Isoflavone intervention and its impact on bone mineral density in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials.

Due to estrogen deficiency, postmenopausal women may suffer from an imbalance in bone metabolism that leads to bone fractures. Isoflavones, a type of phytoestrogen, have been suggested to improve bone metabolism and increase bone mass. Therefore, isoflavones are increasingly recognized as a promising natural alternative to hormone replacement therapy for postmenopausal women who face a heightened risk of osteoporosis and are susceptible to bone fractures. PURPOSE: This study aimed to evaluate the efficacy of isoflavone interventions on bone mineral density (BMD) in postmenopausal women by means of systematic review and meta-analysis. METHODS: The electronic database searches were performed on PubMed, Embase, Scopus, and Cochrane Library databases, covering literature up to April 20, 2023. A random-effects model was used to obtain the main effect estimates, with a mean difference (MD) and its 95% confidence interval (CI) as the effect size summary. The risk of bias assessment was conducted using the Risk of Bias 2 (RoB2) tool. RESULTS: A total of 63 randomized controlled trials comparing isoflavone interventions (n = 4,754) and placebo (n = 4,272) were included. The results indicated that isoflavone interventions significantly improved BMD at the lumbar spine (MD = 0.0175 g/cm2; 95% CI, 0.0088 to 0.0263, P < 0.0001), femoral neck (MD = 0.0172 g/cm2; 95% CI, 0.0046 to 0.0298, P = 0.0073), and distal radius (MD = 0.0138 g/cm2; 95% CI, 0.0077 to 0.0198, P < 0.0001) in postmenopausal women. Subgroup analysis showed that the isoflavone intervention was effective for improving BMD when the duration was ≥ 12 months and when the intervention contained genistein of at least 50 mg/day. CONCLUSION: This systematic review and meta-analysis suggests that isoflavone interventions, especially those containing genistein of at least 50 mg/day, can effectively enhance BMD in postmenopausal women.

Establishing the feasibility and preliminary efficacy of a health belief model based educational training program on health belief perceptions and dementia-preventive behaviors in people with type 2 diabetes.

This quasi-experimental study evaluated feasibility and preliminary efficacy of dementia-preventive educational training intervention program based on the health belief model for improving perceived health beliefs and dementia-preventive behaviors among people with type 2 diabetes mellitus. Two community hospitals with 72 eligible participants were chosen from 12 local institutions using simple random sampling method. One hospital (22 patients) was allocated to dementia-preventive educational training intervention, and the other hospital (23 patients) was allocated to control intervention (using simple random sampling). Primary study outcome was feasibility, and secondary outcomes were changes in dementia prevention behaviors and health belief perceptions. Recruitment rate was 62.5% (45/72) and 22 patients in each group totally completed outcome measures and attended sessions, indicating feasibility of the intervention and study design. There were no significant differences between groups at baseline. After training, participants in the intervention group had significantly higher scores than control group in prevention behaviors and perceptions of health beliefs. The intervention group experienced significant with-group changes in outcomes. Results show that conducting a subsequent fully powered experimental study is feasible, and the intervention has promising efficacy.

Regulatory compliance and readability of informed consent forms in industry-sponsored drug development clinical trials.

BACKGROUND/AIMS: An informed consent form is essential in drug development clinical trials. This study aimed to evaluate regulatory compliance and readability of informed consent forms currently being used in industry-sponsored drug development clinical trials. METHODS: This descriptive, cross-sectional study evaluated the informed consent forms of industry-sponsored drug development clinical trials conducted at the Faculty of Medicine, Chiang Mai University, between 2019 and 2020. The informed consent form's compliance with the three major ethical guidelines and regulations (i.e. International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use E6(R2) Good Clinical Practice; Declaration of Helsinki; and the revised Common Rule) were analyzed. The document length and the readability scores (using Flesch Reading Ease and Flesch-Kincaid Reading Grade) were assessed. RESULTS: Of 64 reviewed informed consent forms, the average page length was 22.0 ± 7.4 pages. More than half of their length was mainly devoted to three elements: trial procedures (22.9%), risks and discomforts (19.1%), and confidentiality and the limit of confidentiality (10.1%). Although most of the required elements of the informed consent form content were included in most informed consent forms, we identified four elements with often missing information in the form: aspects of research that are experimental (n = 43, 67.2%), involvement of whole-genome sequencing (n = 35, 54.7%), commercial profit sharing (n = 31, 48.4%), and posttrial provisions (n = 28, 43.8%). CONCLUSION: The informed consent forms in industry-sponsored drug development clinical trials were long but incomplete. Our findings draw attention to ongoing challenges in industry-sponsored drug development clinical trials, where deficient informed consent form quality continues to exist.

Mycophenolic acid and cancer risk in solid organ transplant recipients: Systematic review and meta-analysis.

AIM: Mycophenolic acid (MPA) is an immunosuppressive drug commonly used for prophylaxis of graft rejection in solid organ transplant recipients. The main concern with the prolonged use of immunosuppressive drugs is the risk of developing cancer. However, it remains unclear whether the immunosuppressive regimens containing MPA confer an increased degree of cancer risk. The present study aimed to determine the association between MPA exposure and the incidence of cancer in solid organ transplant recipients. METHODS: A systematic search was performed on the PubMed, EMBASE and Cochrane Library databases. Relevant articles that had findings on the incidence (or event) of cancer in cohorts with and without MPA exposure were retrieved for data extraction. A meta-analysis was conducted by means of the random-effects model, and the relative risk (RR) and its 95% confidence interval (95% CI) were used as a summary effect measure. RESULTS: A total of 39 studies were eligible for inclusion, with 32 studies that enabled meta-analysis. MPA exposure was significantly associated with a lower risk of cancer when compared to azathioprine exposure (RR = 0.66, 95% CI = 0.53-0.81, P < .001) or no exposure to any additional treatments (RR = 0.85, 95% CI = 0.73-0.99, P = .04). There was no significant difference in cancer risk for the comparison between MPA exposure and mammalian target of rapamycin (mTOR) inhibitor exposure (RR = 1.54, 95% CI = 0.96-2.46, P = .07). CONCLUSIONS: MPA exposure was not associated with an increased risk of cancer and may even be associated with a lower risk of cancer when compared to azathioprine or no treatment.

Drug-Drug Interactions Between Mycophenolic Acid and Proton Pump Inhibitors: A Systematic Review and Meta-Analysis.

PURPOSE: The objective of the present study was to determine the impact of proton pump inhibitors (PPIs) on the pharmacokinetics and pharmacodynamics of mycophenolic acid (MPA). METHODS: PubMed, Embase, Web of Sciences, and Scopus were systematically searched to identify relevant studies reporting pharmacokinetic parameters [including trough concentration (C0), maximum concentration (Cmax), time to maximum concentration (Tmax), the dose-adjusted area under the concentration-time curve from time 0-12 hours (AUC0-12 h/D), and half-life (t1/2)], and pharmacodynamic outcomes of MPA (eg, acute graft rejection and adverse drug reactions), with and without PPI administration. Pooled effect estimates were calculated using a random-effects model. RESULTS: Twelve studies involving 473 participants were eligible for inclusion, 11 of which were included in the meta-analysis. PPI exposure was significantly associated with lower C0 [mean difference (MD) = -0.62 mg/L; P = 0.003] lower Cmax (MD = -4.71 mg/L; P = 0.01), and longer Tmax (MD = 0.30 hours; P = 0.0001) of MPA. However, no significant association was observed between PPI exposure and AUC0-12 h/D, t1/2, or any pharmacodynamic outcomes. Based on subgroup analysis, it can be suggested that a significant association between PPI exposure and altered MPA pharmacokinetics was mainly associated with mycophenolate mofetil but not enteric-coated mycophenolate sodium. CONCLUSIONS: Coadministration of PPIs and mycophenolate mofetil significantly altered the pharmacokinetics of MPA, particularly by decreasing MPA absorption. However, PPI-MPA interactions did not impact pharmacodynamic outcomes of MPA.

What information and the extent of information to be provided in an informed assent/consent form of pediatric drug trials.

BACKGROUND: This study aimed to determine the elements and the extent of information that child participants and their parents would like to read in an informed assent form (IAF)/informed consent form (ICF) of a pediatric drug trial. METHODS: A descriptive survey was conducted to determine the perceived importance of each element of the ICF content from child participants and their parents who underwent informed assent/consent of a multi-center pediatric drug trial. The respondents were asked to indicate the level of importance of each item in a questionnaire, by giving a rating scale from 1 (not important) to 5 (very important). RESULTS: A total of 22 families, 17 child participants with the diagnosis of hematology or oncology diseases and 27 parents, were enrolled. Among 30 items, risk-benefit aspects (i.e., direct health benefit [mean: 4.71 for child respondents, 4.89 for parent respondents], indirect/societal benefit [mean: 4.65, 4.85], major foreseeable risk [mean: 4.47, 4.78], post-trial benefit/provision [mean: 4.59, 4.74], and all adverse effects of the drug including uncommon adverse effects [mean: 4.53, 4.74]) were perceived to be of most concerning items from both child participants' and parents' viewpoint. None of the items were considered 'slightly important' or lower by more than 20% of the respondents. CONCLUSIONS: For pediatric drug trials, risk-benefit information (including direct health benefit, indirect/societal benefit, and post-trial benefit/provision, as well as major foreseeable risk and adverse effects of the drug) should be made a salient feature of an IAF/ICF. This empirical data could help related stakeholders arrange essential information in order of importance and tailor an IAF/ICF to better suit child participants' and parents' needs, particularly for pediatric drug trials involving children with the diagnosis of hematology or oncology diseases.

Perception of benefits and barriers associated with dementia prevention behaviors among people with diabetes.

Type 2 diabetes mellitus is a risk factor for developing dementia and a public health concern around the world. Identifying any predictive factors associated with diabetes-related dementia prevention behaviors are of value in helping to prevent dementia. From six community hospitals in Chiang Mai, Thailand, 182 people aged 30-60 years were enrolled in a cross-sectional study and completed a written questionnaire on dementia prevention behaviors and perceptions of health beliefs. Multiple linear regression analysis was applied to determine possible associations between dementia prevention behaviors and health belief perceptions. A high level of preventive behavior was associated with high perceptions of the benefits of, and barriers to, dementia prevention and longer duration of patients' diabetes. Findings indicate the predictive role of the two factors in the perception of health beliefs about dementia prevention behaviors among the participants. Although further testing with different samples and in different locations is warranted, education programs for health practitioners that integrate the findings of this study would be beneficial to improvement of dementia prevention behaviors in people with diabetes.

In search of TP53 mutational hot spots for Li-Fraumeni syndrome in Asian populations.

OBJECTIVE: Germline mutations of the TP53 tumour suppressor gene are the only known cause of the hereditary autosomal disorder called Li-Fraumeni syndrome (LFS). However, little information is available about TP53 pathogenic variants in Asian LFS patients, making it difficult to provide precise genetic counselling with regard to long-term cancer risk. We conducted a systematic review to gather relevant case-control studies exploring the association between TP53 polymorphisms and the incidence of cancer belonging to the LFS spectrum in Asian populations. METHOD: Systematic review and meta-analysis. The odds ratio was used as a summary effect measure to quantify the strength of the association between TP53 polymorphisms and cancer risk by means of random-effects meta-analysis. RESULTS: In total, 16 studies were included in this systematic review, with 13 studies (involving 10,645 cases and 28,288 controls) that enabled meta-analysis. The majority of the studies focused on a single-nucleotide variation at codon 72 in exon 4 (c.215C>G, p.Arg72Pro, rs1042522). Therefore, we tested either dominant, co-dominant, recessive, or heterozygous models and found that the p.Arg72Pro was not significantly associated with increased cancer risk in any of the models. CONCLUSION: We found the number of studies on cancers belonging to the LFS spectrum in Asia is very small. Thus, at the present time a meta-analysis approach is somewhat useful to identify germline TP53 mutations as potential markers of hereditary cancer associated with LFS in Asian populations.

Ethical considerations and challenges in herbal drug trials with the focus on scientific validity and risk assessment.

Scientific validity and risk assessment are two main ethical issues which raise specific challenges and are unique to clinical trials investigating crude extracts/fractions from herbal materials. There are considerable challenges for both clinical investigators and ethics committee members in dealing with such issues, many of them remain unresolved, resulting in a large variation in ethical requirements, justification, and decisions. Despite a remarkable surge in herbal medicine research globally, a number of clinical investigators or even ethics committee members have limited confidence in dealing with related ethical issues. In this article, we extensively review and discuss the two main ethical issues (i.e., scientific validity and risk assessment) and highlight key considerations that are important for ethical review and justification for the conduct of herbal drug trials.

Phase II, multi-center, open-label, single-arm clinical trial evaluating the efficacy and safety of Mycophenolate Mofetil in patients with high-grade locally advanced or metastatic osteosarcoma (ESMMO): rationale and design of the ESMMO trial.

BACKGROUND: Clinical outcomes of patients with osteosarcoma remain unsatisfactory, with little improvement in a 5-year overall survival over the past three decades. There is a substantial need for further research and development to identify and develop more efficacious agents/regimens in order to improve clinical outcomes of patients for whom the prognosis is unfavorable. Recently, mycophenolate mofetil, a prodrug of mycophenolic acid, has been found to have anticancer activity against osteosarcoma in both in vitro and animal experiments, so that further investigation in humans is warranted. METHODS: A total of 27 patients with high-grade locally advanced or metastatic osteosarcoma will be enrolled into this phase II, multi-center, open-label, single-arm, two-stage clinical trial. The main objectives of this study are to determine the efficacy and safety of mycophenolate mofetil in the patients. The primary endpoint is progression-free survival at 16 weeks; the secondary endpoints include progression-free survival, overall survival, overall response rate, safety parameters, pharmacokinetic parameters, biomarkers, pain score, and quality of life. Mycophenolate mofetil at the initial dose of 5 g/day or lower will be administered for 4 cycles (28 days/cycle) or until disease progression or unacceptable toxicity. The dose of mycophenolate mofetil may be reduced by 1-2 g/day or withheld for some Grade 3 or Grade 4 toxicities whenever clinically needed. The duration of study participation is approximately 4-5 months, with a minimum of 12 study visits. If mycophenolate mofetil proves beneficial to some patients, as evidenced by stable disease or partial response at 16 weeks, administration of mycophenolate mofetil will continue in the extension period. DISCUSSION: This trial is the first step in the translation of therapeutic potential of mycophenolate mofetil emerging from in vitro and animal studies into the clinical domain. It is designed to assess the efficacy and safety of mycophenolate mofetil in patients with high-grade locally advanced or metastatic osteosarcoma. The results will provide important information about whether or not mycophenolate mofetil is worth further development. TRIAL REGISTRATION: This trial was prospectively registered on Thai Clinical Trials Registry (registration number: TCTR20190701001). The posted information will be updated as needed to reflect protocol amendments and study progress.

Informational needs for participation in bioequivalence studies: the perspectives of experienced volunteers.

PURPOSE: The present study aimed to determine the extent of information that healthy volunteers need in an informed consent form (ICF) to support their decision whether to participate in a bioequivalence study, a type of clinical studies involving the testing of pharmacokinetic equivalence of a generic drug with a brand-name drug in volunteer subjects. METHODS: This cross-sectional, descriptive study determined the perspectives of individuals who used to participate in bioequivalence studies, using an electronic-based questionnaire. A 5-point modified Likert scale was used to indicate the importance of each element of the ICF content, with an anchored rating scale from 1 (not important) to 5 (very important) for each item. RESULTS: Of 300 questionnaires distributed, all (100%) were returned. The respondents considered most items to be necessary for their decision, with the score ranging from 3.25 to 4.60 (mean overall score = 4.16 ± 0.30). The four top-rated items were the "major foreseeable risk" (4.60 ± 0.72), "participant's responsibility during participation" (4.52 ± 0.72), "confidentiality and the limit of confidentiality" (4.52 ± 0.82), and "all possible adverse effects of the drug" (4.47 ± 0.74), while the relatively less concerned items were related to general information. CONCLUSIONS: Most elements of the ICF content required were considered as important by the previously experienced volunteers in bioequivalence studies, notwithstanding that some elements were perceived as more important than others. The data from this study could be used to better tailor relevant information in an ICF to the needs of research participants in bioequivalence studies.

The impact of genetic polymorphisms on CYP1A2 activity in humans: a systematic review and meta-analysis.

A large interindividual variation in the activity of cytochrome P450 1A2 (CYP1A2) raises concern about therapeutic failure or toxicity when medical professionals prescribe drugs extensively metabolized by CYP1A2. To date, a number of studies have assessed the association between genetic polymorphisms and CYP1A2 activity; however, there are controversies as to the functional importance of CYP1A2 polymorphisms on the metabolism of CYP1A2 substrates. This systematic review and meta-analysis assessed the effects of genetic polymorphisms on CYP1A2 activity, as measured by caffeine metabolism, in a total of 3570 individual subjects. Higher enzyme activity was observed among those who were homozygous or heterozygous for the -163C>A polymorphism (rs762551), when compared to the wild-type individuals (SMD = 0.40, 95%CI = 0.12-0.68, p = 0.005; SMD = 0.32, 95%CI = 0.11-0.54, p = 0.003, respectively) and this was more pronounced among smokers (SMD = 0.92, 95%CI = 0.27-1.57, p = 0.005; SMD = 0.56, 95%CI = 0.22-0.90, p = 0.001, respectively). For other CYP1A2 polymorphisms, altered caffeine metabolic ratios were not seen. Our results indicate the functional importance of -163C>A polymorphism on CYP1A2 inducibility in humans.

What information and the extent of information research participants need in informed consent forms: a multi-country survey.

BACKGROUND: The use of lengthy, detailed, and complex informed consent forms (ICFs) is of paramount concern in biomedical research as it may not truly promote the rights and interests of research participants. The extent of information in ICFs has been the subject of debates for decades; however, no clear guidance is given. Thus, the objective of this study was to determine the perspectives of research participants about the type and extent of information they need when they are invited to participate in biomedical research. METHODS: This multi-center, cross-sectional, descriptive survey was conducted at 54 study sites in seven Asia-Pacific countries. A modified Likert-scale questionnaire was used to determine the importance of each element in the ICF among research participants of a biomedical study, with an anchored rating scale from 1 (not important) to 5 (very important). RESULTS: Of the 2484 questionnaires distributed, 2113 (85.1%) were returned. The majority of respondents considered most elements required in the ICF to be 'moderately important' to 'very important' for their decision making (mean score, ranging from 3.58 to 4.47). Major foreseeable risk, direct benefit, and common adverse effects of the intervention were considered to be of most concerned elements in the ICF (mean score = 4.47, 4.47, and 4.45, respectively). CONCLUSIONS: Research participants would like to be informed of the ICF elements required by ethical guidelines and regulations; however, the importance of each element varied, e.g., risk and benefit associated with research participants were considered to be more important than the general nature or technical details of research. Using a participant-oriented approach by providing more details of the participant-interested elements while avoiding unnecessarily lengthy details of other less important elements would enhance the quality of the ICF.

Improved participants' understanding of research information in real settings using the SIDCER informed consent form: a randomized-controlled informed consent study nested with eight clinical trials.

PURPOSE: This study aimed to test the applicability and effectiveness of the principles and informed consent form (ICF) template proposed by the Strategic Initiative for Developing Capacity in Ethical Review (SIDCER) across multiple clinical trials involving Thai research participants with various conditions. METHODS: A single-center, randomized-controlled study nested with eight clinical trials was conducted at Thammasat University Hospital, Thailand. A total of 258 participants from any of the eight clinical trials were enrolled and randomly assigned to read either the SIDCER ICF (n = 130) or the conventional ICF (n = 128) of the respective trial. Their understanding of necessary information was assessed using the post-test questionnaire; they were allowed to consult a given ICF while completing the questionnaire. The primary endpoint was the proportion of the participants who had the post-test score of ≥80%, and the secondary endpoint was the total score of the post-test. RESULTS: The proportion of the participants in the SIDCER ICF group who achieved the primary endpoint was significantly higher than that of the conventional ICF group (60.8 vs. 41.4%, p = 0.002). The total score of the post-test was also significantly higher among the participants who read the SIDCER ICF than those who read the conventional ICF (83.3 vs. 76.0%, p < 0.001). CONCLUSIONS: The present study demonstrated that the SIDCER ICF was applicable and effective to improve Thai research participants' understanding of research information in diverse clinical trials. Using the SIDCER ICF methodology, clinical researchers can improve the quality of ICFs for their trials.

Ebola virus disease in children during the 2014-2015 epidemic in Guinea: a nationwide cohort study.

The most recent epidemic of Ebola virus disease (EVD) has resulted in more than 11,000 deaths in West Africa. It has threatened child health in the affected countries, including Guinea. This nationwide retrospective cohort study included all children under 20 years of age with laboratory-confirmed EVD in Guinea during the 2014-2015 Ebola outbreak for analysis. Of 8,448 children with probable or suspected EVD, 695 cases were laboratory-confirmed EVD. The overall case fatality rate (CFR) was 62.9%. Pediatric patients with younger age had a significantly higher rate of death (adjusted OR = 0.995; 95%CI = 0.990-1.000; p = 0.046), with the highest CFR of 82.9% in children aged less than 5 years. Fever (91%), fatigue (87%), and gastrointestinal signs and symptoms (70%) were common clinical features on admission of the pediatric patients, while bleeding signs were not occurring often (24%). None of clinical features and epidemiologic risk factors for Ebola were associated with mortality outcome in our cohort study. CONCLUSION: EVD is a major threat to child health, especially among children under 5 years of age. To date, none of demographic and clinical features, except younger age, have been consistently shown to affect mortality outcome in children infected with Ebola virus. What is Known: • The 2014-2015 West Africa Ebola epidemic is the largest and most widespread outbreak of Ebola virus disease (EVD) in history, with more than 11,000 deaths in Guinea, Liberia, and Sierra Leone. • During ongoing outbreak investigations, it is suggested that young children aged less than 5 years are particularly vulnerable and highly susceptible to death. What is New: • Demographic and clinical characteristics of the nationwide cohort of pediatric patients with laboratory-confirmed EVD in Guinea are reported. • The results confirm the high rate of death among EVD children under 5 years of age, while none of demographic and clinical features, except younger age, could serve as a predictor of mortality outcome in pediatric patients with EVD.

Improved participants' understanding in a healthy volunteer study using the SIDCER informed consent form: a randomized-controlled study.

PURPOSE: This study aimed to evaluate the applicability of the principles and informed consent form (ICF) template proposed by the Strategic Initiative for Developing Capacity in Ethical Review (SIDCER) in a clinical pharmacokinetic study by comparing the volunteers' understanding of the enhanced ICF (developed based on the SIDCER methodology) and the conventional ICF (which was previously approved by local Ethics Committee and used in the clinical study). METHODS: A total of 550 volunteers were randomly assigned to read either the enhanced ICF or the conventional ICF (1:1) in a mock informed consent approach and subsequently performed the post-test questionnaire. The primary endpoint was the proportion of the participants who had the post-test score of ≥ 80 %; the secondary endpoints were the total score of the post-test, the score of the categorized ICF elements, and time spent for participation. RESULTS: The proportion of the participants in the enhanced ICF group who achieved the primary endpoint was significantly higher than the conventional ICF group (82.2 % vs. 60.4 %, p < 0.001). The participants in the enhanced ICF group obtained higher scores and spent less time in reading the given ICF and answering the post-test than those in the conventional ICF group (total score 19/21 vs. 18/21, p < 0.001; time spent 20 min vs. 25 min, p < 0.001). CONCLUSION: The enhanced ICF improved the understanding of the participants in this study. This demonstrates the applicability of the SIDCER ICF principles and its template in the development of an enhanced ICF for improving the quality of ICFs and subjects' understanding in clinical research. TRIAL REGISTRATION: TCTR20140727001.

Heart Rate Variability for Early Detection of Iron Overload Cardiomyopathy in ß-Thalassemia Patients.

Iron overload cardiomyopathy remains the major cause of death in ß-thalassemia (ß-thal). Conventional routine screening parameters such as serum ferritin and echocardiogram (ECG) do not permit early detection of this condition. Although non-transferrin-bound iron (NTBI) is a reliable indicator for iron overload, it is still not universally available. Recently, heart rate variability (HRV), representing cardiac autonomic function, was found to be depressed in thalassemia patients. We hypothesized that HRV can be used for early detection of iron overload cardiomyopathy. Fifty patients (aged 29 ± 11 years; 31 females and 19 males) with ß-thal were enrolled. The 24-hour Holter monitoring for HRV, serum ferritin, NTBI, hematological values and ECG were performed for each patient. Of the 50 patients, 29 carried ß-thal major (ß-TM). Non-transferrin-bound iron was weakly correlated to all time-domain HRV parameters. Low- and high-frequency domain HRV parameters were also inversely weakly correlated with NTBI. Neither HRV nor NTBI was correlated with serum ferritin. With its weak but significant correlation with NTBI, HRV may be considered to be used as a potential indicator of an iron overload condition and an early marker of cardiac involvement in patients with ß-thal.

A systematic review and meta-analysis of animal and human studies demonstrates the beneficial effects of Kaempferia parviflora on metabolic syndrome and erectile dysfunction.

Kaempferia parviflora (KP) has traditionally been used for centuries to promote health and well-being. Scant evidence is available to explain the relationship between KP and metabolic syndrome and impotence. We sought to test the hypothesis that administration of KP extract enriched with active ingredients, such as polymethoxyflavone, could improve metabolic syndrome, erectile dysfunction, and related outcomes in in vivo. We performed a systematic review and meta-analysis to evaluate the in vivo effects of KP extract on metabolic syndrome, erectile dysfunction, and related outcomes. Studies from 4 databases (i.e., PubMed, Scopus, Embase, and Cochrane Library) were searched from inception up to December 2022. Animal experiment studies and randomized controlled trials comparing KP extract to a placebo control were retrieved and analyzed using RevMan 5.4.1 software. The effect estimate was presented as the standardized mean difference along with its 95% confidence interval (CI). Of 664 articles, a total of 57 articles met our prespecified criteria. KP extract significantly decreased fasting blood glucose in both animal and human studies with standardized mean difference of -0.88 (95% CI, -1.63 to -0.14) and -0.51 (95% CI, -0.98 to -0.05), respectively. Furthermore, KP extract also markedly improved sexual function and physical performance. In sum, KP extract is shown to have effects beneficial to metabolic syndrome, erectile dysfunction, and physical performance.

Potential links between platelets and amyloid-ß in the pathogenesis of Alzheimer's disease: Evidence from in vitro, in vivo, and clinical studies.

Cerebral amyloid angiopathy (CAA) is a prevalent comorbidity among patients with Alzheimer's disease (AD), present in up to 80% of cases with varying levels of severity. There is evidence to suggest that CAA might intensify cognitive deterioration in AD patients, thereby accelerating the development of AD pathology. As a source of amyloids, it has been postulated that platelets play a significant role in the pathogenesis of both AD and CAA. Although several studies have demonstrated that platelet activation plays an important role in the pathogenesis of AD and CAA, a clear understanding of the mechanisms involved in the three steps: platelet activation, platelet adhesion, and platelet aggregation in AD pathogenesis still remains elusive. Moreover, potential therapeutic targets in platelet-mediated AD pathogenesis have not been explicitly addressed. Therefore, the aim of this review is to collate and discuss the in vitro, in vivo, and clinical evidence related to platelet dysfunction, including associated activation, adhesion, and aggregation, with specific reference to amyloid-related AD pathogenesis. Potential therapeutic targets of platelet-mediated AD pathogenesis are also discussed. By enriching the understanding of the intricate relationship between platelet dysfunction and onset of AD, researchers may unveil new therapeutic targets or strategies to tackle this devastating neurodegeneration.

The Survival Outcomes, Prognostic Factors and Adverse Events following Systemic Chemotherapy Treatment in Bone Sarcomas: A Retrospective Observational Study from the Experience of the Cancer Referral Center in Northern Thailand.

This study aimed to assess survival outcomes, prognostic factors, and adverse events following chemotherapy treatment for osteosarcoma and Ewing's sarcoma. This retrospective observational study was conducted to collect the data of the patients with osteosarcoma or Ewing's sarcoma who received chemotherapy treatment between 2008 and 2019. The flexible parametric survival model was performed to explore the adjusted survival probability and the prognostic factors. A total of 102 patients (79 with osteosarcoma and 23 with Ewing's sarcoma) were included. The estimated 5-year disease-free survival (DFS) and 5-year overall survival (OS) probabilities in patients with resectable disease were 60.9% and 63.3% for osteosarcoma, and 54.4% and 88.3% for Ewing's sarcoma, respectively, whereas the 5-year DFS and 5-year OS for those with unresectable/metastatic disease remained below 25%. Two prognostic factors for osteosarcoma included a response to neoadjuvant chemotherapy and female gender. Ewing's sarcoma patients aged 25 years and older were significantly associated with poorer survival outcomes. Of 181 chemotherapy treatment cycles, common self-reported adverse symptoms included tumor pain (n = 32, 17.7%), fever (n = 21, 11.6%), and fatigue (n = 16, 8.8%), while common grade III adverse events included febrile neutropenia (n = 13, 7.3%) and neutropenia (n = 9, 5.1%). There was no chemotherapy-related mortality (grade V) or anaphylaxis events.