Background::Dual antiplatelet therapy (DAPT) is key for preventing ischaemic events post-percutaneous coronary intervention (PCI). Various DAPT modifications like the shortened duration or P2Y12 inhibitor (P2Y12i) de-escalation are implemented to reduce bleeding risk. However, these strategies lack direct comparative studies. This study aimed to assess the efficacy and safety of such DAPT strategies, including de-escalated and short DAPT, in patients undergoing PCI.Methods::We searched PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases for relevant randomized controlled trials (RCTs). We performed a network meta-analysis (NMA) to estimate risk ratios (RRs) and 95% confidence intervals (CIs). The primary efficacy endpoint was major adverse cardiac events (MACEs), and the primary safety endpoint was major bleeding. Secondary endpoints included individual components of MACEs and net adverse clinical events (NACEs).Results::A total of 17 RCTs comprising 53,156 patients (median age, 62.0 years, 24.8% female) were included. NMA suggested that de-escalation DAPT was associated with a significantly lower risk of MACEs (risk ratio [RR] = 0.79, 95% confidence interval [CI] = 0.64-0.98), bleeding (RR = 0.63, 95% CI = 0.49-0.82), and NACEs (RR = 0.69, 95% CI= 0.60-0.79) compared with standard DAPT. Short DAPT followed by P2Y12i monotherapy exhibited a significantly decreased risk of major bleeding (RR = 0.63, 95% CI = 0.46-0.86) compared with standard DAPT.Conclusions::De-escalation DAPT was the most effective strategy for preventing the risk of MACEs without increasing bleeding events, while short DAPT followed by P2Y12i monotherapy was the most effective strategy for reducing the risk of bleeding among patients undergoing PCI.

Background::Dual antiplatelet therapy (DAPT) is key for preventing ischaemic events post-percutaneous coronary intervention (PCI). Various DAPT modifications like the shortened duration or P2Y12 inhibitor (P2Y12i) de-escalation are implemented to reduce bleeding risk. However, these strategies lack direct comparative studies. This study aimed to assess the efficacy and safety of such DAPT strategies, including de-escalated and short DAPT, in patients undergoing PCI.Methods::We searched PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases for relevant randomized controlled trials (RCTs). We performed a network meta-analysis (NMA) to estimate risk ratios (RRs) and 95% confidence intervals (CIs). The primary efficacy endpoint was major adverse cardiac events (MACEs), and the primary safety endpoint was major bleeding. Secondary endpoints included individual components of MACEs and net adverse clinical events (NACEs).Results::A total of 17 RCTs comprising 53,156 patients (median age, 62.0 years, 24.8% female) were included. NMA suggested that de-escalation DAPT was associated with a significantly lower risk of MACEs (risk ratio [RR] = 0.79, 95% confidence interval [CI] = 0.64-0.98), bleeding (RR = 0.63, 95% CI = 0.49-0.82), and NACEs (RR = 0.69, 95% CI= 0.60-0.79) compared with standard DAPT. Short DAPT followed by P2Y12i monotherapy exhibited a significantly decreased risk of major bleeding (RR = 0.63, 95% CI = 0.46-0.86) compared with standard DAPT.Conclusions::De-escalation DAPT was the most effective strategy for preventing the risk of MACEs without increasing bleeding events, while short DAPT followed by P2Y12i monotherapy was the most effective strategy for reducing the risk of bleeding among patients undergoing PCI.

Background: Acetaminophen is commonly used for the relief of pain and fever. Advocacy organizations recommend acetaminophen as the drug of choice in patients with kidney disease. Although some studies have suggested a risk of renal impairment after the use of acetaminophen, the effect of acetaminophen on the risk of renal impairment is unclear. The purpose of this research was to demonstrate any correlation linking acetaminophen treatment and renal impairment. Methods: We performed a systematic review and meta-analysis of the association between acetaminophen and renal impairment in adults by searching Cochrane Library, PubMed, and Embase databases from initiation to June 16, 2019. Results Of 13,097 articles identified, 5 studies (2 cohort studies and 3 case-control studies) with a total of 13,114 participants were included. In the random-effects meta-analysis of the cohort study, acetaminophen use was shown to have statistically significant effects on the increased risk of renal impairment (adjusted odds ratio 1.23; 95% confidence interval, 1.07-1.40). The results of sensitivity and subgroup analyses also suggested that acetaminophen use increases the risk of renal impairment. The Egger’s test (P = 0.607) and Begg’s test (P = 0.732) revealed no apparent publication bias.

Background: Infections by Carbapenem-Resistant Enterobacteriaceae (CRE) remain a leading cause of death in critically ill patients. Fosfomycin has been regarded as an alternative therapy for treatment of infections caused by CRE organisms. The purpose of this study is to evaluate clinical outcomes amongst patients with CRE infection who are receiving a fosfomycin dosing regimen using a Monte Carlo simulation and fosfomycin minimum inhibitory concentration (MIC). Materials and Methods: Fosfomycin MIC was defined by the E-test method. We used Fosfomycin pharmacokinetic parameters from a previously published study. The percent of the time period in which the drug concentration exceeded the MIC, or %T>MIC, used in this study were determined to be 70% of T>MIC and 100% of T>MIC, respectively. All dosing regimens were estimated for the probability of target attainment using a Monte Carlo simulation. Results: In this study, we found the MIC's of fosfomycin against CRE isolates ranged from 8 mg/L to 96 mg/L. The total daily dose of fosfomycin ranged from 16 - 24 g and was administered utilizing various fosfomycin dosing regimens to achieve the pharmacokinetic/ pharmacodynamic (PK/PD) target in pathogens with a MIC of 32 mg/L for 70%T>MIC and a MIC of 12 mg/L for 100%T>MIC, respectively. For the twelve patients who received the recommended fosfomycin dosing regimen, eleven achieved bacterial eradication for a microbiological cure rate of 91%; and of those patients achieving eradication, two died despite having negative cultures for CRE; the one remaining patient had bacterial persistence. The most commonly observed adverse drug reactions were hypernatremia (3 cases) and hypokalemia (3 cases) and acute kidney injury (3 cases). Conclusion Our findings suggest fosfomycin has tended to good efficacy when using dosing regimens that achieve the PK/PD target. Nonetheless, further validation of these regimens in larger populations is needed.

Background: Infections by Carbapenem-Resistant Enterobacteriaceae (CRE) remain a leading cause of death in critically ill patients. Fosfomycin has been regarded as an alternative therapy for treatment of infections caused by CRE organisms. The purpose of this study is to evaluate clinical outcomes amongst patients with CRE infection who are receiving a fosfomycin dosing regimen using a Monte Carlo simulation and fosfomycin minimum inhibitory concentration (MIC). Materials and Methods: Fosfomycin MIC was defined by the E-test method. We used Fosfomycin pharmacokinetic parameters from a previously published study. The percent of the time period in which the drug concentration exceeded the MIC, or %T>MIC, used in this study were determined to be 70% of T>MIC and 100% of T>MIC, respectively. All dosing regimens were estimated for the probability of target attainment using a Monte Carlo simulation. Results: In this study, we found the MIC's of fosfomycin against CRE isolates ranged from 8 mg/L to 96 mg/L. The total daily dose of fosfomycin ranged from 16 - 24 g and was administered utilizing various fosfomycin dosing regimens to achieve the pharmacokinetic/ pharmacodynamic (PK/PD) target in pathogens with a MIC of 32 mg/L for 70%T>MIC and a MIC of 12 mg/L for 100%T>MIC, respectively. For the twelve patients who received the recommended fosfomycin dosing regimen, eleven achieved bacterial eradication for a microbiological cure rate of 91%; and of those patients achieving eradication, two died despite having negative cultures for CRE; the one remaining patient had bacterial persistence. The most commonly observed adverse drug reactions were hypernatremia (3 cases) and hypokalemia (3 cases) and acute kidney injury (3 cases). Conclusion Our findings suggest fosfomycin has tended to good efficacy when using dosing regimens that achieve the PK/PD target. Nonetheless, further validation of these regimens in larger populations is needed.

PURPOSE: To develop and evaluate a simple screening tool to assess hearing loss in newborns. A derived score was compared with the standard clinical practice tool. METHODS: This cohort study was designed to screen the hearing of newborns using transiently evoked otoacoustic emission and auditory brain stem response, and to determine the risk factors associated with hearing loss of newborns in 3 tertiary hospitals in Northern Thailand. Data were prospectively collected from November 1, 2010 to May 31, 2012. To develop the risk score, clinical-risk indicators were measured by Poisson risk regression. The regression coefficients were transformed into item scores dividing each regression-coefficient with the smallest coefficient in the model, rounding the number to its nearest integer, and adding up to a total score. RESULTS: Five clinical risk factors (Craniofacial anomaly, Ototoxicity, Birth weight, family history [Relative] of congenital sensorineural hearing loss, and Apgar score) were included in our COBRA score. The screening tool detected, by area under the receiver operating characteristic curve, more than 80% of existing hearing loss. The positive-likelihood ratio of hearing loss in patients with scores of 4, 6, and 8 were 25.21 (95% confidence interval [CI], 14.69–43.26), 58.52 (95% CI, 36.26–94.44), and 51.56 (95% CI, 33.74–78.82), respectively. This result was similar to the standard tool (The Joint Committee on Infant Hearing) of 26.72 (95% CI, 20.59–34.66). CONCLUSION: A simple screening tool of five predictors provides good prediction indices for newborn hearing loss, which may motivate parents to bring children for further appropriate testing and investigations.
Birth Weight ; Child ; Cohort Studies ; Elapidae ; Evoked Potentials, Auditory, Brain Stem ; Hearing Loss* ; Hearing Loss, Sensorineural ; Hearing* ; Humans ; Infant ; Infant, Newborn* ; Joints ; Mass Screening* ; Parents ; Primary Health Care* ; Prospective Studies ; Risk Factors ; ROC Curve ; Tertiary Care Centers ; Thailand