Background: Indigenous peoples (IPs) remain vulnerable to soil-transmitted helminthiasis (STH) due to limited access to sanitary toilets, clean water, quality health education, and services. The World Health Organization recommends periodic mass drug administration (MDA) of anthelminthics, health education, and improvements in water, sanitation, and hygiene (WASH) as control strategies to reduce morbidities caused by STH in target populations such as schoolage children (SAC). This paper complements the published results of the parasitological survey (prevalence and intensity of STH) conducted in selected Aeta and Ata-Manobo communities. Objectives: This study aimed to describe the accessibility of STH control strategies to respond to the needs of SAC in IP communities in Pampanga and Davao del Norte, the Philippines. It likewise intended to describe access of these IP communities to STH control strategies. Methods: Data on accessibility of and access to STH control strategies were collected using key informant interviews (KIIs) and focus group discussions (FGDs). Eleven officials and workers from the departments of health and education, local government units, and two IP leaders were interviewed on the existing STH burden in SAC, implementation of STH control strategies, particularly of MDA, health education campaigns, and improvements in WASH including good practices and challenges in program implementation. Three FGDs with parents, elementary school teachers of IP schools, and rural health midwives were conducted separately. Guide questions focused on accessibility of and access to STH prevention and control strategies for SAC in IP communities. Informed consent to conduct and record KIIs and FGDs were obtained from participants prior to participation. Analysis of a multi-disciplinary team was based on the accessibility framework for IPs accessing indigenous primary health care services by Davy et al. (2016). Results: The characteristics of the STH control strategies and the target populations are interrelated factors that influence accessibility. Challenges in the availability of the MDA program, particularly, inadequate staffing, drug shortages, and delays in delivery affect accessibility of and access to the free STH control strategies. Perceived harm, adverse events, stigma, beliefs, and practices likewise affect access. Lack of information on the similarity of treatment through community- and schoolbased MDA programs also affected engagement of SAC. IP communities are special settings where geographic isolation, peace and order situation as well as water supply need to be considered to help ensure access to STH control strategies, high MDA coverage, and improvements in WASH leading to desired outcomes. Conclusions Considering the context of IP communities and addressing the challenges in the accessibility of and access to STH control strategies are necessary to ensure successful implementation of an integrated approach in STH prevention and control strategies. Challenges in the accessibility of STH control strategies are inadequate staffing, poor inventory, and delays in the delivery of drugs, as well as poor sanitation and hygiene. Access of SAC is likewise affected by misconceptions on safety and efficacy of anthelminthics, including stigma and cultural practices. The similarity of the MDA programs based in school or community need to be disseminated.
Indigenous Peoples ; Mass Drug Administration

This study used UPLC-TQ-MS technology to replicate a Henoch-Schonlein purpura(HSP) model in rats by administering warm drugs by gavage and injecting ovalbumin with Freund's complete adjuvant emulsion. The distribution differences and characteristics of eight major components(ferulic acid, caffeic acid, neochlorogenic acid, cryptochlorogenic acid, benzoyl oxypaeoniflorin, tracheloside, loganin, and paeoniflorin) in rat liver, lung, heart, spleen, and kidney tissues were determined after oral administration of the Liangxue Tuizi Mixture at a dose of 42 g·kg~(-1) in both normal physiological and HSP states at 0.5, 1, 2, 6, and 12 hours. The results showed that the distribution patterns of the eight components of Liangxue Tuizi Mixture in the tissues of normal and HSP model rats were different. The main component, paeoniflorin, in Moutan Cortex and Paeoniae Radix Alba had higher content in all tissues. The eight components were predominantly distributed in the liver, lung, and kidney tissues, followed by spleen and heart tissues.
Rats ; Animals ; IgA Vasculitis/drug therapy* ; Monoterpenes ; Administration, Oral ; Liquid Chromatography-Mass Spectrometry

Objectives: Since the effectiveness of the Zero Open Defecation (ZOD) program as a scaling-up approach in lowering the rates of soil-transmitted helminth (STH) infections has not yet been locally explored, this study aimed to (1) describe the association between environmental determinants and STH cumulative prevalence, and (2) to predict the 2020 STH cumulative prevalence. Methods: A generalized linear regression (GLR) model was used to determine the association of 2014–2015 environmental determinants and observed 2015 STH cumulative prevalence, while a geographically weighted regression (GWR) model was used to produce predicted 2020 STH cumulative prevalence. Results: ArcGIS’ GLR tool with R2 of 63% found that statistically significant environmental determinants include distance near to water bodies, forest land use, access to sanitary toilet, level one water source, and ZOD status, while the ArcGIS’ GWR tool found that barangays, Cabangcalan, Matalangtalang, Talabaan, and Talib in Aroroy hypothetically met the national target below 30% for 2020 STH cumulative prevalence. Conclusion This study showed that barangays with a moderately low percentage of area with freshwater bodies, a moderately high percentage of households with sanitary toilet and level one water source, and a 100% status of ZOD have lower rates of STH cumulative prevalence in preschool-aged children in the selected municipalities in Masbate.
Mass Drug Administration ; Hygiene ; Sanitation ; Geographic Information Systems

BACKGROUNDS: Azithromycin mass drug administration (MDA) is a key part of the strategy for controlling trachoma. This systematic review aimed to comprehensively summarize the present studies of azithromycin MDA on trachoma; provide an overview of the impact of azithromycin MDA on trachoma in different districts; and explore the possible methods to enhance the effectiveness of azithromycin MDA in hyperendemic districts. METHODS: PubMed, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and ClinicalTrials.gov were searched up to February 2021 with no language restriction. Studies reporting the effect of azithromycin MDA on trachoma were included. Mathematical modeling studies, animal studies, case reports, and reviews were excluded. The trachomatous inflammation-follicular (TF) <5.0% was used to judge the effect of azithromycin MDA on eliminating trachoma as a public health problem. Two researchers independently conducted the selection process and risk of bias assessment. RESULTS: A total of 1543 studies were screened, of which 67 studies including 13 cluster-randomized controlled trials and 54 non-randomized studies were included. The effect of azithromycin MDA on trachoma was closely related to the baseline prevalence in districts. For the districts with baseline prevalence between 5.0% and 9.9%, a single round of MDA achieved a TF <5.0%. For the districts with baseline between 10.0% and 29.9%, annual MDA for 3 to 5 years reduced TF <5.0%. However, for the districts with high level of baseline prevalence (TF >30.0%), especially with baseline TF >50.0%, annual MDA was unable to achieve the TF <5.0% even after 5 to 7 years of treatment. Quarterly MDA is more effective in controlling trachoma in these hyperendemic districts. CONCLUSIONS Azithromycin MDA for controlling trachoma depends on the baseline prevalence. The recommendation by the World Health Organization that annual MDA for 3 to 5 years in the districts with TF baseline >10.0% is not appropriate for all eligible districts.
Anti-Bacterial Agents/therapeutic use* ; Azithromycin/therapeutic use* ; Humans ; Infant ; Mass Drug Administration ; Prevalence ; Trachoma/epidemiology*

OBJECTIVE: To select potential molecules that can target viral spike proteins, which may potentially interrupt the interaction between the human angiotension-converting enzyme 2 (ACE2) receptor and viral spike protein by virtual screening. METHODS: The three-dimensional (3D)-coordinate file of the receptor-binding domain (RBD)-ACE2 complex for searching a suitable docking pocket was firstly downloaded and prepared. Secondly, approximately 15,000 molecular candidates were prepared, including US Food and Drug Administration (FDA)-approved drugs from DrugBank and natural compounds from Traditional Chinese Medicine Systems Pharmacology (TCMSP), for the docking process. Then, virtual screening was performed and the binding energy in Autodock Vina was calculated. Finally, the top 20 molecules with high binding energy and their Chinese medicine (CM) herb sources were listed in this paper. RESULTS: It was found that digitoxin, a cardiac glycoside in DrugBank and bisindigotin in TCMSP had the highest docking scores. Interestingly, two of the CM herbs containing the natural compounds that had relatively high binding scores, Forsythiae fructus and Isatidis radix, are components of Lianhua Qingwen (), a CM formula reportedly exerting activity against severe acute respiratory syndrome (SARS)-Cov-2. Moreover, raltegravir, an HIV integrase inhibitor, was found to have a relatively high binding score. CONCLUSIONS A class of compounds, which are from FDA-approved drugs and CM natural compounds, that had high binding energy with RBD of the viral spike protein. Our work provides potential candidates for other researchers to identify inhibitors to prevent SARS-CoV-2 infection, and highlights the importance of CM and integrative application of CM and Western medicine on treating COVID-19.
China ; Computer Simulation ; Coronavirus Infections ; diagnosis ; drug therapy ; Drug Repositioning ; methods ; Drugs, Chinese Herbal ; pharmacology ; Glycoproteins ; drug effects ; metabolism ; Humans ; Imaging, Three-Dimensional ; Mass Screening ; methods ; Molecular Docking Simulation ; methods ; Pandemics ; Peptidyl-Dipeptidase A ; drug effects ; Pneumonia, Viral ; diagnosis ; drug therapy ; Protein Binding ; United States ; United States Food and Drug Administration

A sensitive and specific ultra-performance liquid chromatography-mass spectrometry(UPLC-MS/MS) method was deve-loped for analysis of rutaecarpine(Ru), evodiamine(Ev), rutaevine(Rv), limonin(Li), ginsendside Rb_1(Rb_1), ginsendside Re(Re) in rat plasma and brain tissues of nitroglycerin-induced migraine rats. Male healthy Sprague-Dawley(SD) rats were orally given multiple dose of optimized(OS) and un-optimized Wuzhuyu Decoction(UNOS), and their blood samples and brainstem were collected at different time points after injection of nitroglycerin(10 mg·kg~(-1)) into the frontal region. The drug concentrations of the 6 analytes in plasma and brainstem were determined by UPLC-MS/MS method. Subsequently, the main pharmacokinetics parameters of plasma were calculated by using Phoenix WinNolin 5.2.1 software. The methodological test showed that all of analytes in both plasma and brainstem homogenate exhibited a good linearity within the concentration range(r>0.994 7). The intra-day and inter-day accuracy, precision, matrix effect, stability of the investigated components meet the requirements for biopharmaceutical analysis. The developed method was successfully applied in pharmacokinetic studies on abovementioned ingredients in rat plasma and brain stem. The plasma pharmacokinetic parameters of active ingredients in two different Wuzhuyu Decoction group were compared, it was found that Rb_1 had higher t_(1/2), T_(max), C_(max), AUC_(0-24 h) and AUC_(0-∞ )in OS group. Meanwhile, Ev had higher t_(1/2) and T_(max) but lower C_(max), AUC_(0-24 h) and AUC_(0-∞), Ru has higher t_(1/2 )but lower C_(max), AUC_(0-24 h) and AUC_(0-∞ )in OS group. The brain tissue distribution of each component were compared between the two groups, the component with higher content in OS, such as Ru at 30 min and 2 h after administration, Ev at 30 min, Rb_1 at 30 min and Rb_1 at 2 h after administration have lower brain tissue distribution than those in UNOS group, while the component with higher content in UNOS, such as Rv at 30 min, 2 h and 12 h after administration had higher brain tissue distribution than those in OS group.
Administration, Oral ; Animals ; Brain/drug effects* ; Brain Chemistry ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal/therapeutic use* ; Male ; Migraine Disorders/drug therapy* ; Nitroglycerin ; Plasma/chemistry* ; Rats ; Rats, Sprague-Dawley ; Reproducibility of Results ; Tandem Mass Spectrometry

European Medicines Agency withdrew valsartan from European market in July 2018 because it was contaminated with carcinogen, N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA). Medicines and Healthcare Products Regulatory Agency also found the same contamination and withdrew it from England market. US Food and Drug Administration followed the action after confirming its contamination. Ministry of Food and Drug Safety (MFDS) conducted testing all the valsartans at Korean market and withdrew some of them from market after confirming the contamination with NDMA. MFDS provided the pharmaceutical companies and laboratory institutions with the manual for testing both NDMA and NDEA and educated relevant personnels. MFDS also evaluated the health impact of the contaminated valsartan on the hypertensive patients who took the valsartan, which was shown to be very low risk of additional cancer incidence. MFDS pronounced strengthening of the safety management for the raw materials of the medicines. For guaranteeing the safety of medicines, more comprehensive drug safety management system from developing new drugs to consuming the medicines should be established. For achieving such a goal, active participation of all the stakeholders of the medicines including governmental agencies including MFDS and Ministry of Health and Welfare, the National Assembly, healthcare professionals, pharmaceutical companies, mass media, and general population including patients should be needed.
Antihypertensive Agents ; Delivery of Health Care ; Diethylnitrosamine ; Dimethylnitrosamine ; England ; Humans ; Incidence ; Mass Media ; Safety Management ; United States Food and Drug Administration ; Valsartan

Panax notoginseng saponins (PNS) are the major components of Panax notoginseng, with multiple pharmacological activities but poor oral bioavailability. PNS could be metabolized by gut microbiota in vitro, while the exact role of gut microbiota of PNS metabolism in vivo remains poorly understood. In this study, pseudo germ-free rat models were constructed by using broad-spectrum antibiotics to validate the gut microbiota-mediated transformation of PNS in vivo. Moreover, a high performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) was developed for quantitative analysis of four metabolites of PNS, including ginsenoside F1 (GF1), ginsenoside Rh2 (GRh2), ginsenoside compound K (GCK) and protopanaxatriol (PPT). The results showed that the four metabolites could be detected in the control rat plasma, while they could not be determined in pseudo germ-free rat plasma. The results implied that PNS could not be biotransformed effectively when gut microbiota was disrupted. In conclusion, gut microbiota plays an important role in biotransformation of PNS into metabolites in vivo.
Animals ; Anti-Bacterial Agents ; pharmacology ; Biotransformation ; Chromatography, High Pressure Liquid ; Feces ; microbiology ; Gastrointestinal Microbiome ; drug effects ; physiology ; Ginsenosides ; blood ; Male ; Panax notoginseng ; chemistry ; Rats, Sprague-Dawley ; Sapogenins ; blood ; Saponins ; administration & dosage ; metabolism ; Tandem Mass Spectrometry

INTRODUCTION: Epidural steroid injections are an integral part of nonsurgical management of radicular pain from lumbar spine disorders. We studied the effect of dexamethasone 8 mg epidural injections on the hypothalamic-pituitary-adrenal axis and serum glucose control of Asian patients. METHODS: 18 patients were recruited: six diabetics and 12 non-diabetics. Each patient received a total of dexamethasone 8 mg mixed with a local anaesthetic solution of lignocaine or bupivacaine, delivered into the epidural space. Levels of plasma cortisol, adrenocorticotropic hormone (ACTH), serum glucose after an overnight fast and two-hour postprandial glucose, as well as weight, body mass index, blood pressure and heart rate were measured within one week prior to the procedure (baseline) and at one, seven and 21 days after the procedure. RESULTS: Median fasting blood glucose levels were significantly higher on post-procedure Day 1 than at baseline. However, there was no significant change in median two-hour postprandial blood glucose from baseline levels. At seven and 21 days, there was no significant difference in fasting or two-hour postprandial glucose levels. Both ACTH and serum cortisol were significantly reduced on Day 1 compared to baseline in all patients. There was no significant difference in ACTH and serum cortisol levels from baseline at Days 7 and 21. CONCLUSION Our study shows that epidural steroid injections with dexamethasone have a real, albeit limited, side effect on glucose and cortisol homeostasis in an Asian population presenting with lower back pain or sciatica.
Adrenocorticotropic Hormone ; blood ; Adult ; Aged ; Blood Glucose ; analysis ; Body Mass Index ; Dexamethasone ; administration & dosage ; therapeutic use ; Diabetes Mellitus ; therapy ; Endocrine System ; drug effects ; Female ; Glucocorticoids ; administration & dosage ; Humans ; Hydrocortisone ; blood ; Hypothalamo-Hypophyseal System ; drug effects ; Injections, Epidural ; methods ; Male ; Middle Aged ; Pituitary-Adrenal System ; drug effects ; Postprandial Period ; Singapore ; Young Adult

OBJECTIVES: Inflammation is a major mechanism underlying coronary heart disease (CHD) and C-reactive protein (CRP) is a marker of inflammation. When administered soon after menopause, menopausal hormone therapy (MHT) prevents CHD. This study was conducted to examine the impact of estrogen by administration route on CRP in postmenopausal Korean women using micronized progesterone (MP4) for endometrial protection. METHODS: This retrospective cohort study included 129 healthy women without CHD risk factors. Eighty-nine women took oral estrogen (conjugated equine estrogen, 0.625 mg/day or equivalent), and 40 women applied a 1.5-mg/day 0.1% percutaneous estradiol gel. MP4 was added in 82 women with an intact uterus. The CRP level was measured at baseline and three and six months after initiation of MHT. RESULTS: The baseline characteristics were comparable between the MHT groups except current age and age at menopause. After controlling for age, menopausal age, body mass index, and basal CRP, no significant change in CRP was observed in the oral estrogen group (n = 29). Follow-up CRP levels were also similar to the baseline in the percutaneous estrogen group (n = 18). However, three-month CRP was significantly lower than six-month CRP, and there was a significant time trend within the percutaneous estrogen group. However, the group difference did not reach statistical significance. CRP also did not differ by addition of MP4 in either group. CONCLUSIONS: In postmenopausal Korean women, no change in CRP was observed with oral estrogen, while percutaneous estrogen might decrease CRP. The estrogenic impacts were not influenced by adding MP4.
Body Mass Index ; C-Reactive Protein ; Cohort Studies ; Coronary Disease ; Drug Administration Routes ; Estradiol ; Estrogens ; Female ; Follow-Up Studies ; Hormone Replacement Therapy ; Humans ; Inflammation ; Menopause ; Postmenopause ; Progesterone ; Retrospective Studies ; Risk Factors ; Uterus