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.

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.

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.

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.

Gut Microbiota-Mediated Pharmacokinetic Drug-Drug Interactions between Mycophenolic Acid and Trimethoprim-Sulfamethoxazole in Humans.

Mycophenolic acid (MPA) and trimethoprim-sulfamethoxazole (TMP-SMX) are commonly prescribed together in certain groups of patients, including solid organ transplant recipients. However, little is known about the pharmacokinetic drug-drug interactions (DDIs) between these two medications. Therefore, the present study aimed to determine the effects of TMP-SMX on MPA pharmacokinetics in humans and to find out the relationship between MPA pharmacokinetics and gut microbiota alteration. This study enrolled 16 healthy volunteers to take a single oral dose of 1000 mg mycophenolate mofetil (MMF), a prodrug of MPA, administered without and with concurrent use of TMP-SMX (320/1600 mg/day) for five days. The pharmacokinetic parameters of MPA and its glucuronide (MPAG) were measured using high-performance liquid chromatography. The composition of gut microbiota in stool samples was profiled using a 16S rRNA metagenomic sequencing technique during pre- and post-TMP-SMX treatment. Relative abundance, bacterial co-occurrence networks, and correlations between bacterial abundance and pharmacokinetic parameters were investigated. The results showed a significant decrease in systemic MPA exposure when TMP-SMX was coadministered with MMF. Analysis of the gut microbiome revealed altered relative abundance of two enriched genera, namely the genus Bacteroides and Faecalibacterium, following TMP-SMX treatment. The relative abundance of the genera Bacteroides, [Eubacterium] coprostanoligenes group, [Eubacterium] eligens group, and Ruminococcus appeared to be significantly correlated with systemic MPA exposure. Coadministration of TMP-SMX with MMF resulted in a reduction in systemic MPA exposure. The pharmacokinetic DDIs between these two drugs were attributed to the effect of TMP-SMX, a broad-spectrum antibiotic, on gut microbiota-mediated MPA metabolism.

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.

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.

Efficacy and Safety of the Genistein Nutraceutical Product Containing Vitamin E, Vitamin B3, and Ceramide on Skin Health in Postmenopausal Women: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Skin aging is one of the most concerning issues that occur after menopause. The Genistein Nutraceutical (GEN) product, containing genistein, vitamin E, vitamin B3, and ceramide, has been formulated as a topical anti-aging product for improving the health of postmenopausal women's facial skin. This study aimed to investigate the efficacy and safety of the GEN product on postmenopausal women's facial skin. This randomized, double-blind, placebo-controlled trial randomly assigned 50 postmenopausal women to receive either the GEN product (n = 25) or the placebo (PLA) product (n = 25), topically applied twice daily for 6 weeks. The outcome assessments included multiple skin parameters related to skin wrinkling, color, hydration, and facial skin quality at baseline and week 6. The percentage mean changes or absolute mean changes, where appropriate, in skin parameters were compared between the two groups. The mean age of the participants was 55.8 ± 3.4 years. For skin wrinkling and skin color parameters, only skin redness was significantly higher in the GEN group when compared to the PLA group. Following the application of the GEN product, skin hydration increased while fine pores and their area decreased. Subgroup analysis of older women (age ≥ 56 years) with adequate compliance found significant differences between the two groups in the percentage mean changes of most skin wrinkle parameters. The GEN product has benefits for the facial skin of postmenopausal women, particularly those who are older. It can moisturize facial skin, lessen wrinkles, and enhance redness.

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.

Urinary glyphosate kinetics after occupational exposure.

Glyphosate-surfactant herbicides are the most used and imported herbicide in Thailand. Urinary biomonitoring is a very important tool for evaluating glyphosate exposures and its adverse health effects. However, the data for glyphosate toxicokinetics, especially in Asian populations, is relatively limited. The majority of farmers in Thailand have long term experience with glyphosate use, but they generally follow poor safety practices, including insufficient or incorrect use of personal protective equipment during pesticide handling activities. Therefore, this study aimed to determine the toxicokinetics of glyphosate and its metabolite in urine among maize farmers from the northern region of Thailand. The effects of personal protective equipment usage, as well as farmer behavior during work, on urinary glyphosate levels were also studied. Full-voided spot urine samples were collected over the exposure assessment period (0-72 h). Urinary glyphosate levels were determined by liquid chromatography tandem mass spectrometry. The maximum concentration in urine (uCmax), the time of peak glyphosate levels in urine (uTmax), and the urinary elimination half-life (ut1/2) were analyzed using the PKSolver program. The median of uCmax were 27.9, 29.2 and 17.1 µg/g creatinine in a one-time spray group, a two-time spray group Day 1 and a two-time spray group Day 2, respectively. The uTmax was 11.0 h in both study groups. The median of elimination ut1/2 in the one-time and the two-time spray group were 7.0 and 18.1 h, respectively. Although these estimated urinary elimination half-lives may have been impacted by the variation in exposure doses among the participants, it provides the first urinary toxicokinetic data of glyphosate among the Asian population. The toxicokinetic information could be used to increase knowledge and awareness amongst farmers, particularly to minimize the risk of exposure to glyphosate and reduce possible adverse health effects from using pesticide.

Adverse Effects of Angiotensin-Converting Enzyme Inhibitors in Humans: A Systematic Review and Meta-Analysis of 378 Randomized Controlled Trials.

Background: Although angiotensin-converting enzyme (ACE) inhibitors are among the most-prescribed medications in the world, the extent to which they increase the risk of adverse effects remains uncertain. This study aimed to systematically determine the adverse effects of ACE inhibitors versus placebo across a wide range of therapeutic settings. Methods: Systematic searches were conducted on PubMed, Web of Science, and Cochrane Library databases. Randomized controlled trials (RCTs) comparing an ACE inhibitor to a placebo were retrieved. The relative risk (RR) and its 95% confidence interval (95% CI) were utilized as a summary effect measure. A random-effects model was used to calculate pooled-effect estimates. Results: A total of 378 RCTs fulfilled the eligibility criteria, with 257 RCTs included in the meta-analysis. Compared with a placebo, ACE inhibitors were associated with an significantly increased risk of dry cough (RR = 2.66, 95% CI = 2.20 to 3.20, p < 0.001), hypotension (RR = 1.98, 95% CI = 1.66 to 2.35, p < 0.001), dizziness (RR = 1.46, 95% CI = 1.26 to 1.70, p < 0.001), and hyperkalemia (RR = 1.24, 95% CI = 1.01 to 1.52, p = 0.037). The risk difference was quantified to be 0.037, 0.030, 0.017, and 0.009, respectively. Conclusions: We quantified the relative risk of numerous adverse events associated with the use of ACE inhibitors in a variety of demographics. This information can help healthcare providers be fully informed about any potential adverse consequences and make appropriate suggestions for their patients requiring ACE inhibitor therapy.

A Randomized Controlled Trial of Thai Medicinal Plant-4 Cream versus Diclofenac Gel in the Management of Symptomatic Osteoarthritis of the Knee.

Background: Osteoarthritis of the knee is a common degenerative musculoskeletal condition. Thai Medicinal Plant-4 (TMP-4) cream is made up of Garcinia mangostana peel, Sesamum indicum seeds, Glycine max (L.) Merr. seeds, and Centella asiatica leaves, all of which have anti-inflammatory and analgesic properties. The present study aimed at determining the efficacy and safety of TMP-4 cream versus diclofenac gel in the treatment of symptomatic osteoarthritis of the knee. Methods: A randomized-controlled trial was conducted to assess knee pain on a scale of 100 mm Visual Analog Scale (VAS) and other key metrics, including VAS knee stiffness, a modified 10-step stair climb test, a timed up and go test, the Knee Injury and Osteoarthritis Outcome Score, and safety outcomes, following administration of either TMP-4 cream or diclofenac gel for 4 weeks. Results: A total of 199 patients with moderate knee pain intensity were randomly assigned to either TMP-4 cream or diclofenac gel (allocation ratio 1 : 1). The mean changes of VAS knee pain in the TMP-4 cream and diclofenac gel groups were -31.68 ± 14.18 mm and -31.09 ± 12.41 mm, respectively, (mean difference = -0.58, 95% confidence interval = -4.37-3.20, P=0.761). The upper limit of 95% confidence interval for the comparison between TMP-4 cream and diclofenac gel was within the predefined margin of 7 mm for noninferiority. The safety was comparable between the two interventions. Conclusions: TMP-4 cream was noninferior to diclofenac gel in relieving osteoarthritic knee pain and may be considered as an alternative therapeutic option in the treatment of symptomatic osteoarthritis of the knee.

Preclinical experimental models for assessing laxative activities of substances/products under investigation: a scoping review of the literature.

Constipation is a common gastrointestinal problem worldwide. Its impact on health can range from an unpleasant problem to being seriously troublesome. When lifestyle modification fails to deal with constipation, laxatives are the mainstay of therapy. There are several types of laxatives currently available; however, there still remains a need for better laxatives because certain currently available laxatives are not appropriate for or accessible to some patients. Preclinical experiments to study the laxative potential of substances/products of interest are vital to improving that situation. The selection of appropriate experimental models for assessing the laxative activities of substances/products under investigation is crucial to achieving valid and meaningful results. This article provides a scoping review of the literature, outlining, and summarizing models currently being used in preclinical experiments assessing the laxative activities of substances/products under investigation. The review includes both screening models, e.g., the isolated organ bath system, in vivo fecal assessment and intestinal transit assay, and confirmation models, e.g., in vivo constipation models. Chemical substances/drugs used to induce constipation in in vivo constipation models, e.g., loperamide, diphenoxylate, montmorillonite, and clonidine, as well as standard laxative agents used as a positive control in experimental models, e.g., bisacodyl, carbachol, lactulose, sodium picosulfate, castor oil, phenolphthalein, and yohimbine, are described in detail. The purpose of this article is to assist researchers in the design and implementation of preclinical experimental models for assessing laxative activities of substances/products under investigation to achieve valid and meaningful preclinical results prior to experimentation in humans.

Analysis of study designs and primary outcome measures in clinical trials of investigational suture materials.

BACKGROUND: Clinical trials are a prerequisite for any investigational suture materials before a market approval application. The appropriate study designs and primary outcome measures are key to the validity and reliability of clinical trial results. This study aimed to characterize the study designs and primary outcome measures being applied in clinical trials of investigational suture materials. METHODS: The systematic searches on PubMed, EMBASE, Web of Sciences, Scopus, and Cochrane databases were conducted to gather relevant studies published between January-2019 and May-2021. Data on general characteristics, suture intervention, study design, and primary outcome measures were extracted and analyzed. RESULTS: Of 46 included studies, the majority of them were conducted with a randomized-controlled (93.5%), single-blind (50.0%), two-arm (84.8%), and parallel (76.1%) design with a 1:1 allocation ratio (95.7%). Through correlation network and heatmap analysis, the moderate-to-very strong correlations between some types of investigational suture materials and primary outcome measures were found including barbed vs non-barbed suture and suturing time, antibacterial-coated vs non-coated suture and wound infection, mono- vs multi-filament suture and wound healing index/markers, and different sizes of suture materials and scar assessment. CONCLUSIONS: Our analysis provides guidance, with several key considerations, for designing a clinical trial evaluating investigational suture materials.

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.

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.

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.

Awareness and preparedness of healthcare workers against the first wave of the COVID-19 pandemic: A cross-sectional survey across 57 countries.

BACKGROUND: Since the COVID-19 pandemic began, there have been concerns related to the preparedness of healthcare workers (HCWs). This study aimed to describe the level of awareness and preparedness of hospital HCWs at the time of the first wave. METHODS: This multinational, multicenter, cross-sectional survey was conducted among hospital HCWs from February to May 2020. We used a hierarchical logistic regression multivariate analysis to adjust the influence of variables based on awareness and preparedness. We then used association rule mining to identify relationships between HCW confidence in handling suspected COVID-19 patients and prior COVID-19 case-management training. RESULTS: We surveyed 24,653 HCWs from 371 hospitals across 57 countries and received 17,302 responses from 70.2% HCWs overall. The median COVID-19 preparedness score was 11.0 (interquartile range [IQR] = 6.0-14.0) and the median awareness score was 29.6 (IQR = 26.6-32.6). HCWs at COVID-19 designated facilities with previous outbreak experience, or HCWs who were trained for dealing with the SARS-CoV-2 outbreak, had significantly higher levels of preparedness and awareness (p<0.001). Association rule mining suggests that nurses and doctors who had a 'great-extent-of-confidence' in handling suspected COVID-19 patients had participated in COVID-19 training courses. Male participants (mean difference = 0.34; 95% CI = 0.22, 0.46; p<0.001) and nurses (mean difference = 0.67; 95% CI = 0.53, 0.81; p<0.001) had higher preparedness scores compared to women participants and doctors. INTERPRETATION: There was an unsurprising high level of awareness and preparedness among HCWs who participated in COVID-19 training courses. However, disparity existed along the lines of gender and type of HCW. It is unknown whether the difference in COVID-19 preparedness that we detected early in the pandemic may have translated into disproportionate SARS-CoV-2 burden of disease by gender or HCW type.

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.