UPLC-QTOF mass spectrometry detection of four endocrine disrupting chemicals (Methyl Paraben, 2,4-Dichlorophenoxyacetic acid, Monobutyl Phthalate, and Bisphenol A) in urine of Filipino women

Background and Objective@#Endocrine Disrupting Chemicals (EDCs) are ubiquitously found as low-level contaminants and pose serious threat to women’s health. EDCs may result in various reproductive disorders, fetal birth and developmental abnormalities, and endocrine and metabolic disorders. EDCs can be detected in body fluids of exposed individuals including blood and urine. This study aimed to detect four EDCs — Methyl Paraben (MP), 2,4-Dichlorophenoxyacetic acid (2,4-D), Monobutyl Phthalate (MBP), and Bisphenol A (BPA) in urine samples of women using Ultra-Performance Liquid Chromatography – Quadrupole Time-of-Flight (UPLC-QTOF) mass spectrometry.@*Methods@#Sequential steps of enzymatic deconjugation, liquid-liquid extraction, solid phase extraction, and liquid chromatography separation and mass spectrometry detection were optimized in urine samples. The method was used to analyze 70 urine samples from women of reproductive age.@*Results@#The sample preparation method showed a recovery ranging from 86.6% (MBP) to 100 % (2,4-D). The method demonstrated limits of quantitation ranging from 1.52 ng/m(MP) to 6.46 ng/mL(2,4D). Intra-day precisions expressed as relative standard deviation were all below 15% while accuracy was shown to range from 67.10% (2,4-D) to 102.39% (MBP). MP was detected in nine samples (12.86%) with a geometric mean value of 10.15 ng/ml (range: 3.62-52.39 ng/ml). MBP was detected in 68 samples (97.14%) with a geometric mean value of 97.62 ng/ml (range: 15.32-698.18 ng/ml). BPA was detected only once (9.58 ng/ml) while 2, 4-D was not detected in all samples.@*Conclusion@#A UPLC-QTOF mass spectrometry method to detect four EDCs at parts per billion level (ng/ml) was adapted and applied for analysis of urine samples. This method can find applicability in routine testing of clinical specimens as well as surveillance and other epidemiological studies.

Scabies in the Philippines: A secondary analysis of local patient registries

Background@#Scabies is the second most common cause of disability among skin diseases in the Philippines as of 2019. There is no large nationwide study describing the epidemiologic profile of scabies in the country. Objective. This study aimed to describe the demographic, seasonal, and geographic profile of scabies in the Philippines.@*Methods@# We compared secondary data of two local patient registries (Philippine Dermatological Society, PDS, 2010 to 2021; and Philippine Pediatric Society, PPS, 2009 to 2021) for reported cases of scabies in the Philippines. We reported the frequency and percentage distribution according to age, sex, month, year, and type of diagnosis, and region. @*Results@#The median annual frequency of scabies cases (mostly outpatient) for PDS (from year 2010) was 4087 (range ([QR], 342-6422 [3271.5]), while it was 183 (range [IQR], 64-234 [96.5]) (all inpatient) for PPS (from year 2009). There was a reduction to one-third (PDS) and one-fourth (PPS) of pre-pandemic numbers during the pandemic years (2020- 2021). The peak months for scabies cases were the cooler months: January (median, 12.1% of annual cases; range [IQR], 2.6%-31.4% [3.6%]) to February (median, 10.0% of annual cases; range [IQR], 1.5%-27.8% [2.5%]) based on PDS data, and November (median, 10.0% of annual cases; range [IQR], 0.0%-24.3% [7.0%]) to January (median, 9.0% of annual cases; range [IQR], 0.0%-24.3% [6.6%]) for PPS data. Overall, for PDS, age 1-4 years is the most affected age group (median, PDS, 17.5% of annual cases; range [IQR], 11.9%-25.4% [8.1%]), while it was the less than 1-yearolds (median annual cases, 48.9%; range [IQR], 29.1%-67.3% [13.20%]) among PPS pediatric population aged 0 to 18 years. Males (median, 53.9% of annual cases; range [IQR], 45.0%-67.2% [8.8%]) were more affected than females in PPS. While for PDS during earlier years (prior to 2015), males (median, 51.6% of annual cases from 2010 to 2014; range [IQR], 47.4%-52.9% [0.2%]) were more affected than females. However, males became less affected than females with median, 44.7% of annual cases from 2015 onwards (range [IQR], 43.4%-46.5% [1.2%]). NCR was the region with the highest frequency of cases in PPS (median, 52.6% of annual cases; range [IQR], 22.7%-75.0% [20.4%]). The 2nd most affected regions were Central/Eastern Visayas (34.2%, 2009-2013; range [IQR], 17.9%-54.1% [5.3%]), Bicol region (12%; 2014 to 2018; range [IQR], 17.9%-54.1% [7.4%]), Central Luzon (18%; 2019), Central/Eastern Visayas (29%, 2020), and Northern/Central Mindanao (17%, 2021). @*Conclusion@#Scabies was commonly seen in the younger age group, slightly more in females in the PDS, while slightly more among males in the PPS, in the cooler months of the year, and in the urbanized NCR.

A feasibility study on re-establishing the Bioavailability/Bioequivalence unit of the Department of Pharmacology and Toxicology, College of Medicine-University of the Philippines Manila

Objectives@#The Bioavailability/Bioequivalence Unit (BA/BE Unit) of the Department of Pharmacology and Toxicology, College of Medicine, University of the Philippines Manila which has not been operational since 2012, is due for renewal of its accreditation. To date, there are only three Philippine Food and Drug Administration-accredited laboratories that perform bioequivalence studies in the Philippines. One of the prerequisites of registering specific generic medicines is the conduct of Bioequivalence (BE) studies which are performed to ensure that the generic drug is at par with the innovator drug. Thus, this study aimed to determine the feasibility of re-establishing the BA/BE Unit as a bioequivalence testing center. @*Methods@#The feasibility study done is a qualitative descriptive analysis based on expansive literature review and performance of SWOT analysis within the BA/BE unit. Literatures were selected based on its assessed relevance to the study. The databases checked were PubMed and Google Scholar. The terms used were from the Medical Subject Heading (MeSH) including feasibility studies, therapeutic equivalency, and generic drugs. Literature review was performed on the factors affecting the four types of feasibility studies (market, technical, financial, and organizational). A SWOT analysis of the BA/BE Unit was done through the review of records and documents of previous BE studies and focus group discussion among the BA/BE Unit team members. @*Results@#The BA/BE Unit conducted 24 bioequivalence studies from 2006-2009 and still receives inquiries from drug companies. It implements its QMS throughout the pre-analytical, analytical, and post-analytical stages of the workflow. Its organizational structure consists of qualified professionals with updated GCP and GLP certificates. Because of the adequately equipped facility, lower honoraria for government-employed personnel, and lower expenses for laboratories and in-patient admissions, the cost of conducting a bioequivalence study in the BA/BE Unit will be lower than in other BE centers. @*Conclusion@#Based on the SWOT analysis and market, technical, financial, and organizational considerations, reestablishing the BA/BE Unit as a bioequivalence testing center is feasible.

Exposure of reproductive-aged pregnant and nonpregnant women to common environmental pollutants and endocrine-disrupting chemicals A cross-sectional survey at the University of the Philippines-Philippine General Hospital / Philippine Journal of Obstetrics and Gynecology

Context@#Exposure to environmental pollutants (EP) and Endocrine-disrupting chemicals (EDCs) is associated with several general negative health effects which compromise women's reproductive health, maternal, and neonatal outcomes. Unfortunately, many nonpregnant and pregnant women are unaware of their active exposure to these potentially slow-acting toxic substances, EPs, and EDCs. At any stage of life, and in the long-term minute exposures, there is no established safe level of exposure to these substances. Due to the potentially harmful effects on women in general, and to the pregnant and her unborn child in particular, it is important to establish the prevalence of their exposure. @*Aims@#The aim of this study was to determine the magnitude (prevalence) of exposure among nonpregnant and pregnant women aged 18–49 years to common EPs/EDCs such as bisphenol A, pesticides, phthalates, and perfluorinated compounds among others.@*Settings and Design @#This study was conducted at the Philippine General Hospital, University of the Philippines Manila.@*Subjects and Methods @#The study participants were nonpregnant and pregnant women, with low-risk singleton pregnancy, and had a prenatal checkup and eventual delivery at the Philippine General Hospital. After consent, women were asked to answer a survey focused on their sociodemographics and frequency of exposure to EP- and EDC-containing items.@*Satatistical Analysis Used@#Descriptive statistics were used to summarize the demographic and clinical characteristics of the patients. Null hypotheses were rejected at 0.05 α-level of significance. The computer software STATA 13.1 was used for data analysis.@*Results@#One hundred and fifty-nine survey responses by women were analyzed. Possible EDC-containing household items (carpets, linoleum, upholstered, and stain-resistant furniture) are more prevalent in the homes of pregnant women compared to nonpregnant women. Pregnant women are also exposed to wallpapers compared to nonpregnant individuals. Nonpregnant women were 1.5 times more exposed to lotions. Unexposure to hand sanitizers is 1.3 times higher among pregnant individuals.@*Conclusions@#There are differences in the prevalence of exposure to household EDC-containing items between pregnant and nonpregnant women, with pregnant women having a higher prevalence of exposure.

Cytotoxic and Apoptotic Properties of the Flavonoid-rich Ethyl Acetate Fraction of the Crude Methanol Leaf Extract of Syzygium samarangense (Blume) Merr. (Myrtaceae) against MCF-7 Breast Cancer Cells

Introduction@#Breast cancer is the most common cancer among women in the Philippines and about 3 in every 100 Filipina will be diagnosed with breast cancer in their lifetime. There is a need to discover safe, yet inexpensive herbal extracts with potential cytotoxic properties as potential treatment modalities to treat breast cancer. @*Objectives@#This study seeks to explore the cytotoxic and apoptotic properties of the ethyl acetate fraction of the defatted crude methanol leaf extract of Syzygium samarangense in MCF-7 breast cancer cell lines. @*Methods@#Screening for flavonoids of the extracts was performed using TLC, total flavonoids, total phenols, FTIR and LC-MS spectroscopy. The hydrogen peroxide and ferric reducing anti-oxidant power were used as substrates to assess in vitro anti-oxidative properties of the extracts. The MTT dye viability assay was used to assess the cytotoxic properties of the extracts against MCF-7 cells. Apoptotic properties of the extracts in MCF-7 cells were determined by caspase-3 activation assay, DNA fragmentation patterns and fluorescence microscopy after annexin-V and propidium iodide staining. @*Results@#The abundance of flavonoids in the ethyl acetate fraction of the crude methanol leaf extract was established by TLC, FTIR, LC-MS/MS, total flavonoid and total phenol analyses. The in vitro anti-oxidative properties of this extract was comparable to ascorbic acid. The median inhibitory concentration (IC50) of this extract in MCF-7 breast cancer cell lines was 7.2 mcg/mL while doxorubicin registered an IC50 of 1.2 mcg/mL. At this concentration, the extract was not cytotoxic to normally-dividing breast epithelial cells. Cytotoxicity of the extract was mediated via apoptosis as demonstrated by DNA fragmentation, caspase-3 activation and fluorescence microscopic analyses. @*Conclusion@#The study shows that the flavonoid-rich ethyl acetate fraction of the crude methanol leaf extract of S. samarangense possesses potent apoptotic and cytotoxic properties against MCF-7 breast cancer cell lines at low concentrations.

Comparative efficacy and safety of oral ivermectin, topical permethrin, and its combination in the treatment of scabies: A systematic literature review

@#<p style="text-align: justify;"><strong>INTRODUCTION:</strong> Oral ivermectin is an approved first-line option to topical permethrin in Europe and Japan for the treatment of classic scabies, while combination oral ivermectin and topical permethrin is used in clinical practice for extensive or recurrent cases. There is unclear evidence on comparative efficacy and safety.</p><p style="text-align: justify;"><strong>OBJECTIVES:</strong> To review the evidence on efficacy and safety of oral ivermectin versus topical permethrin or its combination in the treatment of classic scabies.</p><p style="text-align: justify;"><strong>METHODS:</strong> We searched PubMed from January 1, 2016 up to August 7, 2021 for systematic reviews that included RCTs comparing oral ivermectin versus topical permethrin or its combination in the clinical treatment of scabies. We described the characteristics of included studies, assessed reporting quality, and summarized results and conclusion.</p><p style="text-align: justify;"><strong>RESULTS:</strong> We included five systematic reviews. Permethrin did not differ from oral ivermectin in cure rate at the 3 to 6-week time point but had an earlier cure at 1-2 weeks. Adverse effects did not significantly diff er and were few, mild, and transient with both treatments. The evidence ranged widely from low to high certainty and mainly came from three moderate-to-high quality systematic reviews. Combination oral ivermectin and topical permethrin was ranked higher in efficacy but lower in safety compared to either drug alone in one moderate validity network meta-analysis.</p><p style="text-align: justify;"><strong>CONCLUSION:</strong> There is varying certainty of evidence suggesting comparable efficacy and safety of oral ivermectin versus topical permethrin. Limited evidence suggest higher efficacy and lower safety of combination oral ivermectin and topical permethrin compared to either drug alone. An updated systematic review and network meta-analysis is warranted.</p><p style="text-align: justify;"><strong>KEYWORDS:</strong> scabies, ivermectin, permethrin, effectiveness, efficacy, safety</p>

The development of Basic Emergency Obstetric and Newborn Care (BEmONC) and Maternal Health in the Philippines: A historical literature review

Introduction@#Implementation of Basic Emergency Obstetric and Newborn Care (BEmONC) aims to curb maternal mortality. However, the Philippines failed to significantly reduce the maternal mortality rate (MMR) targeted in the Millennium Development Goals (MDGs). Currently, the country is still far from the targeted Sustainable Development Goals (SDGs). This review describes the historical development of BEmONC in the Philippines over the past 13 years and provides insights on its role in decreasing MMR. @*Methods@#We searched online for journal articles, publications, reports, policies, and other issuances related to BEmONC and maternal health in the Philippines. We accessed updates and data via correspondence with the Department of Health (DOH). Statistics were compiled from public databases. The identified citations were screened, appraised, synthesized, and analyzed in a historical approach. @*Results@#A direct result of the Emergency Obstetric Care Approach, BEmONC was developed to respond to the high MMR in the Philippines, in line with global efforts to improve maternal health. However, BEmONC functionality generally remained inadequate. @*Conclusions@#Although the provision of BEmONC services increased facility-based deliveries and skilled birth attendance during childbirth, this failed to decrease MMR and achieve targeted goals substantially. Further capacity-building is needed, especially in rural and resource-poor areas. Government issuances at the national and local levels should be aligned to complement each other. There should be a health systems approach that considers the building blocks of an efficient health care system and the social determinants that impact them.

Assessment of basic emergency obstetric and newborn care functionality of rural health units in Luzon

Background@#Background. Establishing and integrating Basic Emergency Obstetrics and Newborn Care (BEmONC)-capable facilities into the healthcare delivery system is one of the strategies employed by the Philippine government to address high maternal mortality. Objectives. This study aimed to determine the functionality of BEmONC-capable rural health units (RHUs) in Luzon, the largest island in the country. Methods. The study utilized a researcher-administered facility survey and facility observation using a checklist designed to measure BEmONC functionality. Facilities were selected through a two-stage sampling method. A BEmONC Score Card was used to determine the overall functionality of a facility based on three categories — institutional capacity, service capacity, and personnel capacity. The total scores from the three categories provided the overall functionality score.Results. Of the 245 BEmONC-provider RHUs included in the study, 85 (35%) were adequately functional. The mean functionality score for Luzon (60±25.27) corresponded to adequate functionality. The mean institutional and service capacities were consistently high across all regions on the island. Still, the personnel capacity did not reach the minimum average, pulling down the overall score and leading to low overall functionality. Conclusion. The BEmONC facilities continue to function despite being hampered by factors that can be easily remedied. The provision of BEmONC services remains relevant across all regions in Luzon as they fill in the gaps and serve the needs of mothers and pregnant women. This study should be replicated in the Visayas and Mindanao to obtain a complete representation of the BEmONC program.

Selecting indicators for assessing the functionality of basic emergency obstetric and newborn care facilities in the Philippines: A Delphi process

Introduction@#To address the problem of high maternal death, the Department of Health implemented the Basic Emergency Obstetric and Newborn Care (BEmONC) services at the level of primary care health facilities. These are key life-saving interventions that treat obstetric emergencies. Over a decade later, we need to assess and improve the program’s implementation. @*Objective@#The study aims to select indicators for assessing the functionality of BEmONC facilities. @*Methods@#Electronic Delphi process was used to select the indicators. @*Results@#The two-round Delphi process was accepted by 21 respondents, with a 100% response rate. All 30 proposed indicators were retained following the criteria. @*Conclusion@#Thirty indicators to assess the functionality of BEmONC facilities have been selected through the consensus of an expert panel using the Delphi process. These indicators help evaluate BEmONC facilities, formulate policy, and guide new programs that promote maternal health.

Mothers’ perspectives on utilization of maternal health services in Rural Health Units in Luzon: A qualitative study

Introduction@#Despite implementing various maternal health care programs and integrating these into Service Delivery Networks, the Philippines continues to have high maternal mortality. Identifying factors that impede the utilization of available maternal care services may help reduce maternal morbidity and mortality and bridge the gap between the need and actual use of such services among mothers in the community. @*Objectives@#This study identified barriers, hindrances, and other factors influencing mothers in availing maternal health services in Luzon, the largest island in the country and the area that accounted for more than half of total maternal mortality. @*Methods@#Eight focus group discussions participated in by a total of 78 pregnant women and mothers were conducted across all of the eight regions of Luzon. In each session, the participants were asked to answer questions based on a semi-structured interview guide. The interviews were recorded, translated and back-translated, transcribed, and compiled before analysis by the deductive-dominant approach using NVivo12. @*Results@#Factors affecting maternal health service utilization center on the capacity of health facilities to provide services like evaluation of the progress of pregnancy, laboratory examinations, free medicines, and immunizations; and on region-bound individual factors. The availability of skilled health personnel and lack of financial resources were the most common subthemes. @*Conclusion@#This study identified some key factors that deter patients from availing of existing maternal health services in Luzon. Eliminating these barriers will not only help strengthen local health infrastructure and improve service delivery but also promote the utilization of such services, leading to better maternal outcomes.