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.

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.

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.

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.

BACKGROUND

Scabies, caused by Sarcoptes scabiei var. hominis, is a prevalent and burdensome skin disease in the Philippines, ranking second in disability. Recognized as a neglected tropical disease (NTD) by the WHO, scabies management is targeted for inclusion in universal healthcare programs worldwide by 2030. Current treatment involves topical neurotoxic drugs like permethrin, but issues such as expense and inconvenience hinder compliance. Oral ivermectin, recommended by the WHO only recently, is more cost-effective and easier to administer but is considered a second-line option in clinical practice guidelines. This research aimed to determine the comparative efficacy, safety, cost-effectiveness, and acceptability of oral ivermectin, alone or in combination with topical permethrin, versus topical permethrin alone, in the treatment of classic scabies among Filipino patients.

This 4-part study was conducted from July 2021 to September 2023 and aimed to compare the efficacy, safety, cost-effectiveness, and acceptability of oral ivermectin alone or in combination with topical permethrin versus topical permethrin alone for treating classic scabies among Filipino patients. Quantitative methods included a systematic review and network meta-analysis of 38 randomized controlled trials (RCTs) and a pharmacoeconomic evaluation using decision tree modeling. Qualitative methods involved a multiple case study of patient experiences and perceptions and in-depth interviews with physicians.

There seems to be comparable efficacy between oral ivermectin and permethrin, with limited evidence favoring the combination ivermectin/permethrin regimen. Adverse events were minor, and cost-effectiveness analyses favored ivermectin-based regimens over permethrin. Patient and physician perspectives supported the effectiveness of all treatments, with oral ivermectin recognized as safe but underutilized.

Evidence synthesis suggests that oral ivermectin, especially in combination with permethrin, could be a viable and cost-effective alternative for scabies treatment in the Philippines. The optimal dosing regimen, safety in specific populations, and factors influencing treatment choice need further exploration. Recommendations include advocating for oral ivermectin inclusion in regulatory guidelines and national formulary, considering it as a first- or second- line treatment, and conducting further research, including mixed-methods designs, to confirm efficacy, safety, and cost-effectiveness in different settings. Shared decision-making, considering ethical, logistical, socioeconomic, and psychological aspects, is crucial in implementing effective scabies control programs.

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.

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.

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.

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.

BACKGROUND: With the development of traditional Chinese medicine research, berberine has shown good efficacy and safety in the eradication of Helicobacter pylori (H. pylori). The present study aimed to evaluate the efficacy and safety of triple therapy containing berberine, amoxicillin, and vonoprazan for the initial treatment of H. pylori. METHODS: This study was a single-center, open-label, parallel, randomized controlled clinical trial. Patients with H. pylori infection were randomly (1:1:1) assigned to receive berberine triple therapy (berberine 500 mg, amoxicillin 1000 mg, vonoprazan 20 mg, A group), vonoprazan quadruple therapy (vonoprazan 20 mg, amoxicillin 1000 mg, clarithromycin 500 mg, colloidal bismuth tartrate 220 mg, B group), or rabeprazole quadruple therapy (rabeprazole 10 mg, amoxicillin 1000 mg, clarithromycin 500 mg, colloidal bismuth tartrate 220 mg, C group). The drugs were taken twice daily for 14 days. The main outcome was the H. pylori eradication rate. The secondary outcomes were symptom improvement rate, patient compliance, and incidence of adverse events. Furthermore, factors affecting the eradication rate of H. pylori were further analyzed. RESULTS: A total of 300 H. pylori-infected patients were included in this study, and 263 patients completed the study. An intention-to-treat (ITT) analysis showed that the eradication rates of H. pylori in berberine triple therapy, vonoprazan quadruple therapy, and rabeprazole quadruple therapy were 70.0% (70/100), 77.0% (77/100), and 69.0% (69/100), respectively. The per-protocol (PP) analysis showed that the eradication rates of H. pylori in these three groups were 81.4% (70/86), 86.5% (77/89), and 78.4% (69/88), respectively. Both ITT analysis and PP analysis showed that the H. pylori eradication rate did not significantly differ among the three groups (P >0.05). In addition, the symptom improvement rate, overall adverse reaction rate, and patient compliance were similar among the three groups (P >0.05). CONCLUSIONS The efficacy of berberine triple therapy for H. pylori initial treatment was comparable to that of vonoprazan quadruple therapy and rabeprazole quadruple therapy, and it was well tolerated. It could be used as one choice of H. pylori initial treatment.
Humans ; Amoxicillin/therapeutic use* ; Helicobacter pylori ; Anti-Bacterial Agents ; Clarithromycin/therapeutic use* ; Rabeprazole/therapeutic use* ; Berberine/therapeutic use* ; Bismuth ; Helicobacter Infections/drug therapy* ; Drug Therapy, Combination ; Treatment Outcome ; Proton Pump Inhibitors/therapeutic use*

Strigolactones(SLs) are a class of sesquiterpenoids derived from the carotenoid biosynthesis pathway with the core carbon skeleton consisting of tricyclic lactone(ABC tricyclic ring) and α,β-unsaturated furan ring(D ring). SLs are widely distributed in higher plants and are symbiotic signals between plants and Arbuscular mycorrhiza(AM), which play key roles in the evolution of plant colonizing terrestrial habitats. As a new type of plant hormone, SLs possess such important biological functions as inhibiting shoot branching(tillers), regulating root architecture, promoting secondary growth, and improving plant stress resistance. Therefore, SLs have attracted wide attention. The biological functions of SLs are not only closely related to the formation of "excellent shape and quality" of Chinese medicinal materials but also have important practical significance for the production of high-quality medicinal materials. However, SLs have been currently widely studied in model plants and crops such as Oryza sativa and Arabidopsis thaliana, and few related studies have been reported on SLs in medicinal plants, which need to be strengthened. This review focused on the latest research progress in the isolation and identification, biological and artificial synthesis pathways, biosynthesis sites and transport modes, signal transduction pathways and mechanisms, and biological functions of SLs, and prospected the research on the regulation mechanism of SLs in the growth and development of medicinal plants and their related application on targeted regulation of Chinese herbal medicine production, which is expected to provide some references for the in-depth research on SLs in the field of Chinese medicinal resources.
Arabidopsis ; Lactones ; Plants, Medicinal

Tacrolimus (TAC), also called FK506, is one of the classical immunosuppressants to prevent allograft rejection after liver transplantation. However, it has been proved to be associated with post-transplant hyperlipemia. The mechanism behind this is unknown, and it is urgent to explore preventive strategies for hyperlipemia after transplantation. Therefore, we established a hyperlipemia mouse model to investigate the mechanism, by injecting TAC intraperitoneally for eight weeks. After TAC treatment, the mice developed hyperlipemia (manifested as elevated triglyceride (TG) and low-density lipoprotein cholesterol (LDL-c), as well as decreased high-density lipoprotein cholesterol (HDL-c)). Accumulation of lipid droplets was observed in the liver. In addition to lipid accumulation, TAC induced inhibition of the autophagy-lysosome pathway (microtubule-associated protein 1 light chain 3β (LC3B) II/I and LC3B II/actin ratios, transcription factor EB (TFEB), protein 62 (P62), and lysosomal-associated membrane protein 1 (LAMP1)) and downregulation of fibroblast growth factor 21 (FGF21) in vivo. Overexpression of FGF21 may reverse TAC-induced TG accumulation. In this mouse model, the recombinant FGF21 protein ameliorated hepatic lipid accumulation and hyperlipemia through repair of the autophagy-lysosome pathway. We conclude that TAC downregulates FGF21 and thus exacerbates lipid accumulation by impairing the autophagy-lysosome pathway. Recombinant FGF21 protein treatment could therefore reverse TAC-caused lipid accumulation and hypertriglyceridemia by enhancing autophagy.
Animals ; Mice ; Tacrolimus ; Liver ; Cholesterol, LDL ; Autophagy ; Disease Models, Animal

Ivermectin is a US Food and Drug Administration (FDA)-approved antiparasitic agent with antiviral and anti-inflammatory properties. Although recent studies reported the possible anti-inflammatory activity of ivermectin in respiratory injuries, its potential therapeutic effect on pulmonary fibrosis (PF) has not been investigated. This study aimed to explore the ability of ivermectin (0.6 mg/kg) to alleviate bleomycin-induced biochemical derangements and histological changes in an experimental PF rat model. This can provide the means to validate the clinical utility of ivermectin as a treatment option for idiopathic PF. The results showed that ivermectin mitigated the bleomycin-evoked pulmonary injury, as manifested by the reduced infiltration of inflammatory cells, as well as decreased the inflammation and fibrosis scores. Intriguingly, ivermectin decreased collagen fiber deposition and suppressed transforming growth factor-‍β1 (TGF-‍β1) and fibronectin protein expression, highlighting its anti-fibrotic activity. This study revealed for the first time that ivermectin can suppress the nucleotide-binding oligomerization domain (NOD)‍-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome, as manifested by the reduced gene expression of NLRP3 and the apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), with a subsequent decline in the interleukin‍-‍1β (IL‍-‍1β) level. In addition, ivermectin inhibited the expression of intracellular nuclear factor-‍κB (NF‍-‍κB) and hypoxia‑inducible factor‑1α (HIF‍-‍1α) proteins along with lowering the oxidative stress and apoptotic markers. Altogether, this study revealed that ivermectin could ameliorate pulmonary inflammation and fibrosis induced by bleomycin. These beneficial effects were mediated, at least partly, via the downregulation of TGF-‍β1 and fibronectin, as well as the suppression of NLRP3 inflammasome through modulating the expression of HIF‑1α and NF-‍κB.
Animals ; Rats ; Anti-Inflammatory Agents ; Bleomycin/toxicity* ; Fibronectins/metabolism* ; Fibrosis ; Inflammasomes/metabolism* ; Ivermectin/adverse effects* ; NF-kappa B/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Pulmonary Fibrosis/drug therapy*

Introduction: Gitelman Syndrome (GS), a rare autosomal recessive inherited disorder, is frequently unrecognized in the clinical setting. GS typically manifests with severe hypokalemia with debilitating and potentially fatal consequences if untreated. As of writing, confirmatory genetic assays are currently unavailable in the country, and the diagnosis of GS is primarily based on several biochemical laboratory tests. This results in the difficulty with prompt diagnosis of GS in the locality. Case: We present a 52-year-old male who came in with chronic, intermittent paraparesis associated with persistent hypokalemia. A diagnosis of GS was made biochemically based on renal wasting of potassium and magnesium, hypocalciuria, and metabolic alkalosis. Electrolyte correction with lifelong supplementation, and administration of Spironolactone resulted in the resolution of bilateral leg weakness. Electrolyte levels were maintained within normal limits in the outpatient setting. Conclusion GS is an uncommon potentially debilitating disorder that may lead to problematic, potentially fatal consequences to electrolyte abnormalities if left untreated. The lack of awareness and consequent delay in the diagnosis, and the unavailability of confirmatory genetic testing remains a clinical challenge. Timely recognition and initiation of treatment leads to early control of electrolyte levels, and better prognosis.
Gitelman&rsquo ; s Syndrome ; Paraparesis ; Hypokalemia ; Hypomagnesemia ; Spironolactone ; Case Report

Introduction: Plasma cell cheilitis (PCC) is a rare, chronic inflammatory dermatitis of unknown etiology. Due to the limited number of cases reported, no guidelines have been established for its treatment. We present a case of PCC clinically similar to actinic cheilitis or mucosal lichen planus, and squamous cell carcinoma but showed response to topical tacrolimus 0.1% ointment. Case Report: A 62-year-old female with extreme fondness to piping hot food presented with a solitary painful ulceration with some pustules and bleeding on the lower lip with three (3) months duration. Skin punch biopsy revealed a dense band-like infiltrate of plasma cells which is consistent with Plasma cell cheilitis. The patient was given tacrolimus 0.1% ointment and showed significant improvement after a month of treatment. Conclusion PCC is a rare condition that should still be considered in patients presenting with persistent cheilitis. Clinical and histological correlation is advised for proper management and prognostication.
cheilitis ; plasma cell ; tacrolimus