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: Owing to the high prevalence of antibiotic resistance in Helicobacter pylori ( H. pylori ) in China, bismuth-containing quadruple therapies have been recommended for H. pylori eradication. This study compared the efficacy and safety of quadruple regimens containing vonoprazan vs . esomeprazole for H. pylori eradication in a patient population in China. METHODS: This was a phase 3, multicenter, randomized, double-blind study. Patients with confirmed H. pylori infection were randomized 1:1 to receive quadruple therapy for 14 days: amoxicillin 1000 mg and clarithromycin 500 mg after meals, bismuth potassium citrate 600 mg before meals, plus either vonoprazan 20 mg or esomeprazole 20 mg before meals, all twice daily. The primary outcome was the eradication rate of H. pylori , evaluated using a 13 C urea breath test at 4 weeks after treatment. The non-inferiority margin was at 10%. RESULTS: The study included 510 patients, 506 of whom completed the follow-up assessment. The primary analysis revealed eradication rates of 86.8% (210/242) and 86.7% (208/240) for vonoprazan and esomeprazole therapy, respectively (treatment difference: 0.1%; 95% confidence interval [CI]: -5.95, 6.17; non-inferiority P  = 0.0009). Per-protocol analysis showed eradication rates of 87.4% for vonoprazan and 86.3% for esomeprazole (treatment difference: 1.2%; 95% CI: -5.03, 7.36; non-inferiority P  = 0.0004). Vonoprazan and esomeprazole were well tolerated, with similar safety profiles. CONCLUSION: Vonoprazan was found to be well-tolerated and non-inferior to esomeprazole for eradicating H. pylori in patients from China. TRIAL REGISTRATION ClinicalTrials.gov , NCT04198363.
Humans ; Esomeprazole/therapeutic use* ; Double-Blind Method ; Helicobacter Infections/drug therapy* ; Male ; Female ; Middle Aged ; Helicobacter pylori/pathogenicity* ; Pyrroles/therapeutic use* ; Sulfonamides/therapeutic use* ; Adult ; Clarithromycin/therapeutic use* ; Amoxicillin/therapeutic use* ; Aged ; Anti-Bacterial Agents/therapeutic use* ; Pyrrolidines/therapeutic use* ; Drug Therapy, Combination ; Proton Pump Inhibitors/therapeutic use*

OBJECTIVES: To investigate the risk factors for plastic bronchitis (PB) in children with macrolide-unresponsive Mycoplasma pneumoniae pneumonia (MUMPP) and to establish a nomogram prediction model. METHODS: A retrospective analysis was conducted on 178 children with MUMPP who underwent bronchoscopy from January to December 2023. According to the presence or absence of PB, the children were divided into a PB group (49 children) and a non-PB group (129 children). The predictive factors for the development of PB in children with MUMPP were analyzed, and a nomogram prediction model was established. The model was assessed in terms of discriminatory ability, accuracy, and clinical effectiveness. RESULTS: The multivariate logistic regression analysis showed that older age and higher levels of lactate dehydrogenase and fibrinogen were closely associated with the development of PB in children with MUMPP (P<0.05). A nomogram model established based on these factors had an area under the receiver operating characteristic curve of 0.733 (95%CI: 0.651-0.816, P<0.001) and showed a good discriminatory ability. The Hosmer-Lemeshow goodness-of-fit test indicated that the predictive model had a good degree of fit (P>0.05), and the decision curve analysis showed that the model had a good clinical application value. CONCLUSIONS The risk nomogram model established based on age and lactate dehydrogenase and fibrinogen levels has good discriminatory ability, accuracy, and predictive efficacy for predicting the development of PB in children with MUMPP.
Retrospective Studies ; Risk Factors ; Nomograms ; Mycoplasma pneumoniae/isolation & purification* ; Pneumonia, Mycoplasma/microbiology* ; Bronchitis/microbiology* ; Macrolides/therapeutic use* ; Drug Resistance, Bacterial ; Bronchoscopy ; Area Under Curve ; ROC Curve ; Fibrinogen/analysis* ; Age Factors ; Humans ; Male ; Female ; Infant ; Child, Preschool ; Child ; Adolescent ; L-Lactate Dehydrogenase/blood*

(±)-Talapyrones A-F (1-6), six pairs of dimeric polyketide enantiomers featuring unusual 6/6/6 and 6/6/6/5 ring systems, were isolated from the fungus Talaromyces adpressus. Their structures were determined by spectroscopic analysis and HR-ESI-MS data, and their absolute configurations were elucidated using a modified Mosher's method and electronic circular dichroism (ECD) calculations. (±)-Talapyrones A-F (1-6) possess a 6/6/6 tricyclic skeleton, presumably formed through a Michael addition reaction between one molecule of α-pyrone derivative and one molecule of C₈ poly-β-keto chain. In addition, compounds 2/3 and 4/5 are two pairs of C-18 epimers, respectively. Putative biosynthetic pathways of 1-6 were discussed.
Polyketides/isolation & purification* ; Talaromyces/chemistry* ; Stereoisomerism ; Molecular Structure ; Circular Dichroism ; Pyrones/chemistry*

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

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

OBJECTIVES: To investigate the efficacy and safety of prolonged azithromycin (PAZM) versus switching to doxycycline (SDXC) in the treatment of macrolide-unresponsive Mycoplasma pneumoniae pneumonia (MUMPP) in children. METHODS: A total of 173 children with MUMPP who were hospitalized in Baoji Central Hospital, from January to December 2023 were selected as subjects. According to the choice of secondary antibiotic after 72 hours of initial macrolide therapy, they were divided into two groups: PAZM and SDXC. The efficacy and adverse drug reactions were compared between the two groups, and the risk factors for refractory Mycoplasma pneumoniae pneumonia (RMPP) were analyzed. RESULTS: Compared with the PAZM group, the SDXC group had significantly shorter time to defervescence and time to cough relief, a significantly lower proportion of patients using glucocorticoids, and a significantly higher proportion of patients with lung lesion absorption (P<0.05). No adverse reactions such as liver and kidney function impairment and tooth discoloration were observed in either group. RMPP occurred in 47 cases in the PAZM group. The univariate analysis showed that lactate dehydrogenase levels and age were risk factors for RMPP (P<0.05). CONCLUSIONS The efficacy of SDXC is superior to that of PAZM in children with MUMPP, and short-term use of doxycycline is relatively safe.
Humans ; Pneumonia, Mycoplasma/drug therapy* ; Doxycycline/administration & dosage* ; Female ; Male ; Azithromycin/administration & dosage* ; Child ; Child, Preschool ; Anti-Bacterial Agents/administration & dosage* ; Macrolides/administration & dosage* ; Adolescent ; Mycoplasma pneumoniae/drug effects*

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*

Objective: To explore the clinical characteristics, common pathogens in children with vulvovaginitis. Methods: This was a retrospective cases study. A total of 3 268 children with vulvovaginitis were enrolled, who visited the Department of Pediatric and Adolescent Gynecology, Children's Hospital, Zhejiang University School of Medicine from January 2009 to December 2019. Patients were divided into 3 groups according to the age of <7, 7-<10 and 10-18 years. Patients were also divided in to 4 groups according to the season of first visit. The pathogen distribution characteristics of infective vulvovaginitis were compared between the groups. Their clinical data were collected and then analyzed by χ² test. Results: The were 3 268 girls aged (6.2±2.5) years. There were 1 728 cases (52.9%) aged <7 years, 875 cases (26.8%) aged 7-<10 years, and 665 cases (20.3%) aged 10-18 years. Of these cases, 2 253 cases (68.9%) were bacterial vulvovaginitis, 715 cases (21.9%) were fungal vulvovaginitis and 300 cases (9.2%) were vulvovaginitis infected with other pathogens. Bacterial culture of vaginal secretions was performed in 2 287 cases, and 2 287 strains (70.0%) of pathogens were detected, of which the top 5 pathogens were Streptococcus pyogenes (745 strains, 32.6%), Haemophilus influenzae (717 strains, 31.4%), Escherichia coli (292 strains, 12.8%), Staphylococcus aureus (222 strains, 9.7%) and Klebsiella pneumoniae (67 strains, 2.9%). Regarding different age groups, H.influenzae was the most common in children under 7 years of age (40.3%, 509/1 263), S.pyogenes (41.9%, 356/849) was predominantly in children aged 7 to 10 years, and E.coli was predominant in children aged 10 to 18 years (26.3%, 46/175). Susceptibility results showed that S.pyogenes was susceptible to penicillin G (610/610, 100.0%), ceftriaxone (525/525, 100.0%), and vancomycin (610/610, 100.0%); the resistance rates to erythromycin and clindamycin were 91.9% (501/545)and 90.7% (495/546), respectively. For H.influenzae, 32.5% (161/496) produced β-elactamase, and all strains were sensitive to meropenem (489/489, 100.0%) and levofloxacin (388/388, 100.0%), while 40.5% (202/499) were resistant to ampicillin. Among E.coli, all strains were sensitive to imipenem(100%, 175/175). The resistance rates of E.coli to levofloxacin and ceftriaxone were 29.1% (43/148) and 35.1% (59/168), respectively. A total of 48 strains of methicillin-resistant Staphylococcus aureus (MRSA) were isolated with a proportion of 28.3% (45/159) in 3 268 patients. The results of drug susceptibility test showed that all MRSA strains were sensitive to linezolid 100.0% (40/40), vancomycin (45/45, 100.0%), and tigecycline (36/36, 100.0%); the resistance rates of MRSA to penicillin G, erythromycin and clindamycin were 100% (45/45), 95.6% (43/45) and 88.9% (40/45), respectively. All methicillin-sensitive Staphylococcus aureus (MSSA) strains were sensitive to oxacillin (114/114, 100.0%), linezolid (94/94, 100.0%), vancomycin (114/114, 100.0%), and tigecycline (84/84, 100.0%); it's resistance rates to penicillin G, erythromycin and clindamycin were 78.1% (89/114), 59.7% (68/114) and 46.5% (53/114), respectively. The drug resistance rate of MSSA to penicillin G, erythromycin and clindamycin were lower than those of MRSA (χ²=11.71,19.74,23.95, respectively, all P<0.001). Conclusions: The age of consultation for pediatric infectious vulvovaginitis is mainly around 6 years. The most common pathogens are S.pyogenes, H.influenzae and Escherichia coli. Third generation cephalosporins can be used as the first choice of empirical anti-infection drugs. However, the results of drug susceptibility should be considered for targeted treatment.
Female ; Adolescent ; Child ; Humans ; Anti-Bacterial Agents/therapeutic use* ; Vancomycin/therapeutic use* ; Methicillin-Resistant Staphylococcus aureus ; Clindamycin/therapeutic use* ; Ceftriaxone/therapeutic use* ; Tigecycline/therapeutic use* ; Linezolid/therapeutic use* ; Levofloxacin/therapeutic use* ; Retrospective Studies ; Microbial Sensitivity Tests ; Staphylococcus aureus ; Staphylococcal Infections/drug therapy* ; Erythromycin/therapeutic use* ; Methicillin ; Penicillin G/therapeutic use* ; Escherichia coli ; Drug Resistance, Bacterial