Pharmacogenetics May Prevent Psychotropic Adverse Events in Autism Spectrum Disorder: An Observational Pilot Study.

INTRODUCTION: Up to 73% of individuals with autism spectrum disorder (ASD) and intellectual disability (ID) currently have prescriptions for psychotropic drugs. This is explained by a higher prevalence of medical and psychiatric chronic comorbidities, which favors polypharmacy, increasing the probability of the appearance of adverse events (AEs). These could be a preventable cause of harm to patients with ASD and an unnecessary waste of healthcare resources. OBJECTIVE: To study the impact of pharmacogenetic markers on the prevention of AE appearance in a population with ASD and ID. METHODS: This is a cross-sectional, observational study (n = 118, 72 participants completed all information) in the ASD population. Sociodemographic and pharmacological data were gathered. The Udvalg for Kliniske Undersøgelser Scale (UKU Scale) was used to identify AEs related to the use of psychotropic medication. Polymorphisms of DOP2, ABCB1, and COMT were genotyped and correlated with the AE to find candidate genes. Furthermore, a review of all medications assessed in a clinical trial for adults with autism was performed to enrich the search for potential pharmacogenetic markers, keeping in mind the usual medications. RESULTS: The majority of the study population were men (75%) with multiple comorbidities and polypharmacy, the most frequently prescribed drugs were antipsychotics (69%); 21% of the participants had four or more AEs related to psychotropic drugs. The most common were "Neurological" and" Psychiatric" (both 41%). Statistical analysis results suggested a significant correlation between the neurological symptoms and the DOP2 genotype, given that they are not equally distributed among its allelic variants. The final review considered 19 manuscripts of medications for adults with ASD, and the confirmed genetic markers for those medications were consulted in databases. CONCLUSION: A possible correlation between neurologic AEs and polymorphisms of DOP2 was observed; therefore, studying this gene could contribute to the safety of this population's prescriptions. The following studies are underway to maximize statistical power and have a better representation of the population.

Efficacy of Boswellia serrata Extract and/or an Omega-3-Based Product for Improving Pain and Function in People Older Than 40 Years with Persistent Knee Pain: A Randomized Double-Blind Controlled Clinical Trial.

A single-center, randomized, double-blind, controlled clinical trial with four arms was conducted in healthy subjects with persistent knee discomfort (pain intensity on 1-10 cm visual analog scale (VAS) > 3) aged 40 years and older treated with a dietary supplement for 8 weeks. The study groups were Boswellia serrata extract (n = 29), an omega-3-based product (AvailOm® 50 High EPA) (n = 31), Boswellia + AvailOm® (n = 30), and placebo (n = 30). The intake of Boswellia + AvailOm® improved the quality of life (QoL) (WOMAC index) and some variables of muscle strength. Statistically significant differences between the AvailOm® and the placebo groups in the decrease of pain intensity were found. Weekly VAS scores showed a significant decrease in pain perception when comparing the AvailOm® product to the placebo, with the lowest VAS scores at week 8. Consumption of Boswellia improved sleep latency. The time to perform the Up and Go test decreased after the intake of AvailOm®. There was an increase in the omega-3 fatty acids, with the greatest increase in the Boswellia + AvailOm® group. AvailOm® was safe and effective in reducing pain and improving the QoL and functionality of subjects over 40 years with persistent knee pain.

A Systematic Review of Clinical Trials on the Efficacy and Safety of CRLX101 Cyclodextrin-Based Nanomedicine for Cancer Treatment.

CRLX101 is a cyclodextrin-based nanopharmaceutical designed to improve the delivery and efficacy of the anti-cancer drug camptothecin. Cyclodextrins have unique properties that can enhance drug solubility, stability, and bioavailability, making them an attractive option for drug delivery. The use of cyclodextrin-based nanoparticles can potentially reduce toxicity and increase the therapeutic index compared to conventional chemotherapy. CRLX101 has shown promise in preclinical studies, demonstrating enhanced tumor targeting and prolonged drug release. This systematic review followed PRISMA guidelines, assessing the efficacy and toxicity of CRLX101 in cancer treatment using clinical trials. Studies from January 2010 to April 2023 were searched in PubMed, Scopus, Web of Science, and Cochrane Database of Systematic Reviews, using specific search terms. The risk of bias was assessed using ROBINS-I and Cochrane risk-of-bias tools. After screening 6018 articles, 9 were included in the final review. These studies, conducted between 2013 and 2022, focused on patients with advanced or metastatic cancer resistant to standard therapies. CRLX101 was often combined with other therapeutic agents, resulting in improvements such as increased progression-free survival and clinical benefit rates. Toxicity was generally manageable, with common adverse events including fatigue, nausea, and anemia.

Effect of the Combination of Hibiscus sabdariffa in Combination with Other Plant Extracts in the Prevention of Metabolic Syndrome: A Systematic Review and Meta-Analysis.

Metabolic syndrome is a complex and multifactorial disorder associated with increased risk of cardiovascular disease and type 2 diabetes, exacerbated by a sedentary lifestyle and situations such as the COVID-19 pandemic. Recent studies have shown that consumption of fruits and vegetables high in polyphenols has a protective effect, reducing cardiovascular risk. Hibiscus sabdariffa (HS) in combination with other plant extracts has recently attracted scientists' attention due to its potential use in the treatment of metabolic syndrome. This systematic review and meta-analysis examines the effects of HS in combination with other plant extracts on the prevention of metabolic syndrome, exploring their synergistic effects and potential as therapeutic agents. For this purpose, a systematic search of randomized clinical trials (RCTs) was conducted in four different databases and the data obtained were then used for a meta-analysis. Initially, the titles and abstracts of 1368 studies were read. From these, 16 studies were examined closely for their eligibility, and finally, seven RCTs with 332 participants were included in both the meta-analysis and the qualitative analysis. Our results show that HS in combination with other plant extracts improved anthropometric parameters, blood pressure, and lipid profile (low density lipoprotein cholesterol and total cholesterol) compared to a placebo control group. It is important to note that although this meta-analysis suggests that HS in combination with other plant extracts may have a beneficial effect on cardiovascular parameters, further research is needed to determine the optimal dose and intake duration.

Self-Reported Medication Adherence Measured with Morisky Scales in Rare Disease Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: The visibility of Rare Diseases is a new challenge for society. These diseases are numerous, heterogeneous in nature and distribution, characterized by a high mortality rate but low prevalence, and usually presenting a severe evolution. Adherence to medication studies in rare diseases are uncommon, due to treatment scarcity. OBJECTIVES: The main purpose of this study is to do a meta-analysis, evaluating the level of adherence to medication in the most prevalent rare diseases. METHODS: This work is a systematic review, and meta-analysis was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (Registration number: CRD42022372843) and conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Adherence to treatment in this systematic review and meta-analysis was collected from all studies included, based on the crude numerators and denominators reported, using either the Morisky Medication Adherence Scale 4 or -8. RESULTS: A total of 54 records were identified through database searches, or after screening relevant manuscripts' references. Finally, 18 studies were included in this systematic review and meta-analysis. A total of 1559 participants (54.18% women) aged less than 84 years old were included. Twelve studies used the MMAS-8. In 8 of them, they established the level of adherence to treatment in three categories (low, medium, and high), with the mean prevalence in each of them being 41.4%, 30.4%, and 28.2%, respectively. CONCLUSIONS: The results observed in adherence to treatment in patients with rare diseases show great variability, due to the different aspects involved in the greater or lesser applicability of the medication.

Antioxidant Activity in Extracts from Zingiberaceae Family: Cardamom, Turmeric, and Ginger.

An increase in life expectancy leads to a greater impact of chronic non-communicable diseases. This is even more remarkable in elder populations, to whom these become main determinants of health status, affecting mental and physical health, quality of life, and autonomy. Disease appearance is closely related to the levels of cellular oxidation, pointing out the importance of including foods in one's diet that can prevent oxidative stress. Previous studies and clinical data suggest that some plant-based products can slow and reduce the cellular degradation associated with aging and age-related diseases. Many plants from one family present several applications that range from the food to the pharmaceutical industry due to their characteristic flavor and scents. The Zingiberaceae family, which includes cardamom, turmeric, and ginger, has bioactive compounds with antioxidant activities. They also have anti-inflammatory, antimicrobial, anticancer, and antiemetic activities and properties that help prevent cardiovascular and neurodegenerative diseases. These products are abundant sources of chemical substances, such as alkaloids, carbohydrates, proteins, phenolic acids, flavonoids, and diarylheptanoids. The main bioactive compounds found in this family (cardamom, turmeric, and ginger) are 1,8-cineole, α-terpinyl acetate, ß-turmerone, and α-zingiberene. The present review gathers evidence surrounding the effects of dietary intake of extracts of the Zingiberaceae family and their underlying mechanisms of action. These extracts could be an adjuvant treatment for oxidative-stress-related pathologies. However, the bioavailability of these compounds needs to be optimized, and further research is needed to determine appropriate concentrations and their antioxidant effects in the body.

Phase Angle, Handgrip Strength, and Other Indicators of Nutritional Status in Cancer Patients Undergoing Different Nutritional Strategies: A Systematic Review and Meta-Analysis.

Malnutrition in cancer patients is one of the most influential factors in the evolution and mortality of such patients. To reduce the incidence of malnutrition, it is necessary to establish a correct nutritional intervention. For this purpose, precise tools and indicators must be developed to determine the patient's condition. The main objective of this systematic review and meta-analysis was to analyze the relationship between different nutritional strategies, phase angle (PA), and handgrip strength in patients with cancer, with the secondary objectives being the modification of other indicators of nutritional status, such as weight and body mass index (BMI). A systematic review of randomized clinical trials was carried out in March 2023 in the databases PubMed, Web of Science, Cochrane, and Scopus. As a risk-of-bias tool, RoB 2.0 was utilized. A total of 8 studies with a total of 606 participants were included in the analysis. A significant increase in PA was observed after the different nutritional strategies (SMD: 0.43; 95% CI: 0.10 to 0.77; p = 0.01; I2 = 65.63%), also detecting a significant increase in handgrip strength (SMD: 0.27, 95% CI: 0.08 to 0.47; p = 0.01; I2 = 30.70%). A significant increase in PA and handgrip were observed in cancer patients subjected to different nutritional strategies. These results suggest that these indicators could be used in the nutritional and functional assessment of the patients.

Tolerability of Oral Supplementation with Microencapsulated Ferric Saccharate Compared to Ferrous Sulphate in Healthy Premenopausal Woman: A Crossover, Randomized, Double-Blind Clinical Trial.

A single-center, crossover, randomized, double-blind, and controlled clinical study was conducted to assess the tolerability profile, especially with regard to gastrointestinal complaints, of oral supplementation with AB-Fortis®, a microencapsulated ferric saccharate (MFS), as compared with conventional ferrous sulphate (FS) in healthy premenopausal women. A dose of 60 mg/day of elemental iron was used. The test products were administered for 14 consecutive days with a washout period of two menstrual episodes and a minimum of one month between the two intervention periods. The subjects completed simple-to-answer questionnaires daily for 14 days during both the intervention and the washout periods, capturing the symptoms associated with oral iron supplementation and overall health aspects. Following product consumption, the incidences of symptoms, numbers of complaints/symptoms, overall intensity, and total days with symptoms were found to be significantly higher for FS consumption as compared to MFS. The better tolerability profile of MFS over FS was further substantiated when both products were compared to a real-life setting (i.e., the washout period). Overall, the administration of both study products was safe with no serious or significant adverse events reported. In summary, the current study shows the better tolerability of the MFS preparation when compared to that of the FS, presenting MFS as a well-tolerated and safe option for improving iron nutrition.

Dry Needling Alone or in Combination with Exercise Therapy versus Other Interventions for Reducing Pain and Disability in Subacromial Pain Syndrome: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis examined the effects of dry needling alone or in combination with exercise therapy for reducing pain and disability in people with subacromial pain syndrome. Systematic searches of randomized clinical trials (RCTs) were performed in five different databases. A meta-analysis was carried out with the data obtained, and the risk of bias and quality of the studies was assessed using the Cochrane ROB 2.0 and GRADE tools. Finally, five RCTs (n = 315) were included in the meta-analysis and qualitative analysis. Our results determine that dry needling alone or combined with exercise therapy showed improvements in pain in the short-term (5RCTs: SMD: -0.27; [-0.49, -0.05]; low-quality) and mid-term (4RCTs: SMD: -0.27; [-0.51, -0.04]; low-quality) compared to a range of interventions. However, no differences were shown for disability at short-term (3 RCTs: SMD: -0.97; [-2.04, 0.11]; very-low quality) and mid-term (3 RCTs: SMD: -0.85; [-1.74, 0.04]; very-low quality). Dry needling alone or in combination with exercise therapy may result in a slight reduction in pain in the short-term and mid-term. However, the evidence about the effect of this therapy on disability in the short- or mid-term is very uncertain compared to the range of interventions analyzed in this systematic review (Registration: INPLASY202260112).

Randomised Clinical Trial to Analyse the Efficacy of Eggshell Membrane to Improve Joint Functionality in Knee Osteoarthritis.

Osteoarthritis is a source of chronic pain and disability. Dietary supplements have been shown to be a more secure option than NSAIDS. Particularly, the eggshell membrane has demonstrated efficacy in relieving joint pain and stiffness. A clinical trial was designed in which three groups were assigned to two different doses of this supplement and compared to a placebo control group. The primary outcome variable was knee pain, which was assessed using a visual analogue scale. Secondary outcome variables were knee functional ability, quadriceps muscle strength (assessed by isometric and isokinetic trials), and quality of sleep. All groups showed a significant decrease in pain perception, although maximum values were obtained in the high-dose group. Isokinetic and isometric trials showed a significant increase in strength in the high-dose group. Eggshell membrane showed the potential to reduce pain and stiffness symptomatology. Here, for the first time, two quantitative variables (mobility and strength of knee joint) were used to accurately evaluate changes in the quality of life of subjects affected by knee joint pain. The results of this study indicate a dose-dependent response, which should be taken into account for later use in therapeutics to establish the correct dosage.

Effectiveness of a polyphenolic extract (Lippia citriodora and Hibiscus sabdariffa) on appetite regulation in overweight and obese grade I population: an 8-week randomized, double-blind, cross-over, placebo-controlled trial.

INTRODUCTION: Polyphenols have shown capacity to improve appetite sensation, leading to enhanced control of body weight. However, despite being related with hunger-related hormones, metabolic and mechanism are not well known. METHODS: The effectiveness of a nutraceutical composed of extract to Lippia citriodora and Hibiscus sabdarrifa (Lc-Hs) for controlling satiety and hunger was analyzed in a cross-over, placebo-controlled (Pla) clinical intervention. The study was divided in two 60-day periods separated by 30-day length wash-out period. At the end of each period, overweight and obese subjects (n = 33; age = 33.76 ± 12.23; BMI = 28.20 kg/m2 ± 2.47; fat mass 30.65 ± 8.39%; both sexes were proposed to eat an ad-libitum meal. Meanwhile, appetite sensation was determined by visual analog scales at different times. Moreover, blood extraction was performed to determine biochemical parameters (lipid and glucidic profile and safety parameters) and to evaluate hunger-related hormones (insulin, leptin, ghrelin, adiponectin, GLP-1 and peptide YY). RESULTS: A decrease in appetite sensation was observed in Lc-Hs treatment, showing higher satiety quotient (Pla = 3.36 ± 2.33%mm/kcal; Lc-Hs = 5.53 ± 2.91%mm/kcal; p < 0.0001). Area under the curve was higher in Pla compared to Lc-Hs during the test, from baseline to minute 240 (240 (Pla 9136.65 ± 2261.46% x min-1; Lc-Hs 8279.73 ± 2745.71% x min-1; p < 0.014). Energy consumption was lower for subjects treated with Lc-Hs (774.44 ± 247.77 kcal) compared to those treated with Pla (849.52 ± 246.54 kcal) (p < 0.004). Leptin values varied from baseline (Pla 12.36 ± 1.98 ng/mL; Lc-Hs 13.13 ± 1.99 ng/mL) to the end of the study (Pla 12.60 ± 2.02 ng/mL; Lc-Hs 12.06 ± 2.05 ng/mL; p < 0.047). GLP-1 values varied (p < 0.001) in Lc-Hs treatment from baseline (4.34 ± 0.49 ng/mL) to the end of the study (3.23 ± 0.52 ng/mL). CONCLUSION: The supplementation with the Lc-Hs extract decreases appetite sensation in overweight and obese population, reducing calorie intake after an ad-libitum meal. Due to variation on hunger-related hormones and the relationship between satiety feeling, it would be interesting to develop future research focused on the variation of the hormones themselves.

A Randomized, Double-Blind, Placebo-Controlled Trial to Determine the Effectiveness of a Polyphenolic Extract (Hibiscus sabdariffa and Lippia citriodora) for Reducing Blood Pressure in Prehypertensive and Type 1 Hypertensive Subjects.

Hypertension is an important factor of cardiovascular diseases and contributes to their negative consequences including mortality. The World Health Organization estimated that 54% of strokes and 47% of cases of ischemic heart illness are related to high blood pressure. Recently, Hibiscus sabdariffa (HS) and Lippia citriodora (LC) have attracted scientific interest, and they are recognized for their high content of polyphenols as these may prevent several disease factors, such as hypertension. The aim of the present study is to determine if supplementation with an HS-LC blend (MetabolAid®) may be effective for the treatment of type 1 hypertensive sedentary populations. A total of 80 type 1 hypertensive subjects of both sexes were included in the study and were treated with placebo or the HS-LC extract, and both groups were treated over 84 days. The blood pressure (diastolic, systolic, and pulse pressure) was measured throughout the day, for each of the days of the study duration and determined using Ambulatory Blood Pressure Monitoring (ABPM). Physical activity was determined throughout the study to ensure similar conditions related to exercise. The results showed the capacity for reducing the blood pressure parameters in the case of the HS-LC extract. The daily consumption of the HS-LC extract but not the placebo over 84 days was able to reduce the daytime parameters related to blood pressure. The most remarkable results were observed in the measurements performed during the daytime, especially in the systolic blood pressure showing statistically significant variation.

Effects of the Consumption of Low-Fat Cooked Ham with Reduced Salt Enriched with Antioxidants on the Improvement of Cardiovascular Health: A Randomized Clinical Trial.

The aim of the study was to analyze how cardiovascular risk factors can be modified using nutritionally improved cooked ham enriched with a pool of antioxidants to influence relevant metabolic targets. Sixty-five untreated subjects (49.2% males, 50.8% females, mean age 40.92 ± 9.03 years) with total cholesterol level ≥180 mg/dL or LDL cholesterol ≥130 mg/dL participated in a 8-weeks randomized, double-blind controlled trial. Participant in the intervention group (51.5% males, 48.5% females, mean age 41.6 ± 9.8 years and mean BMI 25.1 ± 3.6 kg/m2) consumed cooked ham enriched with antioxidants (100 g/d) and controls (49.9% males, 53.1% females, mean age 40.2 ± 8.3 years and mean BMI 26.3 ± 3.2 kg/m2) received placebo. At 8 weeks, oxidized LDL decreased significantly between experimental and placebo groups (p < 0.036). Experimental group differences were also significant (p < 0.05). Similar findings in malondialdehyde, total cholesterol, high-sensitivity C-reactive protein, and interleukin 6 were observed in the intervention group. Significant between-group differences in these variables were also found, except for total cholesterol and interleukin 6. The effects on inflammation and oxidation support the direct action of these antioxidants on the etiopathogenic factors of atheromatous plaque. We also observed an improvement in the lipid profiles among the subjects.

Effectiveness of Consumption of a Combination of Citrus Fruit Flavonoids and Olive Leaf Polyphenols to Reduce Oxidation of Low-Density Lipoprotein in Treatment-Naïve Cardiovascular Risk Subjects: A Randomized Double-Blind Controlled Study.

The aim of the study was to assess whether oral intake of a nutraceutical product (Citrolive™) could determine changes in low-density lipoprotein (LDL) oxidation and other parameters of lipid metabolism and plasma atherogenic capacity. Citrolive™ is a commercial extract obtained from the combination of citrus fruit flavonoids and olive leaf extracts. Twenty-three untreated subjects (69.6% males, 30.4% females, mean age 41.9 ± 9.4 years) with cardiovascular risk factors and a total cholesterol level >200 mg/dL and LDL cholesterol (LDL-C) > 130 mg/dL participated in a 3-month randomized double-blind controlled study. Participants in the intervention group (71.4% males, 28.6% females, mean age 42.7 ± 9.7 years) consumed Citrolive™ (500 mg, two capsules/day), and controls (66.7% males, 33.3% females, mean age 40.6 ± 9.4 years) received a matched placebo. At 3 months, oxidized LDL (ox-LDL) decreased significantly in the intervention group from 93.8 ± 19.1 U/L to 62.8 ± 28.7 U/L (p < 0.05), whereas the control group increased from 98.2 ± 23.5 U/L to 105.7 ± 21.9 U/L (p = 0.1). Between-group differences were also significant (p < 0.05). Similar findings in the ox-LDL/LDL-C ratio were observed. Serum paraoxonase activity (PON1) increased significantly in the intervention group from 64.5 ± 15.6 U/L to 78.7 ± 28.8 U/L (p < 0.05) but remained unchanged in controls. Consumption of Citrolive™ for 3 months in treatment-naïve subjects with moderate risk of atherosclerosis was associated with a reduction in oxidized LDL-C and LDL-oxidase/LDL-C ratio as compared to controls.

Antioxidant Effect of a Probiotic Product on a Model of Oxidative Stress Induced by High-Intensity and Duration Physical Exercise.

This randomized double-blind and controlled single-center clinical trial was designed to evaluate the effect of a 6-week intake of a probiotic product (1 capsule/day) vs. a placebo on an oxidative stress model of physical exercise (high intensity and duration) in male cyclists (probiotic group, n = 22; placebo, n = 21). This probiotic included three lyophilized strains (Bifidobacterium longum CECT 7347, Lactobacillus casei CECT 9104, and Lactobacillus rhamnosus CECT 8361). Study variables were urinary isoprostane, serum malondialdehyde (MDA), serum oxidized low-density lipoprotein (Ox-LDL), urinary 8-hydroxy-2'-deoxiguanosine (8-OHdG), serum protein carbonyl, serum glutathione peroxidase (GPx), and serum superoxide dismutase (SOD). At 6 weeks, as compared with baseline, significant differences in 8-OHdG (Δ mean difference -10.9 (95% CI -14.5 to -7.3); p < 0.001), MDA (Δ mean difference -207.6 (95% CI -349.1 to -66.1; p < 0.05), and Ox-LDL (Δ mean difference -122.5 (95% CI -240 to -4.5); p < 0.05) were found in the probiotic group only. Serum GPx did not increase in the probiotic group, whereas the mean difference was significant in the placebo group (477.8 (95% CI 112.5 to 843.2); p < 0.05). These findings suggest an antioxidant effect of this probiotic on underlying interacting oxidative stress mechanisms and their modulation in healthy subjects. The study was registered in ClinicalTrials.gov (NCT03798821).

Effect of a Combination of Citrus Flavones and Flavanones and Olive Polyphenols for the Reduction of Cardiovascular Disease Risk: An Exploratory Randomized, Double-Blind, Placebo-Controlled Study in Healthy Subjects.

A single-center, randomized, double-blind controlled trial was conducted to assess the efficacy of a food supplement based on a combination of grapefruit, bitter orange, and olive extracts administered for eight weeks (n = 51) versus placebo (n = 45) on reduction of cardiovascular risk in healthy volunteers. Study variables included flow-mediated vasodilation (FMD), blood pressure (BP), lipid profile, thrombotic status, oxidative stress biomarkers, inflammation-related biomarkers, anthropometric variables, quality of life, and physical activity. The per-protocol data set was analyzed. In the active product group, there were statistically significant within-group differences at eight weeks as compared with baseline in FMD, systolic and diastolic BP, total cholesterol, LDL-C, LDL-oxidase, oxidized/reduced glutathione ratio, protein carbonyl, and IL-6. Significant between-group differences in these variables were also found. Significant changes in anthropometric variables and quality of life were not observed in the study groups. Changes in the level of physical activity were not recorded. Treatment with the active product was well tolerated. All these findings, taken together, support a beneficial effect of supplementation with a mixture of grapefruit, bitter orange fruits, and olive leaf extracts on underlying mechanisms that may interact each other to decrease the cardiovascular risk in healthy people.