Systematic Review and Meta-analysis on Synthetic Antifungal versus Keratolytic Agents for Topical Treatment of Pityriasis Versicolor.

Background: Pityriasis versicolor is a common fungal infection of the superficial skin layer caused by Malassezia furfur, a normal commensal in the skin. Keratolytic agents are popular, cheap, and readily available over-the-counter treatments for pityriasis versicolor. Conventional antifungal agents are more expensive, requiring prescription, and may induce resistant strains. However, evidence of their comparative safety and efficacy is still lacking. Objectives: To assess the efficacy and safety of synthetic antifungals compared to keratolytic agents in the topical treatment of pityriasis versicolor through a systematic review. Methods: We searched the following databases: MEDLINE (from 1966) through PubMed, CENTRAL (Issue 9 of 12, September 2021), EMBASE (from 1974), LILACS (from 1987); Herdin (from 1970), www.clinicaltrials.gov, www.isrctn.com, www.trialregister.nl. We contacted researchers in the field, hand searched relevant conference abstracts, and the Journal of the Philippine Dermatological Society 1992-2019. We included all randomized controlled trials involving patients with diagnosed active pityriasis versicolor where topical antifungal was compared with a topical keratolytic for treatment. Two review authors independently applied eligibility criteria, assessed risk of bias using the Cochrane collaboration tool, and extracted data from included studies. We used RevMan 5.3 to pool dichotomous outcomes using risk ratios (RR) and continuous outcomes using the mean difference (MD), using random-effects meta-analysis. We tested for statistical heterogeneity using both the Chi² test and the I² test. We presented results using forest plots with 95% confidence intervals. We planned to create a funnel plot to determine publication bias but were unable to due to few studies. A Summary of Findings table was created using GRADE profile software for the primary outcomes. Results: We included 8 RCTs with a total of 617 participants that compared azole preparations (ketoconazole, bifonazole and econazole) versus keratolytic agents (selenium sulfide, adapalene, salicylic-benzoic acid). Pooled data showed that azoles did not significantly differ from keratolytic agents for clinical cure (RR 0.99, 0.88, 1.12; 4 RCTs, N=274, I2=55%; very low-quality evidence), and adverse events (0.59 [0.17, 2.06]; very low-quality evidence) based on 6 RCTs (N=536). There were two patients given a keratolytic agent (selenium sulfide shampoo) who had acute dermatitis and discontinued treatment. Conclusion: It is uncertain whether topical azoles are as effective as keratolytic agents in clinical clearance and occurrence of adverse events in patients with pityriasis versicolor. A wider search of grey literature and local studies are warranted. Larger RCTs with low risk of bias are recommended.

Systematic review and meta-analysis on synthetic antifungal versus keratolytic agents for topical treatment of Pityriasis Versicolor

Background@#Pityriasis versicolor is a common fungal infection of the superficial skin layer caused by Malassezia furfur, a normal commensal in the skin. Keratolytic agents are popular, cheap, and readily available over-the-counter treatments for pityriasis versicolor. Conventional antifungal agents are more expensive, requiring prescription, and may induce resistant strains. However, evidence of their comparative safety and efficacy is still lacking. @*Objectives@#To assess the efficacy and safety of synthetic antifungals compared to keratolytic agents in the topical treatment of pityriasis versicolor through a systematic review.@*Methods@#We searched the following databases: MEDLINE (from 1966) through PubMed, CENTRAL (Issue 9 of 12, September 2021), EMBASE (from 1974), LILACS (from 1987); Herdin (from 1970), www.clinicaltrials.gov, www. isrctn.com, www.trialregister.nl. We contacted researchers in the field, hand searched relevant conference abstracts, and the Journal of the Philippine Dermatological Society 1992-2019. We included all randomized controlled trials involving patients with diagnosed active pityriasis versicolor where topical antifungal was compared with a topical keratolytic for treatment. Two review authors independently applied eligibility criteria, assessed risk of bias using the Cochrane collaboration tool, and extracted data from included studies. We used RevMan 5.3 to pool dichotomous outcomes using risk ratios (RR) and continuous outcomes using the mean difference (MD), using random-effects meta-analysis. We tested for statistical heterogeneity using both the Chi² test and the I² test. We presented results using forest plots with 95% confidence intervals. We planned to create a funnel plot to determine publication bias but were unable to due to few studies. A Summary of Findings table was created using GRADE profile software for the primary outcomes. @*Results@#We included 8 RCTs with a total of 617 participants that compared azole preparations (ketoconazole, bifonazole and econazole) versus keratolytic agents (selenium sulfide, adapalene, salicylic-benzoic acid). Pooled data showed that azoles did not significantly differ from keratolytic agents for clinical cure (RR 0.99, 0.88, 1.12; 4 RCTs, N=274, I2=55%; very low-quality evidence), and adverse events (0.59 [0.17, 2.06]; very low-quality evidence) based on 6 RCTs (N=536). There were two patients given a keratolytic agent (selenium sulfide shampoo) who had acute dermatitis and discontinued treatment. @*Conclusion@#It is uncertain whether topical azoles are as effective as keratolytic agents in clinical clearance and occurrence of adverse events in patients with pityriasis versicolor. A wider search of grey literature and local studies are warranted. Larger RCTs with low risk of bias are recommended.

Economic Evaluation of Selected Interleukin Inhibitors Versus Methotrexate for Moderate-to-Severe Plaque Psoriasis From the Philippine Payer Perspective.

OBJECTIVES: We conducted an economic evaluation of interleukin inhibitors (ILIs) guselkumab, ixekizumab (IXE), secukinumab (SEC), and ustekinumab to a methotrexate (MTX) comparator for biologic-naive adult Filipino patients with moderate-to-severe chronic plaque psoriasis. METHODS: A 1-year decision tree and 5-year Markov model were used to estimate incremental cost-effectiveness ratios (ICERs) in Philippine pesos (PHP) per Psoriasis Area Severity Index improvement of at least 75%. For health technology assessment purposes, we also estimated the budget impact of subsidies for SEC to a Government of the Philippines (GoP) payer. Deterministic and probabilistic sensitivity analyses were performed. Data sources included global literature and local intervention prices. RESULTS: All ILIs were more effective but also more expensive than MTX. In the base case, only IXE and SEC were cost-effective treatments at a gross domestic product-benchmarked threshold, yielding ICERs of PHP468 098.01 and PHP483 525.32 per PASI responder, respectively. GUS and UST were less likely to be cost-effective throughout a range of simulated thresholds. ICERs were most responsive to discontinuation rates and drug prices. Full subsidy of SEC for 5 years would cost the GoP PHP1.83 billion more than a similar subsidy for MTX. CONCLUSIONS: ILIs were clearly more effective than MTX, but only IXE and SEC were potentially cost-effective for a GoP payer. Any case in which SEC is fully subsidized is more expensive to the GoP than the base case. This study was limited by a lack of country-specific effectiveness data, underestimation of comparator costs, exclusion of noncutaneous and quality-of-life effects, and indirect costs.

Cutaneous manifestations of COVID-19 in a tertiary COVID-19 referral hospital in the Philippines.

BACKGROUND: Reports on COVID-19 skin manifestations and associated clinical outcomes are limited. Like viral diseases, cutaneous findings may be present and can help in confirmation and prognostication among those suspected or diagnosed with COVID-19. OBJECTIVE: To determine COVID-19 cutaneous manifestations and their association with disease severity and course. METHODS: This study was conducted in a designated COVID-19 referral hospital from January 1 to March 31, 2021. Skin manifestations recorded from January 1 to February 17 were retrospectively gathered. Reports from February 18 to March 31 were prospectively collected using a dermatologic checklist which was incorporated into all official medical records. RESULTS: A total of 507 confirmed patients with COVID-19 were included. COVID-19 skin signs were detected in 39 patients (7.7%). Morbilliform lesions were most common. Skin signs were significantly associated with severe or critical cases (odds ratio, 3.4; 95% CI, 1.3-8.7) and mortality (relative risk, 2.9; 95% CI, 2.0-4.2). LIMITATIONS: Underestimation of prevalence of COVID-19 skin signs due to exclusion of outpatient and discharged patients and the subjective assessment in the retrospective part. CONCLUSION: Cutaneous signs were significantly associated with severe/critical COVID-19 as well as death among 507 hospitalized patients in a Philippine COVID-19 referral hospital.

Modulation of Colorectal Tumor Behavior via lncRNA TP53TG1-Lipidic Nanosystem.

Long non-coding RNAs (lncRNAs) are an emerging group of RNAs with a crucial role in cancer pathogenesis. In gastrointestinal cancers, TP53 target 1 (TP53TG1) is an epigenetically regulated lncRNA that represents a promising therapeutic target due to its tumor suppressor properties regulating the p53-mediated DNA damage and the intracellular localization of the oncogenic YBX1 protein. However, to translate this finding into the clinic as a gene therapy, it is important to develop effective carriers able to deliver exogenous lncRNAs to the targeted cancer cells. Here, we propose the use of biocompatible sphingomyelin nanosystems comprising DOTAP (DSNs) to carry and deliver a plasmid vector encoding for TP53TG1 (pc(TP53TG1)-DSNs) to a colorectal cancer cell line (HCT-116). DSNs presented a high association capacity and convenient physicochemical properties. In addition, pc(TP53TG1)-DSNs showed anti-tumor activities in vitro, specifically a decrease in the proliferation rate, a diminished colony-forming capacity, and hampered migration and invasiveness of the treated cancer cells. Consequently, the proposed strategy displays a high potential as a therapeutic approach for colorectal cancer.

Sphingomyelin nanosystems loaded with uroguanylin and etoposide for treating metastatic colorectal cancer.

Colorectal cancer is the third most frequently diagnosed cancer malignancy and the second leading cause of cancer-related deaths worldwide. Therefore, it is of utmost importance to provide new therapeutic options that can improve survival. Sphingomyelin nanosystems (SNs) are a promising type of nanocarriers with potential for association of different types of drugs and, thus, for the development of combination treatments. In this work we propose the chemical modification of uroguanylin, a natural ligand for the Guanylyl Cyclase (GCC) receptor, expressed in metastatic colorectal cancer tumors, to favour its anchoring to SNs (UroGm-SNs). The anti-cancer drug etoposide (Etp) was additionally encapsulated for the development of a combination strategy (UroGm-Etp-SNs). Results from in vitro studies showed that UroGm-Etp-SNs can interact with colorectal cancer cells that express the GCC receptor and mediate an antiproliferative response, which is more remarkable for the drugs in combination. The potential of UroGm-Etp-SNs to treat metastatic colorectal cancer cells was complemented with an in vivo experiment in a xenograft mice model.

Edelfosine nanoemulsions inhibit tumor growth of triple negative breast cancer in zebrafish xenograft model.

Triple negative breast cancer (TNBC) is known for being very aggressive, heterogeneous and highly metastatic. The standard of care treatment is still chemotherapy, with adjacent toxicity and low efficacy, highlighting the need for alternative and more effective therapeutic strategies. Edelfosine, an alkyl-lysophospholipid, has proved to be a promising therapy for several cancer types, upon delivery in lipid nanoparticles. Therefore, the objective of this work was to explore the potential of edelfosine for the treatment of TNBC. Edelfosine nanoemulsions (ET-NEs) composed by edelfosine, Miglyol 812 and phosphatidylcholine as excipients, due to their good safety profile, presented an average size of about 120 nm and a neutral zeta potential, and were stable in biorelevant media. The ability of ET-NEs to interrupt tumor growth in TNBC was demonstrated both in vitro, using a highly aggressive and invasive TNBC cell line, and in vivo, using zebrafish embryos. Importantly, ET-NEs were able to penetrate through the skin barrier of MDA-MB 231 xenografted zebrafish embryos, into the yolk sac, leading to an effective decrease of highly aggressive and invasive tumoral cells' proliferation. Altogether the results demonstrate the potential of ET-NEs for the development of new therapeutic approaches for TNBC.

Perspectives of a “Good Death” among patients who have recovered from severe COVID-19, immediate family members of patients who have died from COVID-19, and health care providers who took care of patients who have died from COVID-19 in a tertiary hospital

@#<p style="text-align: justify;"><strong>Background.</strong> The premise of a "good death" is vital in delivering proper care of terminally-ill patients but the COVID-19 pandemic has brought about new challenges and necessary protocols. There is a need to explore this gap in knowledge and understand perspectives of various stakeholders in COVID-19-related deaths.<br /><br /><strong>Objectives.</strong> To describe the perception, barriers, and facilitators of a "good death" from COVID-19 survivors, relatives, and healthcare providers in the setting of a COVID-19 tertiary hospital.<br /><br /><strong>Methods.</strong> The study was done in a COVID-19 tertiary hospital in Metro Manila from September to December 2021. Three groups of target respondents were invited to participate in the study: 8 survivors of severe/critical COVID-19, 9 close relatives of COVID-19 patients who had died, and 9 healthcare providers who directly cared for COVID-19 patients who had died. Semi-structured in-depth interviews were conducted by video calls which explored themes on good death. Thematic analysis was also done.<br /><br /><strong>Results.</strong> A total of 26 respondents were included in the study: 8 COVID-19 survivors, 9 relatives, and 9 healthcare providers. The definition of "Good Death" among the participants focused on "being at peace" and having "everything in order". The experience with COVID-19 were influenced by the fear of the infection and isolation restrictions during hospitalization. Recurring themes across all groups were the fear of COVID-19 and death, importance of family in the healthcare process, difficulty in communication, and cremation viewed as necessary but not preferred.<br /><br /><strong>Conclusion.</strong> A "good death" is perceived as a peaceful, prepared experience. The main barriers of a "good death' were the strict restrictions on physically comforting and communicating with patients. Video/voice calls and compassionate health care providers facilitated a better hospitalization experience. Careful study and focus on these factors can improve interventions for terminally ill patients to achieve a "good death" in the Filipino socio-cultural context.</p>

Ocular findings among Filipino patients with Leprosy in a tertiary hospital: A cross-sectional survey

Background@#Leprosy, a chronic granulomatous disease affecting mainly the skin and peripheral nerves, has widely recognized ocular complications. It is a significant cause of visual impairment in countries where it is still prevalent, including the Philippines. @*Methods@#This was a cross-sectional study that determined the clinical profile and distribution of ocular pathology among Filipino patients with leprosy seen at a tertiary institution in the Philippines. @*Results@#A total of 67 patients consented to be included in the study and were evaluated by an ophthalmologist. Thirty-seven out of the 67 patients diagnosed with leprosy had reported ocular findings. The average age was 41.2 ± 13.1 years and the majority of patients were men (78%). Thirty-six patients were multibacillary cases, 10 (27%) had a lepra reaction, and 24 (65%) were undergoing multi-drug therapy. Three patients had varying degrees of visual acuity impairment (one was visually impaired with visual acuity [VA] 6/24-6/60, one with VA 3/60-5/60, and one with VA <3/60). Steroid-induced cataracts occurred in four patients (6%) with concurrent or previous systemic corticosteroid treatment for lepra reactions. Univariate logistic regression and Fisher’s exact test of patient-, disease-, and treatment-related variables on ocular morbidity revealed non-significant values for all variables except for age with an odds ratio of 1.1 (95% CI, 1.04, 1.16) (p = 0.001). @*Conclusions@#No ocular morbidities directly caused by leprosy were seen, and treatment-related ocular findings (steroid-induced cataracts) were the only morbidities documented. There is an age-related risk for developing ocular morbidity in patients with leprosy.

The clinical profile, wound dressings, and clinical outcomes of in-patients with pressure ulcers at a tertiary hospital in the Philippines: A seven-year retrospective study

Objectives@#Currently, there are no local studies examining wound dressing usage among pressure ulcers in Filipino patients. The study aims to provide preliminary Philippine data among in-patients with pressure ulcers: their demographic characteristics, wound characteristics, wound dressing usage, and associated outcomes per wound dressing. @*Methods@#A retrospective chart review of patients admitted at the Philippine General Hospital from 2011 to 2017 with a diagnosis of pressure ulcer was conducted. @*Results@#Eighty-five records were retrieved; 56% were female and 44% male, with a mean age of 47.67 ± 23.03 years. The mean number of ulcers per patient was 1.65 ± 1.37, mostly in Stages 2 and 3, and 90.6% were in the sacral area. Seventy-three (85.9%) had utilized at least one form of the wound dressing, mostly plain gauze (83.5%), usually with silver sulfadiazine or Dakin’s solution. Only a smaller subset used silver-impregnated dressings (10.55%) and hydrocolloid dressings (5.9%). Comparing advanced versus basic dressings for improved wound outcomes, the crude odds ratio was 3.81 (1.62 - 8.99; p-value 0.003), which on stratification accounting for bed turning, became 8.92 (1.66 - 47.97; p-value 0.009) for those bed turned and 3.05 (1.01-9.20; p-value 0.075) for those not bed turned. @*Conclusion@#Filipino in-patients with pressure ulcers were similar to those in the literature in terms of the mean number of ulcers and site of involvement. Basic gauze dressings, combined with topical agents, constitute the majority of wound dressing practice. Use of an advanced wound dressing showed a trend favoring improved outcomes, enhanced by pressure redistribution through bed repositioning.

Dermoscopic patterns in relation to the Clinicopathologic manifestations of Leprosy

Objectives@#Leprosy is a chronic granulomatous infection caused by the obligate intracellular organism Mycobacterium leprae. Current diagnostic tests for confirmation and treatment monitoring such as slit skin smear and biopsy are invasive and require time for processing, reading, and interpretation. Dermoscopy is a technique that allows the visualization of structures not readily seen by the naked eye. It can be performed at the point of care, providing a non-invasive link between clinical and histopathologic examination. This study aimed to determine the dermoscopic findings and associated clinicopathologic findings of the different forms of leprosy. @*Methods@#A cross-sectional study was conducted. All new and follow-up patients aged 19 years old and above clinically diagnosed with leprosy were invited to participate in the study during the three-month investigation period. Clinical and dermoscopic photographs of representative skin lesions were taken, and a review of slit skin smear and histopathology results was done. Data analysis was performed using Stata SE version 13. The association between dermoscopic findings and the following parameters: anatomic location, Ridley-Jopling classification, WHO classification, treatment duration, and average bacteriologic index were analyzed using Fisher’s exact test. The level of significance was set at 5%. @*Results@#A total of 57 lesions were included. Linear vessels (p=0.031), structureless areas (p=0.008), and globules (p=0.002) were found to be significantly associated with the anatomic location. Decreased hair was found to be significantly associated with treatment duration (p=0.038). No significant associations were found between dermoscopic findings and Ridley-Jopling classification, WHO classification, and ABI. Eight biopsies taken at the time of dermoscopy were reviewed, with all sites showing structureless or globular areas corresponding to the presence of granulomas on histopathology (100%). No other notable associations were observed. @*Conclusion@#Dermoscopy is a potentially useful tool to aid in the diagnosis and treatment monitoring of leprosy. Limitations of this study include the small sample size, the preponderance of subjects in the lepromatous pole, and assessments by a single trained dermoscopist. A longer study duration including a larger number of newly diagnosed leprosy patients is recommended.

Acupuncture as an adjunct to standard therapy for Pruritus in patients with Atopic Dermatitis: A patient- and assessor-blinded, randomized, placebo-controlled trial

Background@#Pruritus can impair quality of life in patients with atopic dermatitis. There is evidence that acupuncture reduces pruritus and disease severity, and improves quality of life. @*Objectives@#This study aimed to determine the efficacy of acupuncture in reducing pruritus intensity, disease severity, and medication use, and improving quality of life. @*Methods@#This was a patient- and assessor-blinded, randomized, placebo-controlled trial. Patients diagnosed with atopic dermatitis underwent twice-weekly acupuncture for 12 weeks, with an 8-week follow-up period. Baseline and weekly assessment were done using standard data collection forms and validated assessment tools. @*Results@#Thirty patients were randomized and 28 patients were eligible for the efficacy analysis. There were no significant differences in the baseline demographic and clinical characteristics between the True Acupuncture group (TA) (n=16) and Sham Acupuncture group (SA) (n=12). Both groups showed reduction in mean itch intensity (visual analogue scale, VAS) (p=0.024) but TA showed greater reduction (p=0.009) that was sustained after end of treatment. There was also a reduction in medication use in both groups. The comparable efficacy of SA to TA is attributed to similar peripheral receptive fields and stimulation of cutaneous C-fibers which depletes the neurotransmitters mediating pruritus and results in tachyphylaxis. Mild adverse events, such as petechiae and erythema, were noted in both groups and resolved spontaneously. @*Conclusion@#Acupuncture is a promising adjunct treatment in atopic dermatitis with significant reduction in pruritus, disease severity and medication use and a trend towards improved quality of life. Studies with larger sample size and comparison to acupuncture points farther from the true acupuncture points are recommended. @*Trial Registration@#Food and Drug Administration Philippine Health Research Registry ID PHRR171012-001696

Senna (Cassia) alata (Linn.) Roxb. leaf decoction as a treatment for tinea imbricata in an indigenous tribe in Southern Philippines.

BACKGROUND: Tinea imbricata, a rare form of tinea corporis caused by Trichophyton concentricum, is endemic to the T'boli tribe in the Southern Philippines. Temporary remissions and limited access to antifungal medications make its treatment a pressing public health concern. Anecdotal reports about the use of Senna alata leaf decoction as treatment exist. OBJECTIVE: To determine the efficacy of community-prepared S alata leaf decoction in the treatment of tinea imbricata. METHODS: Tinea imbricata patients were instructed to apply S alata leaf decoction for 4 weeks (28 ± 3 days). Disease severity, pruritus visual analogue scale scores (VAS) and potassium hydroxide (KOH) mounts of skin scrapings were evaluated before and after treatment. Two assessors evaluated disease severity based on photographs. Cohen's kappa statistics were used to assess diagnostic concordance. Adverse drug events were recorded. RESULTS: Twenty patients were enrolled. After 4 weeks, 95% had decreased pruritus VAS scores, with a mean decreased of 4.05 after treatment (P < .0001). There was a significant difference in disease severity scores before and after treatment (P ≤ .05) with an overall agreement of 'moderate' for both assessors (κ = 0.6, 95% CI [0.33, 0.87]). Forty per cent had negative KOH tests after treatment. None had adverse drug events. CONCLUSION: This is the first study that showed the potential of a community-prepared leaf decoction as a treatment option for tinea imbricata. Larger clinical trials establishing its efficacy, effectiveness and safety profile are recommended to enable its promotion among the indigenous people and health authorities as an accessible and affordable treatment for tinea imbricata.

In Vitro-In Silico Modeling Approach to Rationally Designed Simple and Versatile Drug Delivery Systems.

Rational design and development of a nanosystem usually relies on empirical approaches as well as a fair degree of serendipity. Understanding how nanosystems behave at the molecular level is of great importance for potential biomedical applications. In this work, we describe a nanosystem composed of two natural compounds, vitamin E and sphingomyelin, prepared by spontaneous emulsification (vitamin E-sphingomyelin nanosystems (VSNs)). Extensive characterization revealed suitable physicochemical properties, very high biocompatibility in vitro and in vivo, and colloidal stability during storage and in biological media, all relevant properties for clinical translation. We have additionally pursued a computational approach to gain an improved understanding of the assembling, structure, dynamics, and drug-loading capacity of VSNs, using both small molecules and biomolecules (resveratrol, curcumin, gemcitabine, and two peptides). The spontaneous formation of compartmentalized VSNs starting from completely disassembled molecules, observed here for the first time, was accurately assessed from the computational molecular dynamics trajectories. We describe here a synergistic in silico/in vitro approach showing the predictive power of computational simulations for VSNs' structural characterization and description of internal interaction mechanisms responsible for the association of bioactive molecules, representing a paradigm shift in the rational design of nanotechnologies as drug delivery systems for advanced personalized medicine.

Occlusive versus neurotoxic agents for topical treatment of head lice infestation: A systematic review and meta-analysis.

BACKGROUND: Topical occlusive agents, such as petroleum jelly and silicone oils, kill head lice by coating and blocking its excretory system and are unlikely to induce treatment resistance. Although a popular alternative to neurotoxic pediculicides, their efficacy and safety remain unclear. METHODS: We searched CENTRAL, MEDLINE, HERDIN (from inception to October 31, 2017), and other relevant sources for randomized controlled trials that compared topical occlusive agents with neurotoxic pediculicides to treat patients with head lice infestation. Using Cochrane collaboration methods, we selected studies, assessed risk of bias, and pooled similar studies. We assessed certainty of evidence using GRADEPro. RESULTS: Seventeen trials (N = 2005) testing occlusive agents met inclusion criteria. Risk of bias was moderate across trials, mainly from lack of blinding of participants and personnel. As a class, occlusive agents may be more pediculicidal than neurotoxic agents (final cure rate, RR 1.20, 95% CI 1.02, 1.41; 16 RCTs, N = 1779; I2 = 88%; low certainty of evidence). Post hoc subgroup analysis suggests that this benefit may be limited to synthetic combination occlusive products. Adverse effects, such as skin and eye irritation, are similar between groups (RR 0.65, 95% CI 0.36, 1.17; 15 RCTs, N = 1790; I2 = 28%; low certainty of evidence). CONCLUSIONS: In treating head louse infestation, evidence suggests occlusive agents may be superior to or equally efficacious as neurotoxic pediculicides. Adverse effects are few and minor. Future trials should use appropriate comparators and consider effects of confounders such as neurotoxin resistance. Additionally, optimal occlusive formulation and dosing regimen need to be determined.

Gabapentin for uremic pruritus: a systematic review of randomized controlled trials.

Uremic pruritus is one of the most prevalent and bothersome dermatologic symptoms in patients with end-stage renal disease. Some studies suggest a possible neuropathic cause of uremic pruritus. Gabapentin, an anticonvulsant, may control pruritus with neuropathic origin. The objectives of this study were to assess the efficacy of gabapentin in reducing pruritus scores of patients with uremic pruritus and evaluate its safety among dialysis patients. Meta-analysis of randomized controlled trials, using gabapentin as treatment for uremic pruritus among hemodialysis patients was included and analyzed using Review Manager Version 5.1.4 software. Seven out of 17 screened articles were included, with a total of 315 participants. Meta-analysis of the incidence of improved pruritus scores after treatment from four studies (n = 171) showed that treatment with gabapentin decreased the severity of uremic pruritus as compared to the placebo (risk ratio = 0.18; 95% confidence interval: 0.09, 0.33; I2  = 4%: P =< 0.00001). Six studies (n = 290) presented with incidence of adverse drug events such as dizziness, drowsiness, and somnolence. In the pooled analysis, treatment with gabapentin was associated with a higher incidence of adverse drug events compared to the comparator drugs, but the results were not significant (risk ratio = 1.3, 95% confidence interval: 0.81, 2.11; P = 0.28, I2  = 37%). The results of this systematic review suggest that gabapentin is efficacious and safe in improving uremic pruritus among dialysis patients.

Systematic review and meta-analysis on Synthetic Antifungal versus Keratolytic Agents for Topical Treatment of Pityriasis Versicolor

Background@#Pityriasis versicolor is a common fungal infection of the superficial skin layer caused by Malassezia furfur, a normal commensal in the skin. Keratolytic agents are popular, cheap, and readily available over-the-counter treatments for pityriasis versicolor. Conventional antifungal agents are more expensive, requiring prescription, and may induce resistant strains. However, evidence of their comparative safety and efficacy is still lacking. @*Objectives@#To assess the efficacy and safety of synthetic antifungals compared to keratolytic agents in the topical treatment of pityriasis versicolor through a systematic review. @*Methods@#We searched the following databases: MEDLINE (from 1966) through PubMed, CENTRAL (Issue 9 of 12, September 2021), EMBASE (from 1974), LILACS (from 1987); Herdin (from 1970), www.clinicaltrials.gov, www. isrctn.com, www.trialregister.nl. We contacted researchers in the field, hand searched relevant conference abstracts, and the Journal of the Philippine Dermatological Society 1992-2019. We included all randomized controlled trials involving patients with diagnosed active pityriasis versicolor where topical antifungal was compared with a topical keratolytic for treatment. Two review authors independently applied eligibility criteria, assessed risk of bias using the Cochrane collaboration tool, and extracted data from included studies. We used RevMan 5.3 to pool dichotomous outcomes using risk ratios (RR) and continuous outcomes using the mean difference (MD), using random-effects meta-analysis. We tested for statistical heterogeneity using both the Chi² test and the I² test. We presented results using forest plots with 95% confidence intervals. We planned to create a funnel plot to determine publication bias but were unable to due to few studies. A Summary of Findings table was created using GRADE profile software for the primary outcomes. @*Results@#We included 8 RCTs with a total of 617 participants that compared azole preparations (ketoconazole, bifonazole and econazole) versus keratolytic agents (selenium sulfide, adapalene, salicylic-benzoic acid). Pooled data showed that azoles did not significantly differ from keratolytic agents for clinical cure (RR 0.99, 0.88, 1.12; 4 RCTs, N=274, I2=55%; very low-quality evidence), and adverse events (0.59 [0.17, 2.06]; very low-quality evidence) based on 6 RCTs (N=536). There were two patients given a keratolytic agent (selenium sulfide shampoo) who had acute dermatitis and discontinued treatment. @*Conclusion@#It is uncertain whether topical azoles are as effective as keratolytic agents in clinical clearance and occurrence of adverse events in patients with pityriasis versicolor. A wider search of grey literature and local studies are warranted. Larger RCTs with low risk of bias are recommended.

Rapid review on the use of oral fatty acid supplements in the prevention or as adjunct treatment of COVID-19

Key Findings@#There is lack of clinical evidence supporting the role of oral fatty acid supplements as prevention and adjunctive therapy for COVID-19. Long-chain polyunsaturated fatty acids (PUFAs) mediate inflammation and adaptive immune responses. Omega-3 fatty acids promote anti‐inflammatory effects and reduce influenza virus replication. No clinical evidence supporting the use of oral fatty acid supplements as prevention and adjunctive therapy of COVID-19 was found. We found indirect evidence from one systematic review on acute respiratory distress syndrome (ARDS) and two longitudinal cohort studies on community-acquired pneumonia that showed non-significant and inconsistent results. The most common known side effects of omega-3-fatty acids are gastrointestinal in nature. They may also cause allergy and affect blood clotting if taken with other medications that affect clotting. There are 2 ongoing clinical trials on eicosapentaenoic fatty acids as an adjunctive therapy to standard oral nutrition supplements or standard of care in COVID-19 patients. WHO Interim guidelines, CDC interim guidelines, Infectious Diseases Society of America COVID-19 treatment guidelines, and the American Thoracic Society did not give any recommendation on the use of nutritional supplements in patients with COVID-19.

Exosome-mimetic nanoplatforms for targeted cancer drug delivery.

BACKGROUND: Lack of effective tumor-specific delivery systems remains an unmet clinical challenge for successful translation of innovative therapies, such as, therapeutic oligonucleotides. In the past decade, exosomes have been suggested to be ideal drug delivery systems with application in a broad range of pathologies including cancer, due to their organotropic properties. Tumor-derived exosomes, having tumor-homing properties, can efficiently reach cancer cells and therefore behave as carriers for improved drug delivery to the primary tumor and metastases. However, due to their complex composition, and still undefined biological functions, safety concerns arise hampering their translation to the clinics. RESULTS: We propose here the development of exosome-mimetic nanosystems (EMNs) that simulate natural tumor-derived exosomes with respect to their structure and functionality, but with a controlled composition, for the targeted delivery of therapeutic oligonucleotides to lung adenocarcinoma cells (microRNA-145 mimics). Making use of the well-known liposome technology, EMNs can be engineered, loaded with the therapeutic compounds, and tailored with specific proteins (integrin α6ß4) providing them organotropic properties. EMNs show great similarities to natural exosomes with respect to their physicochemical properties, drug loading capacity, and ability to interact with the cancer target cells in vitro and in vivo, but are easier to manufacture, can be produced at high yields, and are safer by definition. CONCLUSIONS: We have designed a multifunctional nanoplatform mimicking exosomes, EMNs, and proved their potential to reach cancer cells with a similar efficient that tumor-derived exosomes but providing important advantages in terms of production methodology and regulations. Additionally, EMNs are highly versatile systems that can be tunable for a broader range of applications.