Nutrition and health

Objectives:
Emergence of Plasmodium falciparum resistance to artemisinin and its derivatives poses a threat to the global effort to control malaria. The emergence of anti-malarial resistance has become a great public health challenge and continues to be a leading threat to ongoing malaria control efforts. Therefore, this review article has been conducted.

What is the efficacy of dihydroartemisinin-piperaquine (DHA-PQ) compared to artemether-lumefantrine (AL) for the treatment of uncomplicated falciparum malaria among children in Africa?

Study design:
This review article included 25 studies which involved a total of 13,198 participants.

Results and conclusions:
The investigators found PCR-unadjusted treatment failure in children aged between 6 months and 15 years was significantly lower in the dihydroartemisinin-piperaquine treatment arm on day 28 than that of artemether-lumefantrine [RR = 0.14, 95% CI = 0.08 to 0.26, I2 = 0%, studies = 4, participants = 1,302, high quality of evidence].

The investigators found, consistently, the PCR-adjusted treatment failure was significantly lower with the dihydroartemisinin-piperaquine treatment group on day 28 [RR = 0.45, 95% CI = 0.29 to 0.68, I2 = 51%, studies = 16, participants = 8,508, high quality of evidence] and on day 42 [RR = 0.60, 95% CI =0.47 to 0.78, I2 = 0%, studies = 17, participants = 5,959, high quality of evidence].
However, the efficacy was ≥ 95% in both treatment groups on day 28.

The investigators concluded that dihydroartemisinin-piperaquine reduces new infection and recrudescence (a new outbreak after a period of abatement or inactivity) on days 28 and 42 more than artemether-lumefantrine. This may trigger dihydroartemisinin-piperaquine to become a first-line treatment option.

Original title:
Efficacy of dihydroartemisinin-piperaquine versus artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria among children in Africa: a systematic review and meta-analysis of randomized control trials by Assefa DG, Yismaw G and Makonnen E.

Link:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8359548/

Additional information of El Mondo:
Find more information/studies on RCTs/cohort/significantly/review article, malaria and malnutrition right here.

Objectives:
Previous studies have provided limited evidence for the effect of carrot intake on bladder cancer incidence. Therefore, this review article has been conducted.

Is there a relationship between dietary carrot intake and bladder cancer incidence?

Study design:
This review article included 3 cohort studies.

Results and conclusions:
The investigators found in a meta-analyse of 3 cohort studies no significant association between dietary carrot intake and bladder cancer risk [summary HR = 1.02, 95% CI = 0.95 to 1.10, I2 = 0.0%, p = 0.859].

The investigators concluded that there is no association between dietary consumption of carrot and the risk of bladder cancer.

Original title:
Association of Dietary Carrot Intake With Bladder Cancer Risk in a Prospective Cohort of 99,650 Individuals With 12.5 Years of Follow-Up by Xu X, Zhu Y, […], Xia D.

Link:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8349976/

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Find more information/studies on carrot consumption and cancer right here.

Objectives:
The effects of vitamin and mineral supplementation on women with gestational diabetes mellitus (GDM) have not been well established. Therefore, this review article has been conducted.

Does vitamin and mineral supplementation improve glycemic control (like, fasting plasma glucose, serum insulin, homeostasis model assessment-insulin resistance and homeostasis model of assessment for β cell function) and decrease risk of inflammation and oxidative stress in women with gestational diabetes mellitus?

Study design:
This review article included 12 RCTs with 698 patients.

Patients included were in the age range of 18-40 years and all reported gestational diabetes mellitus screening was conducted between 24 weeks and 28 weeks gestation.

All trials gave vitamin and mineral supplementation orally.

Types, doses, dose regimens and duration of vitamin and mineral supplementation were as follows: magnesium (100-250 mg), zinc (4-233 mg), selenium (200 μg), calcium (400-1000 mg) and vitamin E (400 IU) every day for 6 weeks, vitamin D (200-50000 IU) every day or every 2 or 3 weeks for 6 weeks. Magnesium, zinc, selenium, calcium, vitamin D or E was given separately or in different combinations: magnesium and vitamin E; zinc and vitamin E; calcium and vitamin D; magnesium, zinc, calcium and vitamin D.

All trials used placebo as control intervention.

Among the 12 trials, 8 were judged to be at low risk of bias and 4 as being at unclear risk of bias. Unclear risks were related to attrition bias and other bias.

No significant publication bias was found for the effect of vitamin and mineral supplementation on all 8 outcomes.

Results and conclusions:
The investigators found magnesium, zinc, selenium, calcium, vitamin D and E (alone or in combination) supplementation significantly improved glycemic control in women with gestational diabetes mellitus compared to those receiving placebos:
-fasting plasma glucose (FPG) [MD = - 9.02, 95% CI = -12.09 to -5.96, p   0.00001];
-serum insulin [MD = -4.33, 95% CI = -5.35 to -3.32, p  0.00001];
-homeostasis model assessment-insulin resistance (HOMA-IR) [MD = -1.34, 95% CI = -1.60 to -1.07, p  0.00001] and;
-homeostasis model of assessment for β cell function (HOMA-B) [MD = - 15.58, 95% CI = -23.70 to -7.46, p = 0.0002].
Significantly because the calculated p-value of 0.0002 was less than the p-value of 0.05.

The investigators found vitamin and mineral supplementation (magnesium, zinc, selenium, calcium, vitamin D and E (alone or in combination)) significantly decreased risk of inflammation and oxidative stress through decreasing high-sensitivity C-reactive protein (hs-CRP) [MD = -1.29, 95% CI = -1.82 to -0.76, p  0.00001], malondialdehyde (MDA) [MD = -0.71, 95% CI = -0.97 to -0.45, p  0.00001] and increasing total antioxidant capacity (TAC) [MD = 45.55, 95% CI = 22.02 to 69.08, p = 0.0001].

The investigators concluded that vitamin and mineral supplementation improves glycemic control and decreases risk of inflammation and oxidative stress in women with gestational diabetes mellitus.

Original title:
The effects of vitamin and mineral supplementation on women with gestational diabetes mellitus by Li D, Cai Z, [...], Zhang J.

Link:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145819/

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Find more information/studies on review article/meta-analysis/significantly, vitamins, minerals and pregnancy right here.
 

Objectives:
Studies indicate that onion supplementation may be effective in the treatment of dyslipidemia; however, the results remain controversial. Therefore, this review article has been conducted.

Does supplementation of onion improve levels of cholesterol and triglycerides or in other words, does eating onions causally lower cholesterol and triglycerides levels?  

Study design:
This review article included 10 RCTs with 446 participants, that were randomly assigned to either the placebo group or the onion group.

The number of participants in each study ranged from 12 to 92.
The duration of intervention in the included studies ranged from 2 to 12 weeks.
There was no evidence of publication bias.

Results and conclusions:
The investigators found the pooled findings of 10 studies showed that onion supplementation significantly increased high-density lipoprotein cholesterol (good cholesterol or HDL cholesterol) levels [MD = 2.29 mg/dL, 95% CI = 0.87 to 3.72, I2 = 0%], when compared to the control group.

The investigators found the pooled findings of 10 studies showed that onion supplementation significantly decreased low-density lipoprotein cholesterol (bad cholesterol or LDL cholesterol) levels [MD = -6.64 mg/dL, 95% CI = -10.91 to -2.36, I2 = 32%], when compared to the control group.
The pooled effect size of LDL cholesterol was not affected by any of the studies in sensitivity analysis.

The investigators found the pooled findings of 10 studies showed no association between onion supplementation and lower triglycerides (TG) levels [MD = -6.55 mg/dL, 95% CI = -15.64 to 2.53, I2 = 45%], when compared to the control group.

The investigators found the pooled findings of 9 studies showed that onion supplementation significantly increased total cholesterol (TC) levels [MD = -5.39 mg/dL, 95% CI = -10.68 to -0.09, I2 = 49%], when compared to the control group.

The investigators found in subgroup analysis that onion supplementation showed a greater benefit in lowering total cholesterol [MD = -17.23 mg/dL, 95% CI = -27.99 to -6.47, I2 = 8%] and LDL cholesterol levels [MD = -12.70 mg/dL, 95% CI = -23.12 to -2.27, I2 = 0%] in subjects with dyslipidemia.

The investigators found in subgroup analysis that onion supplementation longer than 10 weeks showed more increases in HDL cholesterol concentrations [MD = 2.81 mg/dL, 95% CI = 1.08 to 5.54, I2 = 17%].

The investigators concluded supplementation of onion is beneficial to control dyslipidemia, including improving levels of HDL, LDL and total cholesterol, but could not reduce triglycerides levels. The therapeutic benefits of onion for dyslipidemia need to be treated with caution considering that some of the results are not robust.

Original title:
Effect of onion on blood lipid profile: A meta-analysis of randomized controlled trials by Huang W, Tang G, [...], Wei Z.

Link:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269690

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Dyslipidemia is defined as having blood lipid levels that are too high or low. Blood lipids are fatty substances, such as triglycerides and cholesterol.

A causal relationship can be found in RCTs.

Objectives:
Low vitamin D status is a global public health issue that vitamin D food fortification and biofortification may help to alleviate. Therefore, this review article has been conducted.

Does vitamin D food fortification increase circulating 25(OH)D (vitamin D level in blood) concentrations in populations?

Study design:
This review article included data from 34 publications (2,398 adults: 1,345 intervention (group with vitamin D fortification), 1,053 controls (group without vitamin D fortification) and 1,532 children: 970 intervention, 562 controls).

Results and conclusions:
The investigators found random-effects meta-analysis of all studies combined (mean dose 16.2 μg/d) indicated a pooled treatment effect of 21.2 nmol/L [95% CI = 16.2 to 26.2, I2 > 75%], with a greater effect for studies using cholecalciferol (vitamin D3) than ergocalciferol (vitamin D2).

The investigators found metaregression analyses for all studies combined suggested positive effect differences for baseline circulating 25(OH)D concentrations 50 nmol/L, dose ≥10 μg/d and a negative effect difference when the intervention arm included a calcium dose ≥500 mg/d greater than the control arm.

The investigators found dose-response rates was nonlinear [Wald test for nonlinearity p 0.001].
For all studies combined, a threshold occurred at ∼26 nmol/L for a dose of ∼21 μg/d.

The investigators concluded that vitamin D food fortification (at least 10 μg/d) increases circulating 25(OH)D concentrations in populations.

Original title:
Vitamin D Food Fortification and Biofortification Increases Serum 25-Hydroxyvitamin D Concentrations in Adults and Children: An Updated and Extended Systematic Review and Meta-Analysis of Randomized Controlled Trials by Dunlop E, Kiely ME, […], Black LJ.

Link:
https://pubmed.ncbi.nlm.nih.gov/34113994/

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Objectives:
Although current guidelines recommend reduction of salt intake in patients with diabetes, the benefits of reducing salt intake in people with type 2 diabetes mellitus (T2DM) lack clear evidence. Therefore, this review articles has been conducted.

Does dietary sodium restriction causally reduce blood pressure in patients with type 2 diabetes mellitus (T2DM)?

Study design:
This review article included 8 RCTs with 10 trials (7 cross-over and 3 parallel designs).
No publication bias was found from Begg's and Egger's tests.

Results and conclusions:
The investigators found compared with ordinary sodium intake, dietary sodium restriction significantly decreased 24-hour urine sodium level [WMD = -38.430 mmol/24h, 95% CI = -41.665 mmol/24h to -35.194 mmol/24h].

The investigators found dietary sodium restriction significantly lowered systolic blood pressure [WMD = -5.574 mm Hg, 95% CI = -8.314 to -2.834 mm Hg, I2 = 0.0%] and diastolic blood pressure [WMD = -1.675 mm Hg, 95% CI = -3.199 to -0.150 mm Hg, I2 = 0.0%].

The investigators concluded that dietary sodium restriction causally reduces systolic blood pressure and diastolic blood pressure in patients with type 2 diabetes mellitus (T2DM).

Original title:
Effect of dietary sodium restriction on blood pressure in type 2 diabetes: A meta-analysis of randomized controlled trials by Ren Y, Liqiang Qin L, […], Ma Y.

Link:
https://pubmed.ncbi.nlm.nih.gov/33838996/

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Find more information/studies on sodium and diabetes right here.

Salt consists of sodium and chloride. So a dietary sodium restriction means a reduction in dietary salt intake.

A diet with dietary salt restriction is a diet with maximum 0.2 grams of salt per 100 kcal.

The easiest way to follow this diet is to choose only products/meals with maximum 0.2 grams of salt per 100 kcal. These products from the supermarket contain maximum 0.2 grams of salt per 100 kcal.

However, the most practical way to follow this diet is, all your daily consumed products/meals should contain on average maximum 0.2 grams of salt per 100 kcal.
To do this, use the 7-points nutritional profile app to see if your daily diet contains maximum 0.2 grams of salt per 100 kcal.

Objectives:
Evidence regarding associations between potato consumption and type 2 diabetes (T2D) and gestational diabetes mellitus (GDM) risks is accumulating. Therefore, this review article has been conducted.

Does a high potato intake increase type 2 diabetes and gestational diabetes mellitus (diabetes mellitus during pregnancy) risk?

Study design:
This review article included 19 studies (13 for type 2 diabetes and 6 for gestational diabetes mellitus) with a total of 21,357 type 2 diabetes cases among 323,475 participants and 1,516 gestational diabetes mellitus cases among 29,288 pregnancies.

Results and conclusions:
The investigators found meta-analysis showed a significantly increased risk of 19% [RR = 1.19, 95% CI = 1.06 to 1.34] for type 2 diabetes for total potato intakes among Western populations.

The investigators found meta-analysis showed a significantly increased risk of 8% [RR = 1.08, 95% CI = 1.00 to 1.16] for type 2 diabetes for baked/boiled/mashed potato intakes among Western populations.

The investigators found meta-analysis showed a significantly increased risk of 33% [RR = 1.33, 95% CI = 1.03 to 1.70] for type 2 diabetes for French fries/fried potato intakes among Western populations.

The investigators found dose-response meta-analysis demonstrated a significantly increased type 2 diabetes risk by 10% [95% CI = 1.07 to 1.14, p for trend 0.001], 2% [95% CI = 1.00 to 1.04, p for trend = 0.02] and 34% [95% CI = 1.24 to 1.46, p for trend 0.001] among Western populations for each 80 g/day (serving) increment in total potato, unfried potato and fried potato intakes, respectively.

The investigators found dose-response meta-analysis demonstrated a significantly increased gestational diabetes mellitus risk by 22% [95% CI = 1.06 to 1.42, p for trend 0.007] among Western populations for each 80 g/day (serving) increment in total potato intakes.

The investigators found dose-response meta-analysis demonstrated a significantly increased gestational diabetes mellitus risk by 26% [95% CI = 1.07 to 1.48, p for trend = 0.006] among Western populations for each 80 g/day (serving) increment in unfried potato intakes.

The investigators concluded that higher potato intake (at least 80g per day) is associated with higher type 2 diabetes risk among Western populations. The positive relationship presents a significant dose-response manner. Wisely controlled potato consumption may confer potential glucometabolic benefits.

Original title:
Dietary potato intake and risks of type 2 diabetes and gestational diabetes mellitus by Guo F, Zhang Q, [...], Ma L.

Link:
https://pubmed.ncbi.nlm.nih.gov/34130021/

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Objectives:
Whether N-acetylcysteine (NAC) therapy can promote the improvement of clinical symptoms and lung function in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) has not been verified by large-scale randomized controlled trials, only a few small sample studies. Therefore, this review article has been conducted.

Does n-acetylcysteine (NAC) supplementation improve clinical symptoms and lung function in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD)?

Study design:
This review article included 12 retrospective analyses and 3 randomized controlled trials (RCTs) with 1,605 patients.
The 15 included studies were small sample studies, with sample sizes ranging from 72 to 146.

9 studies had a Jadad score of 3-5 points and 6 studies had a Jadad score of 1-2 points.

Results and conclusions:
The investigators found the meta-analysis results of 10 studies (525 cases in the n-acetylcysteine group and 524 cases in the control group) showed that the forced expiratory volume in the first second (FEV1) of the n-acetylcysteine group was markedly higher than that of the control group; the mean difference was 30.63 [95% CI = 25.48 to 35.78, I2 = 92%] and the difference was statistically significant [z = 11.65 and p 0.0001].

The investigators found the meta-analysis results of 6 studies (347 cases in the n-acetylcysteine group and 350 cases in the control group) showed that forced expiratory volume in the first second/forced vital capacity (FEV1/FVC) of the n-acetylcysteine group was markedly higher than that of the control group; the mean difference was 30.42 [95% CI = 24.00 to 36.85, I2 = 93%] and the difference was statistically significant [z = 9.28 and p 0.0001].

The investigators found the meta-analysis results of 6 studies (323 cases in the n-acetylcysteine group and 322 cases in the control group) showed that the glutathione sulfur transferase (GSH-ST) activity of the n-acetylcysteine group was notably greater than that of the control group; the mean difference was 3.10 [95% CI = 1.38 to 4.82, I2 = 91%] and the difference was statistically significant [z = 3.63, p = 0.0004].

The investigators found the meta-analysis results of 4 studies (224 cases in the n-acetylcysteine group and 227 cases in the control group) showed that the ability of the n-acetylcysteine group to inhibit hydroxyl free radicals was higher than that of the control group; the mean difference was 77.52 [95% CI = 61.01 to 94.03, I2 = 44%] and the difference was statistically significant [z = 9.20 and p 0.0001]. 

The investigators found the meta-analysis results of 4 studies (224 cases in the n-acetylcysteine group and 227 cases in the control group) showed that the superoxide anion radical resistance ability of the n-acetylcysteine group was greater than the ability of the control group; the mean difference was 47.75 [95% CI = 36.26 to 59.25, I2 = 35%] and the difference was statistically significant [z = 8.14 and p 0.0001]. 

The investigators concluded n-acetylcysteine (NAC) supplementation could promote the symptom improvement rate of patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD), improve lung function in FEV1 and FEV1/FVC and enhance the body’s antioxidant capacity. Could because the sample size of the literature included in this review article was small. The sample size should be expanded in future randomized controlled trials to verify these findings. All in all, the results of this review article can provide a reliable theoretical basis for the clinical treatment of AECOPD, so that patients can benefit from NAC treatment.

Original title:
Systematic review and meta-analysis of the efficacy of N-acetylcysteine in the treatment of acute exacerbation of chronic obstructive pulmonary disease by Jiang C, Zou J, [...], Yang Y.

Link:
https://apm.amegroups.com/article/view/72787/html

Additional information of El Mondo:
Find here more information/studies about review article/significant, COPD and n-acetylcysteine.

An acute exacerbation of chronic obstructive pulmonary disease is a sudden worsening of chronic obstructive pulmonary disease (COPD) symptoms including shortness of breath, quantity and color of phlegm that typically lasts for several days.
 

Objectives:
Zinc in one of the most abundant trace minerals in human body which is involved in numerous biological pathways and has variety of roles in the nervous system. It has been assumed that zinc exerts its role in nervous system through increasing brain derived neurotrophic factor (BDNF) concentrations. Therefore, this review article has been conducted.

Does zinc supplementation increase brain derived neurotrophic factor (BDNF) levels?

Study design:
This review article included 5 studies with 238 participants. These studies enrolled subjects with premenstrual syndrome, diabetic retinopathy, major depression disorder, overweight/obese and obese with mild to moderate depressive disorders.

Funnel plot did not suggest publication bias.

Results and conclusions:
The investigators found zinc supplementation failed to increase blood brain derived neurotrophic factor concentrations with effect size of 0.30 [95% CI = -0.08 to 0.67, p = 0.119].

The investigators concluded zinc supplementation does not increase brain derived neurotrophic factor (BDNF) levels. However, the small number of included articles and significant heterogeneity between them can increase the risk of a false negative result; therefore, the results should be interpreted with caution.

Original title:
The effect of zinc supplementation on brain derived neurotrophic factor: A meta-analysis by Jafari F, Mohammadi H and Amani R.

Link:
https://pubmed.ncbi.nlm.nih.gov/33831797/

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Find here more information/studies about review article/significant and zinc.

Brain Derived Neurotrophic Factor (BDNF) plays an important role in neuronal survival and growth, serves as a neurotransmitter modulator and participates in neuronal plasticity, which is essential for learning and memory.
Decreased levels of BDNF are associated with neurodegenerative diseases with neuronal loss, such as Parkinson's disease, Alzheimer's disease, multiple sclerosis and Huntington's disease.
 

Objectives:
What is the immunogenicity and safety of the 7 different Ebola virus vaccines in healthy adults?

Study design:
This review article included 21 randomized controlled trials (RCTs), evaluating 7 different vaccines with different doses with a  total of 5,275 participants.

Results and conclusions:
The investigators found the rVSVΔG-ZEBOV-GP (2 × 107) vaccine was more immunogenic [p-score = 0.80].

The investigators found for pain, rVSVΔG-ZEBOV-GP (≤105) had few events [p-score = 0.90].

The investigators found for fatigue and headache, the DNA-EBOV (≤ 4 mg) was the best one with [p-scores of 0.94 and 0.87], respectively.

The investigators found for myalgia, the ChAd3 (1010) had a lower risk [p-score = 0.94].

The investigators found for fever, the Ad5.ZEBOV (≤ 8 × 1010) was the best one [p-score 0.80].

The investigators concluded that the best vaccine to be used to stop future outbreak of Ebola is the rVSVDG-ZEBOV-GP vaccine at dose of 2 × 107 plaque-forming units (PFU).

Original title:
Immunogenicity and safety of Ebola virus vaccines in healthy adults: a systematic review and network meta-analysis by Diallo A, Carlos-Bolumbu M, […], Galtier F.

Link:
https://pubmed.ncbi.nlm.nih.gov/34270366/

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Find more information/studies on RCTs/cohort/significantly/review article, vaccination and food fortification/malnutrition right here.

Ebola virus disease (EVD), formerly known as Ebola haemorrhagic fever, is a rare but severe, often fatal illness in humans and is been caused by the Ebola virus. As the Ebola virus spreads through the body, it damages the immune system and organs. Ultimately, it causes levels of blood-clotting cells to drop. This leads to severe, uncontrollable bleeding.

The Ebola virus is transmitted to people from wild animals and spreads in the human population through human-to-human transmission.

The average Ebola virus disease case fatality rate is around 50%.

The Ebola virus was first discovered in 1976 near the Ebola River in what is now the Democratic Republic of Congo.

Recombinant vesicular stomatitis virus-Zaire Ebola virus (rVSV-ZEBOV), also known as Ebola Zaire vaccine live and sold under the brand name Ervebo, is an Ebola vaccine for adults (18 years and older) that prevents Ebola caused by the Zaire ebolavirus. Ervebo contains a virus known as vesicular stomatitis virus which has been weakened and modified to contain a protein from the Zaire Ebola virus.

Objectives:
Omega-3 polyunsaturated fatty acid (PUFA) supplementation has been proposed as a potential therapy for cancer-related malnutrition, which affects up to 70% of patients with cancer. Therefore, this review article has been conducted.

Do patients with cancer benefit from oral omega-3 PUFA supplements?

Study design:
This review article included 31 RCTs.
Trials supplementing ≥600 mg/d omega-3 PUFA (oral capsules, pure fish oil or oral nutritional supplements) compared with a control intervention for ≥3 weeks.

The Cochrane risk of bias tool graded most trials as “unclear” or “high” risk of bias.

Results and conclusions:
The investigators found meta-analyses showed no significant difference between omega-3 PUFA supplements and control intervention on muscle mass, quality of life and body weight.

The investigators found oral omega-3 PUFA supplements significantly reduced the likelihood of developing chemotherapy-induced peripheral neuropathy with 80% [OR = 0.20, 95% CI = 0.10 to 0.40, p 0.001, I2 = 0%].  

The investigators concluded that oral omega-3 PUFA supplementation may reduce the incidence of chemotherapy-induced peripheral neuropathy in patients with cancer. May reduce because most trials were graded as “unclear” or “high” risk of bias.

Original title:
The effect of oral omega-3 polyunsaturated fatty acid supplementation on muscle maintenance and quality of life in patients with cancer: A systematic review and meta-analysis by Lam CN, Watt AE, [...], van der Meij BS.

Link:
https://pubmed.ncbi.nlm.nih.gov/34130028/

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Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most frequent side effects caused by antineoplastic agents. Antineoplastic drugs are medications used to treat cancer. Antineoplastic drugs are also called anticancer, chemotherapy, chemo, cytotoxic or hazardous drugs.

Objectives:
Personalized nutrition and protective diets and lifestyles represent a key cancer research priority. The association between consumption of specific dietary components and colorectal cancer (CRC) incidence has been evaluated by a number of population-based studies, which have identified certain food items as having protective potential, though the findings have been inconsistent. Therefore, this review article has been conducted.

Which food groups reduce risk of colorectal cancer?

Study design:
This review article included 46 studies (case-control studies and cohort studies).

Results and conclusions:
The investigators found in pooled analyses that colorectal cancer risk was significantly reduced with 10% in patients with higher vs lower consumption of cruciferous vegetables [OR = 0.90, 95% CI = 0.85 to 0.95, p = 0.00, I2 = 31.02%].
This reduced risk was only significant in case-control studies, but not in cohort studies.

The investigators found in pooled analyses that colorectal cancer risk was significantly reduced with 10% in patients with higher vs lower consumption of citrus fruits [OR = 0.90, 95% CI = 0.84 to 0.96, p = 0.00, I2 = 21.65%].
This reduced risk was only significant in case-control studies, but not in cohort studies.

The investigators found in pooled analyses that colorectal cancer risk was significantly reduced with 17% in patients with higher vs lower consumption of garlic [OR = 0.83, 95% CI = 0.76 to 0.91, p = 0.00, I2 = 32.64%].
This reduced risk was only significant in case-control studies, but not in cohort studies.

The investigators found in pooled analyses that colorectal cancer risk was significantly reduced with 11% in patients with higher vs lower consumption of tomatoes [OR = 0.89, 95% CI = 0.84 to 0.95, p = 0.00, I2 = 0%].
This reduced risk was only significant in case-control studies, but not in cohort studies.

The investigators found in subgroup analysis of cohort studies that colorectal cancer risk was significantly reduced with 26% in patients with higher vs lower consumption of nut [OR = 0.74, 95% CI = 0.58 to 0.94, p = 0.01, I2 = 35.48%].

The investigators concluded that an increased consumption of cruciferous vegetables, citrus fruits, garlic and tomatoes may reduce colorectal cancer risk. May reduce because the reduced risk is only found in case-control studies and not in cohort studies.

Original title:
Phytochemically rich dietary components and the risk of colorectal cancer: A systematic review and meta-analysis of observational studies by Borgas P, Gonzalez G, […], Reza Mirnezami R.

Link:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223713/

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Objectives:
Does vitamin C supplementation improve triglyceride and cholesterol levels in patients with type 2 diabetes mellitus?

Study design:
This review article included 15 studies with 872 participants.

Results and conclusions:
The investigators found, findings from 15 studies indicated that vitamin C supplementation significantly decreased triglyceride (TG) levels [WMD= -16.48 mg/dL, 95% CI = -31.89 to -1.08, p 0.001] and total cholesterol (TC) levels [WMD = -13.00 mg/dL, 95% CI = -23.10 to -2.91, p 0.001] in patients with type 2 diabetes mellitus.

The investigators found, however, vitamin C supplementation failed to improve LDL (bad cholesterol) and HDL cholesterol (good cholesterol) levels. 

The investigators found the meta-regression analysis suggested that lipid profile improvement was affected by duration of vitamin C treatment.

The investigators found dose-response analysis showed that vitamin C supplementation changed LDL cholesterol significantly based on vitamin C dose.

The investigators concluded that vitamin C supplementation improves lipid profile via decreases in triglyceride and total cholesterol levels in patients with type 2 diabetes mellitus. It appears that vitamin C supplementation is more beneficial to lipid profile in long-term vs. short term interventions.

Original title:
Does vitamin C supplementation exert profitable effects on serum lipid profile in patients with type 2 diabetes? A systematic review and dose-response meta-analysis by Namkhah Z, Ashtary-Larky D, […], Asbaghi O.

Link:
https://pubmed.ncbi.nlm.nih.gov/33984490/

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Objectives:
Do patients with knee osteoarthritis benefit from vitamin D supplementation?

Study design:
This review article included 6 articles with a total of 1,599 patients with osteoarthritis of the knee.

Results and conclusions:
The investigators found, the results of the meta-analysis showed that vitamin D supplementation statistically significantly improved WOMAC score [SMD = -0.67, 95% CI = -1.23 to -0.12) in patients with knee osteoarthritis, including WOMAC pain score [SMD = -0.32, 95% CI = -0.63 to -0.02], function score [SMD = -0.34, 95% CI = -0.60 to -0.08] and stiffness score [SMD = -0.13, 95% CI = -0.26 to -0.01].

The investigators found, in subgroup analysis, vitamin D supplementation less than 2000 IU (50 mcg) was statistically significant for the reduction of stiffness score [SMD = -0.22, 95% CI = -0.40 to -0.04].

The investigators found vitamin D supplements significantly reduced synovial fluid volume progression in patients with knee osteoarthritis [SMD = -0.20, 95% CI -0.39 to -0.02].

The investigators concluded vitamin D supplements improve WOMAC pain and function in patients with knee osteoarthritis.

Original title:
Does vitamin D improve symptomatic and structural outcomes in knee osteoarthritis? A systematic review and meta-analysis by Zhao ZX, He Y, […], Chen J.

Link:
https://pubmed.ncbi.nlm.nih.gov/33783714/

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The WOMAC is a validated patient-administered questionnaire that assesses 3 components: pain, stiffness and function, with the score range of 0-20 for pain, 0-8 for stiffness and 0-68 for physical function.
 

Objectives:
Vaccination and single-dose rifampin are the main proven effective intervention types for preventing leprosy among contacts of Mycobacterium leprae endemic areas. Currently, no high-quality evidence is available regarding the best prophylactic (preventing or contributing to the prevention of disease) intervention. Therefore, this review article has been conducted.

What is the most effective prophylactic intervention of leprosy among contacts?

Study design:
This review article included 11 RCTs with 326,264 patients; 8 were eligible for NMA while 4 were eligible for MA.

Results and conclusions:
The investigators found that BCG vaccination was the most effective intervention compared to placebo [risk ratio = 0.49, 95% CI = 0.30 to 0.80], followed by combined BCG vaccination and single-dose rifampicin (SDR) with similarly low values [risk ratio = 48%].

The investigators found BCG revaccination was the least effective intervention compared to placebo [RR = 1.08, 95% CI = 0.36 to 3.22].

The investigators concluded that the BCG vaccine is the most effective prophylactic intervention of leprosy among contacts. The combination of BCG vaccination + single-dose rifampicin (SDR) has nearly the same efficacy as BCG vaccination alone, while BCG revaccination is the least effective. Thus, vaccination is proven to be a more effective treatment than SDR alone. A well-designed multicenter RCT is warranted to evaluate the safety of these vaccines.

Original title:
Efficacy of chemoprophylaxis and immunoprophylaxis in leprosy prevention: a systematic review and network meta-analysis of randomized controlled trials by Tawfik GM, Biala M, […], Nguyen TH.

Link:
https://pubmed.ncbi.nlm.nih.gov/34332107/

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Leprosy is a chronic infectious disease, caused by Mycobacterium leprae, that can lead to severe life-long disabilities.

The BCG (Bacillus Calmette-Guérin) vaccination is used against tuberculosis.

Objectives:
There appears to be a sex-specific association between obesity and colorectal neoplasia in patients with Lynch Syndrome (LS). Therefore, this review article has been conducted.

Does obesity (BMI>30) increase colorectal cancer in patients with Lynch Syndrome?

Study design:
This review article included 3 prospective cohort studies with 2,463 subjects (persons), of which 735 subjects with colorectal cancer.

All studies with a prospective study design (cohort studies) expressed the association between obesity and colorectal cancer in terms of adjusted HR (95% CI).

There was no publication bias.

Results and conclusions:
The investigators found a twofold risk of colorectal cancer in obese men with Lynch Syndrome compared to nonobese men with Lynch Syndrome [SRR = 2.09, 95% CI = 1.23 to 3.55, I2 = 33%].  
No significantly increased risk due to obesity was found for women [SRR = 1.41, 95% CI = 0.46 to 4.27, I2 = 68%].  

The investigators found a significantly 49% increased colorectal cancer risk for obesity (BMI>30) for subjects with an MLH1 mutation [SRR = 1.49, 95% CI = 1.11 to 1.99, I2 = 0%].

The investigators concluded that obesity (BMI>30) increases colorectal cancer in men with Lynch Syndrome, particularly with an MLH1 mutation.

Original title:
A Meta-Analysis of Obesity and Risk of Colorectal Cancer in Patients with Lynch Syndrome: The Impact of Sex and Genetics by Lazzeroni M, Bellerba F, […], Gandini S.

Link:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160758

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Lynch syndrome, also known as hereditary non-polyposis colorectal cancer (HNPCC), is an autosomal dominantly inherited disease. People with Lynch syndrome have about a 40% to 80% chance of getting colorectal cancer by age 70. They’re also at risk for cancer of the uterus, ovaries or stomach. And they tend to get cancer at younger ages than other people, often in their 30s and 40s.

An error or mutation, in one copy of the MLH1 gene is one of the causes of Lynch syndrome. Men and women with a mutation in MLH1 have a 52-82% lifetime risk (up to age 70) to develop colon or rectal cancer.
 

Objectives:
Do critically ill patients benefit of thiamine (vitamin B1) supplementation?

Study design:
This review article included 8 RCTs and 10 cohort studies.

Results and conclusions:
The investigators found in the analysis of RCTs, that thiamine supplementation showed a significantly 42% lower odds of developing ICU delirium [OR = 0.58, 95% CI = 0.34 to 0.98].

The investigators found a reduction in mortaliy was observed on performing fixed effect model analysis. However, a level of statistical significance could not be reached on performing randon effect model analysis [OR = 0.78, 95% CI = 0.59 to 1.04].

The investigators found in subgroup analysis of 13 studies in patients with sepsis, there was no difference in mortality between the 2 groups [OR = 0.83, 95% CI = 0.63 to 1.09].

The investigators concluded thiamine (vitamin B1) supplementation in critically ill patients shows a reduction in the incidence of ICU delirium among RCTs. However, there is no significant benefit in terms of overall mortality and mortality in patients with sepsis. Further, large scale randomized prospective studies are warranted to investigate the role of thiamine supplementation in critically ill patients.

Original title:
Effect of thiamine supplementation in critically ill patients: A systematic review and meta-analysis by Sedhai YR, Shrestha DB, […], Kashiouris MG.

Link:
https://pubmed.ncbi.nlm.nih.gov/34118501/

Additional information of El Mondo:
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Intensive Care Unit (ICU) delirium is a nonspecific, potentially preventable and often reversible disorder of impaired cognition, which results from various causes in ICU patients. The term “delirium”is derived from the Latin word “delirare” which literally means “to go out of the furrow” or figuratively “crazy or deranged”.
 

Objectives:
Does calcium reduce the risk of incidence and recurrence of colorectal adenomas and advanced adenomas?

Study design:
This review article included 37 relevant clinical trials and observational studies involving over 10,964 cases.

Results and conclusions:
The investigators found that calcium consumption significantly reduced the risk of colorectal adenomas incidence by 8% [RR = 0.92, 95% CI = 0.89 to 0.96].

The investigators found that calcium intake as a food significantly reduced the risk of colorectal adenomas incidence by 21% [RR = 0.79, 95% CI = 0.72 to 0.86].

The investigators found that calcium intake as dairy product significantly reduced the risk of colorectal adenomas incidence by 12% [RR = 0.88, 95% CI = 0.78 to 0.98].

The investigators found, however, calcium supplements did not show a significant effect on colorectal adenomas incidence [RR = 0.97, 95% CI = 0.89 to 1.05].

The investigators found that total calcium intake significantly reduced the risk of advanced colorectal adenomas incidence by 21% [RR = 0.79, 95% CI = 0.73 to 0.85].

The investigators found that total calcium intake significantly reduced the risk of recurrence of adenomas by 12% [RR = 0.88, 95% CI = 0.84 to 0.93].

The investigators concluded that natural sources of calcium such as dairy products and foods have more effective role than supplementary calcium in terms of reducing the risk of incidence and recurrence of colorectal adenomas and advanced adenomas.

Original title:
Calcium and dairy products in the chemoprevention of colorectal adenomas: a systematic review and meta-analysis by Emami MH, Salehi M, […], Maghool F.

Link:
https://pubmed.ncbi.nlm.nih.gov/33951958/

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Find more information/studies on calcium, dairy products and colorectal cancer right here.

The colorectal adenoma is a benign glandular tumor of the colon and the rectum. It is a precursor lesion of the colorectal adenocarcinoma (colon cancer).

Objectives:
What are the risk factors of leprosy in contacts?

Study design:
This review article included 23 cohort studies and 1 cross-sectional study.
Most of the studies had been conducted in Brazil and India.
The follow-up period ranged from 1 to 20 years and the publication covered the period from 1991 to 2019.
The sample ranged from 68 to 28,092 participants.
19 cohorts (79%) scored ≥ 7, indicating a low risk of bias.

Results and conclusions:
The investigators found illiteracy significantly increased risk of leprosy in contacts with 48% [RR = 1.48, 95% CI = 1.22 to 1.79].

The investigators found living in the same house significantly increased risk of leprosy in contacts with 141% [RR = 2.41, 95% CI = 1.87 to 3.10].

The investigators found leprosy with high bacillary load significantly increased risk of leprosy in contacts with 140% [RR = 2.40, 95% CI = 1.69 to 3.41].

The investigators found seropositivity to the Mycobacterium leprae PGL-1 (phenolic glycolipid-1) antigen significantly increased risk of leprosy in contacts with 254% [RR = 3.54, 95% CI = 2.21 to 5.67].

The investigators found presence of the bacillus in the bloodstream significantly increased risk of leprosy in contacts with 10.61-fold [RR = 10.61, 95% CI = 4.74 to 23.77].

The investigators found negative Mitsuda reaction significantly increased risk of leprosy in contacts with 2.68-fold [RR = 2.68, 95% CI = 1.76 to 4.07].

The investigators found immunization with BCG (bacillus Calmette-Guérin) vaccine had a protective effect against leprosy.

The investigators concluded that young and adults, who live with patients in crowded households, have lower income and low education have a higher risk of leprosy in contacts. The meta-analysis confirms the greatest risk for illiterate contacts.

Original title:
Factors associated with the development of leprosy in contacts: a systematic review and meta-analysis by Niitsuma ENA, de Caux Bueno I, […], Lana CF.

Link:
https://www.scielo.br/j/rbepid/a/6yRXLPSd7gnJ7RTFqJ5mqTb/?lang=en

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Find more information/studies on RCTs/cohort/significantly/review article, vaccination and food fortification/malnutrition right here.
 

Objectives:
Do vegetarians and vegans have a lower bone mineral density than omnivores?

Study design:
This review article included 17 cross-sectional studies with a total of 13,888 patients.

Results and conclusions:
The investigators found the pooled results indicated, those on plant-based diets exhibited a lower bone mineral density at the lumbar spine [MD = -0.04, 95% CI = -0.06 to -0.02, p < 0.0001] and femoral neck [MD = -0.04, 95% CI = -0.05 to -0.02, p < 0.00001] and a reduced whole-body bone mineral density [MD = -0.03, 95% CI = -0.06 to -0.01, p = 0.0009], compared to omnivores.

The investigators found both vegetarians and vegans exhibited lower lumbar spine, femoral neck and whole-body bone mineral density than omnivores.

The investigators concluded both vegetarians and vegans have a lower lumbar spine, femoral neck and whole-body bone mineral density than omnivores.

Original title:
Comparison of human bone mineral densities in subjects on plant-based and omnivorous diets: a systematic review and meta-analysis by Li  T, Li  Y and Wu S.

Link:
https://pubmed.ncbi.nlm.nih.gov/34145511/

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Objectives:
The efficacy and safety of L‐arginine supplements and their effect on maximal oxygen uptake (VO2 max) remained unclear. Therefore, this review article has been conducted.

Does supplementation with arginine increase VO2 max in healthy people?

Study design:
This review article included 11 RCTs.
The different types of arginine supplements were L‐arginine, arginine aspartate, arginine alpha‐ketoglutarate and arginine in combination with antioxidants.
There was no publication bias.

Results and conclusions:
The investigators found subgroup analysis showed that arginine in the form of L‐arginine significantly increased VO2 max compared to the other forms [weighted mean difference = 0.11 L/min, I2 = 0.0%, p = 0.485].

The investigators concluded that supplementation with L‐arginine alone increases VO2 max compared to the other types of arginine or combined with other metabolites or supplements. Future homogeneous and well‐designed randomized clinical trials are needed to a deep understand of the effects of L‐arginine on VO2 max in healthy human subjects.

Original title:
The effect of L-arginine supplementation on maximal oxygen uptake: A systematic review and meta-analysis by Rezaei S, Gholamalizadeh M, […], Doaei S.

Link:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883807/

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VO2 max is the maximum amount of oxygen your body can utilize during exercise. The more oxygen your body can use, the more your muscles can work.

Objectives:
Seventeen per cent of the world's population is estimated to be at risk of inadequate zinc intake, which could in part be addressed by zinc fortification of widely consumed foods. Therefore, this review article has been conducted.

Does zinc fortification (postharvest fortification of an industrially produced food or beverage) alone or with multiple micronutrients (MMN) have positive effects on health outcomes?

Study design:
This review article included 54 observational studies with 73 comparisons.

Results and conclusions:
The investigators found zinc fortification with and without multiple micronutrients significantly increased plasma zinc concentrations [efficacy: 4.68 μg/dL, 95% CI = 2.62 to 6.75, n = 27 and effectiveness: 6.28 μg/dL, 95% CI = 5.03 to 7.77 μg/dL, n = 13].

The investigators found zinc fortification with and without multiple micronutrients significantly reduced the prevalence of zinc deficiency [efficacy: OR = 0.76, 95% CI = 0.60 to 0.96, n = 11 and effectiveness: OR = 0.45, 95% CI = 0.31 to 0.64, n = 10]. 

The investigators found there were statistically significant increases in child weight [efficacy: 0.43 kg, 95% CI = 0.11 to 0.75 kg, n = 11], improvements in short-term auditory memory [efficacy = 0.32 point, 95% CI = 0.13 to 0.50 point, n = 3] and decreased incidence of diarrhea [efficacy: RR = 0.79, 95% CI = 0.68 to 0.92, n = 3] and fever [efficacy: RR = 0.85, 95% CI = 0.74 to 0.97, n = 2].
However, these effects cannot be solely attributed to zinc.

The investigators concluded that zinc fortification with multiple micronutrients increases child weight, improves short-term auditory memory and decreases incidence of diarrhea and fever.

Original title:
Effects of Foods Fortified with Zinc, Alone or Cofortified with Multiple Micronutrients, on Health and Functional Outcomes: A Systematic Review and Meta-Analysis by Tsang BL, Holsted E, […], Manger MS.

Link:
https://pubmed.ncbi.nlm.nih.gov/34167148/

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Find more information/studies on RCTs/cohort/significantly/review article, zinc and food fortification/malnutrition right here.

 

Objectives:
Apart from ruminant fat, trans fatty acids are produced during the partial hydrogenation of vegetable oils, (eg, in the production of ultraprocessed foods). Harmful cardiovascular effects of trans fatty acids are already proven, but the link with cancer risk has not yet been summarized. Therefore, this review article has been conducted.

Does high consumption of dietary trans fat increase risk of cancer?

Study design:
This review article included 17 cohort and case-control studies on breast cancer, 11 cohort and case-control studies on prostate cancer and 9 cohort and case-control studies on colorectal cancer.

Results and conclusions:
The investigators found that high consumption of dietary total trans fat significantly increased prostate cancer with 49% [OR = 1.49, 95% CI = 1.13 to 1.95].
Significantly means that there is an association with a 95% confidence.

The investigators found that high consumption of dietary total trans fat significantly increased colorectal cancer with 26% [OR = 1.26, 95% CI = 1.08 to 1.46].
Significant because OR of 1 was not found in the 95% CI of 1.08 to 1.46. OR of 1 means no risk/association.

The investigators found no association between high consumption of dietary total trans fat and the risk of breast cancer [OR = 1.12, 95% CI = 0.99 to 1.26].
No association ant because OR of 1 was found in the 95% CI of 0.99 to 1.26. OR of 1 means no risk/association.

The investigators found results were dependent on the fatty acid subtype, with even cancer-protective associations for some partially hydrogenated vegetable oils.

The investigators found enhancing moderators in the positive transfat-cancer relation were gender (direction was cancer-site specific), European ancestry, menopause, older age and overweight.

The investigators concluded that high consumption of dietary total trans fat increases prostate cancer and colorectal cancer. Future studies need methodological improvements (eg, using long-term follow-up cancer data and intake biomarkers). Owing to the lack of studies testing trans-fatty acid subtypes in standardized ways, it is not clear which subtypes (eg, ruminant sources) are more carcinogenic.

Original title:
Dietary trans-fatty acid intake in relation to cancer risk: a systematic review and meta-analysis by Michels N, Specht IO and Huybrechts I.

Link:
https://pubmed.ncbi.nlm.nih.gov/34104953/

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A diet high in trans fat is a diet with more than 1 En% trans fat.

Trans fat can be found in doughnuts, cakes, pie crusts, biscuits, frozen pizza, cookies, crackers and stick margarines and other spreads.

Objectives:
Does prenatal alcohol exposure have adverse effects on pregnancy and birth outcomes?

Study design:
This review article included 33 studies.
The quality assessment identified that 61% of studies were high quality, 30% were average quality and 9% were low quality.

Results and conclusions:
The investigators found that prenatal alcohol exposure significantly increased the likelihood of placental abruption with 48% [odds ratio = 1.48, 95% CI = 1.37 to 1.60].

The investigators found no association between prenatal alcohol exposure and placenta previa [odds ratio = 1.14, 95% CI = 0.84 to 1.34].

The investigators found that prenatal alcohol exposure significantly reduced placental weight with 51g [95% CI = -82.8g to -19.3g].

The investigators found reports of altered placental vasculature, placental DNA methylation, and gene expression following prenatal alcohol exposure.

The investigators concluded prenatal alcohol exposure increases the likelihood of placental abruption and is associated with decreased placental weight, altered placental vasculature, DNA methylation and molecular pathways. Given the critical role of the placenta in determining pregnancy outcomes, further studies investigating the molecular mechanisms underlying alcohol-induced placental dysfunction are required. Sex-specific placental adaptations to adverse conditions in utero have been well documented; thus, future studies should examine prenatal alcohol exposure-associated placental outcomes separately by sex.

Original title:
Prenatal alcohol consumption and placental outcomes: a systematic review and meta-analysis of clinical studies by Steane SE, Young SL, […], Moritz KM.

Link:
https://pubmed.ncbi.nlm.nih.gov/34181895/

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Objectives:
Is an increased homocysteine (Hcy) level an independent predictor of unfavorable outcomes in acute ischemic stroke (AIS)?

Study design:
This review article included 17 cohort studies (4 of them were retrospective studies and the remaining 13 were prospective studies) with 15,636 patients with acute ischemic stroke.

There was no publication bias.

Results and conclusions:
The investigators found the patients with acute ischemic stroke group had significantly higher levels of homocysteine than the control group [SMD = 5.11, 95% CI = 1.87 to 8.35, p = 0.002].
The results of subgroup analyses on ethnicity showed that the associations were statistically significant in both Caucasian and Asian patients [Caucasian: OR = 3.56, 95% CI = 2.54 to 4.98, p 0.00001, I2 = 20% and Asian: HR = 1.39, 95% CI = 1.19 to 1.63, p 0.00001, I2 = 86%], but not in African patients [OR = 1.04, 95% CI = 0.99 to 1.10, p = 0.11].

The investigators found, moreover, high homocysteine levels were closely associated with gender, B12 deficiency, smoking and patients who received tissue plasminogen activator treatment.
However, no significant difference was found between increased homocysteine levels and age, drinking, hypertension, diabetes mellitus and hyperlipidemia.

The investigators found, in addition, the cut-off value (20.0 μmol/L) might be an optimum cut-off index for acute ischemic stroke patients in clinical practice.

The investigators concluded that the homocysteine level may serve as an independent predictor for unfavorable survival outcomes in acute ischemic stroke patients, particularly in Caucasian and Asian acute ischemic stroke patients. Further studies can be conducted to clarify this relationship.

Original title:
The Prognostic Value of Homocysteine in Acute Ischemic Stroke Patients: A Systematic Review and Meta-Analysis by Huang S, Cai J and Tian Y.

Link:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907516/

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