BACKGROUND: E. hirta or tawa-tawa is a small annual herb common to tropical countries. In the Philippines, the decoction of the whole plant is used for the treatment of dengue because of its apparent platelet increasing property. While efforts are ongoing to determine the role of E. hirta for dengue, this study focused on its safety.

OBJECTIVE: This study determined the median lethal dose (LD50), toxidromes and reversibility of toxic effects following the acute oral administration of the crude aqueous extract in Sprague-Dawley rats.

METHODS: The Up-and-Down Procedure (Organization for Economic Cooperation and Development (OECD) Test Guideline 425) was conducted after the preliminary tests for the aqueous extract such as phytochemical and pesticide residue analyses and tests for aflatoxin and heavy metals.

RESULTS: Phytochemical screening showed the presence of tannins, glycosides and alkaloids in the plant extract. The aqeous extract contained allowable aflatoxin levels. Organochlorines, organophosphates and heavy metals such as arsenic, cadmium, lead and mercury were not detected in the aqueous extract. The LD50 of the aqueous extract was greater than 5000 mg/kg. The test animals did not experience significant body weight alterations. Gross necropsy revealed a hematoma on top of the skull and in the large intestine and a small, round protrusion in the stomach of the test animals. Histopathological examination showed foci of perivascular hemorrhages and neuronal degeneration in the brain, multifocal submucosal hemorrhages in the large intestine and fragmented very dark staining nuclei and fibrin stands with red blood cells in the stomach of test animals.

CONCLUSION: While the acute oral LD50 of the aqueous extract is greater than 5000 mg/kg, there is a need to pay attention to the toxidromes showing evidence of dose-dependent CNS depression. Histopathological examination showed multifocal submucosal hemorrhages and foci of perivascular hemmorrhages and neuronal necrosis indicating an acute hemorrhagic enteritis and cerebral hemorrhage, respectively. These findings and crucial in the light of the anecdotal use of E. hirta for the treatment of dengue hemorrhagic fever.

Animal ; Rats ; Rats, Sprague-dawley ; Severe Dengue ; Lethal Dose 50 ; Pesticide Residues ; Tannins ; Fibrin ; Glycosides ; Aflatoxins ; Erythrocyte Count ; Dengue ; Hematoma ; Cerebral Hemorrhage

Objectives. The patient medication counseling (PMC) services at Philippine General Hospital (PGH) started 21 years ago. While several changes have been incorporated into the program, no formal evaluation has been conducted to date. The objective of this evaluation was to assess the relevance, usefulness, responsiveness, acceptability, efficiency, impact, and sustainability of the service using the context, input, process (CIPP) model of Stufflebeam.

Methods. The study utilized a mixed-methods study design. Interviews and surveys were conducted on pharmacist-counselors, a purposive sample of doctors, nurses, and other stakeholders. A review of records from the Department of Pharmacy of UP College of Pharmacy (UPCP) and PGH, such as patient and student satisfaction surveys and monthly reports of counseled patients served from 2015 to 2019, was conducted. The results were analyzed using descriptive statistics for quantitative data and content analysis for qualitative data.

Results. Context evaluation revealed that the establishment of PMC resulted from informal interactions with hospitalized patients due to incorrect use of prescription medicines. Correct information was envisioned to address the irresponsible use of medicines. The input evaluation revealed that only 24% (N=75) of the pharmacists are involved in PMC, which comprise only 10% of their workload. There was also a lack of comprehensive training for counseling and insufficient physical facilities. The process evaluation identified lack of time (94%) as a significant limiting factor for the involvement of pharmacists in PMC. The interns became an additional workforce for the service, but scheduling and the consistent availability of both students and faculty-preceptors were experienced. The product evaluation revealed positive perceptions among the pharmacists, faculty, and student interns. From the patient satisfaction survey records of 5,071 patients counseled, 98 to 100% expressed high service satisfaction, and 100% were likely to recommend PMC to other patients. The pharmacists, interns, and faculty-preceptors suggested that PMC improved their confidence, communication skills, and decision-making.

Conclusion. The PMC service is relevant and valuable to ensure patients' rational and quality use of medicines. As a value-added service to existing hospital pharmacy services, it serves as a venue for enhancing soft skills among pharmacists and students alike. However, physical and human resources and current processes need to be upgraded to improve efficiency, ensure sustainability, and expand service coverage to more patients.

Pharmacists ; Patient Safety ; Quality Improvement

The COVID-19 pandemic created the urgent need to use online and virtual platforms to facilitate development of skills and competencies as part of remote learning of students. MyDispense®, a learning management system developed by Monash University in Australia, is a practice-based online tool utilized by the University of the Philippines College of Pharmacy to teach dispensing skills in Dispensing and Incompatibilities courses (Phar 154 and Pharm 133). This commentary describes how MyDispense® was used as an online retail pharmacy simulation through the SEIPS (Systems Engineering Initiative for Patient Safety) model, with discussion on how the person, tasks, organization, tools and technology, and virtual environment work within the teaching and learning process in dispensing. The application of MyDispense® as a learning platform both in remote and traditional teaching can be further explored to maximize its features and utility.
COVID-19

The COVID-19 pandemic created the urgent need to use online and virtual platforms to facilitate development of skills and competencies as part of remote learning of students. MyDispense®, a learning management system developed by Monash University in Australia, is a practice-based online tool utilized by the University of the Philippines College of Pharmacy to teach dispensing skills in Dispensing and Incompatibilities courses (Phar 154 and Pharm 133). This commentary describes how MyDispense® was used as an online retail pharmacy simulation through the SEIPS (Systems Engineering Initiative for Patient Safety) model, with discussion on how the person, tasks, organization, tools and technology, and virtual environment work within the teaching and learning process in dispensing. The application of MyDispense® as a learning platform both in remote and traditional teaching can be further explored to maximize its features and utility.
Remote learning

OBJECTIVES

The objectives of the study were to determine the antibiotic consumption of restricted antibiotics and to correlate this with resistance rate.

METHODS

A retrospective review of pharmacy dispensing records was conducted in the adult internal medicine wards of a tertiary level teaching hospital in the Philippines between March 2019 to February 2020. Antibiotic consumption was determined using Defined Daily Dose (DDD) per 1000 patient-days (PD). Correlations between antibiotic consumption and antibiotic resistance of restricted antibiotics were done. Outcomes were compared between Ward 1 (with the presence of a unit-dose pharmacist) and Ward 3 (without a unit-dose pharmacist).

RESULTS

Both wards showed decreasing trends of piperacillin-tazobactam consumption and increasing trends of ceftazidime consumption from quarter 1 to quarter 4. It was observed that levofloxacin was the most prescribed fluoroquinolone with the highest consumption recorded from March to May 2019 in Ward 3 of 350.2 DDD/1000 PD as compared with ciprofloxacin which has the highest consumption (23.3 DDD/1000 PD) during the period June to August 2019 in Ward 1. Antibiotic resistance of Acinetobacter baumannii against ciprofloxacin, levofloxacin, and piperacillin-tazobactam were statistically significantly different between the wards. In Ward 1, ciprofloxacin consumption was strongly positively correlated with Escherichia coli resistance (r = 0.90). In Ward 3, a significantly moderately positive association was observed for ceftazidime consumption and A. baumannii resistance (r = 0.61), positive correlation between piperacillin-tazobactam and E. coli resistance (r = 0.65), and a strong positive correlation in Ward 3 between levofloxacin and Pseudomonas aeruginosa resistance (r = 0.71).

CONCLUSION

The restriction and pre-authorization strategy of the AMS program has greatly contributed to the decrease in the consumption of almost all restricted antibiotics. This strategy has been helpful in minimizing unnecessary antibiotic use associated with inappropriate drug therapy. The success of the AMS program has been based on the collective efforts of the AMS team with the implementation of hospital policies, such as the AMS program, across the different sites in the hospital in order to achieve optimum patient health outcomes. It was noted that the resistance rates of A. baumannii against ciprofloxacin, levofloxacin, and piperacillin-tazobactam were higher in Ward 3 compared to Ward 1 which makes infections very difficult to treat which may result to prolonged hospital stay, increased health-care costs and increased mortality rate. This study has supported the involvement of pharmacists in the AMS team by conducting auditing activities that promote safe compliance of restricted antibiotic use among patients. Pharmacists can greatly participate on either prospective or retrospective review of antibiotic utilization and analyze trends of antibiotic consumption data to provide feedback to prescribing physicians on prescribing patterns and possible correlation with occurrence of antibiotic resistance.

Antibiotic Resistance ; Drug Resistance, Microbial

Background: Based on the 2017-2020 annual report of the Department of Health-Antimicrobial Resistance Surveillance Program, significant resistance patterns have been observed for common disease-causing pathogens. In the hospital setting, antimicrobial stewardship programs have been implemented to optimize the use of antimicrobials. Drug utilization review studies provide essential feedback to improve prescribing and use of medications. Objectives: This study aimed to review drug utilization of monitored parenteral antimicrobials among patients admitted from January to December 2019. Methods: The study employed a retrospective, cross-sectional, descriptive research design. A retrospective chart review of drugs administered to patients was conducted. : Results. A total of 821 patients charts met the inclusion criteria. The patients’ ages ranged from 18 to 98 years old and 52% were females. General Internal Medicine practitioners (28%) were the top prescribers of monitored parenteral antimicrobials primarily for the management of moderate-risk community-acquired pneumonia (39%). They were mostly indicated for empirical treatment of infections (94%) and were given for an average of 5.73 days. Only 58% of the total cases had orders for culture and sensitivity testing. Of which, principally 47% had colony cultures. Blood (29%) and sputum (27%) were the most common specimens taken for culture and sensitivity testing. The microorganisms often isolated were Escherichia coli (19%), Klebsiella pneumoniae (18%), and Staphylococcus aureus (9%). In addition, extended-spectrum beta lactamase-producing gram-negative pathogens (4%) and methicillin-resistant S. aureus (1%) were also isolated. All the microorganisms isolated showed most resistance to ampicillin (81%) and most susceptibility to colistin (100%). There were drug therapy-related problems encountered. There was one case of an adverse drug reaction (0.1%) and two cases of contraindications (0.2%). Therapeutic duplication was also observed in 5% of the cases. Moreover, 39% had instances of drug-drug interactions.Piperacillin-tazobactam had the highest consumption (79.50 defined daily doses/1,000-patient days) among the monitored parenteral antimicrobials. Some prescriptions were deemed inappropriate upon evaluation. 12% of cases were inappropriate based on the justification indicator. As for the critical indicators, duration of therapy (78%) was the main reason. Only four components of the DUE criteria indicators have met or exceeded the established threshold level.The cost analysis indicated that the total actual cost of therapy with the monitored parenteral antimicrobials amounted to ₱17,645,601.73. Considering Department of Health National Antibiotic Guidelines recommenda-tions, ideal total cost of treatment was ₱14,917,214.29. Potential cumulative cost savings of ₱2,728,387.44 could have been achieved for patients admitted last 2019. Conclusion Consumption of piperacillin-tazobactam was relatively high as compared to the other monitored parenteral antimicrobials covered in this study. Physicians at the study site seldom prescribe monitored parenteral antimicrobials as recommended by the National Antibiotic Guidelines. This is evidenced in the incidence of inappropriate therapy regimens, with inapt duration of therapy as the leading explanation.From the patient’s perspective, the main economic implication was on the direct medical costs, particularly the increased cost of the actual antimicrobial therapy prescribed to manage various infections. Adherence of physicians to the established guidelines and selection of the most cost-effective therapy could have resulted in considerable cost savings.
Drug Utilization Review ; Antimicrobial Stewardship

INTRODUCTION: Oral ivermectin is an approved first-line option to topical permethrin in Europe and Japan for the treatment of classic scabies, while combination oral ivermectin and topical permethrin is used in clinical practice for extensive or recurrent cases. There is unclear evidence on comparative efficacy and safety.

OBJECTIVES: To review the evidence on efficacy and safety of oral ivermectin versus topical permethrin or its combination in the treatment of classic scabies.

METHODS: We searched PubMed from January 1, 2016 up to August 7, 2021 for systematic reviews that included RCTs comparing oral ivermectin versus topical permethrin or its combination in the clinical treatment of scabies. We described the characteristics of included studies, assessed reporting quality, and summarized results and conclusion.

RESULTS: We included five systematic reviews. Permethrin did not differ from oral ivermectin in cure rate at the 3 to 6-week time point but had an earlier cure at 1-2 weeks. Adverse effects did not significantly diff er and were few, mild, and transient with both treatments. The evidence ranged widely from low to high certainty and mainly came from three moderate-to-high quality systematic reviews. Combination oral ivermectin and topical permethrin was ranked higher in efficacy but lower in safety compared to either drug alone in one moderate validity network meta-analysis.

CONCLUSION: There is varying certainty of evidence suggesting comparable efficacy and safety of oral ivermectin versus topical permethrin. Limited evidence suggest higher efficacy and lower safety of combination oral ivermectin and topical permethrin compared to either drug alone. An updated systematic review and network meta-analysis is warranted.

KEYWORDS: scabies, ivermectin, permethrin, effectiveness, efficacy, safety

Background and Objective: Oral ivermectin is recommended as an alternative to topical permethrin in Japanese, European, and CDC-STI guidelines for treating classic scabies. The combination of oral ivermectin and topical permethrin is also used in some settings. Partial economic evaluations conducted in India and Egypt have conflicting results, and no cost-effectiveness analysis in the Philippines has compared ivermectin-based regimens to permethrin for scabies treatment. We aimed to determine the cost-effectiveness of oral ivermectin, alone or in combination with permethrin, compared to permethrin, in the treatment of Filipino adult patients with classic scabies. Methods: We used a decision tree model to estimate the cost-effectiveness of two regimens, oral ivermectin alone or in combination with permethrin, compared with permethrin to treat adults and children aged five years and older with classic scabies in the outpatient setting from the household perspective in the Philippines. We estimated total costs and disability-adjusted life years (DALYs) over a one-month follow-up. Input parameters were obtained from secondary data, such as effect estimates for probabilities of clinical outcomes from a network meta-analysis, DALYs from the Global Burden of Disease 2019, and prevailing market cost in the Philippines (DPRI 2022 with recommended markup by DOH, and leading drugstores) as of August 2022. We computed for incremental cost-effectiveness ratio (ICER) and net monetary benefit (NMB) to determine which of the interventions are cost-effective. Univariate and probabilistic sensitivity analyses, and scenario analyses were conducted to assess the impact of parameter and structural uncertainty. Results: Ivermectin-based regimens are suggested to be likely cost-saving compared to permethrin in the Philippine outpatient setting. Base case analysis showed that oral ivermectin had higher cost-savings (change in cost, -1,039.31; change in DALYS, 0.00027), while combination oral ivermectin/permethrin had higher DALYs averted (change in cost, PhP -1,019.78; change in DALYs, 0.00045), compared to permethrin. Combination oral ivermectin/permethrin (56%) was the most cost-effective, followed by oral ivermectin (44%) compared to permethrin (0%) through probabilistic sensitivity analysis. Estimates for ivermectin were sensitive to risk of cure for ivermectin vs permethrin using 1-way deterministic sensitivity analysis. Oral ivermectin was favored over combination oral ivermectin/permethrin at all thresholds based on the cost-effectiveness acceptability curve. Conclusion Both ivermectin-based regimens seem to be cost-saving compared to permethrin in the treatment of classic scabies in the Philippine outpatient setting. Clinicians may consider oral ivermectin, alone or in combination with permethrin as an alternative first-line or second-line treatment depending on patient preference, adverse event risk profile, availability, and economic capacity. This needs to be confirmed using primary data from Filipino patients to enhance the robustness of the findings and support evidence-based local decision-making in different settings. Less uncertainty in modelled parameters can give greater confidence in the results, which can be adopted for budget impact analysis and allow more rational resource allocation. Value of information analysis can be done to determine whether the expense of future RCTs or surveys in Filipinos to collect primary data is worth it. The cost of reducing uncertainty, if deemed worth the cost of further studies, may facilitate population-level decision-making and budget planning. Findings may further inform practice guideline development, coverage decisions, and national control program planning by providing the most cost-effective scabies intervention.
Scabies ; Ivermectin ; Permethrin ; Cost-Benefit Analysis

BACKGROUND AND OBJECTIVE

Oral ivermectin, a broad-spectrum anti-parasitic drug, alone or in combination with permethrin, may be a cheaper and more convenient alternative drug to topical permethrin alone in the treatment of classic scabies. There are no previous studies on the treatment acceptability of the three interventions among individual patients with scabies in the Philippines. The purpose of this study was to understand the experiences and perceptions on treatment acceptability for oral ivermectin, topical permethrin or combination treatment among patients with scabies using the multiple-case study approach.

METHODS

We conducted a qualitative multiple case study among adult Filipino patients with classic scabies who were prescribed oral ivermectin, topical permethrin or its combination at a government tertiary hospital dermatology outpatient clinic from December 2022 to September 2023. Semi-structured interviews were used as the primary source of data and analyzed together with chart reviews, Dermatology Life Quality Index (DLQI) scores, and clinical images. Interviews were transcribed, coded, and triangulated with other secondary data. A three-person research team employed a reflexive and iterative process of familiarization, coding, and thematic analysis using a modified Theoretical Framework of Acceptability (TFA) to generate case descriptions, within-case analyses, and cross-case syntheses.

RESULTS

The acceptability of scabies treatments (permethrin, ivermectin, and combination therapy) was generally positive. Permethrin, used in three patient cases, was generally perceived as effective but itch relief varied. The burden of whole-body application of permethrin was context-dependent, influenced by living arrangements and family support. Perceived affordability of permethrin was linked to socioeconomic status. Ivermectin, used by one patient case, was perceived as highly effective with no side effects. Its single dose use did not interfere with patient routine. Combination therapy was also considered effective but potential antagonistic effects and the cost of adding permethrin made it less preferred. Reluctance in taking oral pills was noted. All patients valued medical advice and deferred to their physicians for treatment decisions.

CONCLUSION AND RECOMMENDATIONS

All three treatment options were considered effective and safe. Patients generally preferred permethrin over oral ivermectin due to its topical nature and perceived lower side effects. However, affordability and logistical challenges, especially for large households and low-income families, were noted with permethrin. Oral ivermectin elicited hesitation due to its controversial role in COVID-19 and veterinary use. Concerns about added costs and potential antagonism in combination therapy were raised. Despite these considerations, patients ultimately relied on physicians for treatment decisions. This study underscores the importance of understanding patient perspectives, experiences, and the patient-physician relationship in choosing scabies interventions. Addressing patient concerns, providing education, and ensuring ease of use and affordability can enhance treatment acceptability and adherence for better outcomes.

Human ; Scabies ; Ivermectin ; Permethrin ; Case Study ; Case Reports ; Qualitative Research