OBJECTIVES

In response to the need for a simple and fast way of ensuring that generic drugs especially those that contain rifampicin are bioequivalent with reference drugs, this study validated an ultra-high-performance liquid chromatography (UHPLC) method of quantifying rifampicin in human plasma. The study also validated the method's selectivity, linearity, sensitivity, accuracy, precision, and the absence of a carry-over effect adhering to the Philippine Food and Drug Administration guidelines.

Plasma samples were prepared via protein precipitation using methanol containing ascorbic acid. Three microliters (3 uL) of the prepared samples were then analyzed in a Waters Acquity H-Class UPLC® system coupled to a tunable ultraviolet (TUV) detector with an attached UPLC® BEH C-18 column using a developed and optimized method. Briefly, the column temperature was set to 40°C and the sample temperature was set to 10°C. Elution was done using a linear gradient flow of a water-acetonitrile mixture that started with 45% acetonitrile increasing to 60% acetonitrile at 0.5 minutes and back to 45% acetonitrile at 3 minutes and having a constant flow rate of 0.5 mL/min. Detection was done at 340 nm. Method validation was performed following the ICH guidelines for Bioanalytical Method Validation, the same guidelines referenced by the ASEAN Guideline for Harmonisation of Standards and the Philippine Food and Drug Administration (FDA).

The method had an analysis time of 3 minutes wherein rifampicin eluted at 1.4 minutes while the internal standard, rifapentine (IS) eluted at 1.7 minutes. Since no co-eluting endogenous materials were observed for the rifampicin and the internal standard, the method was confirmed to be selective. Its linearity over the range of 2 ug/mL to 25 ug/mL has been validated where it has a limit of detection (LOD) and limit of quantification (LOQ) values of 0.64 ug/mL and 1.94 ug/mL, respectively. The interday and intraday precision, reported as % coefficient of variance (%CV), and interday and intraday accuracy, reported as %error all within the limits of ±20% for the LLOQ and ±15% for the rest indicating its reliability and reproducibility. Lastly, due to the nature of the injection of the sample into the system, wherein a blank immediately follows the highest concentration standard, the method has been cleared of a carry-over effect.

The study successfully validated a UHPLC method of quantifying rifampicin in human plasma. Due to the sample processing method used and the chromatographic conditions set, the method can prepare and analyze samples in a simple yet fast, sensitive, reliable, and reproducible manner. The method can be applied in bioavailability and bioequivalence studies of rifampicin.

BACKGROUND AND OBJECTIVE

Oral ivermectin is recommended as an alternative to topical permethrin in Japanese, European, and CDC-STI guidelines for treating classic scabies. The combination of oral ivermectin and topical permethrin is also used in some settings. Partial economic evaluations conducted in India and Egypt have conflicting results, and no cost-effectiveness analysis in the Philippines has compared ivermectin-based regimens to permethrin for scabies treatment. We aimed to determine the cost-effectiveness of oral ivermectin, alone or in combination with permethrin, compared to permethrin, in the treatment of Filipino adult patients with classic scabies.

We used a decision tree model to estimate the cost-effectiveness of two regimens, oral ivermectin alone or in combination with permethrin, compared with permethrin to treat adults and children aged five years and older with classic scabies in the outpatient setting from the household perspective in the Philippines. We estimated total costs and disability-adjusted life years (DALYs) over a one-month follow-up. Input parameters were obtained from secondary data, such as effect estimates for probabilities of clinical outcomes from a network meta-analysis, DALYs from the Global Burden of Disease 2019, and prevailing market cost in the Philippines (DPRI 2022 with recommended markup by DOH, and leading drugstores) as of August 2022. We computed for incremental cost-effectiveness ratio (ICER) and net monetary benefit (NMB) to determine which of the interventions are cost-effective. Univariate and probabilistic sensitivity analyses, and scenario analyses were conducted to assess the impact of parameter and structural uncertainty.

Ivermectin-based regimens are suggested to be likely cost-saving compared to permethrin in the Philippine outpatient setting. Base case analysis showed that oral ivermectin had higher cost-savings (change in cost, -1,039.31; change in DALYS, 0.00027), while combination oral ivermectin/permethrin had higher DALYs averted (change in cost, PhP -1,019.78; change in DALYs, 0.00045), compared to permethrin. Combination oral ivermectin/permethrin (56%) was the most cost-effective, followed by oral ivermectin (44%) compared to permethrin (0%) through probabilistic sensitivity analysis. Estimates for ivermectin were sensitive to risk of cure for ivermectin vs permethrin using 1-way deterministic sensitivity analysis. Oral ivermectin was favored over combination oral ivermectin/permethrin at all thresholds based on the cost-effectiveness acceptability curve.

Both ivermectin-based regimens seem to be cost-saving compared to permethrin in the treatment of classic scabies in the Philippine outpatient setting. Clinicians may consider oral ivermectin, alone or in combination with permethrin as an alternative first-line or second-line treatment depending on patient preference, adverse event risk profile, availability, and economic capacity. This needs to be confirmed using primary data from Filipino patients to enhance the robustness of the findings and support evidence-based local decision-making in different settings. Less uncertainty in modelled parameters can give greater confidence in the results, which can be adopted for budget impact analysis and allow more rational resource allocation. Value of information analysis can be done to determine whether the expense of future RCTs or surveys in Filipinos to collect primary data is worth it. The cost of reducing uncertainty, if deemed worth the cost of further studies, may facilitate population-level decision-making and budget planning. Findings may further inform practice guideline development, coverage decisions, and national control program planning by providing the most cost-effective scabies intervention.

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.

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.

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.

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.

BACKGROUND

Diabetes mellitus (DM) is a significant and growing global health concern. Worldwide, 537 million adults have diabetes and 206 million of them are from the Western Pacific Region1. Local prevalence continues to remain high at 7.5%, with 4,303,899 adult Filipinos suffering from diabetes in 2021. DM significantly contributes to the growing burden of chronic kidney disease (CKD) worldwide with about 50% of end-stage renal disease (ESRD) being due to diabetic nephropathy alone. Likewise, 60% of Filipinos on maintenance dialysis have ESRD due to DM and hypertension. The primary care setting is the initial point of contact between healthcare providers and patients with type 2 diabetes, hence, the development of clinical practice guidelines that will provide guidance in caring for patients with stable complications of diabetes. The guideline is the first of 3 that are being developed by the Philippine Academy of Family Physicians for the diagnosis and management of adult patients with type 2 diabetes and stable microvascular complications – nephropathy, retinopathy and neuropathy.

This guideline aims to provide evidence-based recommendations on the diagnosis and management of adults with type 2 diabetes mellitus (T2DM) and early stage CKD and is divided into 5 main sections – Clinical Assessment, Diagnostic Tests, Pharmacologic Treatment, Non-pharmacologic Treatment and Patient Outcomes.

The method of guideline development followed the ADAPTE process. The Technical Working Group identified 19 key questions after consultation with colleagues and patients. Recommendations were adopted from high-quality clinical practice guidelines whenever applicable for most of the key clinical questions. On the other hand, the De Novo method of evidence review was used to answer key clinical questions for which recommendations from reviewed guidelines were not available. A modified GRADEPro was used in assessing the quality of evidence – high, moderate, low or very low. Following external review by a nephrologist, the draft recommendations were sent to the members of the consensus panel. Voting on whether to include or not by the consensus panel was facilitated to determine the strength of each recommendation – strong, moderate or weak.

After reviewing 3 high-quality clinical practice guidelines and the current evidence, the technical working group was able to develop 40 recommendations for the 19 key clinical questions.

Background and Objective: Oral ivermectin is recommended as an alternative to topical permethrin in Japanese, European, and CDC-STI guidelines for treating classic scabies. The combination of oral ivermectin and topical permethrin is also used in some settings. Partial economic evaluations conducted in India and Egypt have conflicting results, and no cost-effectiveness analysis in the Philippines has compared ivermectin-based regimens to permethrin for scabies treatment. We aimed to determine the cost-effectiveness of oral ivermectin, alone or in combination with permethrin, compared to permethrin, in the treatment of Filipino adult patients with classic scabies. Methods: We used a decision tree model to estimate the cost-effectiveness of two regimens, oral ivermectin alone or in combination with permethrin, compared with permethrin to treat adults and children aged five years and older with classic scabies in the outpatient setting from the household perspective in the Philippines. We estimated total costs and disability-adjusted life years (DALYs) over a one-month follow-up. Input parameters were obtained from secondary data, such as effect estimates for probabilities of clinical outcomes from a network meta-analysis, DALYs from the Global Burden of Disease 2019, and prevailing market cost in the Philippines (DPRI 2022 with recommended markup by DOH, and leading drugstores) as of August 2022. We computed for incremental cost-effectiveness ratio (ICER) and net monetary benefit (NMB) to determine which of the interventions are cost-effective. Univariate and probabilistic sensitivity analyses, and scenario analyses were conducted to assess the impact of parameter and structural uncertainty. Results: Ivermectin-based regimens are suggested to be likely cost-saving compared to permethrin in the Philippine outpatient setting. Base case analysis showed that oral ivermectin had higher cost-savings (change in cost, -1,039.31; change in DALYS, 0.00027), while combination oral ivermectin/permethrin had higher DALYs averted (change in cost, PhP -1,019.78; change in DALYs, 0.00045), compared to permethrin. Combination oral ivermectin/permethrin (56%) was the most cost-effective, followed by oral ivermectin (44%) compared to permethrin (0%) through probabilistic sensitivity analysis. Estimates for ivermectin were sensitive to risk of cure for ivermectin vs permethrin using 1-way deterministic sensitivity analysis. Oral ivermectin was favored over combination oral ivermectin/permethrin at all thresholds based on the cost-effectiveness acceptability curve. Conclusion Both ivermectin-based regimens seem to be cost-saving compared to permethrin in the treatment of classic scabies in the Philippine outpatient setting. Clinicians may consider oral ivermectin, alone or in combination with permethrin as an alternative first-line or second-line treatment depending on patient preference, adverse event risk profile, availability, and economic capacity. This needs to be confirmed using primary data from Filipino patients to enhance the robustness of the findings and support evidence-based local decision-making in different settings. Less uncertainty in modelled parameters can give greater confidence in the results, which can be adopted for budget impact analysis and allow more rational resource allocation. Value of information analysis can be done to determine whether the expense of future RCTs or surveys in Filipinos to collect primary data is worth it. The cost of reducing uncertainty, if deemed worth the cost of further studies, may facilitate population-level decision-making and budget planning. Findings may further inform practice guideline development, coverage decisions, and national control program planning by providing the most cost-effective scabies intervention.
Scabies ; Ivermectin ; Permethrin ; Cost-Benefit Analysis

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.
Endocrine Disruptors

BACKGROUND

Scabies, caused by Sarcoptes scabiei var. hominis, is a prevalent and burdensome skin disease in the Philippines, ranking second in disability. Recognized as a neglected tropical disease (NTD) by the WHO, scabies management is targeted for inclusion in universal healthcare programs worldwide by 2030. Current treatment involves topical neurotoxic drugs like permethrin, but issues such as expense and inconvenience hinder compliance. Oral ivermectin, recommended by the WHO only recently, is more cost-effective and easier to administer but is considered a second-line option in clinical practice guidelines. This research aimed to determine the comparative efficacy, safety, cost-effectiveness, and acceptability of oral ivermectin, alone or in combination with topical permethrin, versus topical permethrin alone, in the treatment of classic scabies among Filipino patients.

This 4-part study was conducted from July 2021 to September 2023 and aimed to compare the efficacy, safety, cost-effectiveness, and acceptability of oral ivermectin alone or in combination with topical permethrin versus topical permethrin alone for treating classic scabies among Filipino patients. Quantitative methods included a systematic review and network meta-analysis of 38 randomized controlled trials (RCTs) and a pharmacoeconomic evaluation using decision tree modeling. Qualitative methods involved a multiple case study of patient experiences and perceptions and in-depth interviews with physicians.

There seems to be comparable efficacy between oral ivermectin and permethrin, with limited evidence favoring the combination ivermectin/permethrin regimen. Adverse events were minor, and cost-effectiveness analyses favored ivermectin-based regimens over permethrin. Patient and physician perspectives supported the effectiveness of all treatments, with oral ivermectin recognized as safe but underutilized.

Evidence synthesis suggests that oral ivermectin, especially in combination with permethrin, could be a viable and cost-effective alternative for scabies treatment in the Philippines. The optimal dosing regimen, safety in specific populations, and factors influencing treatment choice need further exploration. Recommendations include advocating for oral ivermectin inclusion in regulatory guidelines and national formulary, considering it as a first- or second- line treatment, and conducting further research, including mixed-methods designs, to confirm efficacy, safety, and cost-effectiveness in different settings. Shared decision-making, considering ethical, logistical, socioeconomic, and psychological aspects, is crucial in implementing effective scabies control programs.

BACKGROUND AND OBJECTIVE

Oral ivermectin, a broad-spectrum anti-parasitic drug, alone or in combination with permethrin, may be a cheaper and more convenient alternative drug to topical permethrin alone in the treatment of classic scabies. There are no previous studies on the treatment acceptability of the three interventions among individual patients with scabies in the Philippines. The purpose of this study was to understand the experiences and perceptions on treatment acceptability for oral ivermectin, topical permethrin or combination treatment among patients with scabies using the multiple-case study approach.

We conducted a qualitative multiple case study among adult Filipino patients with classic scabies who were prescribed oral ivermectin, topical permethrin or its combination at a government tertiary hospital dermatology outpatient clinic from December 2022 to September 2023. Semi-structured interviews were used as the primary source of data and analyzed together with chart reviews, Dermatology Life Quality Index (DLQI) scores, and clinical images. Interviews were transcribed, coded, and triangulated with other secondary data. A three-person research team employed a reflexive and iterative process of familiarization, coding, and thematic analysis using a modified Theoretical Framework of Acceptability (TFA) to generate case descriptions, within-case analyses, and cross-case syntheses.

The acceptability of scabies treatments (permethrin, ivermectin, and combination therapy) was generally positive. Permethrin, used in three patient cases, was generally perceived as effective but itch relief varied. The burden of whole-body application of permethrin was context-dependent, influenced by living arrangements and family support. Perceived affordability of permethrin was linked to socioeconomic status. Ivermectin, used by one patient case, was perceived as highly effective with no side effects. Its single dose use did not interfere with patient routine. Combination therapy was also considered effective but potential antagonistic effects and the cost of adding permethrin made it less preferred. Reluctance in taking oral pills was noted. All patients valued medical advice and deferred to their physicians for treatment decisions.

All three treatment options were considered effective and safe. Patients generally preferred permethrin over oral ivermectin due to its topical nature and perceived lower side effects. However, affordability and logistical challenges, especially for large households and low-income families, were noted with permethrin. Oral ivermectin elicited hesitation due to its controversial role in COVID-19 and veterinary use. Concerns about added costs and potential antagonism in combination therapy were raised. Despite these considerations, patients ultimately relied on physicians for treatment decisions. This study underscores the importance of understanding patient perspectives, experiences, and the patient-physician relationship in choosing scabies interventions. Addressing patient concerns, providing education, and ensuring ease of use and affordability can enhance treatment acceptability and adherence for better outcomes.

BACKGROUND

Appropriate use of medication is an important indicator of quality healthcare delivery among children. Previously published studies on drug utilization involved Filipino households in general and were conducted in the 1990s. No recent Philippine studies have been conducted that focus on drug utilization in children.

To describe the current prescribing patterns in one primary care service in a rural site in the Philippines using the World Health Organization (WHO) prescribing indicators.

A cross-sectional study was conducted by review of electronic medical records of patients seen at the primary care facility under the Philippine Primary Care Studies (PPCS) rural site from April 2019 to March 2020. Out of 9,930 total encounters, 623 patient encounters with prescriptions for pediatric patients were included in the study through systematic sampling. The average number of drugs per encounter, percentage of drugs prescribed by their generic names, percentage of encounters with prescribed antibiotics, percentage of encounters with prescribed injections, and percentage of drugs prescribed from the Philippine Drug Formulary were calculated. Values were compared to the cut-offs considered “good practice” for outpatient care in the WHO manual: (1) an average number of less than two drugs per encounter; (2) less than 30% of encounters are prescribed with antibiotics; (3) less than 20% of encounters are prescribed with injections; (4) 100% of drugs are prescribed by generic name; and (5) 100% of drugs are from the formulary.

On the average, three drugs were prescribed per encounter. Most patient encounters (80.9%) involved antibiotics prescription — higher than the WHO standard value of 30%. All drugs were prescribed by generic name and were prescribed from the formulary. Only 0.5% of encounters were prescribed injections, all of which were administered through the intramuscular route. Of the 1,962 prescriptions generated, antibiotics was the most prescribed medication (25.7%). The most common diagnosis was infectious in nature (88.8%).

The primary care service achieved the WHO standard values in terms of prescribing by injections and by generic names. There was a high rate of antibiotic prescriptions at 83%, and a high average number of drugs prescribed per encounter, exceeding the WHO standard value.

Objectives: The availability of emergency obstetric and newborn care (EmONC) services is one of the key strategies in improving maternal health and achieving Sustainable Development Goal 3. Health staff knowledge and competency on these interventions are crucial to ensure the effective handling and management of obstetric and newborn emergencies. Health workers, despite having undergone formal training, require regular refresher courses to keep up with new, evidence-based information on EmONC intervention; and to ensure compliance with national and local referral guidelines. A two-day workshop was implemented to assess the knowledge and skills of health workers in Legazpi, Albay, regarding obstetric emergency cases and referral guidelines.

Methods: A pretest was conducted on the first day to assess the knowledge of the participants. A series of lectures were given before administering a posttest at the end of these lectures. An Objective Structured Clinical Examination (OSCE) was conducted on the second day, which aimed to assess the skills of the participants.

Results: The pretest findings indicated that the participants are generally knowledgeable about areas such as handwashing and prenatal care. Results of the posttest show that participants had difficulty with the category of referrals. Moreover, comparing the pretest and posttest scores, there is strong evidence that there is a difference in the median values of the pretest scores as compared to the posttest scores. The results of the OSCE also indicate the need for further training on partograph use and adherence to an EINC protocol. More than half of the participants passed all five parts of the OSCE.

Conclusion: The workshop contributed to an improvement in the knowledge of health care workers in obstetric emergency cases. Skills-wise, more frequent training may need to be conducted to improve other competencies such as partograph utilization and the practice of EINC interventions.

Key Words: emergency obstetric care, training, skilled birth attendants, knowledge, skills