Scedosporiosis and lomentosporiosis: modern perspectives on these difficult-to-treat rare mold infections.

SUMMARYAlthough Scedosporium species and Lomentospora prolificans are uncommon causes of invasive fungal diseases (IFDs), these infections are associated with high mortality and are costly to treat with a limited armamentarium of antifungal drugs. In light of recent advances, including in the area of new antifungals, the present review provides a timely and updated overview of these IFDs, with a focus on the taxonomy, clinical epidemiology, pathogenesis and host immune response, disease manifestations, diagnosis, antifungal susceptibility, and treatment. An expansion of hosts at risk for these difficult-to-treat infections has emerged over the last two decades given the increased use of, and broader population treated with, immunomodulatory and targeted molecular agents as well as wider adoption of antifungal prophylaxis. Clinical presentations differ not only between genera but also across the different Scedosporium species. L. prolificans is intrinsically resistant to most currently available antifungal agents, and the prognosis of immunocompromised patients with lomentosporiosis is poor. Development of, and improved access to, diagnostic modalities for early detection of these rare mold infections is paramount for timely targeted antifungal therapy and surgery if indicated. New antifungal agents (e.g., olorofim, fosmanogepix) with novel mechanisms of action and less cross-resistance to existing classes, availability of formulations for oral administration, and fewer drug-drug interactions are now in late-stage clinical trials, and soon, could extend options to treat scedosporiosis/lomentosporiosis. Much work remains to increase our understanding of these infections, especially in the pediatric setting. Knowledge gaps for future research are highlighted in the review.

Costs associated with invasive Scedosporium and Lomentospora prolificans infections: a case-control study.

BACKGROUND: Little is known about the short- and long-term healthcare costs of invasive Scedosporium/Lomentospora prolificans infections, particularly in patient groups without haematological malignancy. This study investigated excess index hospitalization costs and cumulative costs of these infections. The predictors of excess cost and length of stay (LOS) of index hospitalization were determined. These estimates serve as valuable inputs for cost-effectiveness models of novel antifungal agents. METHODS: A retrospective case-control study was conducted at six Australian hospitals. Cases of proven/probable invasive Scedosporium/L. prolificans infections between 2011 and 2021 (n = 34) were matched with controls (n = 66) by predefined criteria. Cost data were retrieved from activity-based costing systems and analysis was performed from the Australian public hospital perspective. All costs were presented in 2022 Australian dollars (AUD). Median regression analysis was used to adjust excess costs of index hospitalization whereas cumulative costs up to 1.5 years follow-up were estimated using interval-partitioned survival probabilities. RESULTS: Invasive Scedosporium/L. prolificans infections were independently associated with an adjusted median excess cost of AUD36 422 (P = 0.003) and LOS of 16.27 days (P < 0.001) during index hospitalization. Inpatient stay was the major cost driver (42.7%), followed by pharmacy cost, of which antifungal agents comprised 23.8% of the total cost. Allogeneic haematopoietic stem cell transplant increased the excess cost (P = 0.013) and prolonged LOS (P < 0.001) whereas inpatient death within ≤28 days reduced both cost (P = 0.001) and LOS (P < 0.001). The median cumulative cost increased substantially to AUD203 292 over 1.5 years in cases with Scedosporium/L. prolificans infections. CONCLUSIONS: The economic burden associated with invasive Scedosporium/L. prolificans infections is substantial.

Single-centre study of therapeutic drug monitoring of posaconazole in lung transplant recipients: factors affecting trough plasma concentrations.

Objectives: This study describes therapeutic drug monitoring (TDM) of posaconazole suspension and modified release (MR) tablets in lung transplant (LTx) recipients and evaluates factors that may affect posaconazole trough plasma concentration (Cmin). Methods: A single-centre, retrospective study evaluating posaconazole Cmin in LTx recipients receiving posaconazole suspension or MR tablets between January 2014 and December 2016. Results: Forty-seven LTx patients received posaconazole suspension, and 78 received the MR tablet formulation; a total of 421 and 617 Cmin measurements were made, respectively. Posaconazole was concurrently administered with proton pump inhibitor in ≥ 90% of patients. The median (IQR) of initial posaconazole Cmin following 300 mg daily of posaconazole tablet was significantly higher than that of 800 mg daily of posaconazole suspension [1.65 (0.97-2.13) mg/L versus 0.81 (0.48-1.15) mg/L, P < 0.01]. Variability in posaconazole Cmin was apparent regardless of the formulations prescribed and dose adjustments were routinely undertaken to maintain therapeutic Cmin. A clear dose-response relationship was observed in patients receiving posaconazole MR tablets. Non-specific adverse events (fatigue, tremor, lethargy, sweating, nausea/vomiting and weight loss) were reported in 3/78 (4%) patients receiving posaconazole MR tablets. Posaconazole Cmin in these three patients was determined to be 9.6, 6.2 and 2.3 mg/L. Conclusions: The current study has provided clinically important insights into the TDM of posaconazole in LTx recipients. Routine TDM should be undertaken in LTx recipients receiving posaconazole suspension and/or MR tablets.

Economic evaluation of micafungin versus liposomal amphotericin B (LAmB) for treating patients with candidaemia and invasive candidiasis (IC) in Turkey.

Micafungin was reported to be non-inferior to liposomal amphotericin B (LAmB) in treating patients with candidaemia and invasive candidiasis (IC). The current study aimed to evaluate the economic impact of using micafungin versus LAmB for treatment of candidaemia and IC in Turkey. A decision analytic model, which depicted economic consequences upon administration of micafungin or LAmB for treating patients with candidaemia and IC in the Turkish hospitals, was constructed. Patients were switched to an alternative antifungal agent if initial treatment failed due to mycological persistence. All patients were followed up until treatment success or death. Outcome probabilities were obtained from published literature and cost inputs were derived from the latest Turkish resources. Expert panels were used to estimate data that were not available in the literature. Cost per patient treated for each intervention was then calculated. Sensitivity analyses including Monte Carlo simulation were performed. For treatment of candidaemia and IC, micafungin (€4809) was associated with higher total cost than LAmB (€4467), with an additional cost of €341 per treated patient. Cost of initial antifungal treatment was the major cost driver for both comparators. The model outcome was robust over a wide variation in input variables except for drug acquisition cost and duration of initial antifungal treatment with micafungin or LAmB. LAmB is cost-saving relative to micafungin for the treatment of candidaemia and IC from the Turkish hospital perspective, with variation in drug acquisition cost of the critical factor affecting the model outcome.

Clinical effectiveness of early posaconazole suspension pre-emptive therapy in lung transplant recipients: The Alfred's experience.

Objectives: This study describes the clinical outcomes and therapeutic drug monitoring (TDM) following posaconazole suspension pre-emptive therapy in lung transplant (LTx) recipients. Methods: This was a single-centre, retrospective cohort study evaluating posaconazole suspension pre-emptive therapy in LTx recipients between January 2009 and December 2015. Results: Forty-two LTx recipients were prescribed posaconazole suspension pre-emptively. Aspergillus fumigatus was the most commonly isolated fungal organism. Of the patients receiving posaconazole suspension as the initial antifungal post-LTx, 93% had eradication of colonization at 6 months after commencing therapy. In contrast, only 61% had eradication of fungal colonization when posaconazole suspension was administered following initial therapy with voriconazole. Posaconazole suspension appeared to be well tolerated, although one case was curtailed following concern about abnormal liver function and another due to nausea/vomiting. TDM was performed in 37 patients. The initial median (IQR) trough plasma concentration ( C min ) following 400 mg twice-daily posaconazole suspension was 0.78 (0.46-1.19) mg/L. Doses beyond 800 mg daily did not appear to result in a higher median C min. Conclusions: Early initiation of posaconazole suspension pre-emptive therapy in LTx recipients appears to be well tolerated and may potentially afford favourable clinical outcomes.

Pricing appraisal of anti-cancer drugs in the South East Asian, Western Pacific and East Mediterranean Region.

BACKGROUND: Globally, cancer is one of the leading causes of mortality. High treatment cost, partly owing to higher prices of anti-cancer drugs, presents a significant burden on patients and healthcare systems. The aim of the present study was to survey and compare retail prices of anti-cancer drugs between high, middle and low income countries in the South-East Asia, Western Pacific and Eastern Mediterranean regions. METHODS: Cross-sectional survey design was used for the present study. Pricing data from ten counties including one from South-East Asia, two from Western Pacific and seven from Eastern Mediterranean regions were used in this study. Purchasing power parity (PPP)-adjusted mean unit prices for 26 anti-cancer drug presentations (similar pharmaceutical form, strength, and pack size) were used to compare prices of anti-cancer drugs across three regions. A structured form was used to extract relevant data. Data were entered and analysed using Microsoft Excel®. RESULTS: Overall, Taiwan had the lowest mean unit prices while Oman had the highest prices. Six (23.1%) and nine (34.6%) drug presentations had a mean unit price below US$100 and between US$100 and US$500 respectively. Eight drug presentations (30.7%) had a mean unit price of more than US$1000 including cabazitaxel with a mean unit price of $17,304.9/vial. There was a direct relationship between income category of the countries and their mean unit price; low-income countries had lower mean unit prices. The average PPP-adjusted unit prices for countries based on their income level were as follows: low middle-income countries (LMICs): US$814.07; high middle income countries (HMICs): US$1150.63; and high income countries (HICs): US$1148.19. CONCLUSIONS: There is a great variation in pricing of anticancer drugs in selected countires and within their respective regions. These findings will allow policy makers to compare prices of anti-cancer agents with neighbouring countries and develop policies to ensure accessibility and affordability of anti-cancer drugs.

Economic Evaluations on Antimicrobial Stewardship Programme: A Systematic Review.

PURPOSE: To systematically review studies on cost-effectiveness of implementing Antimicrobial stewardship programmes (ASP) in the hospital setting. METHODS: A systematic literature search was performed using electronic databases, such as EMBASE, PubMed/Medline, CINAHL, NHS and CEA Registry from 2000 until 2017. The quality of each included study was assessed using Joanna Briggs Institute Critical Appraisal Checklist for Economic Evaluations and Consolidated Health Economic Evaluation Reporting Standards Statement checklist. RESULTS: Of the 313 papers retrieved, five papers were included in this review after assessment for eligibility. The majority of the studies were cost-effectiveness studies, comparing ASP to standard care. Four included economic studies were conducted from the provider (hospital) perspective while the other study was from payer (National Health System) perspective. The cost included for economic analysis were as following: personnel costs, warded cost, medical costs, procedure costs and other costs. CONCLUSIONS: All studies were generally well-conducted with relatively good quality of reporting. Implementing ASP in the hospital setting may be cost-effective. However, comprehensive cost-effectiveness data for ASP remain relatively scant, underlining the need for more prospective clinical and epidemiological studies to incorporate robust economic analyses into clinical decisions. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Cost-effectiveness analysis of anidulafungin vs fluconazole for the treatment of invasive candidiasis (IC) in Turkey.

Anidulafungin has been shown to be non-inferior to, and possibly more efficacious, than fluconazole in treating patients with invasive candidiasis (IC). This study aimed to determine the cost-effectiveness of anidulafungin vs fluconazole for treatment of IC in the Turkish setting. A decision analytic model was constructed to depict downstream economic consequences of using anidulafungin or fluconazole for treatment of IC in the Turkish hospitals. Transition probabilities (ie treatment success, observed or indeterminate treatment failures) were obtained from a published randomised clinical trial. Cost inputs were from the latest Turkish resources. Data not available in the literature were estimated by expert panels. Sensitivity analyses were performed to assess the robustness of the model outcome. While anidulafungin [TL 17 171 (USD 4589)] incurred a higher total cost than fluconazole [TL 8233 (USD 2200) per treated patient, treatment with anidulafungin was estimated to save an additional 0.58 life-years, with an incremental cost-effectiveness ratio of TL 15 410 (USD 4118) per life-years saved. Drug acquisition cost and hospitalisation were the main cost drivers for anidulafungin and fluconazole arms respectively. The model findings were robust over a wide range of input variables except for anidulafungin drug cost. Anidulafungin appears to be a cost-effective therapy in treating IC from the Turkish hospital perspective.

Open-Label Study of Absorption and Clearance of 1% Voriconazole Eye Drops.

Twenty participants undergoing elective cataract surgery received 1% voriconazole eye drops (1 drop per eye) either 20, 40, 60, or 80 min before surgery. Median voriconazole concentrations of 1.9 to 3.2 mg/liter in aqueous humor samples were attained over the first 80 min, which were higher than in vitro MIC90 values for typical fungi that cause keratitis.

The immediate effect of traditional Malay massage on substance P, inflammatory mediators, pain scale and functional outcome among patients with low back pain: study protocol of a randomised controlled trial.

BACKGROUND: The treatment of low back pain is very challenging due to the recurrent nature of the problem. It is believed that traditional Malay massage helps to relieve such back pain but there is a lack of scientific evidence to support both the practice of traditional Malay massage and the mechanism by which it exerts its effect. The aim of this study is to investigate the immediate effect of traditional Malay massage on the pain scale, substance P, inflammatory mediators, and functional outcomes among low back pain patients. METHODS: A non-blinded, randomised controlled trial will be conducted. A total of sixty-six patients who fulfil the inclusion criteria will be recruited. The participants will be randomly allocated into intervention (traditional Malay massage) and control (relaxation position) groups. Blood and saliva samples will be collected before and immediately after intervention. All collected samples will be analysed. The primary outcomes are the changes in the level of substance P in both saliva and blood samples between both groups. The secondary outcomes include the levels of inflammatory mediators [i.e. TNF-α, IL-1ß, IL-8, monocyte chemotactic protein-1, IL-6 and IL-10, and the soluble form of the intercellular adhesion molecule], the pain intensity as measured by a visual analogous scale and functional outcomes using the Roland-Morris Disability Questionnaire. DISCUSSION: Massage is a type of physical therapy that has been proven to be potentially capable of reducing unpleasant pain sensations by a complex sensory response and chemical mediators such as substance P and various inflammatory mediators. Previous studies conducted using Thai, Swedish, or other forms of massage therapies, have showed inconsistent findings on substance P levels pre and post the interventions. Each massage genre varies in terms of massage and joint mobilization points, as well as the lumbar spinous process. Traditional Malay massage, known locally as "Urut Melayu", involves soft-tissue manipulation of the whole body applied using the hands and fingers. This massage technique combines both deep muscular tissue massage and spiritual rituals. This trial is expected to give rise to new knowledge underlying the mechanisms for pain and inflammation relief that are activated by traditional Malay massage. TRIAL REGISTRATION: Australian New Zealand Clinical Trials ACTRN12615000537550 .

Economic evaluation of micafungin vs. liposomal amphotericin B (LAmB) for the treatment of candidaemia and invasive candidiasis (IC).

Micafungin was non-inferior to liposomal amphotericin B (LAmB) for the treatment of candidaemia and invasive candidiasis (IC) in a major clinical trial. The present study investigated the economic impact of micafungin vs. LAmB in treating candidaemia and IC. A decision analytical model was constructed to capture downstream consequences of using micafungin or LAmB as primary definitive therapy. The main outcomes were treatment success and treatment failure due to mycological persistence, or death. Outcome probabilities were derived from key published sources. Resource used was estimated by an expert panel and cost inputs were from the latest Australian resources. The analysis was from an Australian hospital perspective. Sensitivity analyses using Monte Carlo simulation were conducted. Micafungin (AU$61 426) had a lower total cost than LAmB (AU$72 382), with a total net cost-saving of AU$10 957 per patient. This was primarily due to the lower cost associated with initial antifungal treatment and shorter length of stay for patients in the micafungin arm. Hospitalisation was the main cost driver for both arms. Results were robust over a wide range of variables. The uncertainty analysis demonstrated that micafungin had a 99.9% chance of being cost-saving compared with LAmB. Micafungin was associated with cost-saving relative to LAmB in the treatment of candidaemia and IC in Australia.

"A person who do not smoke will not understand a person who smokes and trying to quit " Insights From Quit Smoking Clinics' Defaulters: A Qualitative Study.

This study explored the factors contributing to discontinuation of people who smoke (PWS) from quit smoking clinic prior to achieving 6-month abstinence. Fifteen active PWS were interviewed via telephone and face-to-face. Interviews were audio-recorded, transcribed and analysed using thematic analysis. At individual level, low intrinsic motivation including unreadiness to quit, low self-efficacy and ambivalence on smoking cessation were barriers to attain successful cessation. Influence of extrinsic factors such as work-related factors, social interaction and ill-health burden lead to poor commitment with QSC. At the clinic level, healthcare professional's competency, personal attributes, pharmacotherapy's efficacy, safety and availability were important components that may affect a participant's effort to quit. Working commitment was highlighted as the primary barrier for a successful cessation. Hence, effective intervention and collaborative effort between healthcare facilities and employers are essential to optimise cessation adherence among employees who smoke which subsequently will enhance their abstinence rates.

The antifungal pipeline for invasive fungal diseases: what does the future hold?

INTRODUCTION: Over the last two decades, we have experienced pressing needs for new additions to the antifungal armamentarium given the emergence of resistant fungi, the growth of at-risk patient populations for invasive fungal diseases (IFD), the high morbidity and mortality associated with IFD. AREAS COVERED: The current review will discuss the five promising antifungal agents for IFD (i.e. fosmanogepix, ibrexafungerp, olorofim, rezafungin, and opelconazole), now in the late-phase clinical studies, and likely to be available for clinical use in the near future. For each agent, we describe its mechanism of action, pharmacokinetic and pharmacodynamic properties, spectrum of activity as well as the safety and efficacy data, including findings from ongoing clinical trials. The potential roles of these novel antifungals in clinical practice and the key considerations for clinical use will also be discussed. EXPERT OPINION: There are unmet needs of these novel agents that should be addressed in the future studies. These include defining their indications and benefits, how to best target them appropriately, surveillance and stewardship of their use.

Invasive Scedosporium and Lomentospora prolificans Infections in Australia: A Multicenter Retrospective Cohort Study.

Background: Management of Scedosporium/Lomentospora prolificans infections remains challenging. We described predisposing factors, clinical manifestations, and outcomes of these rare mold infections, including predictors of early (1-month) and late (18-month) all-cause mortality and treatment failure. Methods: We conducted a retrospective Australian-based observational study of proven/probable Scedosporium/L prolificans infections from 2005 to 2021. Data on patient comorbidities, predisposing factors, clinical manifestations, treatment, and outcomes up to 18 months were collected. Treatment responses and death causality were adjudicated. Subgroup analyses, multivariable Cox regression, and logistic regression were performed. Results: Of 61 infection episodes, 37 (60.7%) were attributable to L prolificans. Forty-five of 61 (73.8%) were proven invasive fungal diseases (IFDs), and 29 of 61 (47.5%) were disseminated. Prolonged neutropenia and receipt of immunosuppressant agents were documented in 27 of 61 (44.3%) and 49 of 61 (80.3%) episodes, respectively. Voriconazole/terbinafine was administered in 30 of 31 (96.8%) L prolificans infections, and voriconazole alone was prescribed for 15 of 24 (62.5%) Scedosporium spp infections. Adjunctive surgery was performed in 27 of 61 (44.3%) episodes. Median time to death post-IFD diagnosis was 9.0 days, and only 22 of 61 (36.1%) attained treatment success at 18 months. Those who survived beyond 28 days of antifungal therapy were less immunosuppressed with fewer disseminated infections (both P < .001). Disseminated infection and hematopoietic stem cell transplant were associated with increased early and late mortality rates. Adjunctive surgery was associated with lower early and late mortality rates by 84.0% and 72.0%, respectively, and decreased odds of 1-month treatment failure by 87.0%. Conclusions: Outcomes associated with Scedosporium/L prolificans infections is poor, particularly with L prolificans infections or in the highly immunosuppressed population.

Stability of extemporaneously prepared 0.5-percent caspofungin eye drops: a potential cost-savings exercise.

While the successful use of topical caspofungin for patients has been reported, topical caspofungin is not commercially available and its stability is unknown, limiting its usefulness in treating fungal keratitis. Caspofungin (0.5%) eye drops were aseptically prepared, and the concentrations were measured using a validated high-performance liquid chromatography (HPLC) analysis. The preparations remained stable for 28 days under refrigerated condition but not at 25.0 °C. Our study supports the cost-saving use of caspofungin eye drops in the clinical setting.

Hepatoprotection of Probiotics Against Non-Alcoholic Fatty Liver Disease in vivo: A Systematic Review.

Probiotic supplements have been increasingly reported for their usefulness in delaying the development and progression of non-alcoholic fatty liver disease (NAFLD). Literature on the impact of probiotics on NAFLD covered various aspects of the disease. This study was undertaken to systematically review in vivo findings on hepatoprotection of probiotics against NAFLD. The literature search was performed through Cochrane, PubMed/MEDLINE, Embase, and Web of Science databases. Interventions of known probiotics in NAFLD-induced animal model with at least one measurable NAFLD-related parameter were included. The data were extracted by all authors independently. Quality assessment was conducted using the Systematic Review Center for Laboratory animal Experimentation (SYRCLE's) Risk of Bias (RoB) tool. P-values of measures were compared inter- and intra-study for each parameter. Forty-four probiotic-based studies of NAFLD-induced rodents were shortlisted. The majority of the studies were presented with low/unclear risk of bias. Probiotics improved the histopathology of NAFLD rodents (primary outcome). Most of the probiotic-supplemented NAFLD rodents were presented with mixed effects on serum liver enzymes but with improved hepatic and serum lipid profiles (including increased serum high-density lipoprotein cholesterol). The findings were generally accompanied by downregulation of hepatic lipogenic, oxidative, and inflammatory signallings. Probiotics were found to modulate gut microbiota composition and its products, and intestinal permeability. Probiotics also resulted in better glycaemic control and reduced liver weight. Altogether, the present qualitative appraisals strongly implied the hepatoprotective potential of probiotics against NAFLD in vivo.

Differential gut microbiota and intestinal permeability between frail and healthy older adults: A systematic review.

This systematic review appraised previous findings on differential gut microbiota composition and intestinal permeability markers between frail and healthy older adults. A literature search was performed using PubMed, Scopus, ScienceDirect and the Cochrane Library. Relevant studies were shortlisted based on inclusion and exclusion criteria as well as assessed for risk of bias. The primary outcome was the differential composition of gut microbiota and/ or intestinal permeability markers between frail and healthy older adults. A total of 10 case-control studies and one cohort study were shortlisted. Based on consistent findings reported by more than one shortlisted study, the microbiota of frail older adults was characterised by decreased phylum Firmicutes, with Dialister, Lactobacillus and Ruminococcus being the prominent genera. Healthy controls, on the other hand, exhibited higher Eubacterium at the genera level. In terms of intestinal permeability, frail older adults were presented with increased serum zonulin, pro-inflammatory cytokines (TNF-α, HMGB-1, IL-6, IL1-ra, MIP-1ß) and amino acids (aspartic acid and phosphoethanolamine) when compared to healthy controls. Altogether, frail elderlies had lower gut microbiota diversity and lower abundance of SCFA producers, which may have led to leaky guts, upregulated pro-inflammatory cytokines, frailty and sarcopenia.

Global Consumption Trend of Antifungal Agents in Humans From 2008 to 2018: Data From 65 Middle- and High-Income Countries.

BACKGROUND: Understanding the trend of global antifungal agent consumption could assist with identification of global healthcare policy inadequacies and promote accessibility and availability of antifungal agents. METHODS: Using pharmaceutical sales data from the IQVIA-multinational integrated data analysis system database, we assessed use of systemic antifungal agents in humans in 27 middle- and 38 high-income countries from 2008 through 2018. RESULTS: Consumption of systemic antifungal agents increased from 0.50 (in 2008) to 0.92 defined daily dose (DDD)/1000 inhabitants/day (in 2018), with a compound annual growth rate of 6.2%. High-income countries remain major consumers of antifungal agents with large variance in quantities consumed, with a gradual decline in consumption in recent years. Consumption in middle-income countries increased. Itraconazole (0.32 DDD/1000 inhabitants/day), terbinafine (0.30 DDD/1000 inhabitants/day), and fluconazole (0.23 DDD/1000 inhabitants/day) were the most commonly used antifungal agents in middle- and high-income countries in 2018. Following incorporation into the World Health Organization Essential Medicines List, itraconazole consumption in middle-income countries surged. Consumption of ketoconazole slowly declined, with 5.04% annual decrease, probably due to labelling changes in 2013 to reflect hepatotoxicity concerns. The use of polyenes (0.004 DDD/1000 inhabitants/day) and echinocandins (0.003 DDD/1000 inhabitants/day) were lowest among all the antifungal drug classes. CONCLUSION: Global consumption of triazoles and terbinafine has gradually increased in middle- and high-income countries. Life-saving antifungal agents, including echinocandins and polyenes, are available only parenterally and may be underutilized, mainly in middle-income countries. Future research on country-specific epidemiology is warranted to guide health policy coordination to ensure equitable access to appropriate use of antifungal agents.

A systematic review on the effectiveness of herbal interventions for the treatment of male infertility.

Background: Male infertility is an emerging health issue in the world today. Surgical interventions for the treatment of male infertility are available but are quite expensive. Herbal interventions pose a popular alternative for the treatment of infertility. However, much has to be learned regarding their safety and efficacy. Objective: The aim of the study was to investigate the efficacy of herbal interventions in male infertility and also assess the possibility of these interventions as complementary and alternative medicine (CAM) in the future. Method: From inception until 16 December 2021, all articles emphasizing the efficacy of herbal interventions in the treatment of male infertility are included in this review. Seven databases are searched. The literature obtained is screened and extracted. Semen parameters, hormonal concentration, and conception are the outcomes of interest. Results: A total of 19 articles were included in this review. Herbal interventions might improve semen parameters in males with infertility. Among all the interventions, Hochu-ekki-to and W. somnifera have shown the most promising results and should be studied further in a larger sample size. Conclusion: This systematic review has demonstrated the efficacy of herbal interventions, especially Hochu-ekki-to and W. somnifera, in treating male infertility.

Penetration of topically administered 0.5-percent caspofungin eye drops into human aqueous humor.

Ten participants attending elective anterior segment eye surgery received 0.5% caspofungin eye drops either 1 drop hourly for 4 h or 1 drop an hour before surgery. The eye drops were generally well tolerated. In the absence of inflammation or corneal abrasion, topical caspofungin does not achieve clinically relevant concentrations.