time in the postanesthesia care unit (PACU) (WMD = 2.65 min, 95% CI 0.76~4.53, P = 0.006) were slightly increased. There were no significant differences in the time to discharge of day patients (WMD = 3.72 min, 95% CI -2.80~10.24, P = 0.26).

Conclusion

Our meta-analysis suggests that fentanyl decreases the incidence of EA under sevoflurane anesthesia in children and postoperative pain, but has a higher incidence of PONV. Considering the inherent limitations of the included studies, more RCTs with extensive follow-up should be performed to validate our findings in the future.     

Predictive Role of Child-To-Adult Blood Pressure Trajectories for Incident Metabolic Syndrome: 30-Year Hanzhong Adolescent Hypertension Study

ObjectiveThe relationship between child-to-adult blood pressure (BP) trajectories and metabolic syndrome (MetS) is unknown. We aimed to determine the predictive role of BP trajectories for incident MetS and its components.MethodsThe prospective Hanzhong Adolescent Hypertension study began in 1987 and included 2692 participants free of MetS at baseline with at least 3 BP measurements available from 1987 to 2017.ResultsThe systolic BP (SBP) trajectory patterns were grouped as normal (class 1, 18.7%), high normal (class 2, 60.3%), prehypertensive (class 3, 13.1%), stage 1 hypertensive (class 4, 5.7%), and stage 2 hypertensive (class 5, 2.2%). Compared with those in the normal group, individuals in classes 2 to 5 had significantly higher risks of MetS (all Ps < .05), and those with hypertension had more than an 8-fold higher risk of MetS (both P < .05). The fully adjusted risk ratios (RRs) of central obesity increased significantly in a stepwise manner as the SBP trajectory group increased from class 1 to class 5 (P < .05). Compared with those with a normal SBP trajectory, participants in the prehypertensive group and stage 1 and stage 2 hypertensive groups had significantly higher RRs for high-risk triglycerides after full adjustment (RR = 1.89 [1.22-2.94]; RR = 3.61 [2.16-6.02]; and RR = 3.22 [1.52-6.84], respectively).ConclusionOur study suggests that BP trajectories are predictive of incident MetS outcomes. Early detection of hypertension or modest elevations in BP is crucial. The stage of hypertension based on SBP level showed a greater association with central obesity.     

Efficacy of Corneal Collagen Cross-Linking for Treatment of Keratoconus: A Meta-Analysis of Randomized Controlled Trials

ObjectiveTo evaluate the efficacy of corneal collagen cross-linking (CXL) for the treatment of keratoconus.MethodsWe performed a literature search for randomized controlled trials that assessed the effect of CXL in slowing progression of keratoconus. The primary outcome measures included changes of topographic parameters, visual acuity, and refraction. Efficacy estimates were evaluated by weighted mean difference (WMD) and 95% confidence interval (CI) for absolute changes of the interested outcomes.ResultsSignificant decrease in mean keratometry value, maximum keratometry value and minimum keratometry value were demonstrated in the CXL group compared with the control group (WMD = -1.65; 95% CI: -2.51 to -0.80; P < 0.00001; WMD = -2.05; 95% CI: -3.10 to -1.00; P < 0.00001; WMD = -1.94; 95% CI: -2.63 to -1.26; P < 0.00001; respectively). Best spectacle-corrected visual acuity improved significantly in CXL group (WMD = -0.10; 95% CI: -0.15 to -0.05; P < 0.00001), whereas uncorrected visual acuity did not differ statistically. Manifest cylinder error decreased significantly in patients undergoing CXL procedure compared with control patients in sensitivity analysis (WMD = -0.388; 95% CI: -0.757 to -0. 019; P = 0.04). The changes in central corneal thickness and intraocular pressure were not statistically significant.ConclusionCXL may be an effective option in stabilizing keratoconus. Further long-term follow-up studies will be necessary to assess the persistence of CXL.     

Dialysis-Associated Hypertension Treated with Telmisartan – DiaTel: A Pilot,Placebo-Controlled,Cross-Over,Randomized Trial

Treatment of hypertension in hemodialysis (HD) patients is characterised by lack of evidence for both the blood pressure (BP) target goal and the recommended drug class to use. Telmisartan, an Angiotensin receptor blocker (ARB) that is metabolised in the liver and not excreted via HD extracorporeal circuit might be particularly suitable for HD patients. We designed and conducted a randomised, placebo-controlled, double-blind and cross-over trial for treatment of dialysis–associated hypertension with telmisartan 80 mg once daily or placebo on top of standard antihypertensive treatment excluding other Renin-Angiotensin-System (RAS) blockers. In 29 patients after randomization we analysed BP after a treatment period of 8 weeks, while 13 started with telmisartan and 16 with placebo; after 8 weeks 11 continued with telmisartan and 12 with placebo after cross-over, respectively. Patients exhibited a significant reduction of systolic pre-HD BP from 141.9±21.8 before to 131.3±17.3 mmHg after the first treatment period with telmisartan or placebo. However, no average significant influence of telmisartan was observed compared to placebo. The latter may be due to a large inter-individual variability of BP responses reaching from a 40 mmHg decrease under placebo to 40 mmHg increase under telmisartan. Antihypertensive co-medication was changed for clinical reasons in 7 out of 21 patients with no significant difference between telmisartan and placebo groups. Our starting hypothesis, that telmisartan on top of standard therapy lowers systolic office BP in HD patients could not be confirmed. In conclusion, this small trial indicates that testing antihypertensive drug efficacy in HD patients is challenging due to complicated standardization of concomitant medication and other confounding factors, e.g. volume status, salt load and neurohormonal activation, that influence BP control in HD patients.

Trial Registration

Clinicaltrialsregister.eu 2005-005021-60     

The association between serum selenium and gestational diabetes mellitus: A systematic review and meta-analysis

BackgroundResults of the studies about association between serum selenium concentration and gestational hyperglycemia are inconsistent. Some studies have demonstrated that women with gestational diabetes mellitus (GDM) have lower Se concentrations while contrary results are reported in other studies.AimThe aim of this study is to compare the serum Se concentration in women with GDM and normoglycemic pregnant women via a systematic review and meta-analysis.MethodsA computerized literature search on four databases (PubMed, Cochrane register of control trials, Scopus and Google scholar) was performed from inception through August 2013. Necessary data were extracted and random effects model was used to conduct the meta-analysis.ResultsSix observational studies (containing 147 women with GDM and 360 normoglycemic pregnant women) were found, which had compared serum Se concentration in women suffering from GDM with normal pregnant ones. Our meta-analysis revealed that serum Se concentration was lower in women with GDM compared to normoglycemic pregnant women (Hedges = −1.34; 95% CI: −2.33 to −0.36; P < 0.01). Stratified meta-analysis demonstrated that concentration of Se in the sera of women with GDM was lower than normal pregnant women both in second and third trimesters, but the result was not significant in second trimester (second trimester: Hedges = −0.68; 95% CI: −1.60−0.25; P = 0.15, third trimester: Hedges = −2.81; 95% CI: −5.21 to −0.42; P < 0.05). It was also demonstrated that serum Se status was lower in pregnant women with impaired glucose tolerance (IGT) compared to normoglycemic pregnant women (Hedges = −0.85; 95% CI: −1.18 to −0.52).ConclusionThe available evidences suggest that serum Se concentration is significantly lower in pregnant women with gestational hyperglycemia compared to normal pregnant women.     

Effects of curcumin supplementation on blood glucose,insulin resistance and androgens in patients with polycystic ovary syndrome: A randomized double-blind placebo-controlled clinical trial

BackgroundCurcumin is a biologically active phytochemical ingredient found in turmeric. It has several pharmacologic effects that might benefit patients with polycystic ovary syndrome (PCOS).ObjectiveWe hypothesized curcumin to be effective in improving blood sugar levels, insulin resistance and hyperandrogenism in individuals with PCOS.MethodsIn a randomized double-blind placebo-controlled trial, individuals with PCOS were treated with curcumin (500 mg three times daily) or placebo for 12 weeks. Primary outcome measures were fasting plasma glucose (FPG), fasting insulin (FI), sex hormone levels, and hirsutism (Ferriman-Gallwey [mFG] score). Secondary outcomes included anthropometric measurements.ResultsOf 72 randomized individuals, 67 completed the trial. The two groups were comparable at baseline. At the end of the study, FPG and Dehydroepiandrosterone levels had decreased significantly in the intervention group compared to control (difference of change (post-pre) between intervention and placebo groups: -4.11 mg/dL; 95% CI: -8.35, -0.35 mg/dL; p = 0.033 and -26.53 microg/dL; 95% CI: -47.99, -4.34 µg/dL; p = 0.035, respectively). We also observed a statistically non-significant increase (p = 0.082) in Estradiol levels in the intervention group compared to control. No serious adverse events were reported throughout the trial.ConclusionsCurcumin might be a safe and useful supplement to ameliorate PCOS-associated hyperandrogenemia and hyperglycemia. However, longer trials investigating different dosages in longer durations are needed to underpin these findings.     

Selenium supplementation decreases CRP and IL-6 and increases TNF-alpha: A systematic review and meta-analysis of randomized controlled trials

Inflammation is an initiating cause of infectious and non-infectious diseases. Studies have shown that selenium (Se) has anti-inflammatory effects. However, its’ effects on serum c-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) plasma concentrations are equivocal. Therefore, we performed a systematic review and meta-analysis of randomized controlled trials (RCTs), evaluating the effects of per oral (PO) and intravenous (IV) Se supplementation on CRP, TNF-α, and IL-6. A systematic search was conducted using four databases, including PubMed, Google Scholar, Cochrane Library, and Scopus to find randomized clinical trials, published up to April 2023. From 19476 papers, after screening and removing duplicate articles, 24 studies were analyzed in the present meta-analysis. In the pooled analysis, PO Se administration showed no significant effect on CRP (WMD: 0.12; 95 % CI −0.11, 0.38; P-value= 0.30). However, IV Se supplementation had a significant negative association with CRP concentration (−2.24; 95 % CI: −4.24, −0.24; p-value: 0.02). Se administration had no significant association with TNF-α plasma concentration (9.64, 95 % CI: −0.59, 19.88, p-value= 0.06; and heterogeneity: 98 %). However, a significant positive association was present between Se and plasma TNF-α concentrations (0.15, 95 % CI: 0.14, 0.17, P-value<0.0001). Moreover, Se supplementation had a significant negative correlation with IL-6 plasma concentration in PO (−0.54; 95 % CI: −1.61, 0.52; P-value = 0.31) and IV administrations (−4.77; 95 % CI: −7.61, −1.93; P-value<0.0001), respectively. This study demonstrated that IV Se administration reduced CRP and IL-6 plasma concentrations. Conversely, IV Se supplementation increased TNF-α plasma concentration. It is evident that further, well-controlled clinical trials are required.     

Thyroid Feedback Quantile-Based Index Is Associated With Blood Pressure and Other Hemodynamic Measures: A Cross-sectional Study

ObjectivePrevious studies have reported inconsistent relationships between thyroid function and blood pressure (BP) levels. We aimed to explore the associations between thyroid hormone sensitivity and BP parameters.MethodsThis retrospective study included 6272 participants who underwent a health examination at the First Hospital of China Medical University between January 2017 and December 2018. The Thyroid Feedback Quantile-based Index (TFQI), Parametric TFQI, thyroid-stimulating hormone index, and thyrotroph thyroxine resistance index were calculated to reflect thyroid hormone sensitivity. Mean arterial pressure, pulse pressure, and rate-pressure product were used to indirectly represent arterial stiffness.ResultsThe TFQI was positively associated with systolic BP (β = 3.22), diastolic BP (β =2.32), and mean arterial pressure (β = 2.62) (P < .001, for all). Analyses of the Parametric TFQI, thyroid-stimulating hormone index, and thyrotroph thyroxine resistance index yielded similar results. The TFQI was positively related to pulse pressure and rate-pressure product. With a 1 SD increase in the TFQI, the adjusted odds ratio for hypertension was 1.11 (95% CI 1.04-1.18). When comparing the fourth quartile of the TFQI with the first, the odds ratio for hypertension was 1.27 (95% CI 1.07-1.51, P_{for trend} = .006). These relationships remained significant when stratified by age, sex, and body mass index. Similar results were observed in a euthyroid or normotensive population.ConclusionThe TFQI was positively associated with BP and markers of arterial stiffness. Impaired thyroid hormone sensitivity was related to increased risk for hypertension.     

The Efficacy and Safety of the Probiotic Bacterium Lactobacillus reuteri DSM 17938 for Infantile Colic: A Meta-Analysis of Randomized Controlled Trials

Objective

To evaluate the efficacy and safety of Lactobacillus reuteri DSM 17938 for treating infantile colic.

Methods

A systematic literature retrieval was carried out to obtain randomized controlled trials of L. reuteri DSM 17938 for infantile colic. Trials were performed before May 2015 and retrieved from the PubMed, EMBASE, Cochrane library, CNKI, WanFang, VIP, and CBM databases. Data extraction and quality evaluation of the trials were performed independently by two investigators. A meta-analysis was performed using STATA version 12.0.

Results

Six randomized controlled trials of 423 infants with colic were included. Of these subjects, 213 were in the L. reuteri group, and 210 were in the placebo group. Lactobacillus reuteri increased colic treatment effectiveness at two weeks (RR = 2.84; 95% CI: 1.24–6.50; p = 0.014) and three weeks (relative risk [RR] = 2.33; 95% CI: 1.38–3.93; P = 0.002) but not at four weeks (RR = 1.41; 95% CI: 0.52–3.82; P = 0.498). Lactobacillus reuteri decreased crying time (min/d) at two weeks (weighted mean difference [WMD] = –42.89; 95% CI: –60.50 to –25.29; P = 0.000) and three weeks (WMD = –45.83; 95% CI: –59.45 to –32.21; P = 0.000). In addition, L. reuteri did not influence infants’ weight, length or head circumference and was not associated with serious adverse events.

Conclusions

Lactobacillus reuteri possibly increased the effectiveness of treatment for infantile colic and decreased crying time at two to three weeks without causing adverse events. However, these protective roles are usurped by gradual physiological improvements. The study is limited by the heterogeneity of the trials and should be considered with caution. Higher quality, multicenter randomized controlled trials with larger samples are needed.     

Drug-induced orthostatic hypotension: A systematic review and meta-analysis of randomised controlled trials

BackgroundDrug-induced orthostatic hypotension (OH) is common, and its resulting cerebral hypoperfusion is linked to adverse outcomes including falls, strokes, cognitive impairment, and increased mortality. The extent to which specific medications are associated with OH remains unclear.Methods and findingsWe conducted a systematic review and meta-analysis to evaluate the extent to which specific drug groups are associated with OH. EMBASE, MEDLINE, and Web of Science databases were searched from inception through 23 November 2020. Placebo-controlled randomised controlled trials (RCTs) on any drug reporting on OH as an adverse effect in adults (≥18 years) were eligible. Three authors extracted data on the drug, OH, dose, participant characteristics, and study setting. The revised Cochrane risk-of-bias tool for randomised trials (RoB 2) was used to appraise evidence. Summary odds ratios (ORs) were estimated for OH using fixed effects Mantel–Haenszel statistics. We conducted subgroup analysis on validity of OH measurement, drug dose, risk of bias, age, and comorbidity. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool was used to summarise the certainty of evidence. Of 36,940 citations, 69 eligible RCTs were included in the meta-analysis comprising 27,079 participants. Compared with placebo, beta-blockers and tricyclic antidepressants were associated with increased odds of OH (OR 7.76 [95% CI 2.51, 24.03]; OR 6.30 [95% CI 2.86, 13.91]). Alpha-blockers, antipsychotics, and SGLT-2 inhibitors were associated with up to 2-fold increased odds of OH, compared to placebo. There was no statistically significant difference in odds of OH with vasodilators (CCBs, ACE inhibitors/ARBs, SSRIs), compared to placebo. Limitations of this study are as follows: data limited to placebo-controlled studies, (excluding head-to-head trials), many RCTs excluded older participants; therefore results may be amplified in older patients in the clinical setting. The study protocol is publicly available on PROSPERO (CRD42020168697).ConclusionsMedications prescribed for common conditions (including depression, diabetes, and lower urinary tract symptoms) were associated with significantly increased odds of OH. Drugs causing sympathetic inhibition were associated with significantly increased odds of OH, while most vasodilators were associated with small nonsignificant differences in odds of OH, compared to placebo. Drugs targeting multiple parts of the orthostatic blood pressure (BP) reflex pathway (e.g. sympathetic inhibition, vasodilation, cardio-inhibitory effects) may carry cumulative risk, suggesting that individuals with polypharmacy could benefit from postural BP monitoring.

Cini Bhanu and colleagues evaluate the extent to which different drug groups are associated with orthostatic hypertension in this systematic review and meta-analysis.     

The Efficacy and Tolerability of ‘Polypills’: Meta-Analysis of Randomised Controlled Trials

Background

To assess the blood pressure and lipid-lowering efficacy and tolerability of ‘polypills’ used in cardiovascular disease prevention trials.

Methodology/Principal Findings

Systematic review and meta-analysis. Search strategy: The Cochrane Central Register of Controlled Trials, Medline, and PubMed databases were searched for eligible trials. Study inclusion criteria: Randomised controlled trials of at least six weeks duration, which compared a ‘polypill’ (that included at least one anti-hypertensive and one lipid-lowering medication) with a placebo (or one active component). Outcome measures: Change from baseline in systolic and diastolic blood pressures, and total and LDL-cholesterol; discontinuation of study medication and reported adverse effects. Of 44 potentially eligible studies, six trials (including 2,218 patients without previous cardiovascular disease) fulfilled the inclusion criteria. Compared with placebo, ‘polypills’ reduced systolic blood pressure by −9.2 mmHg (95% confidence interval (CI): −13.4, −5.0) diastolic blood pressure by −5.0 mmHg (95%CI: −7.4, −2.6), total cholesterol by −1.22 mmol/L (95%CI: −1.60, −0.84) and LDL-cholesterol by −1.02 mmol/L (95%CI: −1.37, −0.67). However, those taking a ‘polypill’ (vs. placebo or component) were more likely to discontinue medication (20% vs 14%) (Odds ratio: 1.5 (95% CI: 1.2, 1.9)). There was no significant difference in reported adverse effects amongst those on a ‘polypill’ (36% vs. 28%) (OR: 1.3 (95%CI: 0.7, 2.5)). There was high statistical heterogeneity in comparisons for blood pressure and lipid-lowering but use of random-effects and quality-effects models produced very similar results.

Conclusions/Significance

Compared with placebo, the ‘polypills’ reduced blood pressure and lipids. Tolerability was lower amongst those on ‘polypills’ than those on placebo or one component, but differences were moderate. Effectiveness trials are needed to help clarify the status of ‘polypills’ in primary care and prevention strategies.