Combined Aerobic and Resistance Training Improves Body Composition, Alters Cardiometabolic Risk, and Ameliorates Cancer-Related Indicators in Breast Cancer Patients and Survivors with Overweight/Obesity: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Breast cancer survivors with obesity are at a high risk of cancer recurrence, comorbidity, and mortality. This review aims to systematically evaluate the effects of combined aerobic and resistance training (CART) on body composition, lipid homeostasis, inflammation, adipokines, cancer-related fatigue, sleep, and quality of life in breast cancer patients and survivors with overweight/obesity. An electronic search was conducted in PubMed, Web of Science, Scopus, Science Direct, Cochrane, and Google Scholar databases from inception up to January 8, 2024. Randomized controlled trials (RCTs) meeting the inclusion criteria were selected for the analysis. The Cochrane risk of bias tool was used to assess eligible studies, and the GRADE method to evaluate the quality of evidence. A random-effects model was used, and data were analyzed using mean (MD) and standardized mean differences (SMD) for continuous variables with 95% confidence intervals (CI). We assessed the data for risk of bias, heterogeneity, sensitivity, reporting bias, and quality of evidence. A total of 17 randomized controlled trials were included in the systematic review involving 1,148 female patients and survivors (mean age: 54.0 ± 3.4 years). The primary outcomes showed significant improvements in body mass index (SMD -0.57 kg/m2, p = 0.04), body fat (SMD -0.50%, p = 0.02), fat mass (SMD -0.63 kg, p = 0.04), hip circumference (MD -3.14 cm, p = 0.02), and fat-free mass (SMD 1.03 kg, p < 0.001). The secondary outcomes indicated significant increases in high-density lipoprotein cholesterol (MD -0.05 mmol/L, p = 0.008), natural killer cells (SMD 0.42%, p = 0.04), reductions in triglycerides (MD -81.90 mg/dL, p < 0.01), total cholesterol (SMD -0.95 mmol/L, p < 0.01), tumor necrosis factor α (SMD -0.89 pg/mL, p = 0.03), and leptin (SMD -0.63 ng/mL, p = 0.03). Also, beneficial alterations were found in cancer-related fatigue (SMD -0.98, p = 0.03), sleep (SMD -1.17, p < 0.001), and quality of life (SMD 2.94, p = 0.02) scores. There was very low to low confidence in the estimated effect of most of the outcomes. The present findings reveal that CART could be considered an adjunct therapy in supporting the conventional clinical approach observed following exercise. However, further high-quality research is needed to evaluate whether CART would be a valuable intervention to lower aggressive pharmacologic use in breast cancer patients with overweight/obesity.

Effects of L-carnitine supplementation for women with polycystic ovary syndrome: a systematic review and meta-analysis.

Background: Polycystic ovary syndrome (PCOS) is a disorder in reproductive age women and is characterized by hyperandrogenic anovulation and oligo-amenorrhea, which leads to infertility. Anovulation in PCOS is associated with low follicle-stimulating hormone levels and the arrest of antral follicle development in the final stages of maturation. L-carnitine (LC) plays a role in fatty acid metabolism, which is found to be lacking in PCOS patients. This systematic review and meta-analysis aimed to determine the effectiveness of LC supplementation for patients with PCOS. Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Psychological Information Database (PsycINFO), and the World Health Organization International Clinical Trials Registry Platform for all randomized control trials, comparing LC alone or in combination with other standard treatments for the treatment of PCOS from inception till June 2021. We independently screened titles and abstracts to identify available trials, and complete texts of the trials were checked for eligibility. Data on the methods, interventions, outcomes, and risk of bias from the included trials were independently extracted by the authors. The estimation of risk ratios and mean differences with a 95 percent confidence interval (CI) was performed using a random-effects model. Results: Nine studies with 995 participants were included in this review. Five comparison groups were involved. In one comparison group, LC reduced the fasting plasma glucose (FPG) (mean differences (MD) -5.10, 95% CI [-6.25 to -3.95]; P = 0.00001), serum low-density lipoprotein (LDL) (MD -25.00, 95% CI [-27.93 to -22.07]; P = 0.00001), serum total cholesterol (MD -21.00, 95% CI [-24.14 to -17.86]; P = 0.00001), and serum triglyceride (TG) (MD -9.00, 95% CI [-11.46 to -6.54]; P = 0.00001) with moderate certainty of evidence. Another comparison group demonstrated that LC lowers the LDL (MD -12.00, 95% CI [-15.80 to -8.20]; P = 0.00001), serum total cholesterol (MD -24.00, 95% CI [-27.61 to -20.39]; P = 0.00001), and serum TG (MD -19.00, 95% CI [-22.79 to -15.21]; P = 0.00001) with moderate certainty of evidence. Conclusion: There was low to moderate certainty of evidence that LC improves Body Mass Index (BMI) and serum LDL, TG, and total cholesterol levels in women with PCOS.

Effectiveness of Bioinks and the Clinical Value of 3D Bioprinted Glioblastoma Models: A Systematic Review.

Many medical applications have arisen from the technological advancement of three-dimensional (3D) bioprinting, including the printing of cancer models for better therapeutic practice whilst imitating the human system more accurately than animal and conventional in vitro systems. The objective of this systematic review is to comprehensively summarise information from existing studies on the effectiveness of bioinks in mimicking the tumour microenvironment of glioblastoma and their clinical value. Based on predetermined eligibility criteria, relevant studies were identified from PubMed, Medline Ovid, Web of Science, Scopus, and ScienceDirect databases. Nineteen articles fulfilled the inclusion criteria and were included in this study. Alginate hydrogels were the most widely used bioinks in bioprinting. The majority of research found that alginate bioinks had excellent biocompatibility and maintained high cell viability. Advanced structural design, as well as the use of multicomponent bioinks, recapitulated the native in vivo morphology more closely and resulted in bioprinted glioblastoma models with higher drug resistance. In addition, 3D cell cultures were superior to monolayer or two-dimensional (2D) cell cultures for the simulation of an optimal tumour microenvironment. To more precisely mimic the heterogenous niche of tumours, future research should focus on bioprinting multicellular and multicomponent tumour models that are suitable for drug screening.

Worldwide prevalence, risk factors and psychological impact of infertility among women: a systematic review and meta-analysis.

OBJECTIVES: To assess the prevalence, risk factors and psychological impact of infertility among females. This review summarises the available evidence, effect estimates and strength of statistical associations between infertility and its risk factors. STUDY DESIGN: Systematic review and meta-analysis. DATA SOURCES: MEDLINE, CINAHL and ScienceDirect were searched through 23 January 2022. ELIGIBILITY CRITERIA: The inclusion criteria involved studies that reported the psychological impact of infertility among women. We included cross-sectional, case-control and cohort designs, published in the English language, conducted in the community, and performed at health institution levels on prevalence, risk factors and psychological impact of infertility in women. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted and assess the quality of data using the Joanna Briggs Institute Meta-Analysis. The outcomes were assessed with random-effects model and reported as the OR with 95% CI using the Review Manager software. RESULTS: Thirty-two studies with low risk of bias involving 124 556 women were included. The findings indicated the overall pooled prevalence to be 46.25% and 51.5% for infertility and primary infertility, respectively. Smoking was significantly related to infertility, with the OR of 1.85 (95% CI 1.08 to 3.14) times higher than females who do not smoke. There was a statistical significance between infertility and psychological distress among females, with the OR of 1.63 (95% CI 1.24 to 2.13). A statistical significance was noted between depression and infertility among females, with the OR of 1.40 (95% CI 1.11 to 1.75) compared with those fertile. CONCLUSIONS: The study results highlight an essential and increasing mental disorder among females associated with infertility and may be overlooked. Acknowledging the problem and providing positive, supportive measures to females with infertility ensure more positive outcomes during the therapeutic process. This review is limited by the differences in definitions, diagnostic cut points, study designs and source populations. PROSPERO REGISTRATION NUMBER: CRD42021226414.

Elagolix treatment in women with heavy menstrual bleeding associated with uterine fibroid: a systematic review and meta-analysis.

BACKGROUND: Elagolix is effective and safe for treating menorrhagia in women with uterine fibroid. However, it is reported to be associated with hypoestrogenism that can be alleviated by adding estradiol/norethindrone acetate. This systematic review and meta-analysis aimed to determine the effectiveness of elagolix treatment in women with heavy menstrual bleeding associated with uterine fibroid by comparing: elagolix versus placebo and elagolix versus estradiol/norethindrone acetate. METHODOLOGY: The Cochrane Central Register of Controlled Trials (CENTRAL 2021, Issue 3 of 12), MEDLINE databases (1980 to December week 1, 2020), and trial registries for relevant randomized clinical trials were used. All randomized clinical trials were reviewed and evaluated. Random effects models were used to estimate the dichotomous outcomes and mean differences with 95% confidence intervals. Data for risk of bias, heterogeneity, sensitivity, reporting bias and quality of evidence were assessed. RESULTS: Four randomized controlled trials with 1949 premenopausal women from 323 locations were included. Elagolix improved menstrual blood loss of less than 80 ml (RR 4.81, 95% CI 2.45 to 9.45; four trials, 869 participants; moderate quality evidence) or more than 50% reduction from baseline (RR 4.87, 95% CI 2.55 to 9.31; four trials, 869 participants; moderate quality evidence) compared to placebo. There was no difference in menstrual blood loss of less than 80 ml (RR 1.08, 95% CI 1.00 to 1.16; five trials, 1365 participants; moderate quality evidence) or more than 50% reduction from baseline between the elagolix (RR 1.08, 95% CI 1.01 to 1.15; five trials, 1365 participants; high quality evidence) and elagolix with estradiol/norethindrone acetate. In both comparisons, elagolix has reduced the mean percentage change in uterine and fibroid volume, improved symptoms, and health-related quality of life. More patients had hot flush, and bone mineral density loss in the elagolix treatment compared to both placebo and elagolix with estradiol/norethindrone acetate. CONCLUSIONS: Elagolix appeared to be effective in reducing heavy menstrual bleeding caused by uterine fibroid and combination with estradiol/norethindrone acetate was able to alleviate the hypoestrogenism side effects in premenopausal women. Review registration PROSPERO CDR 42021233898.

A Systematic Review and Meta-Analysis of the Efficacy of Evening Primrose Oil for Mastalgia Treatment.

Mastalgia, or breast pain, is common among women which can lead to significant impairment in daily living. Hence, finding an effective treatment that can alleviate the symptom is very important. Thus, we carry out this study to determine the efficacy of evening primrose oil (EPO) for mastalgia treatment in women. The review included published randomised clinical trials that evaluated EPO used for treating mastalgia against a placebo or other treatments, irrespective of the blinding procedure, publication status, or sample size. Two independent authors screened the titles and abstracts of the identified trials; full texts of relevant trials were evaluated for eligibility. Two reviewers independently extracted data on the methods, interventions, outcomes, and risk of bias. The random-effects model was used for estimating the risk ratios and mean differences with 95% confidence intervals. Thirteen trials with 1752 randomised patients were included. The results showed that EPO has no difference to reduce breast pain compared to topical NSAIDS, danazol, or vitamin E. The number of patients who achieved pain relief was no different compared to the placebo or other treatments. The EPO does not increase adverse events, such as nausea, abdominal bloating, headache or giddiness, increase weight gain, and altered taste compared to a placebo or other treatments. EPO is a safe medication with similar efficacy for pain control in women with mastalgia compared to a placebo, topical NSAIDS, danazol, or vitamin E.

Olive leaf extract effect on cardiometabolic profile among adults with prehypertension and hypertension: a systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis aimed to determine the effectiveness of olive leaf extract on cardiometabolic profiles among prehypertensive and hypertensive groups. METHODOLOGY: The Cochrane central register of controlled trials, Medline (1966 to April week 1, 2020), Embase (1966 to April week 1, 2020) and trial registries for relevant randomized clinical trials were used. Published and unpublished randomized clinical trials were reviewed and evaluated. Random effects models were used to estimate the continuous outcomes and mean differences (MDs); both with 95% confidence intervals (CIs). The primary outcomes were changes in systolic and diastolic BP. The secondary outcomes were changes in lipid profile, glucose metabolism, inflammatory markers for CVD, kidney and liver functions safety parameters. We assessed the data for risk of bias, heterogeneity, sensitivity, reporting bias and quality of evidence. RESULTS: Five trials were included involving 325 patients aged 18-80 years. Two trials involved high-income countries and three trials involved moderate-income countries. The analysis performed was based on three comparisons. No significant changes were found between systolic or diastolic blood pressure (BP) for the first comparison, 1,000 mg per day for a combined formulation of olive leaf extract versus a placebo. The second comparison, 500 mg per day of olive leaf extract versus placebo or no treatment, showed a significant reduction in systolic BP over a period of at least 8 weeks of follow up (MD -5.78 mmHg, 95% CI [-10.27 to -1.30]) and no significant changes on diastolic BP. The third comparison, 1,000 mg per day of olive leaf extract versus placebo shows no significant difference but an almost similar reduction in systolic BP (-11.5 mmHg in olive leaf extract and -13.7 mmHg in placebo, MD 2.2 mmHg, 95% CI [-0.43-4.83]) and diastolic BP (-4.8 mmHg in olive leaf extract and -6.4 mmHg in placebo, MD 1.60 mmHg, 95% CI [-0.13-3.33]). For secondary outcomes, 1,000 mg per day of olive leaf extract versus captopril showed a reduction in LDL (MD -6.00 mg/dl, 95% CI [-11.5 to -0.50]). The 500 mg per day olive leaf extract versus placebo showed a reduction in inflammatory markers for CVD IL-6 (MD -6.83 ng/L, 95% CI [-13.15 to -0.51]), IL-8 (MD -8.24 ng/L, 95% CI [-16.00 to -0.48) and TNF-alpha (MD -7.40 ng/L, 95% CI [-13.23 to -1.57]). CONCLUSIONS: The results from this review suggest the reduction of systolic BP, LDL and inflammatory biomarkers, but it may not provide a robust conclusion regarding the effects of olive leaf extract on cardiometabolic profile due to the limited number of participants in the included trials. REVIEW REGISTRATIONS: PROSPERO CDR 42020181212.

Effectiveness of iron polymaltose complex in treatment and prevention of iron deficiency anemia in children: a systematic review and meta-analysis.

BACKGROUND: Iron deficiency anemia (IDA) is commonly treated with iron formulations. Despite the expanding acceptance of iron polymaltose complex (IPC) among clinicians, there is sparse and contradictory evidence regarding its efficacy in the management of IDA in children. This systematic review and meta-analysis aimed to assess the effectiveness of IPC in the treatment and prevention of IDA in children. METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE and Epistemonikos for all randomized control trials (RCTs) comparing oral IPC with standard oral iron supplementation for the treatment or prevention of IDA in children. We independently screened the titles and abstracts of identified trials before the full text of relevant trials was evaluated for eligibility. We then independently extracted data on the methods, interventions, outcomes, and risk of bias from the included trials. A random-effects model was used to estimate the risk ratios and mean differences with 95% confidence intervals. RESULTS: Eight trials comprising 493 randomized patients were included and analyzed using three comparison groups. The comparison group of which was used to evaluate IPC and ferrous sulphate (FS) for treatment of IDA showed that IPC is less effective in increasing Hb (MD -0.81, 95% CI -1.08 to -0.53; I2 = 48%, P < 0.001; six studies, 368 participants; high certainty of evidence), ferritin (MD -21.24, 95% CI -39.26 to -3.23, random-effects; I2 = 65%, P = 0.020; 3 studies, 183 participants; moderate certainty of evidence) and MCV levels (MD -3.20, 95% CI -5.35 to -1.05; P = 0.003; one study, 103 participants; low certainty of evidence). There was no difference in the occurrence of side effects between IPC and FS group (MD 0.78, 95% CI 0.47 to 1.31; I2 = 4%, P = 0.35; three studies, 274 participants; high certainty of evidence). CONCLUSIONS: There was moderate to high certainty evidence that FS is superior to IPC with a clinically meaningful difference in improving the Hb and ferritin levels in the treatment of IDA in children. There was no difference in the occurrence of gastrointestinal side effects with high certainty evidence between the IPC and FS groups. The body of evidence did not allow a clear conclusion regarding the effectiveness of IPC with iron gluconate and iron bisglycinate in the prevention and treatment of IDA. The certainty of evidence was low. Adequately powered and high-quality trials with large sample sizes that assess both hematological and clinical outcomes are required.

Metoprolol for prophylaxis of postoperative atrial fibrillation in cardiac surgery patients: systematic review and meta-analysis.

PURPOSE: Postoperative atrial fibrillation (POAF) is a potentially lethal and morbid complication after open heart surgery. This systematic review and meta-analysis aimed to investigate metoprolol compared with other treatments for prophylaxis against POAF. METHODS: We searched CENTRAL, MEDLINE, EMBASE and trial registries for randomised controlled trials that evaluated metoprolol for preventing the occurrence of POAF after surgery against other treatments or placebo. Random-effects model was used for estimating the risk ratios (RRs) and mean differences with 95% CIs. RESULTS: Nine trials involving 1570 patients showed metoprolol reduced POAF compared with placebo (416 patients; RR 0.46, 95% CI 0.33 to 0.66; I²=21%; risk difference (RD) -0.19, 95% CI -0.28 to -0.10). However, metoprolol increased the risk of POAF compared with carvedilol (159 patients; RR 1.59, 95% CI 1.20 to 2.12; I²=4%; RD 0.13, 95% CI 0.06 to 0.20). There was no difference when compared with sotalol or amiodarone. The occurrence of cardiovascular conditions after drugs administration or death between the groups was not different. The overall quality of evidence was moderate to high. Subgroup analysis and funnel plot were not performed. CONCLUSIONS: Metoprolol is effective in preventing POAF compared with placebo and showed no difference with class III antiarrhythmic drugs. Death and thromboembolism are associated with open heart surgery, but not significant in relation to the use of metoprolol. PROSPERO REGISTRATION NUMBER: CRD42019131585.

Colorectal cancer screening practices of primary care providers: results of a national survey in Malaysia.

The incidence of colorectal cancer has been increasing in many Asian countries including Malaysia during the past few decades. A physician recommendation has been shown to be a major factor that motivates patients to undergo screening. The present study objectives were to describe the practice of colorectal cancer screening by primary care providers in Malaysia and to determine the barriers for not following recommendations. In this cross sectional study involving 132 primary care providers from 44 Primary Care clinics in West Malaysia, self-administered questionnaires which consisted of demographic data, qualification, background on the primary care clinic, practices on colorectal cancer screening and barriers to colorectal cancer screening were distributed. A total of 116 primary care providers responded making a response rate of 87.9%. About 21% recommended faecal occult blood test (FOBT) in more than 50% of their patients who were eligible. The most common barrier was "unavailability of the test". The two most common patient factors are "patient in a hurry" and "poor patient awareness". This study indicates that colorectal cancer preventive activities among primary care providers are still poor in Malaysia. This may be related to the low availability of the test in the primary care setting and poor awareness and understanding of the importance of colorectal cancer screening among patients. More awareness programmes are required for the public. In addition, primary care providers should be kept abreast with the latest recommendations and policy makers need to improve colorectal cancer screening services in health clinics.