Treatments for Moderate-to-Severe Acne Vulgaris: A Systematic Review and Network Meta-analysis.

BACKGROUND: Multiple treatment options exist for the management of moderate-to-severe acne. However, the comparative effectiveness (efficacy/safety) of moderate-to-severe acne treatments has not been systematically examined. METHODS: A systematic literature review (SLR) was conducted to identify randomized controlled trials of ≥4 weeks of treatment (topical, oral, physical, or combinations) for moderate-to-severe facial acne in patients aged ≥9 years. Efficacy outcomes included: percentage of patients achieving ≥2-grade reduction from baseline and “clear” or “almost clear” for global severity score (treatment success); absolute change in inflammatory (ILs reduction); and noninflammatory lesion counts (NILs reduction). A random-effects network meta-analysis (NMA) was conducted for the efficacy outcomes. Treatments were ranked with posterior rank plots and surface under cumulative ranking values.  Results: Eighty-five studies were included in the SLR/NMA. Topical triple-agent fixed-dose combination (FDC) gel (clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1%) and combinations of double-agent fixed-dose topical treatments with oral antibiotics (TOA3) consistently ranked in the top 3 treatments. Topical triple-agent FDC gel was numerically superior to TOA3 for treatment success (log-odds ratios: 1.84 [95% credible interval (CrI) 1.36 to 2.29]) and 1.69 (95% CrI: 1.01 to 2.32) vs placebo/vehicle). TOA3 was numerically superior to topical triple-agent FDC gel for reduction of ILs (mean difference: -8.21 [-10.33 to -6.13]) and -10.40 [-13.44 to -7.14] vs placebo/vehicle) and NILs (mean difference: -13.41 [-16.69 to -10.32] and -17.74 [-22.56 to -12.85] vs placebo/vehicle). CONCLUSIONS: Based on this SLR/NMA, topical triple-agent FDC gel was the most efficacious and safe treatment for moderate-to-severe acne. J Drugs Dermatol. 2024;23(4):     doi:10.36849/JDD.8148.

Nasal MRSA carriage is a risk factor for development of antibiotic resistance in diabetic foot ulcers and is significantly higher than diabetic and non-diabetic individuals without foot ulcer.

BACKGROUND: Diabetic foot ulcer (DFU) is a major complication of diabetes often impacted by polymicrobial infection in the wound site. Diabetic patients are immunocompromised in nature and hence vulnerable to infection once the skin barrier is breached. Microbiological culture-based methods show that Staphylococcus aureus (SA) is the most frequently isolated bacteria from the DFU wounds. SA and its most clinically important antibiotic resistant variant methicillin-resistant S. aureus (MRSA) are commonly found in the nasal vestibule and colonization of SA as well as MRSA in any wound site can aggravate the condition. We hypothesize that the presence of nasal MRSA carriage can serve as a potential risk factor contributing to the emergence of antibiotic resistance in diabetic foot ulcer wounds. METHODS: In the present study, we have compared the carriage of SA and MRSA in nasal cavity and foot skin among DFU patients (D+F+, n = 50), diabetic patients without any ulcer (D+F-, n = 50), and healthy controls (D-F-, n = 40) by using bacterial culture and PCR based methods. The D+F+, D+F- and D-F-individuals were further categorized based on the presence or absence of MRSA and clinical parameters were compared between MRSA+ ve and MRSA-ve individuals in each of the three groups mentioned above. RESULTS: Our results show that, (a) nasal MRSA carriage is significantly higher (p < 0.05) in D+F+ group than the D+F- and D-F- and significantly associated with wound MRSA carriage in D+ F+ individuals (O.R. = 4.09; 95% C.I. = 1.12-15.05) and (b) the HbA1C level is significantly higher (p < 0.02) in wound MRSA positive, compared to MRSA negative D+F+ patients. Interestingly more than half of the MRSA (64%) isolated from DFU wound were identified to be multidrug resistant. CONCLUSION: These findings strongly suggest that nasal MRSA carriage can act as a risk factor for development of antibiotic resistance in diabetic foot ulcers and it is therefore important to screen nasal and wound sites of these patients regularly. We have also developed a rapid multiplex PCR assay to detect MRSA from clinical isolates or microbial DNA isolated from clinical samples in the hospital settings.

Quantile connectedness in agri-commodity markets: What has changed over past six decades?

Agri commodities have been investigated in the past to determine their inter-relationships. However, no study has checked their risk spillover/connectedness for six decades using extreme quantiles. Various shocks (positive/negative) often pose challenges to these commodities over the past six decades. Such shocks' impact is usually observed in extreme quantiles or tails. Therefore, we have investigated fourteen agri commodities (namely Coffee, Cocoa, Soyabean, Wheat, Sugar, Orange, Chicken, Beef, Maize, Tea, Coconut Oil, Groundnut Oil, Palm Oil & Rice) from January 1, 1960 to June 1, 2022 (covering 62 years on a monthly basis), deploying Quantile VAR or QVAR as suggested by [1](extended [2,3] calibration). We found that the risk spillover/connectedness never came down for these Agri commodities. It is always at a higher level (more than 55%) proving that agri commodities remain vulnerable to various shocks throughout. Spillover looks symmetric as both the extreme tails enjoy about 92-93% connectedness levels, whereas the median is below 60%. Rice, Orange Juice, Chicken, Tea and Groundnut Oil were consistent net receivers across such a long-time frame, whereas Palm Oil, Soyabeans, Maize and Wheat were net emitters all through. Further, we found decreasing complexity (network connectedness reduction) with increased quantiles. Since these findings are over such an extended period, policy decisions can be made based on them.

COVID-19 and the quantile connectedness between energy and metal markets.

This study analyzes the relationship between clean and dirty energy sources and energy metals during the COVID-19 pandemic. We document a sharp increase in connectedness after the COVID-19 pandemic, that is asymmetric at the lower and upper quantiles, with stronger dependence among the variables at the upper quantiles. Among the energy metals, cobalt is the least connected to the energy markets. Finally, our empirical results show a switch in the net connectedness indexes of energy metals and clean energy after January 2021. Our results have implication for investors and policy makers for energy and metal under various market conditions.

Is Bitcoin's Carbon Footprint Persistent? Multifractal Evidence and Policy Implications.

The Bitcoin mining process is energy intensive, which can hamper the much-desired ecological balance. Given that the persistence of high levels of energy consumption of Bitcoin could have permanent policy implications, we examine the presence of long memory in the daily data of the Bitcoin Energy Consumption Index (BECI) (BECI upper bound, BECI lower bound, and BECI average) covering the period 25 February 2017 to 25 January 2022. Employing fractionally integrated GARCH (FIGARCH) and multifractal detrended fluctuation analysis (MFDFA) models to estimate the order of fractional integrating parameter and compute the Hurst exponent, which measures long memory, this study shows that distant series observations are strongly autocorrelated and long memory exists in most cases, although mean-reversion is observed at the first difference of the data series. Such evidence for the profound presence of long memory suggests the suitability of applying permanent policies regarding the use of alternate energy for mining; otherwise, transitory policy would quickly become obsolete. We also suggest the replacement of 'proof-of-work' with 'proof-of-space' or 'proof-of-stake', although with a trade-off (possible security breach) to reduce the carbon footprint, the implementation of direct tax on mining volume, or the mandatory use of carbon credits to restrict the environmental damage.

Reasons for discontinuing oral anticoagulation therapy for atrial fibrillation: a systematic review.

INTRODUCTION: Atrial fibrillation (AF) is the most common cardiac arrhythmia and can lead to significant comorbidities and mortality. Persistence with oral anticoagulation (OAC) is crucial to prevent stroke but rates of discontinuation are high. This systematic review explored underlying reasons for OAC discontinuation. METHODS: A systematic review was undertaken to identify studies that reported factors influencing discontinuation of OAC in AF, in 11 databases, grey literature and backwards citations from eligible studies published between 2000 and 2019. Two reviewers independently screened titles, abstracts and papers against inclusion criteria and extracted data. Study quality was appraised using Gough's weight of evidence framework. Data were synthesised narratively. RESULTS: Of 6,619 sources identified, 10 full studies and 2 abstracts met the inclusion criteria. Overall, these provided moderate appropriateness to answer the review question. Four reported clinical registry data, six were retrospective reviews of patients' medical records and two studies reported interviews and surveys. Nine studies evaluated outcomes relating to dabigatran and/or warfarin and three included rivaroxaban (n = 3), apixaban (n = 3) and edoxaban (n = 1). Bleeding complications and gastrointestinal events were the most common factors associated with discontinuation, followed by frailty and risk of falling. Patients' perspectives were seldom specifically assessed. Influence of family carers in decisions regarding OAC discontinuation was not examined. CONCLUSION: The available evidence is derived from heterogeneous studies with few relevant data for the newer direct oral anticoagulants. Reasons underpinning decision-making to discontinue OAC from the perspective of patients, family carers and clinicians is poorly understood.

Dissolution of Enamel on Exposure to Various Commercial Beverages Available in India.

AIM: The study was aimed to estimate the pH of the commonly available soft drinks in the Indian market and to assess the detrimental effects of the juices and beverages on the tooth surface by measuring the weight loss of the tooth sample. MATERIALS AND METHODS: The study was done with eight different types of commercially available carbonated drink and fruit juices available in the Indian market among which six were carbonated drinks and two were juices. Carbonated drinks experimented were Coca-Cola, Pepsi, Fanta, Mirinda, 7Up and Sprite, and two fruit juices were Tropicana orange juice and real orange juice. Ten different bottles from each category were obtained, and the pH was estimated. Each of the beverages was divided into batch of 10 containers containing the tooth sample. Weight of all samples was measured at 24, 48, 72, 96, and 120 hours with subsequently changing each solution at an interval of 24 hours. RESULTS: The mean pH of the beverages was found ranging from 2.13 ± 0.02 in Pepsi to 3.41 ± 0.02 in Tropicana on opening. The mean pH of water was found to be 6.98 ± 0.01. Among carbonated drinks, the mean weight loss after 24 hours was highest in Coca-Cola and least in 7Up. Tropicana fruit juice had a higher tooth loss than real orange juices. When compared with water, the tooth loss was significantly higher in Coca-Cola after all specified time (hours). CONCLUSION: The pH of both carbonated drinks and fruit juices was below the critical pH. The weight loss was also seen after every 24 hours in all the carbonated drinks and beverages. The study showed that these commercial beverages are harmful to the tooth structures, and hence, the health professionals play a major role in educating the population about its effects and advising them to use these products precisely. CLINICAL SIGNIFICANCE: The change in lifestyle has increased the demand of soft drinks and artificial juice in Indian market. The use of these carbonated drinks and fruit juices causes damage to the tooth structure in all ages, especially in young mass. Our study provides an idea about the deleterious effects of these commercial drinks on dental hard tissues.