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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.
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Acne Vulgar , Fármacos Dermatológicos , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença , Acne Vulgar/tratamento farmacológico , Acne Vulgar/diagnóstico , Humanos , Resultado do Tratamento , Fármacos Dermatológicos/administração & dosagem , Fármacos Dermatológicos/uso terapêutico , Administração Cutânea , Combinação de Medicamentos , Clindamicina/administração & dosagem , Clindamicina/uso terapêutico , Administração OralRESUMO
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.
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Diabetes Mellitus , Pé Diabético , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Humanos , Pé Diabético/tratamento farmacológico , Resistência a Meticilina , Staphylococcus aureus , Fatores de Risco , Infecções Estafilocócicas/complicações , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Reação em Cadeia da Polimerase Multiplex , Diabetes Mellitus/tratamento farmacológicoRESUMO
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.
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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.
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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.
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Fibrilação Atrial , Acidente Vascular Cerebral , Administração Oral , Anticoagulantes/efeitos adversos , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Dabigatrana/uso terapêutico , Humanos , Piridonas/uso terapêutico , Estudos Retrospectivos , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controleRESUMO
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.
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Bebidas Gaseificadas , Esmalte Dentário/química , Sucos de Frutas e Vegetais , Humanos , Concentração de Íons de Hidrogênio , Índia , SolubilidadeRESUMO
The complex interplay between agricultural and energy commodities has been a subject of interest in past research, gaining more relevance recently due to geopolitical events such as the conflict between Ukraine and Russia. This conflict has systematically driven up the prices of both energy and agricultural commodities. Deeply understanding the dynamic interconnections between these commodities and the cascading events resulting from the war is crucial for comprehensive market analysis. Our study leverages the connectedness or risk of spillover based on a Quantile Vector Autoregression (QVAR) model, allowing us to track connectedness over time through the examination of extreme quantiles. This approach facilitates the identification of shocks triggered by exogenous events, such as the Russian-Ukrainian war, which are often observable in these extreme quantiles or tails. The investigation encompasses several agricultural commodities: Wheat, Barley, Soybean, Soybean Oil, Soybean Meal, and Sunflower Oil, along with energy commodities represented by Crude Oil and Natural Gas. Furthermore, we considered the prices of crucial fertilizers, DAP & Urea, given their significance in agricultural production. The timeframe for our study extends from January 2010 to January 2023, providing a comprehensive review of market trends during various geopolitical scenarios. This research contributes valuable insights into the intersection of global events, agricultural trends, and energy commodity markets. The study revealed that Soybean and its derivatives consistently play a leading role in the market, with Soybean being the primary shock transmitter. This is particularly true for the upper Quantile, where Soybean and Soybean Meal's influence remains stable. On the other hand, Soybean Oil's, Barley, and Wheat risk of spillover has increased, especially during the Ukraine-Russia conflict. Finally, spillover appears symmetric, with both extreme tails exhibiting around 91-87 % connectedness, while the median Quantile is under 49 %. We observed a diminution in network complexity, manifested as a decline in network connectedness, in correlation with extreme quantiles. Policymakers can use this information to draft proactive measures, ensuring stability and sustainability in both domestic and international markets.
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The price transmission in international soybean market has been extensively examined. However, recent econometric advancements have enabled the application of dynamic connectedness methodology as outlined by Antonakakis and Gabauer (2017) [1], which is based on a Time-varying Parameter Vector Autoregressive (TVP-VAR) model. This approach captures the time-varying connectedness of time series, considering potential risk shock emitters and receivers. The connectedness index (Diebold and Yilmaz, Jan. 2012) [2] was developed using Generalized Forecast Error Variance Decomposition (GFEVD) and the Generalized Impulse Response Function (GIRF) (Koop et al., Sep. 1996; Pesaran and Shin, Jan. 1998) [3,4]. This study aims to understand the dynamic connectedness and price leadership. The research examined markets including the US Soybean futures market (Chicago Board of Trade), Rotterdam Port spot market representing the European soybean market, Paranaguá port representing Brazil, Argentina represented by Rosario Futures and Spot, and the Chinese domestic spot market and the Dalian futures on behalf of China. The research spanned approximately ten years, from September 2009 to May 2019. The findings suggest that the soybean market has reached a high level of maturity, able to withstand exogenous shocks for at least the past seven years. The net pairwise directional connectedness revealed dynamic and bidirectional causality. The dynamic connectedness index showed a highly connected and developed market in the West (Chicago Futures, Rotterdam, Paranaguá, and Rosario Futures and Spot). However, the connectedness between Western and Eastern markets was relatively low, indicating some level of market isolation. Furthermore, the pairwise connectedness index between Eastern market (China spot and Dalian Futures) was also considerable low. Lastly, Paranaguá and Rosario overtook Rotterdam as price-leading markets and were identified as the primary net transmitters of shocks, indirectly implying causality. Chicago, Rosario, and Paranaguá formed a triumvirate leading international prices, while Rotterdam adopted a secondary leading position, deviating from its historical role as the price leader.
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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.