OBJECTIVE

Phenobarbital is an inductor of microsomal hepatic enzyme and used as choleretic for cholestatic liver disease to enhance bile flow. It is also used as a premedication for hepatobiliary scintigraphy (HIDA) scan to improve diagnostic accuracy for an obstructive liver disease. We reviewed the available literature on the use of Phenobarbital for treatment of cholestasis and its utility as a premedication for HIDA scan.

All published studies before June 30, 2023 that investigated the efficacy, effectiveness or safety of Phenobarbital in cholestatic jaundice and its effect on the accuracy of hepatobiliary scintigraphy in diagnosis of obstructive jaundice were included. Electronic databases were searched including MEDLINE via PubMed, Cochrane Library, medRxIV, BioRxIV, as well as the following registries for ongoing and completed trials: ClinicalTrials.gov (USA); ChiCTR.org. (China); and the WHO International Clinical Trials Registry Platform. We screened abstracts, reviewed full texts, and extracted relevant information on study design, settings, population and outcomes. There was no age and language restriction. Two reviewers independently rated the quality of included studies using: Joanna Briggs Institute critical appraisal tool for case reports, case series, and diagnostic accuracy; Newcastle – Ottawa Quality Assessment Scale for cohort studies, and Cochrane Risk of Bias for Randomized Trials. Risk of bias was appraised and GRADE certainty of evidence was judged. Pooled analysis was done using Stata 14 and reported as sensitivity and specificity.

Included were nine reports on Phenobarbital as treatment for cholestasis (one case report, five case series, one cohort and two randomized studies) and seven studies (four diagnostics, two cohorts, one randomized trial) on its use as a premedication for HIDA scan. The quality of case report and case series were considered fair; cohort studies as good; and diagnostic studies were included based on overall assessment. The randomized studies had some or high risk for bias due to concerns in randomization process, measurement of outcome, and risk in the selection of reported results.

There were 31 patients (16 adults and 15 children) from case reports and case series. Of the 16 adults, serum total bilirubin concentrations declined from 4 to 70% from baseline in 13 of 15 (87%) patients after Phenobarbital was given at 120 to 250 mg per day from 22 days to f ive months. Eleven of 14 with pruritus at onset also had improvement in intensity of itching. Of the 15 pediatric patients, ten (67%) showed a decrease from 10 to 60% of the baseline total bilirubin but not a normalization with Phenobarbital intake at a dose of 3 to 12 mg/kg/day from one to 21 months. Five of 14 children also had relief of itching after treatment.

Phenobarbital compared to Ursodeoxycholic acid had limited efficacy in reducing the bilirubin levels in neonates and young infants with cholestasis.

Phenobarbital compared to Ursodeoxycholic acid had limited efficacy in reducing the bilirubin levels in neonates and young infants with cholestasis.

Moderate certainty evidence showed that with Phenobarbital pretreatment, the hepatobiliary scan done on patients with neonatal cholestasis had 100% (CI 99.2, 100; I2 = 0.0%) sensitivity and 80.2% (CI 65.4, 92.1; I2 = 76.6%) specificity while no Phenobarbital pretreatment had 100% (94.9, 100; I2 = 0.0%) sensitivity and 89.5% (CI 77.0, 98.1; I2 = 11.4%) specificity. Adverse effects of Phenobarbital were drowsiness, lethargy, poor feeding, and irritability.

There was limited effectiveness of Phenobarbital in decreasing bilirubin levels in cholestatic liver disease. Moderate certainty evidence demonstrated that premedication with Phenobarbital did not improve the specificity of HIDA scan in the diagnosis of obstructive jaundice of infancy. Neurologic symptoms were observed with Phenobarbital intake.

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.

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: Virgin coconut oil (VCO) has anti-viral and anti-inflammatory properties, making it a potential therapeutic candidate against COVID-19 infection. Objective: To determine the efficacy and safety of VCO as adjunctive therapy for hospitalized patients with COVID-19. Methods: We conducted a randomized, open-label controlled trial involving laboratory-confirmed COVID-19 patients admitted at the Philippine General Hospital. The study participants were randomized to the intervention group who received virgin coconut oil with local standard of care, or to the control group who received local standard of care alone. Results: We enrolled 39 participants into the VCO group and 38 participants into the control group. Significantly fewer participants in the VCO group had abnormal CRP levels at the end of treatment compared to control. (relative risk [RR] 0.75, 95% confidence interval [CI] 0.58 to 0.95; p=0.02) No significant difference was found in the duration of hospital stay (mean 9.33 days for VCO vs. 10.29 days for control; p=0.45) and time to symptom resolution (mean 6.8 days for VCO, vs. 6.74 days for control; p=0.91). Although the proportion of patients who developed the secondary outcomes of mortality, need for ICU admission, need for invasive ventilation, and negative viral conversion was lower in the VCO group, results did not reach statistical significance. The VCO group had larger reduction in the inflammatory markers ferritin, lactate dehydrogenase, TNF-alpha, IP-10 and IL-6, but results did not reach statistical significance. Adverse events were significantly higher in the VCO group (RR 4.87, 95% CI 1.14 to 20.79; p=0.03). Conclusion This clinical trial on hospitalized patients showed significant benefit in CRP levels of participants given VCO compared to control. There was no significant benefit in the use of VCO as adjunctive therapy in reducing duration of hospital stay. Larger studies are needed to conclusively demonstrate the effect of VCO on other clinical outcomes and inflammatory markers.
COVID-19 ; Clinical Trial

BACKGROUND

Remdesivir is an intravenously administered antiviral drug that inhibits RNA-dependent RNA polymerase. In vitro studies have shown that remdesivir can inhibit the growth of the COVID-19 virus in infected Vero cells and can inhibit infection in human cell lines.

To determine the efficacy and safety of remdesivir in treating patients with COVID-19 infection.

A systematic search of electronic medical literature databases was done from inception until September 4, 2022. Search for ongoing studies and preprints was also done. Risk of bias assessment was done using Cochrane risk of bias tool version 2.0. Measures of effect used were relative risk (RR) and 95% confidence interval (CI). Subgroup analysis by disease severity was preplanned. The estimates for efficacy and safety of remdesivir was calculated using Review Manager 5.4 software.

Nine randomized controlled trials with 13,085 participants were identified. Eight of the included studies recruited confirmed COVID-19 patients needing hospitalization, while one study limited recruitment to nonhospitalized patients. Remdesivir showed significant benefit for outpatients with mild to moderate disease with at least one risk factor for disease progression in terms of COVID 19-related hospitalization (RR 0.13 95% CI 0.03 to 0.59), all-cause hospitalization (RR 0.28, 95% CI 0.10 to 0.75), and need for medically-attended visits (RR 0.19, 95% CI 0.07 to 0.56). For hospitalized patients, remdesivir had a slight benefit in reducing all-cause mortality at day 28 (RR 0.90, 95% CI 0.83 to 0.98). Subgroup analysis by disease severity showed a trend towards reduction in mortality among those with severe disease (RR 0.61, 95% CI 0.35 to 1.07), with no effect on those with critical disease (RR 0.96, 95% CI 0.87 to 1.04), and inconclusive effect for those with mild-moderate disease (RR 0.74, 95% CI 0.49 to 1.11). Remdesivir showed benefit in decreasing clinical deterioration (RR 0.75, 95% CI 0.61 to 0.89), improving recovery rate (RR 1.07, 95% CI 1.01 to 1.13), and reducing the need for mechanical ventilation (RR 0.68, 95% CI 0.51 to 0.90). There was inconclusive effect on the need for ICU admission (RR 0.98, 95% CI 0.43 to 2.22). No increased risk of adverse events (RR 0.98, 95% CI 0.91 to 1.06), including serious adverse events (RR 0.77, 95% CI 0.57 to 1.03), was seen.

Based on the available evidence, remdesivir shows benefit in the treatment for patients with mild, moderate, and severe COVID-19 infection. However, there was no benefit in mortality noted among those with critical disease requiring mechanical ventilation. Remdesivir demonstrated a good safety profile, with no increased risk of adverse events compared to control. These results are consistent with the international agencies’ recommendations for the use of remdesivir among patients with mild, moderate or severe COVID-19 infection, but not for those with critical infection.

Current evidence supports the use of remdesivir as treatment for selected patients with COVID-19.

BACKGROUND AND OBJECTIVES

The Department of Clinical Epidemiology (DCE) of the University of the Philippines Manila is the only higher education institution in the Philippines offering graduate studies in clinical epidemiology. The Master of Science Epidemiology (Clinical Epidemiology) was first offered in 1992, while the Diploma in Epidemiology (Clinical Epidemiology) was offered in 1998. While the courses of the programs are continuously updated based on students’ feedback and advances on topics covered, the point of view of the students and alumni on the program as a whole has not been done. This study aimed to determine 1) self-reported current positions and affiliations, work areas where clinical epidemiology (CE) training is useful, and skills gained from CE training; 2) research studies completed and deemed by respondents to have considerable impact; and 3) strengths, weaknesses, and areas of improvement of the DCE graduate programs.

This is an online survey of students and alumni of the DCE graduate programs. We sent email invites to all 287 students and alumni. We collected data on their profession, institutional affiliations, positions, skills gained from their training, areas of clinical epidemiology applications, important research involvement, reasons for recommending or not recommending the programs, and how the graduate programs can be improved. Responses were summarized by frequencies and percentages. An analyst performed qualitative content analysis (QCA) to generate strengths and weaknesses of the program. We validated the results of the QCA through 1) presentation to the research team, 2) sending the survey report to study participants and other students and alumni for feedback, and 3) presentation to the DCE faculty and staff.

We received 159 responses (55.4% of the total study population)—145 (91.2%) were from the MSc program and 11 (6.9%) were from the Diploma program. Majority of the respondents were physicians (93.7%), had hospital affiliations (81.8%), and were affiliated with the academe (61%). Majority of the respondents used clinical epidemiology in their research endeavors (87.4%), clinical practice (85.5%), and teaching (78%). Majority (93.1%) would recommend the program they have taken. Eleven (6.9%) respondents were hesitant due to the possible mismatch with the students’ career path, challenging thesis work, and potential conflicting personal responsibilities. Several strengths of the programs were identified, including excellent and well-implemented programs, supportive faculty and staff, and relevant course work. While completing the course work had not been a problem in general, the main challenge encountered by students is the completion of their thesis, leading to a low graduation rate in the Master of Science program. Suggestions to improve the Master of Science and Diploma programs include 1) Improvement in program implementation, including thesis policies and support, smoother transition from Diploma to MSc Program and vice-versa, and implementation of a blended learning platform; 2) Curricular improvements such as wider choices for electives and tracking towards specialty areas; 3) Innovations in conduct of courses; and 4) Personnel and infrastructure development.

This survey reiterated the importance of clinical epidemiology graduate programs in research capacity building of health care professionals. Students and alumni occupied diverse positions in academic, research, clinical, and pharmaceutical setting, and majority accomplished research studies with considerable impact. A major challenge leading to a low graduation rate in the Master of Science program is the completion of thesis work. The survey identified several initiatives towards continuous quality improvement of clinical epidemiology programs, including improvement of thesis policies and support, updating the curriculum content and materials, increasing allotment of hours for hands-on activities, exploring possibilities of offering electives in partnership with other institutions, offering a blended learning platform, maintaining an efficient administrative support for students, and continuing education for alumni. Strong institutional support for personnel and infrastructure development is essential for these initiatives to succeed.

BACKGROUND AND OBJECTIVE

Inequity in access to healthcare continues to be a problem in the Philippines. This was further aggravated by the COVID-19 pandemic. Telemedicine is considered a potential strategy to address inequitable access to healthcare; however, it only gained popularity during the pandemic. This study aims to determine the pediatric conditions diagnosed through telemedicine consults and the platforms utilized by patients in the Philippine Primary Care Studies pilot sites during the pandemic.

This is a cross-sectional study of pediatric patients below 19 years of age who sought consult using telemedicine. Using the electronic medical records (EMR) system adapted by the Philippine Primary Care Studies in UP Health Service (UPHS) Quezon City, Metro Manila (urban site), Samal, Bataan (rural site), and Bulusan, Sorsogon (remote site), pediatric conditions diagnosed through telemedicine consults and the platforms utilized by patients from September 2021 to August 2022 were extracted and summarized. Data was summarized using descriptive statistics.

A total of 5,388 consults involving pediatric patients were recorded from September 2021 to August 2022, of which 1,562 (29.0%) were done through telemedicine. Majority of the telemedicine consults (67.5%, n=1,055) were in the rural site. There were 274 telemedicine consults (17.6%) in the remote site, and 233 (14.9%) in the urban site. The most common diagnosis was acute upper respiratory tract infection (30.8%). Other common conditions diagnosed through telemedicine were lower respiratory tract infections, skin infections, urinary tract infections, obesity, anxiety disorders, allergic rhinitis, conditions related to pregnancy, and myalgia. The most common platforms used by patients are video calls (20.2%, n=315) and voice calls (18.4%, n=287) across all three sites. However, the most common platform differed per area—video calls for the urban site (85.8%), live chat for the rural site (76.1%), and voice calls for the remote site (60.6%).

The most common condition diagnosed among pediatric patients consulting through telemedicine is upper respiratory tract infection. The most common platforms used to seek consult through telemedicine are live chat, video calls, and voice calls, with differences noted per site.

BACKGROUND

Primary care for pediatric patients focuses on providing comprehensive, accessible, and coordinated healthcare from the neonatal period to adolescence. The implementation and use of electronic medical records (EMR) in pediatric primary care facilities is an efficient strategy to gather necessary information on the epidemiology of common pediatric diseases in the Philippines.

This study aimed to determine the frequency distribution of pediatric diseases in a rural primary healthcare facility in the Philippines.

This cross-sectional study reviewed the EMR of all pediatric patients who consulted in a primary care facility in Samal, Bataan from April 2019 to March 2021. Data gathered include sex, age in years, chief complaint, diagnosis, and month of consultation. Data was summarized using descriptive statistics.

A total of 14,462 pediatric consults were recorded from April 2019 to March 2021. There were slightly more male patients (52.1%). The mean age of the patients was 6.5 years (standard deviation 5.22). The highest number of consults came from the 1- to 4-year-old age group (41.5%). The most common chief complaints were cough (45.9%), fever (25.5%), and colds (24.9%). The most frequent diagnoses were upper respiratory tract infections (47.4%), followed by lower respiratory tract infections (6.9%), and skin and soft tissue infections (5.3%). Majority of the consults for respiratory tract infections, skin and soft tissue infections, gastroenteritis, asthma, and dermatitis were in the 1- to 4-year-old age group. Urinary tract infections and otitis media or externa were recorded more frequently in the 5- to 9-year-old age group.

Respiratory tract infections, followed by skin and soft tissue infections, were the most frequently identified diseases in children consulting a primary care facility at a rural site in the Philippines. The most common chief complaints, defined as the primary reason for seeking consult, were cough, fever, and colds. Data was gathered through EMR review, which may aid in the planning of programs and policies to improve primary care service delivery.

BACKGROUND

The Philippine Primary Care Studies (PPCS) is a network of pilot studies that developed, implemented, and tested strategies to strengthen primary care in the country. These pilot studies were implemented in an urban, rural, and remote setting. The aim is to use the findings to guide the policies of the national health insurance program (PhilHealth), the main payor for individualized healthcare services in the country.

The objective of this report is to compare baseline outpatient benefit utilization, hospitalization, and health spending, including out-of-pocket (OOP) expenses, in three health settings (urban, rural, and remote). These findings were used to contextualize strategies to strengthen primary care in these three settings.

Cross-sectional surveys were carried out using an interviewer-assisted questionnaire on a random sample of families in the urban site, and a stratified random sample of households in the rural and remote sites. The questionnaire asked for out-patient and hospitalization utilization and spending, including the OOP expenses.

A total of 787 families/households were sampled across the three sites. For outpatient benefits, utilization was low in all sites. The remote site had the lowest utilization at only 15%. Unexpectedly, the average annual OOP expenses for outpatient consults in the remote site was PhP 571.92/per capita. This is 40% higher than expenses shouldered by families in the rural area, but similar with the urban site. For hospital benefits, utilization was lowest in the remote site (55.7%) compared to 75.0% and 78.1% for the urban and rural sites, respectively. OOP expenses per year were highest in the remote site at PhP 2204.44 per capita, probably because of delay in access to healthcare and consequently more severe conditions. Surprisingly, annual expenses per year for families in the rural sites (PhP 672.03 per capita) were less than half of what families in the urban sites spent (PhP 1783.38 per capita).

Compared to families in the urban site and households in the rural sites, households in remote areas have higher disease rates and consequently, increased need for outpatient and inpatient health services. When they do get sick, access to care is more difficult. This leads to lower rates of benefit utilization and higher out-of-pocket expenses. Thus, provision of “equal” benefits can inadvertently lead to “inequitable” healthcare, pushing disadvantaged populations into a greater disadvantage. These results imply that health benefits need to be allocated according to need. Families in poorer and more remote areas may require greater subsidies.

Objective: Phenobarbital is an inductor of microsomal hepatic enzyme and used as choleretic for cholestatic liver disease to enhance bile flow. It is also used as a premedication for hepatobiliary scintigraphy (HIDA) scan to improve diagnostic accuracy for an obstructive liver disease. We reviewed the available literature on the use of Phenobarbital for treatment of cholestasis and its utility as a premedication for HIDA scan. Methods: All published studies before June 30, 2023 that investigated the efficacy, effectiveness or safety of Phenobarbital in cholestatic jaundice and its effect on the accuracy of hepatobiliary scintigraphy in diagnosis of obstructive jaundice were included. Electronic databases were searched including MEDLINE via PubMed, Cochrane Library, medRxIV, BioRxIV, as well as the following registries for ongoing and completed trials: ClinicalTrials.gov (USA); ChiCTR.org. (China); and the WHO International Clinical Trials Registry Platform. We screened abstracts, reviewed full texts, and extracted relevant information on study design, settings, population and outcomes. There was no age and language restriction. Two reviewers independently rated the quality of included studies using: Joanna Briggs Institute critical appraisal tool for case reports, case series, and diagnostic accuracy; Newcastle – Ottawa Quality Assessment Scale for cohort studies, and Cochrane Risk of Bias for Randomized Trials. Risk of bias was appraised and GRADE certainty of evidence was judged. Pooled analysis was done using Stata 14 and reported as sensitivity and specificity. Results: Included were nine reports on Phenobarbital as treatment for cholestasis (one case report, five case series, one cohort and two randomized studies) and seven studies (four diagnostics, two cohorts, one randomized trial) on its use as a premedication for HIDA scan. The quality of case report and case series were considered fair; cohort studies as good; and diagnostic studies were included based on overall assessment. The randomized studies had some or high risk for bias due to concerns in randomization process, measurement of outcome, and risk in the selection of reported results. There were 31 patients (16 adults and 15 children) from case reports and case series. Of the 16 adults, serum total bilirubin concentrations declined from 4 to 70% from baseline in 13 of 15 (87%) patients after Phenobarbital was given at 120 to 250 mg per day from 22 days to f ive months. Eleven of 14 with pruritus at onset also had improvement in intensity of itching. Of the 15 pediatric patients, ten (67%) showed a decrease from 10 to 60% of the baseline total bilirubin but not a normalization with Phenobarbital intake at a dose of 3 to 12 mg/kg/day from one to 21 months. Five of 14 children also had relief of itching after treatment. Phenobarbital compared to Ursodeoxycholic acid had limited efficacy in reducing the bilirubin levels in neonates and young infants with cholestasis. Phenobarbital compared to Ursodeoxycholic acid had limited efficacy in reducing the bilirubin levels in neonates and young infants with cholestasis. Moderate certainty evidence showed that with Phenobarbital pretreatment, the hepatobiliary scan done on patients with neonatal cholestasis had 100% (CI 99.2, 100; I2 = 0.0%) sensitivity and 80.2% (CI 65.4, 92.1; I2 = 76.6%) specificity while no Phenobarbital pretreatment had 100% (94.9, 100; I2 = 0.0%) sensitivity and 89.5% (CI 77.0, 98.1; I2 = 11.4%) specificity. Adverse effects of Phenobarbital were drowsiness, lethargy, poor feeding, and irritability. Conclusion There was limited effectiveness of Phenobarbital in decreasing bilirubin levels in cholestatic liver disease. Moderate certainty evidence demonstrated that premedication with Phenobarbital did not improve the specificity of HIDA scan in the diagnosis of obstructive jaundice of infancy. Neurologic symptoms were observed with Phenobarbital intake.
phenobarbital ; cholestasis ; scintigraphy ; radionuclide imaging ; pruritus