BACKGROUND AND OBJECTIVE

Randomized controlled trials (RCTs) are essential for advancing evidence-based healthcare by evaluating the effectiveness and safety of health interventions. Despite the increasing recognition of clinical research, the Philippines has had limited contributions to global RCT output. This bibliometric analysis aims to assess the trends, characteristics, and impact of RCTs conducted in the Philippines and published online.

A systematic search of Medline (PubMed), and EMBASE, along with Acta Medica Philippina, was conducted to identify published RCTs from January 1990 to October 2022. Eligible studies were screened and analyzed based on publication trends, funding sources, study designs, research settings, and institutional contributions. Descriptive statistics were used to summarize key findings.

A total of 391 RCTs were identified, with a notable increase in number of RCTs published over time. Most studies (91.8%) were published in international journals, and funding was primarily sourced from pharmaceutical companies (47.1%). The predominant RCT design was two-arm parallel (64.7%), with hospitals being the most common research setting (54.2%). Research areas were led by infectious diseases, particularly vaccine-preventable illnesses (23.8%). While the University of the Philippines Manila (21.1%) and the Research Institute for Tropical Medicine (13.7%) were the leading institutions in terms of highest number of published RCTs, foreign authors accounted for nearly half (47.3%) of primary authorships. The most cited studies focused on cardiovascular diseases, infectious diseases, and oncology.

The increasing number of published RCTs in the Philippines reflects growth in research capacity and institutional engagement. Strengthening national research dissemination platforms and fostering regional collaborations will be essential in advancing the Philippines’ contribution to global clinical research.

High-grade differentiated thyroid carcinoma (HGDTC) is a recently recognized entity in the 2022 World Health Organization classification, representing a more aggressive subtype of differentiated thyroid carcinoma. Previously, high-grade features such as increased mitotic activity and tumor necrosis were often overlooked, despite being important independent prognostic factors. Although rare, HGDTC carries significant diagnostic, prognostic, and therapeutic implications. Data remain limited in Indonesia. Methods: This retrospective descriptive study reviewed 565 thyroid carcinoma cases diagnosed at Cipto Mangunkusumo Hospital from 2019 to 2024. Eleven cases (1.9%) met HGDTC criteria. Clinicopathological characteristics, histologic subtypes, Ki-67 proliferation index, molecular alterations, treatment modalities, and clinical outcomes were analyzed. Results: Patients had a mean age of 54.6 years, with a female-to-male ratio of 2.7:1. Papillary thyroid carcinoma was the main type (90.9%), with the tall cell subtype predominating. Mean tumor size was 6.4 cm. Lymphatic invasion, vascular invasion, and extrathyroidal extension were present in 54.5%, 18.2%, and 45.5% of cases, respectively. All tumors showed necrosis. Mean mitotic count was 3 per 2 mm². The Ki-67 index ranged from 5% to 45% (median, 14%). BRAFV600E and TERT promoter mutations were detected in 18.2% and 36.4% of cases, respectively, with co-mutations in 18.2%. Six cases (54.5%) had metastases at time of diagnosis. During a mean follow-up of 20.5 months, one patient (9.1%) developed new vertebral metastases and all patients (100%) remained alive. Conclusions: HGDTC presents with more aggressive characteristics and a worse prognosis. Accurate diagnosis, molecular profiling, and long-term monitoring are essential for optimal management.

Prebiotics are substrates selectively utilized by microorganisms to confer health benefits to their hosts. Various prebiotics have been supplemented in standard milk formulas for infants who cannot be exclusively breastfed, aiming to provide benefits similar to those of breast milk. One of the most commonly used prebiotics is a mixture of 90% short-chain galacto-oligosaccharides and 10% long-chain fructo-oligosaccharides (scGOS/lcFOS [9:1]). Systematic review and metaanalysis were conducted to determine the effectiveness of scGOS:lcFOS (9:1) supplementation in standard milk formula for improving gastrointestinal health and immunity among healthy infants and toddlers, using parameters such as stool pH and intestinal colonization with beneficial bacteria. This systematic review was prepared in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. Randomized clinical trials comparing scGOS/lcFOS (9:1)-supplemented formula versus placebo- or nonsupplemented formula milk were eligible for inclusion. Related studies on gastrointestinal health and immunity among healthy infants up to five years old were searched from the earliest available date until February 29, 2024. Eighteen publications (number of participants=1,675) were selected for the systematic review, of which 11 were subsequently subjected to a metaanalysis. Results showed that the standard formula supplemented with scGOS/lcFOS (9:1) was well tolerated and conferred various gastrointestinal health and immunity to healthy infants and toddlers. These findings support the supplementation of standard milk formula with scGOS/lcFOS (9:1) for healthy infants and toddlers.

Prebiotics are substrates selectively utilized by microorganisms to confer health benefits to their hosts. Various prebiotics have been supplemented in standard milk formulas for infants who cannot be exclusively breastfed, aiming to provide benefits similar to those of breast milk. One of the most commonly used prebiotics is a mixture of 90% short-chain galacto-oligosaccharides and 10% long-chain fructo-oligosaccharides (scGOS/lcFOS [9:1]). Systematic review and metaanalysis were conducted to determine the effectiveness of scGOS:lcFOS (9:1) supplementation in standard milk formula for improving gastrointestinal health and immunity among healthy infants and toddlers, using parameters such as stool pH and intestinal colonization with beneficial bacteria. This systematic review was prepared in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. Randomized clinical trials comparing scGOS/lcFOS (9:1)-supplemented formula versus placebo- or nonsupplemented formula milk were eligible for inclusion. Related studies on gastrointestinal health and immunity among healthy infants up to five years old were searched from the earliest available date until February 29, 2024. Eighteen publications (number of participants=1,675) were selected for the systematic review, of which 11 were subsequently subjected to a metaanalysis. Results showed that the standard formula supplemented with scGOS/lcFOS (9:1) was well tolerated and conferred various gastrointestinal health and immunity to healthy infants and toddlers. These findings support the supplementation of standard milk formula with scGOS/lcFOS (9:1) for healthy infants and toddlers.

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

Bronchial asthma is one of the most common chronic childhood diseases encountered in the primary care setting. Adherence to recommendations from clinical practice guidelines on asthma can be utilized as an indicator of quality of care when evaluating the implementation of the universal health care in the Philippines.

To determine the clinical profile of pediatric patients with bronchial asthma; and to evaluate the prescription patterns for asthma treatment in a primary care setting.

This was a retrospective cohort study that involved review of the electronic medical records in a rural site of the Philippine Primary Care Studies (PPCS). All patients less than 19 years old who were diagnosed with asthma from April 2019 to March 2021 were included. Quality indicators for asthma care were based on adherence to recommendations from the 2019 Global Initiative for Asthma (GINA) Guidelines.

This study included 240 asthmatic children with mean age of 6 years (SD ± 4.9) and a slight male preponderance (55.4%). Majority (138 children or 57.5%) were less than 6 years old. Out of the 240 children, 224 (93.3%) were prescribed inhaled short-acting beta-agonists (SABA) and 66 (27.5%) were prescribed oral SABA. Only 14 children (5.8%) were prescribed inhaled corticosteroids (ICS), with 13 children (5.4%) given ICS with longacting beta-agonists (LABA) preparations, and one child (0.4%) given ICS alone. Quality indicators used in this study revealed underutilization of ICS treatment across all age groups, and an overuse of SABA-only treatment in children 6 years old and above. Moreover, 71.3% of the total patients were prescribed antibiotics despite the current GINA recommendation of prescribing antibiotics only for patients with strong evidence of lung infection, such as fever or radiographic evidence of pneumonia.

There were 240 children diagnosed with asthma over a 2-year period in a rural community, with a mean age of 6 years old and a slight male predominance. This quality-of-care study noted suboptimal adherence of rural health physicians to the treatment recommendations of the GINA guidelines, with overuse of SABA and underuse of ICS for asthma control.

BACKGROUND AND OBJECTIVE

Primary care providers are key players in providing quality care to patients and advancing Universal Health Care (UHC). However, effective and quality healthcare delivery may be affected by inadequate knowledge and failure to adhere to evidence-based guidelines among providers. The Philippine Primary Care Studies (PPCS) is a five-year program that pilot tested interventions aimed at strengthening the primary care system in the country. Evidence-based training modules for healthcare providers were administered in Sorsogon and Bataan from the years 2018 to 2021. Module topics were selected based on common health conditions encountered by providers in rural and remote settings. This program aimed to evaluate the effectiveness of training in increasing provider knowledge.

A series of training workshops were conducted among 184 remote- and 210 rural-based primary care providers [nurses, midwives, barangay or village health workers (BHWs)]. They covered four modules: essential intrapartum and newborn care (EINC), integrated management of childhood illness (IMCI), non-communicable diseases (NCD), and geriatrics. A decision support system (UpToDate) was provided as a supplementary resource for all participants. We administered pre-tests and post-tests consisting of multiple-choice questions on common health conditions. Data was analyzed using paired one-tailed t-test, with an alpha of 0.05.

The knowledge of nurses, midwives, and BHWs improved after the training workshops were conducted. The largest increase from pre-test to post-test scores were observed among the midwives, with a mean difference (MD) of 32.9% (95% CI 23.9 to 41.9) on the EINC module, MD of 25.0% (95% CI 16.6 to 33.4) in the geriatrics module, and MD of 13.5% (95% CI 6.9 to 20.1) in the NCDs module. The nurses had the greatest improvement in the IMCI module (MD 10.8%, 95% CI 2.5 to 19.1). The knowledge of BHWs improved in all participated modules, with greatest improvement in the NCD module (MD 9.0%, 95% CI 5.77 to 12.14).

Primary care workshops, even if conducted as single-sessions and on a short-term basis, are effective in improving short-term knowledge of providers. However, this may not translate to long-term knowledge and application in practice. Furthermore, comparisons across provider categories cannot be made as participant composition for each training workshop varied. Ultimately, this study shows enhancing provider knowledge and competence in primary care will therefore require regular and diverse learning interventions and access to clinical decision support tools.

Tumor microenvironment is intrinsically hypoxic with abundant hypoxia-inducible factors-1α (HIF-1α), a primary regulator of the cellular response to hypoxia and various stresses imposed on the tumor cells. HIF-1α increases radioresistance and chemoresistance by reducing DNA damage, increasing repair of DNA damage, enhancing glycolysis that increases antioxidant capacity of tumors cells, and promoting angiogenesis. In addition, HIF-1α markedly enhances drug efflux, leading to multidrug resistance. Radiotherapy and certain chemotherapy drugs evoke profound anti-tumor immunity by inducing immunologic cell death that release tumor-associated antigens together with numerous pro-immunological factors, leading to priming of cytotoxic CD8+ T cells and enhancing the cytotoxicity of macrophages and natural killer cells. Radiotherapy and chemotherapy of tumors significantly increase HIF-1α activity in tumor cells. Unfortunately, HIF-1α effectively promotes various immune suppressive pathways including secretion of immune suppressive cytokines, activation of myeloid-derived suppressor cells, activation of regulatory T cells, inhibition of T cells priming and activity, and upregulation of immune checkpoints. Consequently, the anti-tumor immunity elevated by radiotherapy and chemotherapy is counterbalanced or masked by the potent immune suppression promoted by HIF-1α. Effective inhibition of HIF-1α may significantly increase the efficacy of radiotherapy and chemotherapy by increasing radiosensitivity and chemosensitivity of tumor cells and also by upregulating anti-tumor immunity.

The size of nanodrugs plays a crucial role in shaping their chemical and physical characteristics, consequently influencing their therapeutic and diagnostic interactions within biological systems. The optimal size of nanomedicines, whether small or large, offers distinct advantages in disease treatment, creating a dilemma in the selection process. Addressing this challenge, size-transformable nanodrugs have surfaced as a promising solution, as they can be tailored to entail the benefits associated with both small and large nanoparticles. In this review, various strategies are summarized for constructing size-transformable nanosystems with a focus on nanotherapeutic applications in the field of biomedicine. Particularly we highlight recent research developments in cancer therapy. This review aims to inspire researchers to further develop various toolboxes for fabricating size-transformable nanomedicines for improved intervention against diverse human diseases.