1.Bibliometric analysis of randomized clinical trials in the Philippines.
Ian Theodore G. Cabaluna ; Sarah F. Sevilla ; Arianna Maever L. Amit ; Timothy Hudson David C. Carandang ; Adrian Espiritu ; Carol Stephanie C. Tan-Lim
Acta Medica Philippina 2026;60(4):7-14
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.
METHODSA 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.
RESULTSA 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.
CONCLUSIONThe 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.
Human ; Bibliometrics ; Bibliometric Analysis ; Philippines ; Publications
2.Efficacy, effectiveness, and safety of phenobarbital in the treatment of cholestasis and as a premedication to improve diagnostic accuracy of hepatobiliary scintigraphy: A systematic review
Germana Emerita V. Gregorio ; Katrina Loren R. Rey ; Carol Stephanie C. Tan-lim
Acta Medica Philippina 2025;59(10):95-109
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.
METHODSAll 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.
RESULTSIncluded 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.
CONCLUSIONThere 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
3.Clinical profile and prescribing patterns of therapy in children with bronchial asthma in a rural site in the Philippines: A retrospective cohort study.
Gayle Therese K. Gonzales-javier ; Leonila F. Dans ; Kristine Tanega-aliling ; Carol Stephanie C. Tan-lim ; Cara Lois T. Galingana ; Mia P. Rey ; Maria Rhodora D. Aquino ; Josephine T. Sanchez ; Antonio L. Dans
Acta Medica Philippina 2025;59(1):84-90
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.
OBJECTIVESTo determine the clinical profile of pediatric patients with bronchial asthma; and to evaluate the prescription patterns for asthma treatment in a primary care setting.
METHODSThis 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.
RESULTSThis 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.
CONCLUSIONThere 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.
Human ; Male ; Infant Newborn: First 28 Days After Birth ; Infant: 1-23 Months ; Child Preschool: 2-5 Yrs Old ; Child: 6-12 Yrs Old ; Asthma ; Lung
4.Effect of a brief training program on the knowledge of Filipino primary care providers in a rural and a remote setting: A before and after study
Julianne Keane M. Pascual ; Arianna Maever Loreche ; Regine Ynez H. De mesa ; Noleen Marie C. Fabian ; Josephine T. Sanchez ; Janelle Micaela S. Panganiban ; Mia P. Rey ; Carol Stephanie C. Tan-lim ; Mark Anthony U. Javelosa ; Ramon Pedro P. Paterno ; Ray U. Casile ; Leonila F. Dans ; Antonio L. Dans
Acta Medica Philippina 2025;59(1):66-72
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.
METHODSA 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.
RESULTSThe 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).
CONCLUSIONSPrimary 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.
Capacity Building ; Health Workforce ; Philippines ; Primary Health Care
5.Osteoporosis Management after the Occurrence of Medication-Related Osteonecrosis of the Jaw: A 13-Year Experience at a Tertiary Center
Chun Ho WONG ; Kimberly Hang TSOI ; Jingya Jane PU ; Nancy Su JIANG ; Stacey Sheung Yi CHAN ; Connie Hong Nin LOONG ; Xincheng ZOU ; Carol Ho Yi FONG ; Eunice Ka Hong LEUNG ; Alan Chun Hong LEE ; Chi Ho LEE ; Kathryn Choon Beng TAN ; Yu Cho WOO ; Yu-xiong SU ; David Tak Wai LUI
Endocrinology and Metabolism 2025;40(6):974-990
Background:
We investigated osteoporosis management strategies and clinical outcomes following the occurrence of medicationrelated osteonecrosis of the jaw (MRONJ).
Methods:
We retrospectively studied individuals diagnosed with MRONJ during osteoporosis treatment who were managed in the Osteoporosis Center or the Oral Maxillofacial Surgery & Dental Unit at Queen Mary Hospital in Hong Kong between 2010 and 2022. We examined subsequent osteoporosis management plans, fracture events, and bone mineral density (BMD).
Results:
Thirty-six individuals were included (mean age, 78.5 years; 94.4% women). The estimated prevalence of MRONJ was 0.26%. All patients had been exposed to bisphosphonates, and seven had also received denosumab before MRONJ. Following MRONJ, only 14 individuals continued anti-osteoporosis treatment, a decision influenced by a higher fracture probability at MRONJ onset. The most common regimen was a teriparatide-raloxifene sequence (n=8): three patients achieved stable BMD, four achieved improving BMD, and one exhibited a mixed response. The patient with a mixed BMD response had also been treated with denosumab. Six patients sustained incident fractures after MRONJ, and these patients had lower BMD T-scores than their counterparts. Two patients experienced MRONJ recurrence, which was associated with the resumption of bisphosphonate or denosumab therapy after MRONJ. These patients had higher BMD T-scores than those who did not experience MRONJ recurrence.
Conclusion
MRONJ is challenging because high fracture risk necessitates discontinuation of antiresorptive agents. Teriparatide followed by raloxifene may be a reasonable regimen. Individualised decisions in osteoporosis management after MRONJ are required to balance fracture risk reduction with minimising MRONJ recurrence.
6.Survey of students and alumni of Clinical Epidemiology Graduate Programs in the Philippines: A descriptive cross-sectional study of program strengths and weaknesses.
Cynthia P. Cordero ; Carol Stephanie C. Tan-Lim ; Carlo Irwin A. Panelo ; Ian Theodore G. Cabaluna ; Girlie C. Monis ; Paul Erich R. Famador
Acta Medica Philippina 2024;58(15):11-23
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.
METHODSThis 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.
RESULTSWe 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.
CONCLUSIONThis 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.
Cross-sectional Studies
7.Pediatric conditions and platforms of telemedicine used in Philippine primary care: A cross-sectional study
Angelique Celina F. Lahoz ; Leonila F. Dans ; Carol Stephanie C. Tan-Lim ; Angelica Cecilia V. Tomas ; Cara Lois T. Galingana ; Josephine T. Sanchez ; Maria Rhodora N. Aquino ; Arianne Maever L. Amit ; Mia P. Rey ; Janelle Micaela S. Panganiban ; Antonio L. Dans
Acta Medica Philippina 2024;58(15):39-45
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.
METHODSThis 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.
RESULTSA 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%).
CONCLUSIONThe 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.
Telemedicine ; Primary Health Care
8.Frequency distribution of pediatric primary care cases in a rural site in the Philippines: A cross-sectional study.
Jonah Mikka B. Dorado ; Leonila F. Dans ; Carol Stephanie C. Tan-Lim ; Cara Lois T. Galingana ; Janelle Micaela S. Panganiban ; Mia P. Rey ; Josephine T. Sanchez ; Herbert S. Zabala ; Maria Rhodora N. Aquino ; Antonio L. Dans
Acta Medica Philippina 2024;58(18):71-78
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.
OBJECTIVESThis study aimed to determine the frequency distribution of pediatric diseases in a rural primary healthcare facility in the Philippines.
METHODSThis 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.
RESULTSA 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.
CONCLUSIONSRespiratory 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.
Electronic Health Records ; Electronic Medical Record
9.Health benefit utilization and out-of-pocket expenses in outpatient care and hospitalizations: Baseline surveys of three primary care sites in the Philippines.
Leonila F. Dans ; Jose Rafael A. Marfori ; Regine Ynez H. De Mesa ; Cara Lois T. Galingana ; Noleen Marie C. Fabian ; Mia P. Rey ; Josephine T. Sanchez ; Jesusa T. Catabui ; Nannette B. Sundiang ; Ramon Pedro P. Paterno ; Edna Estifania A. Co ; Carol Stephanie C. Tan-Lim ; Antonio Miguel L. Dans
Acta Medica Philippina 2024;58(16):133-140
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.
OBJECTIVEThe 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.
METHODSCross-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.
RESULTSA 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).
CONCLUSIONSCompared 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.
Primary Health Care ; Insurance, Health
10.Efficacy, effectiveness, and safety of phenobarbital in the treatment of cholestasis and as a premedication to improve diagnostic accuracy of hepatobiliary scintigraphy: A systematic review
Germana Emerita V. Gregorio ; Katrina Loren R. Rey ; Carol Stephanie C. Tan-Lim
Acta Medica Philippina 2024;58(Early Access 2024):1-15
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
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cholestasis
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scintigraphy
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radionuclide imaging
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pruritus


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