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.

RATIONALE AND OBJECTIVES

The COVID- 19 pandemic and the subsequent designation of the Philippine General Hospital lead to necessary adjustments in internal medicine residency training. This study investigated the impact of the COVID-19 pandemic on internal medicine (IM) residents in the Philippine General Hospital.

A questionnaire was developed and distributed among internal medicine residents employed in the years 2020 and 2021. Qualitative data was then gathered through on line and face-to-face interviews.

A total of 43 Internal Medicine residents responded. This study found that the pandemic significantly affected internal medicine residents and their overall training. The participants reported changes in the number and profile of patients seen, the limited outpatient clinical exposure, the difficulties of telemedicine, and the reduced interactions with consultants and subspecialty fellows. Infection control protocols and workforce limitations also affected the number of procedures done by the residents. Resident participants reported that they were able to allot more time to studying from the textbook because of the skeletal schedules and decreased number of patients. Other learning avenues were shifted to online conferences and lectures.

The COVID-19 pandemic a lso brought about changes in residents' day-to-day routines, schedules, and rotations. Communicating with patients and relatives was also reported to be more difficult. Lifestyle changes varied among resident s. Socialization also shifted to online avenues and social messaging platforms. Having colleagues who test positive tor COVID and subsequently requiring quarantine lead to constant changes in workforce dynamics. This lead to feelings of anxiety and isolation among its trainees.

However, a number of participants still believed that the pandemic allowed them to become better physicians. This was brought about by a sense of service and pride, camaraderie among colleagues, commitment to finishing the program, financial stability, and administrative support. Still, the participants stated areas for improvement, including more consistent protocol measures, additional financial compensation, added workforce, and more transparent administrative support. All in all, participants felt that they were still able to meet the learning outcomes and minimum competencies. Majority of the participants believed the experiences brought about by the pandemic helped them become a better internist.

Ultimately, the new challenges from the pandemic strengthened the sense of service, resilience and clinical acumen of the residents.

BACKGROUND AND OBJECTIVE

Prolactinoma is the most common functioning tumor of the pituitary gland. While its clinical course and outcomes among different populations have been vastly described in the past, data of prolactinoma among Filipinos has not been explored. This paper aims to describe the clinical profile and outcome of prolactinoma among adult Filipino patients.

We conducted a retrospective cohort study including 41 patients with prolactinoma seen at the Philippine General Hospital. The clinical profile, cranial imaging features, treatment modalities given, and their outcomes over a mean follow up of 16 months were evaluated.

The mean age at diagnosis was 36.76 ± 13.99 years. Majority of our cohort were females. Macroprolactinoma were found in 75.61% and giant prolactinoma in 9.76%. The remaining 12.2% were mixed GH and PRL secreting tumors. Most common symptoms at presentation were blurring of vision, headache, and amenorrhea. Median PRL levels was 353 (200-470) ng/ml. Medical therapy with Bromocriptine was the primary treatment modality used in 78% of patients. We found no significant difference between patients who underwent surgical and medical primary treatment modalities in terms of outcomes. At the end of follow up, 82.6% of patients achieved at least more than 50% reduction in their prolactin levels.

Overall, our study showed that adult Filipino patients with prolactinoma have a larger tumor size at diagnosis and a lower rate of improvement of gonadal function after treatment. There were no statistically significant differences in clinical and biochemical outcomes between the treatment modalities used.

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.
Feasibility Studies ; Therapeutic Equivalency ; Drugs, Generic

Background and Objective: Diabetes, a prevalent metabolic disorder characterized by hyperglycemia primarily due to insulin action and secretion, poses significant health challenges, particularly in low to medium-income countries such as the Philippines. Quassia amara, a shrub indigenous to South America and present in the Philippines, holds a rich history of utilization in alternative and complementary therapies. While previous studies have demonstrated the hypoglycemic effects of Quassia amara stem wood, investigations into the potential impact of its leaves on blood glucose levels remain scarce. Thus, this study aimed to assess the blood glucose-lowering effects of the aqueous leaf extract of Quassia amara (ALQa) on ICR strain mice. Methods: Diabetes was induced in thirty male ICR mice via intraperitoneal administration of alloxan monohydrate (200 mg/kg) dissolved in 0.9% Normal Saline. The mice were divided into five groups (n=6), Group I: negative control (distilled water), Group II: reference standard glibenclamide (4 mg/kg): Groups III-V: three doses of ALQa (125, 250, and 500 mg/kg) via oral gavage. A glucometer was used to monitor the fasting blood glucose levels at 0, 1-, 2-, 6-, and 24-hour postadministration. Results: Administration of alloxan monohydrate increased the FBS in the treated group to diabetic levels of >200 mg/dL. The treatment of diabetic mice with ALQa extract significantly reduced fasting blood sugar (FBS) levels in a dose-dependent manner with the highest dose of ALQa (500 mg/kg) having glucoselowering effects comparable to glibenclamide beginning with the 2-hour mark until 24-hour post-intervention. The mean FBS at 0-hour (baseline) and 1-hour postintervention were similar for all the groups. However, there was an increase in the mean FBS of the negative control group treated with distilled water in the first hour while there was already a decrease in the FBS of those allocated to glibenclamide and the three doses of ALQa. At both the second and 6-hour mark post-intervention, the mean FBS of the mice treated with ALQa 250 mg/ kg and 500 mg/kg was comparable to glibenclamide. Finally, at the 24th hour post-intervention, only the mice allocated to 500 mg/kg of ALQa had comparable FBS to glibenclamide. The degree of reduction [mean percent reduction] of the FBS from baseline to the 24th hour was 78% for glibenclamide and 69% for ALQa 500 mg/kg (p =0.816). Conclusions The aqueous extract of Quassia amara leaf at 250 and 500 mg/kg produced a dose-dependent significant blood glucose-lowering effect in the alloxan-induced diabetic mice model. The 500 mg dose demonstrated a statistically comparable reduction in FBS to glibenclamide from the 2-hour time point. These f indings suggest the potential of ALQa as an antidiabetic agent. Thus, warranting further investigation into its therapeutic mechanisms and clinical applications.
Quassia amara ; Quassia

OBJECTIVES

This study aimed to determine the maternal and fetal effects of hyperglycemia, and to compare the clinical outcomes between pregnant teenagers and adult women with gestational diabetes mellitus (GDM).

This was a retrospective cohort study among pregnant women who tested positive for GDM by 75-gram oral glucose tolerance test (OGTT). Data was collected from the 1st of January 2015 to the 31st of December 2019. Maternal and fetal outcomes and the factors associated with maternal and neonatal outcomes among teenage women and adult women with GDM were studied.

A total of 254 charts of women with GDM were reviewed. Overall, adverse maternal outcomes were found in 94.12% and 90% of teenage and adults, respectively; and were almost more likely among primigravida (OR=3.984, CI=1.32-12, p=0.014). The study also showed less probability of having adverse maternal outcomes among multipara and grand multipara women (OR=0.2545, CI=0.08-0.79, P=0.018 and OR=0.1091, CI=0.03-0.45, p=0.002) respectively. Adverse neonatal outcomes were more likely among women who had prior delivery of macrosomic baby (OR=21.9091, CI=1.28-3.73, P=0.033). No adverse fetal outcome records were seen among teenage mothers, while adult women had 5.45% incidence.

Adverse maternal and neonatal outcomes were not significantly higher in the teenage GDM population compared to adult GDM. However, diagnosing and managing GDM among these groups would be beneficial considering their life expectancy and the need for a lifelong preventive program to avoid future development of Type 2 DM (T2DM) and its complications.

Objective: A diabetes prevention program is being proposed in the rural agricultural town of San Juan, Batangas, Philippines. This study aims to determine the prevailing level of food intake, physical activity, and health beliefs prior to any intervention. Methodology: Adults were recruited via random sampling with proportional allocation. Interviews were done to determine food intake and physical activity. Small group discussions were held to determine prevailing health beliefs. Results: The average energy intake (1,547 kcal/d) is only 72% of the recommended values for Filipinos. Only 12% of the respondents achieved the recommended energy intake. Carbohydrates comprise a large part (71%) of calorie intake. A majority (91%) already have moderate to high levels of physical activity. There are prevailing health beliefs that need to be considered when dietary modifications and physical activity interventions are to be done. Conclusion Internationally recommended diabetes prevention interventions such as reducing calorie intake and increasing physical activity may not be directly applicable here. We recommend that the features of a diabetes prevention program for this locale must include the following: 1) introduction of affordable plant sources of proteins; 2) decreasing the proportion of rice as a source of carbohydrates in the diet; 3) maintaining the level of physical activity; and 4) being sensitive to the prevailing health beliefs.
Culture ; Diet ; Life Style ; Prediabetic State ; Rural Population

Objectives: We determined the clinical characteristics and prevalence of metabolic syndrome among adult Filipinos with overt hypothyroidism. Methodology: This is a cross-sectional study of 151 adults. Patients were recruited by sequential enrollment. Anthropometric and blood pressure measurements were performed followed by blood extraction for metabolic parameters and thyroid function tests. Clinical and laboratory characteristics were compared between patients with and without metabolic syndrome. Results: The prevalence of metabolic syndrome is 40.4% (95%CI: 32.5%, 48.7%). Patients with metabolic syndrome have a waist circumference of 88.4 ± 7.7 cm in females and 93.3 ± 9.0 cm in males. The median fasting blood glucose was 111.4 (52.2) mg/dL, median systolic blood pressure of 120 (30) mm Hg and diastolic blood pressure of 80 (20) mmHg, median serum triglycerides of 174.3 (114.2) mg/dL, median HDL-C of 42.3 (19.2) mg/dL and a proportion of patients with diabetes (23.0%) and hypertension (44.3%), respectively. The presence of increased waist circumference is the most prevalent component seen among hypothyroid patients. There were no differences in terms of age, sex, etiology of hypothyroidism and anti-TPO levels in those with and without metabolic syndrome. Conclusion The prevalence of metabolic syndrome in adult Filipinos with hypothyroidism is high. Emphasis must be placed on early screening using waist circumference and metabolic parameters among hypothyroid patients who are at high risk of developing metabolic syndrome.
Dyslipidemias ; Hypothyroidism ; Metabolic Syndrome ; Prevalence

Background and Objective: Prolactinoma is the most common functioning tumor of the pituitary gland. While its clinical course and outcomes among different populations have been vastly described in the past, data of prolactinoma among Filipinos has not been explored. This paper aims to describe the clinical profile and outcome of prolactinoma among adult Filipino patients. Methods: We conducted a retrospective cohort study including 41 patients with prolactinoma seen at the Philippine General Hospital. The clinical profile, cranial imaging features, treatment modalities given, and their outcomes over a mean follow up of 16 months were evaluated. Results: The mean age at diagnosis was 36.76 ±13.99 years. Majority of our cohort were females. Macroprolactinoma were found in 75.61% and giant prolactinoma in 9.76%. The remaining 12.2% were mixed GH and PRL secreting tumors. Most common symptoms at presentation were blurring of vision, headache, and amenorrhea. Median PRL levels was 353 (200-470) ng/ml. Medical therapy with Bromocriptine was the primary treatment modality used in 78% of patients. We found no significant difference between patients who underwent surgical and medical primary treatment modalities in terms of outcomes. At the end of follow up, 82.6 % of patients achieved at least more than 50% reduction in their prolactin levels. Conclusion Overall, our study showed that adult Filipino patients with prolactinoma have a larger tumor size at diagnosis and a lower rate of improvement of gonadal function after treatment. There were no statistically significant differences in clinical and biochemical outcomes between the treatment modalities used.
Prolactinoma ; Pituitary Neoplasms ; Prolactin

BACKGROUND AND OBJECTIVE

The technical review process involves an evaluation of the scientific merits of the research proposal and is a necessary part of the ethics review but can be done separately and ahead of the formal ethics evaluation. The aim of this paper is to determine the efficiency and quality of the technical review process of the Philippine General Hospital (PGH) Department of Medicine Research Office.

This is a cross-sectional study which involved retrieval of the technical review forms of protocols evaluated in the PGH Department of Medicine from the years 2018-2019, and then an evaluation of these metrics: timelines of the review process indicating efficiency, including time from (1) receipt of submission to receipt of reviewer (secretariat efficiency); (2) receipt of reviewer to first decision (reviewer metric); (3) initial receipt to final decision (total review time); and (4) number of re-submissions. To evaluate the quality of the reviews, the specific review findings in each part or section of the protocol were also extracted.

In the years 2018-2019, a total of 199 protocols underwent technical review, with one protocol having no further data after the submission so only 198 proposals were analyzed. Majority of the protocols or 139/198 (70.2%) were submitted only once and were approved without comments, while the remaining 59/198 (29.8%) were submitted twice for technical review (mode of 1, mean of 1.32). The protocols were sent to the reviewers within the same day of receipt 100% of the time. The time from receipt of submission to receipt of reviewer was within the same day and the time from receipt of reviewer to first decision (mean, standard deviation working days) was 10.52, 8.54 days, range 0-51 days. Around one-fourth (21.51%) of the protocols were returned to the secretariat beyond the 14-working day deadline. The time from second review of technical reviewer to return to secretariat was a mean, SD of 6.72, 6.45 days, with a range of 1 day to 36 days, and time from initial receipt to final decision was a mean of 16.16 days, SD 18.3 days, range 0-111 days. The most common reason for the delay was the failure of the author to resubmit the paper for the second review in 17/23 (74%), while the other reason was the long duration of the initial review by the reviewer in 6/23 (26%). Half of the protocols (49.5%) were returned without comments. Majority of the comments were on the methodology.

The technical review process is generally efficient with each step within the acceptable timelines. However, for 12% of the protocols, the over-all review process was still prolonged (>28 working days) because of the failure of the author to submit the paper for the second review in 74% of cases, and the long duration of the initial review in 26% of papers.