SAMe-TT2R2 to Predict Clinical Outcomes and Time in Therapeutic Range in Patients on Vitamin K Antagonists: A Systematic Review and Meta-Analysis.

BACKGROUND: The SAMe-TT2R2 score identifies patients on vitamin K antagonists (VKAs) who are more likely to have poor time in therapeutic range (TTR); however, the association between SAMe-TT2R2 and clinical outcomes remains controversial. OBJECTIVES: The objective is to assess the association of SAMe-TT2R2 score with clinical outcomes and poor TTR in patients on VKAs. METHODS: We searched using the term "SAMe-TT2R2." Original articles reporting clinical outcomes and SAMe-TT2R2 scores before October 2021 were included. Odds ratios (ORs) of clinical outcomes, diagnostic accuracy parameters of poor TTR (<60%-70%), and mean TTR were extracted. Meta-analysis was performed using random-effects models. RESULTS: Ten studies were included (N = 22 894); 4 showed pooled changes in TTR of -3.61% (95% CI:-4.88% to -2.35%) and -3.98% (95% CI: -6.08% to -1.87%) at SAMe-TT2R2 scores ≥2 and ≥3, respectively, compared with lower scores. The diagnostic accuracy parameters for poor TTR were too heterogeneous to conclude. SAMe-TT2R2 ≥3 significantly correlated with all adverse events (OR = 1.43 [95% CI: 1.29-1.54; P < 0.001]), composite thromboembolism (OR = 1.53 [95% CI: 1.19-1.97; P = 0.001]), and composite bleeding (OR = 1.33 [95% CI: 1.12-1.59; P = 0.001] regardless of the indication, while an SAMe-TT2R2 ≥2 significantly correlated with mortality (OR = 1.32 [95% CI: 1.02-1.70; P = 0.033]). We found no relationship between an SAMe-TT2R2 ≥3 and mortality or between a score ≥2 and clinical outcomes. CONCLUSIONS AND RELEVANCE: Patients on VKAs with SAMe-TT2R2 ≥3 experienced more adverse events, bleeding, and thromboembolism compared with patients who had an SAMe-TT2R2 <3. However, the score had limited and inconclusive predictability for poor TTR in the study.

Effect of Laser and Energy-based Device Therapies to Minimize Surgical Scar Formation: A Systematic Review and Network Meta-analysis.

Utilization of lasers and energy-based devices for surgical scar minimization has been substantially evaluated in placebo-controlled trials. The aim of this study was to compare reported measures of efficacy of lasers and energy-based devices in clinical trials in preventing surgical scar formation in a systematic review and network meta-analyses. Five electronic databases, PubMed, Scopus, Embase, ClinicalTrials.gov, and the Cochrane Library, were searched to retrieve relevant articles. The search was limited to randomized controlled trials that reported on clinical outcomes of surgical scars with treatment initiation no later than 6 months after surgery and a follow-up period of at least 3 months. A total of 18 randomized controlled trials involving 482 participants and 671 postsurgical wounds were included in the network meta-analyses. The results showed that the most efficacious treatments were achieved using low-level laser therapy) (weighted mean difference -3.78; 95% confidence interval (95% CI) -6.32, -1.24) and pulsed dye laser (weighted mean difference -2.46; 95% CI -4.53, -0.38). Nevertheless, low-level laser therapy and pulsed dye laser demonstrated comparable outcomes in surgical scar minimization (weighted mean difference -1.32, 95% CI -3.53, 0.89). The findings of this network meta-analyses suggest that low-level laser therapy and pulsed dye laser are both effective treatments for minimization of scar formation following primary closure of surgical wounds with comparable treatment outcomes.

Effects of instructional video and community radio broadcasting interventions to improve knowledge and behavior of antibiotic use in the COVID-19 era.

BACKGROUND: Antibiotic overuse is a serious health issue. It has been demonstrated that improper antibiotic use is linked to a lack of knowledge in the public. To encourage judicious antibiotic use in the COVID-19 ERA, it is critical to provide accessible and secure therapies. OBJECTIVES: This study aimed to assess the effects of instructional video and community radio broadcasting interventions on knowledge and behavior of antibiotic use. METHODS: Adults over the age of 20 were enrolled in a quasi-experimental study. A total of 369 representatives were divided into two groups: 185 participants in the control group and 184 participants in the intervention group. Data were collected twice, before and after the educational program by community health workers. Both descriptive and inferential statistics were used to analyze the data. RESULTS: The participants' average age was 56.4 ± 0.6 years. Most of the respondents were female (264, 71.5%) and had only received an elementary education (186, 50.4%). A mean difference score was produced for the control and intervention groups. Both groups experienced a statistically significant gain in mean difference score of knowledge following the educational program (3.42 ± 4.18, [95% CI 2.81-4.02] vs 5.42 ± 4.97, [95% CI 4.69-6.14]) (P < 0.001). A mean difference score was produced with behavior (1.78 ± 3.45, [95% CI 1.28-2.28] vs 2.77 ± 3.06, [95% CI 2.28-3.27]) (P < 0.001). A mean difference in knowledge score between the groups was greater, with the intervention group scoring higher; all significant variables were controlled by multivariable regression analysis (1.31 [95% CI 0.53-2.09]) (P = 0.001). Similarly, a mean difference behavior score (1.34 [95% CI 0.82-1.86]) (P < 0.001). CONCLUSION: The integration of an educational poster, instructional video, and community radio broadcasting interventions about antibiotic use through CHWs in local communities is beneficial. This program should be implemented at the national level to promote rational drug use. Future studies should investigate how the educational program affects antibiotic use rates in the long term.

Exposure to PM10, PM2.5, and NO2 and gross motor function in children: a systematic review and meta-analysis.

Air pollution exposure has been related to negative gross motor development in children. However, there is currently a lack of conclusive evidence for such a relationship. We carried out a systematic review and meta-analysis using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria to examine whether exposure to air pollution has an impact on children's gross motor development. Of the 9746 papers found, 7 studies examined the impact of air pollutant characteristics, such as PM2.5, PM10, and NO2, on children's gross motor development. The results of the study reveal a significant association between air pollutants and an increased likelihood of negative gross motor development. PM10 was discovered to be considerably riskier for children's gross motor development (effect: - 1.83, 95% CI: - 3.04, - 0.62, p value = 0.002). Additionally, NO2 exhibited indications of a tendency to be connected to a detrimental impact on children's gross motor development (effect - 0.18, 95% CI: - 0.42, 0.07, p value = 0.097).  Conclusion: Our study indicates that exposure to PM10, PM2.5, and NO2, especially PM2.5 and PM10, is negatively associated with children's gross motor development. However, further research is required to determine how exposure to prenatal air pollution affects children's gross motor development. What is Known - What is New: • In this study, we provide an overview of emerging data related to PM10, PM2.5, and NO2 exposure in child development, especially on the gross motor function that continues to emerge, and key findings are highlighted. • Additionally, we summarize the evidence on the underlying effect of air pollution on gross motor function from human studies.. • Overall, we emphasize that evidence from human studies is critical in suggesting detrimental child health outcomes of an action to promote preventive strategies that will effectively protect children's health..

Cost-utility and budget impact analyses of cervical cancer screening using self-collected samples for HPV DNA testing in Thailand.

INTRODUCTION: Cervical cancer ranks as the third most prevalent cancer among women in Thailand. However, the effectiveness of cervical cancer screening programs is limited by several factors that impede the screening rate. The utilization of self-collected samples for screening purposes has the potential to alleviate barriers to screening in Thai women. This study assessed the cost-utility and budget impact of implementing cervical cancer screening using self-collected samples for human papillomavirus (HPV) deoxyribonucleic acid (DNA) testing in Thailand. MATERIALS AND METHODS: We employed a decision tree integrated with a Markov model to estimate the lifetime costs and health benefits associated with the cervical cancer screening program for women aged 25-65. The analysis was conducted from a societal perspective. Four screening policy options were compared: (1) additional self-collected samples for HPV DNA testing, (2) clinician-collected samples for HPV DNA testing only, (3) clinician-collected samples for cytology test (i.e., status quo), and (4) no screening. The model inputs were based on unvaccinated women. The screening strategies and management in those with positive results were assumed followed to the Thai clinical practice guideline. Costs were reported in 2022 Thai baht. Sensitivity analyses were conducted. The ten-year budget impacts of the additional self-collected samples for HPV DNA testing were calculated from a payer perspective. RESULTS: All screening policies were cost-saving compared to no screening. When comparing the additional self-collected samples for HPV DNA testing with the clinician-collected samples policy, it emerged as the dominant strategy. The incremental benefit in cervical cancer prevention achieved by incorporating self-collected samples for screening was observed at any additional screening rate that could be achieved through their use. Sensitivity analyses yielded consistently favorable results for the screening policies. The average annual budget impact of the additional self-collected samples for screening policy amounted to 681 million Thai baht. This budget allocation could facilitate cervical cancer screening for over 10 million women. CONCLUSIONS: An addition of self-collected samples for HPV DNA testing into the cervical cancer screening program is cost-saving. The benefits of this screening policy outweigh the associated incremental costs. Policymakers should consider this evidence during the policy optimization process.

Efficacy of Phrenic Nerve Block and Suprascapular Nerve Block in Amelioration of Ipsilateral Shoulder Pain after Thoracic Surgery: A Systematic Review and Network Meta-Analysis.

Background and Objectives: Ipsilateral shoulder pain (ISP) is a common complication after thoracic surgery. Severe ISP can cause ineffective breathing and impair shoulder mobilization. Both phrenic nerve block (PNB) and suprascapular nerve block (SNB) are anesthetic interventions; however, it remains unclear which intervention is most effective. The purpose of this study was to compare the efficacy and safety of PNB and SNB for the prevention and reduction of the severity of ISP following thoracotomy or video-assisted thoracoscopic surgery. Materials and methods: Studies published in PubMed, Embase, Scopus, Web of Science, Ovid Medline, Google Scholar and the Cochrane Library without language restriction were reviewed from the publication's inception through 30 September 2022. Randomized controlled trials evaluating the comparative efficacy of PNB and SNB on ISP management were selected. A network meta-analysis was applied to estimate pooled risk ratios (RRs) and weighted mean difference (WMD) with 95% confidence intervals (CIs). Results: Of 381 records screened, eight studies were eligible. PNB was shown to significantly lower the risk of ISP during the 24 h period after surgery compared to placebo (RR 0.44, 95% CI 0.34 to 0.58) and SNB (RR 0.43, 95% CI 0.29 to 0.64). PNB significantly reduced the severity of ISP during the 24 h period after thoracic surgery (WMD -1.75, 95% CI -3.47 to -0.04), but these effects of PNB were not statistically significantly different from SNB. When compared to placebo, SNB did not significantly reduce the incidence or severity of ISP during the 24 h period after surgery. Conclusion: This study suggests that PNB ranks first for prevention and reduction of ISP severity during the first 24 h after thoracic surgery. SNB was considered the worst intervention for ISP management. No evidence indicated that PNB was associated with a significant impairment of postoperative ventilatory status.

Efficacy and Safety of Low-Dose Prasugrel Versus Clopidogrel in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: a Systematic Review and Meta-analysis.

PURPOSE: To assess the efficacy and safety of low-dose prasugrel compared to clopidogrel based on the occurrence of major adverse cardiac events (MACEs) and major bleeding in patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI). METHODS: The PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were systematically searched up to May 2020 to identify relevant randomized controlled trials (RCTs) and observational studies. A meta-analysis was conducted using a random effects model to estimate relative risks (RRs) with 95% confidence intervals (CIs). The primary efficacy and safety endpoints were MACE and major bleeding, respectively. RESULTS: Three RCTs (n = 2884) and five observational studies (n = 30,117) were included. A meta-analysis of RCTs revealed no significant differences in terms of MACE (RR 0.92, 95% CI 0.74 to 1.16) or major bleeding (RR 0.97, 95% CI 0.57 to 1.65) between low-dose prasugrel and clopidogrel. A meta-analysis of observational studies revealed no significant difference in terms of MACE (RR 1.13, 95% CI 0.82 to 1.55) between the two groups, but low-dose prasugrel was associated with a significantly increased risk of major bleeding (RR 1.33, 95% CI 1.02 to 1.72). CONCLUSIONS: We found that low-dose prasugrel was not associated with changes in MACE or major bleeding compared with clopidogrel in RCTs. However, analysis of data from observational studies revealed that low-dose prasugrel was associated with an increased risk of major bleeding compared with clopidogrel.

Effects of home drug delivery on drug-related problems: preliminary evidence for improved patient outcomes during the COVID-19 pandemic in Thailand.

BACKGROUND: Drug-related problems cause severe disabilities, premature deaths, and unnecessary costs. Telepharmacy offer easier access to needed medications, preventing DRPs. Adoption has been slow, and it is unclear what aspects of telepharmacy are most important. The COVID-19 pandemic disrupted health services, forcing the rapid adoption of telepharmacy. In Phayao, Thailand, a program was implemented for home delivery of drugs for patients with chronic disease. OBJECTIVES: This study aimed to explore the prevalence and factors associated with DRPs of patients with chronic disease who received home drug-delivery services. METHODS: A cross-sectional study was undertaken in Phayao Province located in North Thailand. Simple random sampling was used to select patients from 6 public hospitals between July and August 2020. Logistic regression was used to analyze multivariate factors that might be related to DRPs. RESULTS: A total of 246 participants reported at least 1 DRP (49.30%). Most participants were female (58.32%) with elementary education (60.72%). Their mean age was 63.69 (SD = 12.97) years. The 5 most common DRPs were changes of drug packaging or drug brands (18.84%), leftover medications of more than 2 weeks (18.44%), nonadherence (17.43%), having conditions or diseases requiring additional medications (6.81%), and adverse drug reactions (5.21%). Univariate analysis identified number of chronic conditions, diabetes mellitus, dyslipidemia, chronic kidney disease, education level, and drug-delivery channel as predictors of DRPs. In multivariate analysis, predictors of DRPs were the number of drugs used per day (adjusted odds ratio [aOR] 1.11 [95% CI 1.03-1.19], P = 0.004) and dyslipidemia (aOR 1.83 [95% CI 1.18-2.84], P = 0.007). Nonadherence was associated with leftover medicines (aOR 4.22 [95% CI 2.44-7.28], P < 0.001) CONCLUSION: The present results indicate that home delivery caused no increase and may have caused a decrease in DRPs, and patients were highly satisfied. These promising results suggest that home delivery should be continued and further investigated even as the COVID-19-induced emergency subsides.

Spectrum of cutaneous adverse reactions to aromatic antiepileptic drugs and human leukocyte antigen genotypes in Thai patients and meta-analysis.

Aromatic antiepileptic drugs (AEDs)-induced cutaneous adverse drug reactions (cADRs) add up to the limited use of the AEDs in the treatment and prevention of seizures. Human leukocyte antigen-B (HLA-B) alleles have been linked to AEDs-induced cADRs. We investigated the association between cADRs (including Stevens-Johnson syndrome; SJS/toxic epidermal necrolysis; TEN, drug reaction with eosinophilia and systemic symptoms; DRESS, and Maculopapular eruption; MPE) caused by AEDs (phenytoin, carbamazepine, lamotrigine, phenobarbital and oxcarbazepine) and HLA-B alleles in Thai population. Through the case-control study, 166 patients with AEDs-induced cADRs, 426 AEDs-tolerant patients (AEDs-tolerant controls), and 470 healthy subjects (Thai population) were collected. The HLA genotypes were detected using the polymerase chain reaction-sequence specific oligonucleotide probe (PCR-SSOP) method. We also performed a meta-analysis with these data and other populations. The carrier rate of HLA-B*15:02 was significantly different between AEDs-induced cADRs group and AEDs-tolerant group (Odds ratio; OR 4.28, 95% Confidence interval; CI 2.64-6.95, p < 0.001), AEDs-induced cADRs group and Thai population (OR 2.15, 95%CI 1.41-3.29, p < 0.001). In meta-analysis showed the strong association HLA-B*15:02 with AEDs-induced cADRs (OR 4.77, 95%CI 1.79-12.73, p < 0.001). Furthermore, HLA-B*15:02 was associated with SJS/TEN induced by AEDs (OR 10.28, 95%CI 6.50-16.28, p < 0.001) Phenytoin (OR 4.12, 95%CI 1.77-9.59, p = 0.001) and carbamazepine (OR 137.69, 95%CI 50.97-371.98, p < 0.001). This study demonstrated that genetic association for AEDs-induced cADRs was phenotype-specific. A strong association between HLA-B*15:02 and AEDs-induced SJS/TEN was demonstrated with an OR of 10.79 (95%CI 5.50-21.16, p < 0.001) when compared with AEDs-tolerant group. On the other hand, the carrier rates of HLA-B*08:01, HLA-B*13:01, and HLA-B*56:02 were significantly higher in the DRESS group compared with the AEDs-tolerant group (p = 0.029, 0.007, and 0.017, respectively). The HLA-B*15:02 allele may represent a risk factor for AEDs-induced cADRs.

Harnessing the Potential of CRISPR/Cas in Atherosclerosis: Disease Modeling and Therapeutic Applications.

Atherosclerosis represents one of the major causes of death globally. The high mortality rates and limitations of current therapeutic modalities have urged researchers to explore potential alternative therapies. The clustered regularly interspaced short palindromic repeats-associated protein 9 (CRISPR/Cas9) system is commonly deployed for investigating the genetic aspects of Atherosclerosis. Besides, advances in CRISPR/Cas system has led to extensive options for researchers to study the pathogenesis of this disease. The recent discovery of Cas9 variants, such as dCas9, Cas9n, and xCas9 have been established for various applications, including single base editing, regulation of gene expression, live-cell imaging, epigenetic modification, and genome landscaping. Meanwhile, other Cas proteins, such as Cas12 and Cas13, are gaining popularity for their applications in nucleic acid detection and single-base DNA/RNA modifications. To date, many studies have utilized the CRISPR/Cas9 system to generate disease models of atherosclerosis and identify potential molecular targets that are associated with atherosclerosis. These studies provided proof-of-concept evidence which have established the feasibility of implementing the CRISPR/Cas system in correcting disease-causing alleles. The CRISPR/Cas system holds great potential to be developed as a targeted treatment for patients who are suffering from atherosclerosis. This review highlights the advances in CRISPR/Cas systems and their applications in establishing pathogenetic and therapeutic role of specific genes in atherosclerosis.

Anti-Influenza with Green Tea Catechins: A Systematic Review and Meta-Analysis.

Influenza is one of the most serious respiratory viral infections worldwide. Although several studies have reported that green tea catechins (GTCs) might prevent influenza virus infection, this remains controversial. We performed a systematic review and meta-analysis of eight studies with 5,048 participants that examined the effect of GTC administration on influenza prevention. In a random-effects meta-analysis of five RCTs, 884 participants treated with GTCs showed statistically significant effects on the prevention of influenza infection compared to the control group (risk ratio (RR) 0.67, 95%CIs 0.51-0.89, P = 0.005) without evidence of heterogeneity (I2= 0%, P = 0.629). Similarly, in three cohort studies with 2,223 participants treated with GTCs, there were also statistically significant effects (RR 0.52, 95%CIs 0.35-0.77, P = 0.001) with very low evidence of heterogeneity (I2 = 3%, P = 0.358). Additionally, the overall effect in the subgroup analysis of gargling and orally ingested items (taking capsules and drinking) showed a pooled RR of 0.62 (95% CIs 0.49-0.77, P = 0.003) without heterogeneity (I2= 0%, P = 0.554). There were no obvious publication biases (Egger's test (P = 0.138) and Begg's test (P = 0.103)). Our analysis suggests that green tea consumption is effective in the prophylaxis of influenza infections. To confirm the findings before implementation, longitudinal clinical trials with specific doses of green tea consumption are warranted.

Effects of Inspiratory Muscle Training and Early Mobilization on Weaning of Mechanical Ventilation: A Systematic Review and Network Meta-analysis.

OBJECTIVE: To compare the effectiveness and rank order of physical therapy interventions, including conventional physical therapy (CPT), inspiratory muscle training (IMT), and early mobilization (EM) on mechanical ventilation (MV) duration and weaning duration. DATA SOURCES: PubMed, The Cochrane Library, Scopus, and CINAHL complete electronic databases were searched through August 2019. STUDY SELECTION: Randomized controlled trials (RCTs) investigating the effect of IMT, EM, or CPT on MV duration and the weaning duration in patients with MV were included. Studies that were determined to meet the eligibility criteria by 2 independent authors were included. A total of 6498 relevant studies were identified in the search, and 18 RCTs (934 participants) were included in the final analysis. DATA EXTRACTION: Data were extracted independently by 2 authors and assessed the study quality by the Cochrane risk-of-bias tool. The primary outcomes were MV duration and weaning duration. DATA SYNTHESIS: Various interventions of physical therapy were identified in the eligible studies, including IMT, IMT+CPT, EM, EM+CPT, and CPT. The data analysis demonstrated that compared with CPT, IMT+CPT significantly reduced the weaning duration (mean difference; 95% confidence interval) (-2.60; -4.76 to -0.45) and EM significantly reduced the MV duration (-2.01; -3.81 to -0.22). IMT+CPT and EM had the highest effectiveness in reducing the weaning duration and MV duration, respectively. CONCLUSION: IMT or EM should be recommended for improving the weaning outcomes in mechanically ventilated patients. However, an interpretation with caution is required due to the heterogeneity.

Development of a hyponatremia screening tool (ABCDF-S score) for patients with hypertension using thiazide diuretic agents.

WHAT IS KNOWN AND OBJECTIVE: Hyponatremia is a common side effect of thiazide diuretics that can lead to increased mortality and hospitalization. A rapid and accurate screening tool is needed for rapid and appropriate management. In this study, we report on the development of a simple clinical screening tool for hyponatremia using thiazide diuretics. METHODS: This nested case-control study was performed by collecting data from 1 January 2015 to 30 June 2017. Univariable and multivariable logistic regressions were used to identify potential risk factors. The regression coefficients were converted into item scores by dividing each regression coefficient with the minimum coefficient in the model and rounding to the nearest integer. This value was then summed to the total score. The prediction power of the model was determined by the area under the receiver operating characteristic curve (AuROC). RESULTS AND DISCUSSION: Six clinical risk factors, namely age ≥65 years, benzodiazepine use, history of a cerebrovascular accident, dose of hydrochlorothiazide ≥25 mg, female sex and statin use, were included in our ABCDF-S score. The model showed good power of prediction (AuROC 81.53%, 95% confidence interval [CI]: 78%-84%) and good calibration (Hosmer-Lemeshow X2  = 23.20; P = .39). The positive likelihood ratios of hyponatremia in patients with low risk (score ≤ 6) and high risk (score ≥ 8) were 0.26 (95% CI: 0.21-0.32) and 3.89 (95% CI: 3.11-4.86), respectively. WHAT IS NEW AND CONCLUSION: The screening tool with six risk predictors provided a useful prediction index for thiazide-associated hyponatremia. However, further validation of the tool is warranted prior to its utilization in routine clinical practice.

Clinical outcomes of theophylline use as add-on therapy in patients with chronic obstructive pulmonary disease: A propensity score matching analysis.

To examine clinical outcomes of theophylline use in patients with chronic obstructive pulmonary disease (COPD) receiving inhaled corticosteroids (ICS) and long-acting beta-2 agonists (LABA). Electronic data from five hospitals located in Northern Thailand between January 2011 and December 2015 were retrospectively collected. Propensity score (PS) matching (2:1 ratio) technique was used to minimize confounding factors. The primary outcome was overall exacerbations. Secondary outcomes were exacerbation not leading to hospital admission, hospitalization for exacerbation, hospitalization for pneumonia, and all-cause hospitalizations. Cox's proportional hazards models were used to estimate adjusted hazard ratio (aHR) and 95% confidence interval (CI). After PS matching, of 711 patients with COPD (mean age: 70.1 years; 74.4% male; 60.8% severe airflow obstruction), 474 theophylline users and 237 non-theophylline users were included. Mean follow-up time was 2.26 years. Theophylline significantly increased the risk of overall exacerbation (aHR: 1.48, 95% CI: 1.11-1.96; p = 0.008) and exacerbation not leading to hospital admission (aHR: 1.47, 95% CI: 1.06-2.03; p = 0.020). Theophylline use did not significantly increase the risk of hospitalization for exacerbation (aHR: 1.11, 95% CI: 0.79-1.58; p = 0.548), hospitalization for pneumonia (aHR: 1.28, 95% CI: 0.89-1.84; p = 0.185), and all-cause hospitalizations (aHR: 1.03, 95% CI: 0.80-1.33; p = 0.795). Theophylline use as add-on therapy to ICS and LABA might be associated with an increased risk for overall exacerbation in patients with COPD. A large-scale prospective study of theophylline use investigating both safety and efficacy is warranted.

Comparative efficacy and safety of treatment options for MDR and XDR Acinetobacter baumannii infections: a systematic review and network meta-analysis.

OBJECTIVES: To comprehensively compare and rank the efficacy and safety of available treatment options for patients with MDR and XDR Acinetobacter baumannii (AB) infection. METHODS: We searched PubMed, Embase and the Cochrane register of trials systematically for studies that examined treatment options for patients with MDR- and XDR-AB infections until April 2016. Network meta-analysis (NMA) was performed to estimate the risk ratio (RR) and 95% CI from both direct and indirect evidence. Primary outcomes were clinical cure and microbiological cure. Secondary outcomes were all-cause mortality and nephrotoxic and non-nephrotoxic adverse events. RESULTS: A total of 29 studies with 2529 patients (median age 60 years; 65% male; median APACHE II score 19.0) were included. Although there were no statistically significant differences between treatment options, triple therapy with colistin, sulbactam and tigecycline had the highest clinical cure rate. Colistin in combination with sulbactam was associated with a significantly higher microbiological cure rate compared with colistin in combination with tigecycline (RR 1.23; 95% CI 1.03-1.47) and colistin monotherapy (RR 1.21; 95% CI 1.06-1.38). No significant differences in all-cause mortality were noted between treatment options. Tigecycline-based therapy also appeared less effective for achieving a microbiological cure and is not appropriate for treating bloodstream MDR- and XDR-AB infections. CONCLUSIONS: Combination therapy of colistin with sulbactam demonstrates superiority in terms of microbiological cure with a safety profile similar to that of colistin monotherapy. Thus, our findings support the use of this combination as a treatment for MDR- and XDR-AB infections.

Cost-effectiveness analysis of patient self-testing therapy of oral anticoagulation.

Patient Self-testing (PST) could be an option for present anticoagulation therapy monitoring, but current evidence on its cost-effectiveness is limited. This study aims to estimate the cost-effectiveness of PST to other different care approaches for anticoagulation therapy in Thailand, a low-to-middle income country (LMIC). A Markov model was used to compare lifetime costs and quality-adjusted life years (QALYs) accrued to patients receiving warfarin through PST or either anticoagulation clinic (AC) or usual care (UC). The model was populated with relevant information from literature, network meta-analysis, and database analyses. Incremental cost-effectiveness ratios (ICERs) were presented as the year 2015 values. A base-case analysis was performed for patients at age 45-year-old. Sensitivity analyses including one-way and probabilistic sensitivity analyses (PSA) were constructed to determine the robustness of the findings. From societal perspective, PST increased QALY by 0.87 and costs by 112,461 THB compared with UC. Compared with AC, PST increased QALY by 0.161 and costs by 21,019 THB. The ICER with PST was 128,697 (3625 USD) and 130,493 THB (3676 USD) per QALY gained compared with UC and AC, respectively. The probability of PST being cost-effective is 74.1% and 51.9%, compared to UC and AC, respectively, in Thai context. Results were sensitive to the efficacy of PST, age and frequency of hospital visit or self-testing. This analysis suggested that PST is highly cost-effective compared with usual care and less cost-effective against anticoagulation clinic. Patient self-testing strategy appears to be economically valuable to include into healthcare system within the LMIC context.

Prevention and Control of Multidrug-Resistant Gram-Negative Bacteria in Adult Intensive Care Units: A Systematic Review and Network Meta-analysis.

BACKGROUND: This study evaluated the relative efficacy of strategies for the prevention of multidrug-resistant gram-negative bacteria (MDR-GNB) in adult intensive care units (ICUs). METHODS: A systematic review and network meta-analysis was performed; searches of the Cochrane Library, PubMed, Embase, and CINAHL (Cumulative Index to Nursing and Allied Health Literature) included all randomized controlled trials and observational studies conducted in adult patients hospitalized in ICUs and evaluating standard care (STD), antimicrobial stewardship program (ASP), environmental cleaning (ENV), decolonization methods (DCL), or source control (SCT), simultaneously. The primary outcomes were MDR-GNB acquisition, colonization, and infection; secondary outcome was ICU mortality. RESULTS: Of 3805 publications retrieved, 42 met inclusion criteria (5 randomized controlled trials and 37 observational studies), involving 62068 patients (median age, 58.8 years; median APACHE [Acute Physiology and Chronic Health Evaluation] II score, 18.9). The majority of studies reported extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae and MDR Acinetobacter baumannii. Compared with STD, a 4-component strategy composed of STD, ASP, ENV, and SCT was the most effective intervention (rate ratio [RR], 0.05 [95% confidence interval {CI}, .01-.38]). When ENV was added to STD+ASP or SCT was added to STD+ENV, there was a significant reduction in the acquisition of MDR A. baumannii (RR, 0.28 [95% CI, .18-.43] and 0.48 [95% CI, .35-.66], respectively). Strategies with ASP as a core component showed a statistically significant reduction the acquisition of ESBL-producing Enterobacteriaceae (RR, 0.28 [95% CI, .11-.69] for STD+ASP+ENV and 0.23 [95% CI, .07-.80] for STD+ASP+DCL). CONCLUSIONS: A 4-component strategy was the most effective intervention to prevent MDR-GNB acquisition. As some strategies were differential for certain bacteria, our study highlighted the need for further evaluation of the most effective prevention strategies.

Effectiveness of Probiotic, Prebiotic, and Synbiotic Therapies in Reducing Postoperative Complications: A Systematic Review and Network Meta-analysis.

BACKGROUND: Microbiome-directed therapies are increasingly used preoperatively and postoperatively to improve postoperative outcomes. Recently, the effectiveness of probiotics, prebiotics, and synbiotics in reducing postoperative complications (POCs) has been questioned. This systematic review aimed to examine and rank the effectiveness of these therapies on POCs in adult surgical patients. METHODS: We searched for articles from PubMed, Embase, Cochrane, Web of Science, Scopus, and CINAHL plus. From 2002 to 2015, 31 articles meeting the inclusion criteria were identified in the literature. Risk of bias and heterogeneity were assessed. Network meta-analyses (NMA) were performed using random-effects modeling to obtain estimates for study outcomes. Risk ratios (RRs) and 95% confidence intervals (CIs) were estimated. We then ranked the comparative effects of all regimens with the surface under the cumulative ranking (SUCRA) probabilities. RESULTS: A total of 2,952 patients were included. We found that synbiotic therapy was the best regimen in reducing surgical site infection (SSI) (RR = 0.28; 95% CI, 0.12-0.64) in adult surgical patients. Synbiotic therapy was also the best intervention to reduce pneumonia (RR = 0.28; 95% CI, 0.09-0.90), sepsis (RR = 0.09; 95% CI, 0.01-0.94), hospital stay (mean = 9.66 days, 95% CI, 7.60-11.72), and duration of antibiotic administration (mean = 5.61 days, 95% CI, 3.19-8.02). No regimen significantly reduced mortality. CONCLUSIONS: This network meta-analysis suggests that synbiotic therapy is the first rank to reduce SSI, pneumonia, sepsis, hospital stay, and antibiotic use. Surgeons should consider the use of synbiotics as an adjunctive therapy to prevent POCs among adult surgical patients. Increasing use of synbiotics may help to reduce the use of antibiotics and multidrug resistance.

Effects of aspirin and non-aspirin nonsteroidal anti-inflammatory drugs on the incidence of recurrent colorectal adenomas: a systematic review with meta-analysis and trial sequential analysis of randomized clinical trials.

BACKGROUND: Beneficial effects of aspirin and non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) against recurrent colorectal adenomas have been documented in systematic reviews; however, the results have not been conclusive. Uncertainty remains about the appropriate dose of aspirin for adenoma prevention. The persistence of the protective effect of NSAIDs against recurrent adenomas after treatment cessation is yet to be established. METHODS: Our objective was to update and systematically evaluate the evidence for aspirin and other NSAIDs on the incidence of recurrent colorectal adenomas taking into consideration the risks of random error and to appraise the quality of evidence using GRADE (The Grading of Recommendations, Assessment, Development and Evaluation) approach. Retrieved trials were evaluated using Cochrane risk of bias instrument. Meta-analytic estimates were calculated with random-effects model and random errors were evaluated with trial sequential analysis (TSA). RESULTS: In patients with a previous history of colorectal cancer or adenomas, low-dose aspirin (80-160 mg/day) compared to placebo taken for 2 to 4 years reduces the risk of recurrent colorectal adenomas (relative risk (RR), 0.80 [95% CI (confidence interval), 0.70-0.92]). TSA indicated a firm evidence for this beneficial effect. The evidence indicated moderate GRADE quality. Low-dose aspirin also reduces the recurrence of advanced adenomas (RR, 0.66 [95% CI, 0.44-0.99]); however, TSA indicated lack of firm evidence for a beneficial effect. High-dose aspirin (300-325 mg/day) did not statistically reduce the recurrent adenomas (RR, 0.90 [95% CI, 0.68-1.18]). Cyclooxygenase-2 (COX-2) inhibitors (e.g. celecoxib 400 mg/day) were associated with a significant decrease in the recurrence of both adenomas (RR, 0.66 [95% CI, 0.59-0.72]) and advanced adenomas (RR, 0.45 [95% CI, 0.33-0.57]); however, this association did not persist and there was a trend of an increased risk of recurrent adenomas observed 2 years after the withdrawal. CONCLUSION: Our findings confirm the beneficial effect of low-dose aspirin on recurrence of any adenomas; however, effect on advanced adenomas was inconclusive. COX-2 inhibitors seem to be more effective in preventing recurrence of adenomas; however, there was a trend of an increased risk of recurrence of adenomas observed after discontinuing regular use.

Clinical risk scoring for predicting non-alcoholic fatty liver disease in metabolic syndrome patients (NAFLD-MS score).

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) can progress from simple steatosis to hepatocellular carcinoma. None of tools have been developed specifically for high-risk patients. This study aimed to develop a simple risk scoring to predict NAFLD in patients with metabolic syndrome (MetS). METHODS: A total of 509 patients with MetS were recruited. All were diagnosed by clinicians with ultrasonography-confirmed whether they were patients with NAFLD. Patients were randomly divided into derivation (n=400) and validation (n=109) cohort. To develop the risk score, clinical risk indicators measured at the time of recruitment were built by logistic regression. Regression coefficients were transformed into item scores and added up to a total score. A risk scoring scheme was developed from clinical predictors: BMI ≥25, AST/ALT ≥1, ALT ≥40, type 2 diabetes mellitus and central obesity. The scoring scheme was applied in validation cohort to test the performance. RESULTS: The scheme explained, by area under the receiver operating characteristic curve (AuROC), 76.8% of being NAFLD with good calibration (Hosmer-Lemeshow χ2 =4.35; P=.629). The positive likelihood ratio of NAFLD in patients with low risk (scores below 3) and high risk (scores 5 and over) were 2.32 (95% CI: 1.90-2.82) and 7.77 (95% CI: 2.47-24.47) respectively. When applied in validation cohort, the score showed good performance with AuROC 76.7%, and illustrated 84%, and 100% certainty in low- and high-risk groups respectively. CONCLUSIONS: A simple and non-invasive scoring scheme of five predictors provides good prediction indices for NAFLD in MetS patients. This scheme may help clinicians in order to take further appropriate action.