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, re-establishing the BA/BE Unit as a bioequivalence testing center is feasible.

Characteristics and Prevalence of Metabolic Syndrome Among Adult Filipinos with Hypothyroidism: A Cross-sectional Study.

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.

Prevailing Food Intake, Physical Activity and Health Beliefs in a Rural Agricultural Community in the Philippines: Factors to Consider Prior to a Diabetes Prevention Program.

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.

Critical Illness-Related Corticosteroid Insufficiency (CIRCI) Among Patients with COVID-19 at a Tertiary Hospital: Clinical Characteristics and Outcomes.

Objectives: Among critically ill patients, there is usually impairment of the hypothalamic-pituitary-adrenal axis, leading to a condition known as critical illness-related corticosteroid insufficiency (CIRCI). This investigation aims to determine the incidence of and characterize CIRCI among patients with COVID-19 as well as to analyze the outcomes of these critically ill patients. Methodology: This is a single-center, retrospective cohort study that investigated the occurrence of CIRCI among critically ill patients infected with COVID-19. Results: In this cohort, there were 145 COVID-19-positive patients with refractory shock, which reflects that 22.94% of the COVID-19 admissions have probable CIRCI.Patients who were given corticosteroids were found to have statistically significant longer median days on a ventilator (p=0.001). However, those on the corticosteroid arm were at higher risk of morbidity and mortality and a greater proportion had organ dysfunction. Multivariable logistic regression analysis revealed that SOFA score was a significant predictor of mortality in CIRCI (p=0.013). Conclusion: CIRCI has a unique presentation among patients with COVID-19 because of the presence of a high level of inflammation in this life-threatening infection. It is possibly a harbinger of a markedly increased risk of mortality in these patients.

The Development of a Protocol for Critical Illness-Related Corticosteroid Insufficiency (CIRCI) at a Tertiary Hospital.

Objectives: The diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) remains a challenge. This initiative aimed to develop a protocol for the diagnosis and management of CIRCI which will facilitate informed decision-making among clinicians through consensus-building among a multi-disciplinary team. Methodology: This was a single-center, qualitative study which utilized the modified Delphi method, consisting of a sequential iterative process with two rounds of voting. A cut-off value of 70% was set as the threshold for reaching consensus. Results: The protocol on the diagnosis and management of CIRCI was approved after two rounds of voting, with all the components reaching 83.3%-100% agreement. This protocol on CIRCI provided a framework for the clinical approach to refractory shock. It was advocated that all cases of probable CIRCI should immediately be started on hydrocortisone at 200 mg/day. The definitive diagnosis of CIRCI is established through a random serum cortisol <10 mcg/dL or increase in cortisol of <9 mcg/dL at 60 minutes after a 250 mcg ACTH stimulation test in patients with indeterminate random cortisol levels. Conclusion: The presence of refractory shock unresponsive to fluid resuscitation and vasopressors should warrant the clinical suspicion for the existence of CIRCI and should trigger a cascade of management strategies.

Weekly Versus Daily Levothyroxine Tablet Replacement in Adults with Hypothyroidism: A Meta-Analysis.

OBJECTIVES: Daily levothyroxine is the treatment of choice and standard of care in hypothyroidism, sufficient to restore thyroid stimulating hormone (TSH) to normal range. For many patients, daily lifelong therapy is required, making adherence a major issue. In such cases, weekly replacement may be a suitable alternative to improve adherence. In this study, we aimed to determine the efficacy and safety of weekly levothyroxine replacement among adults with hypothyroidism. METHODOLOGY: Electronic databases were searched. Two reviewers (HCC and RBL) independently screened the abstracts, reviewed full-text papers, critically appraised the quality of included studies using PRISMA guidelines. Meta-analysis was performed using the random-effects model. The primary outcome is the difference in serum TSH levels between weekly and daily administration, while secondary outcomes included adverse events and symptoms of hypothyroidism. RESULTS: The primary outcome is the difference in serum TSH levels between weekly and daily administration. Secondary outcomes included adverse events and clinical symptoms. The study included two randomized trials (n=109) in the primary analysis. The difference in TSH levels was 1.78 mIU/mL higher [(95% confidence interval (CI): 1.28 to 2.28, p<0.00001] at 6 weeks and 1.22 mIU/mL higher (95% CI: 0.76 to 1.67, p<0.00001) at 12 weeks for the weekly regimen. There was no significant heterogeneity between the two groups. There was no significant difference in hypothyroid symptoms and adverse events before and after levothyroxine treatment within each group. CONCLUSIONS: Weekly levothyroxine resulted in less suppression and higher mean serum TSH levels, while still remaining within the normal reference range. It may be a suitable alternative for non-adherent patients. However, larger randomized trials with longer duration of follow-up are needed to firmly establish its role.

Direct medical costs of type 2 diabetes mellitus in the Philippines: findings from two hospital databases and physician surveys.

OBJECTIVE: To estimate the annual direct medical cost of type 2 diabetes mellitus (T2DM) in hospitals and outpatient care clinics from a healthcare payer perspective in the Philippines. DESIGN AND PARTICIPANTS: (1) A review of electronic hospital records of people with T2DM in two tertiary hospitals-Ospital ng Makati (OsMak) and National Kidney and Transplant Institute (NKTI) and (2) a cross-sectional survey with 50 physicians providing outpatient care for people with T2DM. SETTING: Primary, secondary and tertiary healthcare facilities in Metro Manila. OUTCOME MEASURES: Cost of managing T2DM and its related complications in US dollars (USD) in 2016. RESULTS: A total of 1023 and 1378 people were identified in OsMak and NKTI, with a complication rate of 66% and 74%, respectively. In both institutions, the average annual cost per person was higher if individuals were diagnosed with any complication (NKTI: US$3226 vs US$2242 and OsMak: US$621 vs US$127). Poor diabetes control was estimated to incur higher per person cost than good control in both public outpatient care (poor control, range: US$727 to US$2463 vs good control, range: US$614 to US$1520) and private outpatient care (poor control, range: US$848 to US$2507 vs good control, range: US$807 to US$1603). CONCLUSION: The results highlight the high direct medical cost resulting from poor diabetes control and the opportunity for cost reduction by improving control and preventing its complications.

A systematic review and meta-analysis on the efficacy and safety of metformin as adjunctive therapy among women with metastatic breast cancer.

BACKGROUND: Breast cancer is the most common cancer among women worldwide and is one of the leading causes of cancer-related mortalities. Metformin has been found to have direct and indirect antitumor mechanisms, and because of its availability and good safety profile, it has been investigated to be useful in various malignancies including breast cancer. OBJECTIVE: This study aims to determine the efficacy and safety of metformin administration as adjunctive therapy on mortality among females with breast cancer. METHODS: This is a systematic review and meta-analysis of randomized clinical trials (RCTs) on the use of metformin as adjunctive therapy when combined with standard chemotherapy on the outcomes of progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and clinical benefit rate (CBR). RESULTS: After a comprehensive literature search, only three phase 2 RCTs on the use of metformin as adjunctive therapy for locally advanced and metastatic breast cancer were included. Clinical trials on early breast cancer are still ongoing and none were included in the present review. This study, based on the systematic review, revealed that metformin added to standard chemotherapy does not improve the PFS and OS among women with metastatic breast cancer, and likewise, has no impact on the ORR with a relative risk of 1.42 95% CI 0.45-4.55 and CBR with an RR of 0.87, 95% CI 0.55-1.37. It appears to be safe and may even be protective for the development of neutropenia based on at least one study. CONCLUSION: This study clarifies that there is insufficient evidence on the benefits of metformin on survival among women with metastatic breast cancer.

Executive summary of the 2020 clinical practice guidelines for the management of hypertension in the Philippines.

Hypertension is the most common cause of death and disability worldwide with its prevalence rising in low to middle income countries. It remains to be an important cause of morbidity and mortality in the Philippines with poor BP control as one of the main causes. Different societies and groups worked and collaborated together to develop the 2020 Philippine Clinical Practice Guidelines of hypertension arising for the need to come up with a comprehensive local practice guideline for the diagnosis, treatment, and follow up of persons with hypertension. A technical working group was organized into six clusters that analyzed the 30 clinical questions commonly asked in practice, looking into the definition of hypertension, treatment thresholds, blood pressure targets, and appropriate medications to reach targets. This guideline also includes recommendations for the specific management of hypertension among individuals with uncomplicated hypertension, hypertension among those with diabetes, stroke, chronic kidney disease, as well as hypertension among pregnant women and pediatric populations. It also looked into the appropriate screening and monitoring of patients when managing hypertension, and identification of groups who are at high risk for cardiovascular (CV) events. The ADAPTE process was used in developing the statements and recommendations which were then presented to a panel of experts for discussion and approval to come up with the final statements. This guideline aims to aid Filipino healthcare professionals to provide evidence-based care for persons with hypertension and help those with hypertension adequately control their blood pressure and reduce their CV risk.

Executive Summary of the 2020 Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines.

Dyslipidemia is a cardiovascular risk factor that is increasing in prevalence in the country. The need to treat and manage elevated cholesterol levels, both pharmacologic and non-pharmacologic, is of utmost importance. Different medical societies and groups bonded together to formulate the 2020 Philippine Clinical Practice Guidelines for dyslipidemia. The group raised nine clinical questions that are important in dyslipidemia management. A technical working group analyzed the clinical questions dealing with non-pharmacologic management, primary prevention for both non-diabetic and individuals with diabetes, familial hypercholesterolemia, secondary prevention, adverse events of statins and the use of other lipid parameters as measurement of risk for cardiovascular disease. Randomized controlled trials and meta-analyses were included in the GRADE-PRO analysis to come up with the statements answering the clinical questions. The statements were presented to a panel consisting of government agencies, members of the different medical societies, and private institutions, and the statements were voted upon to come up with the final statements of the 2020 practice guidelines. The 2020 CPG is aimed for the Filipino physician to confidently care for the individual with dyslipidemia and eventually lower his risk for cardiovascular disease.

Cardiometabolic Risk Factors leading to Diabetes Mellitus among the Young (YOD) from the 8th Philippine National Nutrition Survey.

OBJECTIVES: This study looked into the prevalence of diabetes mellitus (DM) and risks for cardiovascular and metabolic diseases among young adults with diabetes (age 20-44 years old, YOD) and late-onset DM (≥45 years old, LOD) in Filipinos. METHODOLOGY: Weighted data from 546,580 adults with DM from the 8th Philippine National Nutrition and Health Survey (NNHeS) were utilized. Differences in sociodemographic, anthropometric, clinical profiles and metabolic risks were compared between YOD and LOD. RESULTS: The aggregated prevalence of DM is 5.43% (95%CI, 5.10-5.79), YOD were 2.64% (95% CI, 2.32-3.00) and LOD 9.85% (95%CI, 9.18-10.56). Mean age of YOD was 37,6 years, LOD 59,9 years. The YOD were mostly males (56%), with higher BMI (26.24 kg/m2 vs 25 kg/m2, p=0.002), lower mean SBP (122.41±19.17 mmHg vs 135.45±22.47 mmHg, p<0.001), more daily smokers (23% vs 14%), and alcoholic beverage drinkers (39% vs 31%). Physical activity was similar between groups (44% vs 51%, p=0.078). However, average total caloric intake (1776.78±758.38 kcal vs 1596.88±639.16 kcal, p=0.023) and carbohydrate intake (306.13±142.16 grams vs 270.53±104.74 g, p=0.014) were higher in YOD. Dietary carbohydrate proportions were higher than recommended (69% vs 68%) for both groups. Young Filipinos had higher risk to develop diabetes when they are obese II (22% vs 12%), current drinker (56% vs 37%), and current smoker (28% vs 18%). Eighty percent of YOD and LOD had metabolic syndrome (MetS). With every unit increase in age and fat intake, the odds of having MetS were raised by 5.4% (95%CI 1%-10%, p=0.029) and 1.6% (95%CI 0.04%-3%, p=0.044), respectively. CONCLUSION: Early-onset diabetes mellitus appears to be driven by obesity, MetS and social behaviors. Modifiable risk factors can be improved early to decrease hazards to develop cardiometabolic complications.

An Exploration of Knowledge and Themes on Diabetes during Outpatient Consultation in a Tertiary Referral Hospital.

OBJECTIVES: Effective communication has been correlated with improved outcomes in diabetes mellitus. Patient comprehension bears an effect on understanding, improving healthcare access and utilization, interaction with healthcare providers, caring for one's own health, and shared decision making. Currently, there is a gamut of information on diabetes-related terms from various sources. However, no material has yet been available for clinical use in the third world setting. Hence, we explored the most common themes discussed during an outpatient diabetes consult in our hospital. METHODOLOGY: Consultation audio recordings (N = 96) and focus group discussions (N = 32) were conducted among adults with diabetes. Transcribed results underwent qualitative content and thematic analyses to develop the conceptual framework. RESULTS: The study generated the following themes: diabetes mellitus diagnosis, lifestyle modification, treatment targets, hypoglycemia precautions, diabetes complications, and medication safety. There was a good understanding of these themes among patients with a higher educational attainment, however, among those with lower educational attainment, the attitude of patients toward diabetes care is paternalistic. CONCLUSION: The themes discussed in outpatient diabetes consult reflects the dimensions of diabetes care mainly influenced by socio-cultural factors, patient-doctor relationships and adaptability to limitations of resources. The results will be used to develop and validate a culturally appropriate diabetes health literacy tool.

Metformin extended-release versus metformin immediate-release for adults with type 2 diabetes mellitus: A systematic review and meta-analysis of randomized controlled trials.

AIM: To compare the efficacy and tolerability of metformin extended-release (MXR) and the conventional metformin immediate-release (MIR) formulations in adults with type 2 diabetes mellitus (T2DM) METHODS: PubMed, the Cochrane Library, ClinicalTrials.gov and other sources were searched until 19 March 2021 for randomized controlled trials (RCTs) that compared equal daily doses of MXR and MIR in adults with T2DM. Random-effects model meta-analysis was performed to obtain pooled mean difference (MD) of change from baseline for continuous outcomes and risk ratio (RR) for dichotomous outcomes. Primary outcomes considered were HbA1c and key gastrointestinal (GI) symptoms (abdominal discomfort or pain, diarrhea, dyspepsia, and nausea & vomiting). RESULTS: Nine RCTs that randomized a total of 2609 adults revealed that MIR was statistically associated with better HbA1c lowering (MD 0.09% [95% confidence interval or CI, 0.01%, 0.17%]), MXR only reduced dyspepsia (RR 0.58 [95% CI, 0.34, 0.98]), and both formulations were associated with similar cumulative incidence of other key GI symptoms. CONCLUSIONS: MXR was associated with statistically worse but likely clinically similar HbA1c lowering and minimal improvement of GI intolerance compared to MIR. Protocol Registration: PROSPERO (CRD42019148008).

Individualizing Time-in-Range Goals in Management of Diabetes Mellitus and Role of Insulin: Clinical Insights From a Multinational Panel.

Diabetes mellitus is a global health concern associated with significant morbidity and mortality. Inadequate control of diabetes leads to chronic complications and higher mortality rates, which emphasizes the importance of achieving glycemic targets. Although glycated hemoglobin (HbA1c) is the gold standard for measuring glycemic control, it has several limitations. Therefore, in recent years, along with the emergence of continuous glucose monitoring (CGM) technology, glycemic control modalities have moved beyond HbA1c. They encompass modern glucometrics, such as glycemic variability (GV) and time-in-range (TIR). The key advantage of these newer metrics over HbA1c is that they allow personalized diabetes management with person-centric glycemic control. Basal insulin analogues, especially second-generation basal insulins with properties such as longer duration of action and low risk of hypoglycemia, have demonstrated clinical benefits by reducing GV and improving TIR. Therefore, for more effective and accurate diabetes management, the development of an integrated approach with second-generation basal insulin and glucometrics involving GV and TIR is the need of the hour. With this objective, a multinational group of endocrinologists and diabetologists reviewed the existing recommendations on TIR, provided their clinical insights into the individualization of TIR targets, and elucidated on the role of the second-generation basal insulin analogues in addressing TIR.

Association of sunlight exposure with 25-hydroxyvitamin D levels among working urban adult Filipinos.

OBJECTIVES: To determine the association of different levels of sunlight exposure, measured using the Filipino sunlight exposure questionnaire (SEQ) with 25-hydroxyvitamin D (25-OHD) levels among working urban adult Filipinos. METHODS: Seventy-five adult participants, living and working in Metro Manila, for at least 1 year, were grouped according to their perceived sunlight exposure pattern: low sunlight exposure (mostly indoor work); moderate sunlight exposure (both indoor and outdoor work); and high sunlight exposure (mostly outdoor work). After completion of the self-administered Filipino SEQ, they underwent serum 25-OHD level determination. Strength of correlation between the SEQ scores and 25-OHD levels was computed. RESULTS: Serum 25-OHD levels generally increased with increasing sunlight exposure levels. The overall Pearson's correlation between the SEQ scores and 25-OHD levels of the participants was 0.396 (P = 0.001). The correlation for the individual domains was 0.342 for intensity of sunlight exposure (P = 0.003), 0.321 for factors affecting sunlight exposure (P = 0.005), and 0.256 for sun protection practices (P = 0.027). CONCLUSIONS: The sunlight exposure of working urban adult Filipinos, as measured by the Filipino SEQ, has an overall significant, direct and moderate association with serum 25-OHD levels. This Filipino SEQ can serve as a valuable clinical tool for sunlight exposure assessment to identify individuals at risk for vitamin D deficiency.

COVID-19 in cancer patients can be challenging to screen in a resource limited setting.

During this COVID-19 pandemic, patients with symptoms such as fever, cough, sore throat, and coryza were advised to have RT-PCR testing for SARS-CoV-2 infection. We described here an elderly female with chronic lymphocytic leukemia, who presented with atypical symptoms that were not directly attributable to COVID-19. This patient was admitted to the non-COVID-19 ward for supportive care. Later, her chest x-ray revealed pneumonia that was confirmed to be COVID-19 by RT-PCR testing several days later. In resource-poor settings where molecular testing results suffered from delays or were altogether unavailable, the use of diagnostic imaging such as a chest x-ray could serve as a quick guide in the assessment and management of these patients especially if the imaging results suggest COVID-19 infection.

Estimating direct medical costs of type 2 diabetes mellitus in the Philippines: a protocol.

INTRODUCTION: Diabetes and its complications are a major cause of morbidity and mortality in the Philippines. The prevalence of diabetes in the Philippines has increased from 3.4 million in 2010 to 3.7 million in 2017. The government has formulated strategies to control this increase, for example, through its non-communicable disease prevention and control plan. However, there is scarce research on the financial burden of diabetes. Filling this gap may further help policymakers to make informed decisions while developing and implementing resource planning for relevant interventions. The primary objective of the current study is to estimate the direct medical costs associated with type 2 diabetes mellitus (T2DM). METHODS AND ANALYSIS: This is a 1-year retrospective cohort study of patients with T2DM in 2016. Data will be collected from: (1) hospital databases from public institutions to estimate the cost of diabetes treatment and (2) physician interviews to estimate the cost of management of diabetes in outpatient care. We will perform descriptive and comparative analyses on direct medical costs and healthcare resource utilisation, stratified by the presence of diabetes-associated complications. ETHICS AND DISSEMINATION: Research ethics board approval has been obtained from the Department of Health Single Joint Research Ethics Board and Cardinal Santos Medical Center Research Ethics Review Committee. Findings from the study will be reported in peer-reviewed scientific journals and local researcher meetings.