Publications by authors named "Nathorn Chaiyakunapruk"

223 Publications

Economic evaluation of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) for stroke prevention in patients with atrial fibrillation: a systematic review and meta-analysis.

BMJ Evid Based Med 2021 Oct 11. Epub 2021 Oct 11.

Mahidol University Health Technology Assessment (MUHTA) Graduate Program, Mahidol University, Bangkok, Thailand.

Objectives: To assess cost-effectiveness of direct oral anticoagulants (DOACs) compared with vitamin K antagonists (VKAs) for stroke prevention in atrial fibrillation (AF) by pooling incremental net benefits (INBs).

Design: Systematic review and meta-analysis.

Setting: We searched PubMed, Scopus and Centre for Evaluation of Value and Risks in Health Registry from inception to December 2019.

Participants: Patients with AF.

Main Outcome Measures: The INB was defined as a difference of incremental effectiveness multiplied by willing to pay threshold minus the incremental cost; a positive INB indicated favour treatment. These INBs were pooled (stratified by level of country income, perspective, time-horizon, model types) with a random-effects model if heterogeneity existed, otherwise a fixed effects model was applied. Heterogeneity was assessed using Q test and I statistic. Risk of bias was assessed using the economic evaluations bias (ECOBIAS) checklist.

Results: A total of 100 eligible economic evaluation studies (224 comparisons) were included. For high-income countries (HICs) from a third-party payer (TPP) perspective, the pooled INBs for DOAC versus VKA pairs were significantly cost-effective with INBs (95% CI) of $6632 ($2961.67 to $10 303.72; I=59.9%), $6353.24 ($4076.03 to $8630.45; I=0%), $7664.58 ($2979.79 to $12 349.37; I=0%) and $8573.07 ($1877.05 to $15 269.09; I=0%) for dabigatran, apixaban, rivaroxaban and edoxaban relative to VKA, respectively but only dabigatran was significantly cost-effective from societal perspective (SP) with an INB of $11 746.96 ($2429.34 to $21 064.59; I=52.4%). The pooled INBs of all comparisons for upper-middle income countries (UMICs) were not significantly cost-effective. The ECOBIAS checklist indicated that risk of bias was mostly low for most items with the exception of five items which should be less influenced on pooling INBs.

Conclusions: Our meta-analysis provides comprehensive economic evidence that allows policy makers to generalise cost-effectiveness data to their local context. All DOACs may be cost-effective compared with VKA in HICs with TPP perspective. The pooling results produced moderate to high heterogeneity particularly in UMICs. Further studies are required to inform UMICs with SP.

Prospero Registeration Number: CRD 42019146610.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjebm-2020-111634DOI Listing
October 2021

Association of proton pump inhibitor use with adverse health outcomes: A systematic umbrella review of meta-analyses of cohort studies and randomised controlled trials.

Br J Clin Pharmacol 2021 Oct 7. Epub 2021 Oct 7.

Department of Pharmacotherapy, College of Pharmacy, University of Utah, Salt Lake City, UT, USA.

Aims: The aim was to perform an umbrella review to summarise the existing evidence on proton pump inhibitor (PPI) use and adverse outcomes and to grade the certainty of evidence.

Methods: Electronic databases were searched up until July 2021 for meta-analyses of cohort studies and/or randomised controlled trials (RCTs). Summary effect sizes from a random-effects model, between-study heterogeneity, 95% prediction interval, small-study effect, excess significance, and credibility ceilings were devised to classify the credibility of evidence from meta-analyses of cohort studies, whereas the GRADE approach was used for meta-analyses of RCTs.

Results: In meta-analyses of cohort studies, 52 of the 91 examined associations were statistically significant (P ≤ 0.05). Convincing evidence emerged from main analysis for the association between PPI use and risk of all-site fracture and chronic kidney disease (CKD) in the elderly population. However, none of these associations remained supported by convincing evidence after sensitivity analyses. The use of PPI is also associated with an increased risk of mortality due to COVID-19 infection and other related adverse outcomes, but the quality of evidence was weak. In meta-analyses of RCTs, 38 of the 63 examined associations were statistically significant. However, no associations were supported by high or moderate-quality evidence.

Conclusion: This study's findings imply that most putative adverse outcomes associated with PPI use may not be supported by high-quality evidence and are likely to have been affected by underlying confounding factors. Future research is needed to confirm the causal association between PPI use and risk of fracture and CKD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bcp.15103DOI Listing
October 2021

Assessment of health equity consideration in masking/PPE policies to contain COVID-19 using PROGRESS-plus framework: a systematic review.

BMC Public Health 2021 09 16;21(1):1682. Epub 2021 Sep 16.

School of Pharmacy, University of Utah, Salt Lake City, UT, USA.

Introduction: There is increasing evidence that COVID-19 has unmasked the true magnitude of health inequity worldwide. Policies and guidance for containing the infection and reducing the COVID-19 related deaths have proven to be effective, however the extent to which health inequity factors were considered in these policies is rather unknown. The aim of this study is to measure the extent to which COVID-19 related policies reflect equity considerations by focusing on the global policy landscape around wearing masks and personal protection equipment (PPE).

Methods: A systematic search for published documents on COVID-19 and masks/PPE was conducted across six databases: PubMed, EMBASE, CINAHL, ERIC, ASSIA and Psycinfo. Reviews, policy documents, briefs related to COVID-19 and masks/PPE were included in the review. To assess the extent of incorporation of equity in the policy documents, a guidance framework known as 'PROGRESS-Plus': Place of residence, Race/ethnicity, Occupation, Gender/sex, Religion, Education, Socioeconomic status, Social capital, Plus (age, disability etc.) was utilized.

Results: This review included 212 policy documents. Out of 212 policy documents, 190 policy documents (89.62%) included at least one PROGRESS-plus component. Most of the policy documents (n = 163, 85.79%) focused on "occupation" component of the PROGRESS-plus followed by personal characteristics associated with discrimination (n = 4;2.11%), place of residence (n = 2;1.05%) and education (n = 1;0.53%). Subgroup analysis revealed that most of the policy documents (n = 176, 83.01%) were focused on "workers" such as healthcare workers, mortuary workers, school workers, transportation workers, essential workers etc. Of the remaining policy documents, most were targeted towards whole population (n = 30; 14.15%). Contrary to "worker focused" policy documents, most of the 'whole population focused' policy documents didn't have a PROGRESS-plus equity component rendering them equity limiting for the society.

Conclusion: Our review highlights even if policies considered health inequity during the design/implementation, this consideration was often one dimensional in nature. In addition, population wide policies should be carefully designed and implemented after identifying relevant equity related barriers in order to produce better outcomes for the whole society.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12889-021-11688-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8443429PMC
September 2021

Effects of Telemedicine on Obese Patients With Non-alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis.

Front Med (Lausanne) 2021 19;8:723790. Epub 2021 Aug 19.

Division of Ambulatory Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

Little is known of the efficacy of telemedicine on the clinical outcomes of the high-risk group of non-alcoholic fatty liver disease (NAFLD) patients, such as those with obesity. This study aimed to determine the effects of telemedicine vs. usual care for the management of obese patients with NAFLD. Literature searches were performed from inception to 1st June 2021 in the following databases: Cochrane CENTRAL, ScienceDirect, PubMed, and Scopus. Prospective trials assessed the effects of telemedicine on obese patients with NAFLD were included. The outcomes of interest were alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride, high-density lipoprotein cholesterol levels, and body mass index, which were reported as weighted mean difference (WMD) with 95% confidence interval (CI). Four studies were examined in the systematic review, one was excluded from the meta-analysis due to an inappropriate group-comparison. In all, 285 obese patients with NAFLD were included in the meta-analysis (70% of those received telemedicine intervention). The mean ages of the patients in the telemedicine and usual-care groups were 51.78 ± 5.91 and 47.30 ± 8.14 years, respectively. Telemedicine significantly decreased ALT levels compared with usual care (WMD = -18.93 U/L [95%CI: -25.97, -11.90]; = 53.8%), and it significantly decreased AST levels (WMD = -10.24 U/L [95%CI: -13.43, -7.05]; = 0.0%). However, telemedicine did not show significant benefits for the remaining outcomes. Compared with usual care, telemedicine significantly reduced the AST and ALT levels of obese patients with NAFLD. Further long-term studies with clinical endpoints are needed to determine the best characteristics of telemedicine and to confirm the benefits. PROSPERO [CRD42020207451].
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmed.2021.723790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417362PMC
August 2021

Mid- to long-term outcomes of contemporary total knee arthroplasty in Charcot neuroarthropathy: a systematic review and meta-analysis.

EFORT Open Rev 2021 Jul 8;6(7):556-564. Epub 2021 Jul 8.

Department of Pharmacotherapy, College of Pharmacy, University of Utah, Salt Lake City, Utah, USA.

Total knee arthroplasty (TKA) is an effective procedure to treat many patients with end-stage knee arthropathy. However, the extension of TKA for patients with Charcot neuroarthropathy (CNA) is controversial, with relatively limited evidence defining optimal reconstruction techniques.This systematic review of relevant studies that were published from January 2000 to June 2020 aimed to define survivorship, complications, reoperation, and component revision rates of contemporary TKA performed for CNA.We identified 127 TKA performed for CNA in five studies that comprised ≥ 7 knees with ≥ 5 years of follow-up.Overall implant survivorship was 85.4%. The overall complication rate was 26.4%, with the most common complications including instability (24.0%), periprosthetic fracture (17.4%), infection (13.0%), ligament injury (10.9%) and aseptic loosening (10.9%).The aetiology of CNA and prosthesis type had no influence on clinical outcomes, whereas the effect of staging of disease and ataxia status was still inconclusive.Understanding the potential determinants, survivorship and risk of complications related to TKA performed in CNA may help surgeons to deal with patient expectations. Cite this article: 2021;6:556-564. DOI: 10.1302/2058-5241.6.200103.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1302/2058-5241.6.200103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8335961PMC
July 2021

Effect of pharmacist care on clinical outcomes among people living with HIV/AIDS: A systematic review and meta-analysis.

Res Social Adm Pharm 2021 Jul 28. Epub 2021 Jul 28.

School of Pharmacy, Monash University, Jalan Lagoon Selatan, Bandar Sunway, 47500 Subang Jaya, Selangor, Malaysia; College of Pharmacy, University of Utah, Salt Lake City, UT, USA. Electronic address:

Background: Pharmacists play a significant role in the multidisciplinary care of people living with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) (PLWHA). However, there is less evidence to clarify the impact of pharmacist as an individual team member on HIV care.

Objective: This study aims to determine the effects of pharmacist intervention on improving adherence to antiretroviral therapy (ART), viral load (VL) suppression, and change in CD4-T lymphocytes in PLWHA.

Methods: We identified relevant records from six databases (Pubmed, EMBASE, ProQuest, Scopus, Cochrane, and EBSCOhost) from inception till June 2020. We included studies that evaluated the impact of pharmacist care activities on clinical outcomes in PLWHA. A random-effect model was used to estimate the overall effect [odds ratio (OR) for dichotomous and mean difference (MD) for continuous data] with 95% confidence intervals (CIs). The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was used to evaluate the quality of evidence. The review protocol was published on PROSPERO (CRD42020167994).

Results: Twenty-five studies involving 3206 PLWHA in which pharmacist-provided intervention either in the form of education with or without pharmaceutical-care either alone or as an interdisciplinary team member were included. Eight studies were randomized controlled trials (RCTs), while 17 studies were non-RCTs. Pooled-analyses showed a significant impact of pharmacist care compared to usual care group on adherence outcome (OR: 2.70 [95%, CI 1.80, 4.05]), VL suppression (OR: 4.13 [95% CI 2.27, 7.50]), and rise of CD4-T lymphocytes count (MD: 66.83 cells/mm [95% CI 44.08, 89.57]). The strength of evidence ranged from moderate, low to very low.

Conclusion: The findings suggest that pharmacist care improves adherence, VL suppression, and CD4-T lymphocyte improvement in PLWHA; however, it should be noted that the majority of the studies have a high risk of bias. More research with more rigorous designs is required to reaffirm the impact of pharmacist interventions on clinical and economic outcomes in PLWHA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.sapharm.2021.07.020DOI Listing
July 2021

Urgent need to take action on reducing postoperative respiratory complications.

Lancet Reg Health West Pac 2021 May 12;10:100136. Epub 2021 Apr 12.

Department of Pharmacotherapy, University of Utah, Salt Lake City, UT, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.lanwpc.2021.100136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315624PMC
May 2021

Comparative Safety and Efficacy of Therapeutic Options in Resectable and Advanced/Metastatic Pancreatic Cancer: A Systematic Review and Indirect Comparison.

Oncol Res Treat 2021 27;44(9):476-484. Epub 2021 Jul 27.

Department of Pharmacotherapy, College of Pharmacy, University of Utah, Salt Lake City, Utah, USA.

Objectives: FOLFIRINOX, gemcitabine/nab-paclitaxel (gem-nab/P), and gemcitabine-capecitabine (gem-cap) demonstrated superiority over gemcitabine monotherapy for pancreatic cancer (PC). It is still unclear which chemotherapy regimen is the most optimal. This study aimed to conduct a systematic review (SR) and indirect comparison to compare safety and efficacy of FOLFIRINOX versus gem-nab/P and gem-cap in PC.

Methods: An SR was conducted in several databases from inception to November 2020. RCTs investigating resectable or advanced PC were included. Primary outcomes including overall survival (OS), disease-free survival (DFS)/progression-free survival (PFS)/relapse-free survival (RFS), and grade 3/4 adverse events (AEs) were pooled using a random effects model. Indirect comparisons were done to compare FOLFIRINOX versus gem-cap and gem-nab/P. Heterogeneity was evaluated using Cochran's Q test and I2 statistics.

Results: Nine studies were identified involving 6,564 patients. Indirect comparisons showed FOLFIRINOX had significantly better OS (resectable: HR 0.78 [0.61-0.99]; advanced: HR 0.71 [0.60-0.85]) and RFS/DFS/PFS (resectable: HR 0.67 [0.55-0.82]; advanced: HR 0.65 [0.57-0.74]) compared to gem-cap as well as OS (resectable: HR 0.78 [0.61-1.00]; advanced: HR 0.73 [0.54-0.98]) and DFS/PFS (resectable: HR 0.66 [0.53-0.82]; advanced: HR 0.64 [0.49-0.83]) compared to gem-nab/P. FOLFIRINOX increased grade 3/4 AE risk compared to gem-cap and gem-nab/P.

Conclusions: FOLFIRINOX is associated with significant survival benefits compared to gem-nab/P and gem-cap. However, it is important to consider the increased grade 3/4 AE risk associated with FOLFIRINOX.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000517409DOI Listing
October 2021

The Impact of School Opening Model on SARS-CoV-2 Community Incidence and Mortality: A Nationwide Cohort Study.

Res Sq 2021 Jul 15. Epub 2021 Jul 15.

The role that in-person schooling contributes to community incidence of SARS-CoV-2 infections and deaths remains unknown. We conducted an event study evaluating the effect of in-person school on SARS-CoV-2 cases and deaths per 100,000 persons during the 12-weeks following school opening, stratified by US Census region. There was no impact of in-person school opening and COVID-19 deaths. In most regions, COVID-19 incidence rates were not statistically different in counties with in-person versus remote school modes. However, in the South, there was a significant and sustained increase in cases per week among counties that opened for in-person learning versus remote learning, with weekly effects ranging from 7.8 (95% CI: 1.2-14.5) to 18.9 (95% CI: 7.9-29.9) additional cases per 100,000, driven by increases among 0-9 year olds and adults.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21203/rs.3.rs-712725/v1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8288150PMC
July 2021

A systematic review and meta-analysis of randomized controlled trials of cardiovascular toxicity of medical cannabinoids.

J Am Pharm Assoc (2003) 2021 Sep-Oct;61(5):e1-e13. Epub 2021 Mar 26.

Background: Several systematic reviews (SRs) have summarized the potential effectiveness of medical cannabinoids, but it is unclear to what extent safety-related outcomes were incorporated.

Objective: The objective of this study was to evaluate the cardiovascular toxicity associated with medical use of cannabinoids.

Methods: A 2-stage systematic review (SR) approach was undertaken to assess the current evidence on cannabinoid-associated cardiovascular events reported among randomized controlled trials (RCTs). First, we searched for SRs in multiple sources until June 2019. Second, RCTs identified from the SRs were included if they assessed medical cannabis and reported cardiovascular events. The outcomes of interest were all types of cardiovascular events. Data were extracted by 2 independent reviewers. Study quality was assessed using the Cochrane risk of bias. A statistical test of heterogeneity was performed. The summary risk ratios (RRs) and 95% CIs were calculated using a random-effects model.

Results: A total of 47 studies involving 2800 patients were included. The median duration of cannabinoid use was 15.8 days (range 1 to 322), and 45% of the studies excluded patients with underlying cardiovascular diseases. Cannabinoid use was significantly associated with increased risks of orthostatic hypotension (RR 3.16 [95% CI 2.27-4.40], I = 2.3%) and hypotension (3.55 [1.45-8.71], I = 31.8%), with a trend of increased risk of tachycardia (1.94 [0.81-4.64], I = 48.6%). No study reported serious cardiovascular events.

Conclusions: Cannabinoid use was associated with tachycardia, hypotension, and orthostatic hypotension. There is a paucity of data for other cardiovascular events among medical cannabis users. More data, especially regarding long-term effects among patients with existing cardiovascular diseases, are needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.japh.2021.03.013DOI Listing
October 2021

Economic burden of non-alcoholic steatohepatitis with significant fibrosis in Thailand.

BMC Gastroenterol 2021 Mar 25;21(1):135. Epub 2021 Mar 25.

Department of Pharmacotherapy, College of Pharmacy, University of Utah, Salt Lake City, UT, 84112, USA.

Background: Non-alcoholic steatohepatitis (NASH) has been recognised as a significant form of chronic liver disease and a common cause of cirrhosis and hepatocellular carcinoma, resulting in a considerable financial burden on healthcare resources. Currently, there is no information regarding the economic burden of NASH in low- and middle-income countries (LMICs). The aim of this study was to estimate the economic burden of NASH in Thailand as a lesson learned for LMICs.

Methods: To estimate the healthcare costs and prevalence of NASH with significant fibrosis (fibrosis stage ≥ 2) in the general Thai population, an eleven-state lifetime horizon Markov model with 1-year cycle length was performed. The model comprised Thai population aged 18 years and older. The cohort size was based on Thailand Official Statistic Registration Systems. The incidence of NASH, transitional probabilities, and costs-of-illness were based on previously published literature, including systematic reviews and meta-analyses. The age-specific prevalence of NASH was based on Thai NASH registry data. Costs were expressed in 2019 US Dollars ($). As we undertook analysis from the payer perspective, only direct medical costs were included. All future costs were discounted at an annual rate of 3%. A series of sensitivity analyses were performed.

Results: The estimated total number of patients with significant NASH was 2.9 million cases in 2019, based on a NASH prevalence of 5.74%. The total lifetime cost of significant NASH was $15.2 billion ($5,147 per case), representing approximately 3% of the 2019 GDP of Thailand. The probabilistic sensitivity analysis showed that the lifetime costs of significant NASH varied from $11.4 billion to $18.2 billion.

Conclusions: The economic burden associated with NASH is substantial in Thailand. This prompts clinicians and policy makers to consider strategies for NASH prevention and management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12876-021-01720-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7992785PMC
March 2021

Very-low-dose aspirin and surveillance colonoscopy is cost-effective in secondary prevention of colorectal cancer in individuals with advanced adenomas: network meta-analysis and cost-effectiveness analysis.

BMC Gastroenterol 2021 Mar 20;21(1):130. Epub 2021 Mar 20.

Department of Pharmacotherapy, College of Pharmacy, The University of Utah, 30 2000 E, Salt Lake City, UT, 84112, USA.

Background: Individuals with advanced colorectal adenomas (ACAs) are at high risk for colorectal cancer (CRC), and it is unclear which chemopreventive agent (CPA) is safe and cost-effective for secondary prevention. We aimed to determine, firstly, the most suitable CPA using network meta-analysis (NMA) and secondly, cost-effectiveness of CPA with or without surveillance colonoscopy (SC).

Methods: Systematic review and NMA of randomised controlled trials were performed, and the most suitable CPA was chosen based on efficacy and the most favourable risk-benefit profile. The economic benefits of CPA alone, 3 yearly SC alone, and a combination of CPA and SC were determined using the cost-effectiveness analysis (CEA) in the Malaysian health-care perspective. Outcomes were reported as incremental cost-effectiveness ratios (ICERs) in 2018 US Dollars ($) per quality-adjusted life-year (QALY), and life-years (LYs) gained.

Results: According to NMA, the risk-benefit profile favours the use of aspirin at very-low-dose (ASAVLD, ≤ 100 mg/day) for secondary prevention in individuals with previous ACAs. Celecoxib is the most effective CPA but the cardiovascular adverse events are of concern. According to CEA, the combination strategy (ASAVLD with 3-yearly SC) was cost-saving and dominates its competitors as the best buy option. The probability of being cost-effective for ASAVLD alone, 3-yearly SC alone, and combination strategy were 22%, 26%, and 53%, respectively. Extending the SC interval to five years in combination strategy was more cost-effective when compared to 3-yearly SC alone (ICER of $484/LY gain and $1875/QALY). However, extending to ten years in combination strategy was not cost-effective.

Conclusion: ASAVLD combined with 3-yearly SC in individuals with ACAs may be a cost-effective strategy for CRC prevention. An extension of SC intervals to five years can be considered in resource-limited countries.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12876-021-01715-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7981989PMC
March 2021

Consumer Preferences and Willingness to Pay for Nutraceuticals: A Discrete Choice Experiment.

Value Health Reg Issues 2021 May 11;24:167-172. Epub 2021 Mar 11.

School of Pharmacy, Monash University Malaysia, Selangor, Malaysia; Department of Pharmacotherapy, College of Pharmacy, University of Utah, Salt Lake City, UT, USA. Electronic address:

Objectives: Globally, nutraceuticals have been increasingly used. Nevertheless, the consumer preferences for nutraceuticals have not been quantitatively investigated. This study used discrete choice experiment (DCE) to examine consumer preferences and willingness to pay for nutraceuticals.

Methods: Four attributes (ie, the scientific proof of effectiveness, the scientific proof of safety, the source of recommendation, and cost) were identified from a systematic review and focus group interviews. They were used to develop a DCE questionnaire. Consumers at community pharmacies in Malaysia were asked to respond to 8 DCE choice sets. A conditional logit model was employed to obtain the relative importance of each attribute and to estimate respondents' WTP for nutraceuticals.

Results: A total of 111 valid responses were analyzed. A negative constant term in the developed model indicated that generally the respondents preferred not to use nutraceuticals before they considered the study attributes. The respondents preferred nutraceuticals with no side effect, clear evidence of effectiveness, and recommendation of a healthcare professional. The respondents were willing to pay $252/month more for nutraceuticals proven with no side effect than for those without proof of safety, and $102/month more for nutraceuticals proven with clear effectiveness than for those without proof of effectiveness.

Conclusions: Consumers weighed relatively high on the availability of safety and effectiveness proofs when they chose nutraceuticals. The study highlights on the crucial need to inform consumers using clinical evidences of nutraceuticals as the information is highly preferred by consumers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.vhri.2020.09.003DOI Listing
May 2021

A systematic literature review of economic evaluations of pneumococcal conjugate vaccines in east and southeast Asia (2006-2019).

Expert Rev Vaccines 2021 Mar 22:1-14. Epub 2021 Mar 22.

Health Economics and Outcomes Research, Pfizer Inc, New York, NY, USA.

Introduction: Pneumococcal infections can lead to serious invasive diseases such as meningitis, septicemia and pneumonia, as well as milder but more common illnesses such as sinusitis and otitis media. The World Health Organization (WHO) recommends the inclusion of pneumococcal conjugate vaccines (PCVs) in infant National Immunization Program (NIP) programs worldwide. Decision-makers in Asian countries planning to introduce PCVs in their respective NIP will need a comprehensive evidence of effectiveness of PCVs at the population level and economic evidence including cost-effectiveness.

Areas Covered: A systematic literature review (from 1/1/2016 to 10/11/2019) of PCVs in East and Southeast Asia to understand (1) the contributing factors to cost-effectiveness results of PCVs and (2) whether gaps in evidence exist suggesting why the region may have yet to implement full NIPs.

Expert Opinion: In East and Southeast Asia, vaccination with PCVs was found to significantly reduce the mortality and morbidity of pneumococcal diseases and was cost-effective compared to no vaccination. Study assumptions, specifically vaccine local acquisition, the inclusion or exclusion of indirect effects (serotype replacement and herd effect), cross-protection, and protection against nontypeable and serotype 3, were the main drivers of cost-effectiveness.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14760584.2021.1894933DOI Listing
March 2021

Association of non-alcoholic fatty liver disease and all-cause mortality in hospitalized cardiovascular disease patients: A systematic review and meta-analysis.

Medicine (Baltimore) 2021 Feb;100(5):e24557

Division of Ambulatory Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

Background: Controversy remains concerning the association of the all-cause mortality risk of hospitalized cardiovascular disease (CVD) patients with non-alcoholic fatty liver disease (NAFLD). This study investigated the risks of all-cause mortality among hospitalized CVD patients with NAFLD.

Methods: We used related keywords to search for studies in 3 electronic databases: PubMed, EMBASE, and Cochrane Library. All eligible studies published up to April 2020 were reviewed. The findings of those studies reporting the mortality outcomes of hospitalized CVD patients with and without NAFLD were examined, and the various study results were pooled and analyzed using a random-effects model. A quality assessment using the Newcastle-Ottawa scale was performed on the studies selected for inclusion in a meta-analysis.

Results: A total of 2135 studies were found, of which 3 were included in this meta-analysis. All studies were considered good quality. The mean age of the patients in the analysis was 73 years, and about half of them were men. The comorbidities reported were hypertension, diabetes mellitus, and dyslipidemia. The results showed that hospitalized CVD patients with NAFLD were at a significantly higher risk of all-cause mortality than non-NAFLD patients (adjusted hazard ratio of 2.08 [95% confidence interval, 1.56-2.59], P < .001). The included studies showed low heterogeneity (I2 = 0.0%, P = .473), and Begg and Egger tests revealed no apparent publication bias (P = .327 and P = .682, respectively).

Conclusions: Hospitalized CVD patients with NAFLD were at a higher risk of all-cause mortality than those without NAFLD. More studies that further explore this association are needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000024557DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870191PMC
February 2021

Role of Diet in Colorectal Cancer Incidence: Umbrella Review of Meta-analyses of Prospective Observational Studies.

JAMA Netw Open 2021 02 1;4(2):e2037341. Epub 2021 Feb 1.

Department of Pharmacotherapy, College of Pharmacy, University of Utah, Salt Lake City.

Importance: Several meta-analyses have summarized evidence for the association between dietary factors and the incidence of colorectal cancer (CRC). However, to date, there has been little synthesis of the strength, precision, and quality of this evidence in aggregate.

Objective: To grade the evidence from published meta-analyses of prospective observational studies that assessed the association of dietary patterns, specific foods, food groups, beverages (including alcohol), macronutrients, and micronutrients with the incidence of CRC.

Data Sources: MEDLINE, Embase, and the Cochrane Library were searched from database inception to September 2019.

Evidence Review: Only meta-analyses of prospective observational studies with a cohort study design were eligible. Evidence of association was graded according to established criteria as follows: convincing, highly suggestive, suggestive, weak, or not significant.

Results: From 9954 publications, 222 full-text articles (2.2%) were evaluated for eligibility, and 45 meta-analyses (20.3%) that described 109 associations between dietary factors and CRC incidence were selected. Overall, 35 of the 109 associations (32.1%) were nominally statistically significant using random-effects meta-analysis models; 17 associations (15.6%) demonstrated large heterogeneity between studies (I2 > 50%), whereas small-study effects were found for 11 associations (10.1%). Excess significance bias was not detected for any association between diet and CRC. The primary analysis identified 5 (4.6%) convincing, 2 (1.8%) highly suggestive, 10 (9.2%) suggestive, and 18 (16.5%) weak associations between diet and CRC, while there was no evidence for 74 (67.9%) associations. There was convincing evidence of an association of intake of red meat (high vs low) and alcohol (≥4 drinks/d vs 0 or occasional drinks) with the incidence of CRC and an inverse association of higher vs lower intakes of dietary fiber, calcium, and yogurt with CRC risk. The evidence for convincing associations remained robust following sensitivity analyses.

Conclusions And Relevance: This umbrella review found convincing evidence of an association between lower CRC risk and higher intakes of dietary fiber, dietary calcium, and yogurt and lower intakes of alcohol and red meat. More research is needed on specific foods for which evidence remains suggestive, including other dairy products, whole grains, processed meat, and specific dietary patterns.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamanetworkopen.2020.37341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887658PMC
February 2021

Global Economic Burden of Attention-Deficit/Hyperactivity Disorder: A Systematic Review.

Pharmacoeconomics 2021 04 8;39(4):399-420. Epub 2021 Feb 8.

Department of Pharmacotherapy, School of Pharmacy, University of Utah, Salt Lake City, UT, USA.

Background: Attention-deficit/hyperactivity disorder (ADHD) is one of the most common mental disorders affecting children and adults. Previous systematic reviews have provided estimates of ADHD-associated costs but were limited to the USA and Europe.

Objectives: This study aimed to systematically summarise all global evidence on the economic burden of ADHD.

Methods: A systematic search for published studies on costs of ADHD was conducted in EconLit, EMBASE, PubMed, ERIC, and PsycINFO. Additional literature was identified by searching the reference lists of eligible studies. The quality of the studies was assessed using the Larg and Moss checklist.

Results: This review included 44 studies. All studies were conducted in high-income countries and were limited to North America and Europe except for four studies: two in Asia and two in Australia. Most studies were retrospective and undertook a prevalence-based study design. Analysis revealed a substantial economic impact associated with ADHD. Estimates based on total costs ranged from $US831.38 to 20,538 for per person estimates and from $US356 million to 20.27 billion for national estimates. Estimates based on marginal costs ranged from $US244.15 to 18,751.00 for per person estimates and from $US12.18 million to 141.33 billion for national estimates. Studies that calculated economic burden across multiple domains of direct, indirect, and education and justice system costs for both children and adults with ADHD reported higher costs and translated gross domestic product than did studies that captured only a single domain or age group.

Conclusions: Despite the wide variation in methodologies in studies reviewed, the literature suggests that ADHD imposes a substantial economic burden on society. There is a dire need for cost-of-illness research in low- and middle-income countries to better inform the treatment and management of ADHD in these countries. In addition, guidelines on the conduct and reporting of economic burden studies are needed as they may improve standardisation of cost-of-illness studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40273-020-00998-0DOI Listing
April 2021

Horizon scanning of therapeutic modalities for nonalcoholic steatohepatitis.

Ann Hepatol 2021 Sep-Oct;24:100315. Epub 2021 Jan 27.

Department of Pharmacotherapy, College of Pharmacy, University of Utah, Salt Lake City, UT, USA. Electronic address:

Many interventions have been investigated for the treatment of nonalcoholic steatohepatitis (NASH). This study aims to summarize all investigated options to date and review the use of specific endpoints at different stages of ongoing trials of noncirrhotic NASH treatments. Using a horizon scanning approach, evidence were identified including meta-analyses of randomized controlled trials (RCTs) in PubMed, EMBASE, Cochrane, and AMED (up to February 2020), recently published RCTs in PubMed (2015-April 2020), RCTs presented at conferences (AASL and EASL, 2015-2020), and ongoing RCTs in ClincalTrials.gov (2015-November 2020). We included 6 meta-analyses of RCTs, 30 published RCTs, 11 conference abstracts, and 62 ongoing RCTs. An evidence map was created to demonstrate the treatment effects of 49 therapeutic modalities for NASH. Only six interventions (6/49, 12.24%) met the histological surrogate endpoints for potential conditional FDA approval. Obeticholic acid is the only therapy demonstrating positive benefits in ≥1-point improvement in fibrosis with no worsening of NASH in a phase 3 trial. The other therapies were all phase 2 studies. ≥1-point improvement in fibrosis with no worsening of NASH was shown in patients treated with cenicriviroc. NASH resolution with no worsening of fibrosis was shown in patients treated with liraglutide, semaglutide and resmetirom. Lanifibranor achieved both surrogate histological endpoints. Five ongoing RCTs (5/62, 8.06%) will investigate histological progression to cirrhosis, death, or liver-related clinical outcomes. In conclusion, some therapeutic modalities showed promising benefits, but further studies are warranted to find a definite treatment of NASH which prevents progression to cirrhosis and adverse liver outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.aohep.2021.100315DOI Listing
January 2021

Estimating the preferences and willingness-to-pay for colorectal cancer screening: an opportunity to incorporate the perspective of population at risk into policy development in Thailand.

J Med Econ 2021 Jan-Dec;24(1):226-233

Department of Pharmacotherapy, College of Pharmacy, University of Utah, Salt Lake City, UT, USA.

Aims: Colorectal cancer (CRC) is one of the public health burdens that can be lowered by early detection. This study aims to examine the preferences and willingness-to-pay of a population at risk for CRC screening in Thailand. Understanding the preferences for these individuals at risk would help Thailand, as an example of LMICs, to design effective population-based CRC screening programs.

Materials And Methods: A discrete choice experiment (DCE) was conducted among screening-naïve adults aged 50-75 years, who were at risk of CRC, in the out-patient department of a tertiary care hospital in Thailand. A DCE questionnaire was developed from six CRC screening attributes. Each questionnaire was composed of six choice sets and each contained two alternatives described by the different levels of attributes and an opt-out alternative. Participants were asked to choose one alternative from each choice set. A multinomial logit model was developed to determine the relative preference of each attribute. The willingness-to-pays for all attributes and screening modalities and the estimated preferred choices of the annual fecal immunochemical test (FIT), 10-yearly colonoscopy, 5-yearly double-contrast barium enema (DCBE), 5-yearly computed tomographic colonography (CTC), 5-yearly flexible sigmoidoscopy (FS), and no screening was calculated and compared.

Results: Four hundred participants were included. All attributes, except pain and less bowel preparation, were statistically associated with the participants' preference ( < .05). They preferred screenings with a high-risk reduction of CRC-related mortality, no complication, 5-year interval, and lower cost. The estimated preferred choices of FIT, colonoscopy, DCBE, CTC, and FS were 38.2%, 11.4%, 14.6%, 9.2%, and 11.4%, respectively. The willingness-to-pays for each screening modality was US$251, US$189, US$183, US$154, and US$142 (8,107, 6,105, 5,911, 4,974, and 4,587 THB) per episode, respectively.

Conclusions: The risk reduction of CRC-related mortality, complication, screening interval, and cost influenced the CRC screening preferences of Thai adults. FIT was the most preferred. Policymakers can develop a successful CRC screening campaign using these findings, incorporating the perspective of the population at risk in policy formulation to accomplish their goals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/13696998.2021.1877145DOI Listing
September 2021

The Impact of Halting Elective Admissions in Anticipation of a Demand Surge Due to the Coronavirus Pandemic (COVID-19).

Med Care 2021 03;59(3):213-219

Internal Medicine, VA Salt Lake City Health Care System, University of Utah, Salt Lake City, UT.

Background: In anticipation of a demand surge for hospital beds attributed to the coronavirus pandemic (COVID-19) many US states have mandated that hospitals postpone elective admissions.

Objectives: To estimate excess demand for hospital beds due to COVID-19, the net financial impact of eliminating elective admissions in order to meet demand, and to explore the scenario when demand remains below capacity.

Research Design: An economic simulation to estimate the net financial impact of halting elective admissions, combining epidemiological reports, the US Census, American Hospital Association Annual Survey, and the National Inpatient Sample. Deterministic sensitivity analyses explored the results while varying assumptions for demand and capacity.

Subjects: Inputs regarding disease prevalence and inpatient utilization were representative of the US population. Our base case relied on a hospital admission rate reported by the Center for Disease Control and Prevention of 137.6 per 100,000, with the highest rates in people aged 65 years and older (378.8 per 100,000) and 50-64 years (207.4 per 100,000). On average, elective admissions accounted for 20% of total hospital admissions, and the average rate of unoccupied beds across hospitals was 30%.

Measures: Net financial impact of halting elective admissions.

Results: On average, hospitals COVID-19 demand for hospital bed-days fell well short of hospital capacity, resulting in a substantial financial loss. The net financial impact of a 90-day COVID surge on a hospital was only favorable under a narrow circumstance when capacity was filled by a high proportion of COVID-19 cases among hospitals with low rates of elective admissions.

Conclusions: Hospitals that restricted elective care took on a substantial financial risk, potentially threatening viability. A sustainable public policy should therefore consider support to hospitals that responsibly served their communities through the crisis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MLR.0000000000001496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993651PMC
March 2021

Comparison of noninvasive scoring systems for the prediction of nonalcoholic fatty liver disease in metabolic syndrome patients.

Medicine (Baltimore) 2020 Dec;99(50):e23619

Division of Ambulatory Medicine.

Over half of metabolic syndrome (MetS) patients have nonalcoholic fatty liver disease (NAFLD). To prevent its complications, standard routine screening is required, but the human-resource and budgetary implications need to be taken into consideration. This study compared the performances of 4 noninvasive scoring systems in predicting NAFLD in MetS patients. They were the fatty liver index, hepatic steatosis index, lipid accumulation product index, and nonalcoholic fatty liver disease in metabolic syndrome patients scoring system (NAFLD-MS).Scores were determined for 499 MetS patients, including 249 patients in a type 2 diabetes mellitus (T2DM) subgroup. Ultrasonography was used to diagnose NAFLD. The accuracies and performance of the scoring systems were analyzed using published cutoff values, and comparisons were made of their areas under receiver operating characteristic curves, sensitivities, specificities, positive and negative predictive values, and likelihood ratios.NAFLD was detected in 68% of the MetS patients and 77% of the MetS patients with T2DM. According to the areas under receiver operating characteristic curves, fatty liver index and hepatic steatosis index provided better performances in predicting NAFLD. NAFLD-MS provided the highest specificity of 99% among the MetS patients as a whole, and it provided even better accuracy with similar performance when applied to the subgroup of MetS patients with T2DM. The maximum cost avoidance from unnecessary ultrasonography was also reported by using NAFLD-MS. In terms of simplicity and ease of calculation, the lipid accumulation product index and NAFLD-MS are preferred.All 4 scoring systems proved to be acceptable for predicting NAFLD among MetS and T2DM patients in settings where the availability of ultrasonography is limited. NAFLD-MS provided the highest specificity and cost avoidance, and it is simple to use. All 4 systems can help clinicians decide further investigations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000023619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738027PMC
December 2020

Global systematic review of cost of illness and economic evaluation studies associated with snakebite.

J Glob Health 2020 Dec;10(2):020415

College of Pharmacy, University of Utah, Salt Lake City, Utah, USA.

Background: Snakebite envenoming, a high priority Neglected Tropical Disease categorized by the World Health Organization (WHO), has been considered as a poverty-related disease that requires greater global awareness and collaboration to establish strategies that effectively decrease economic burdens. This prompts the need for a comprehensive review of the global literature that summarizes the global economic burden and a description of methodology details and their variation. This study aimed to systematically identify studies on cost of illness and economic evaluation associated with snakebites, summarize study findings, and evaluate their methods to provide recommendations for future studies.

Methods: We searched PubMed, EMBASE, Cochrane library, and Econlit for articles published from inception to 31 July 2019. Original articles reporting costs or full economic evaluation related with snakebites were included. The methods and reporting quality were assessed. Costs were presented in US dollars (US$) in 2018.

Results: Twenty-three cost of illness studies and three economic evaluation studies related to snakebites were included. Majority of studies (18/23, 78.26%) were conducted in Low- and Middle-income countries. Most cost of illness studies (82.61%) were done using hospital-based data of snakebite patients. While, four studies (17.39%) estimated costs of snakebites in communities. Five studies (21.74%) used societal perspective estimating both direct and indirect costs. Only one study (4.35%) undertook incidence-based approach to estimate lifetime costs. Only three studies (13.04%) estimated annual national economic burdens of snakebite which varied drastically from US$126 319 in Burkina Faso to US$13 802 550 in Sri Lanka. Quality of the cost of illness studies were varied and substantially under-reported. All three economic evaluation studies were cost-effectiveness analysis using decision tree model. Two of them assessed cost-effectiveness of having full access to antivenom and reported cost-effective findings.

Conclusions: Economic burdens of snakebite were underestimated and not extensively studied. To accurately capture the economic burdens of snakebites at both the global and local level, hospital data should be collected along with community survey and economic burdens of snakebites should be estimated both in short-term and long-term period to incorporate the lifetime costs and productivity loss due to premature death, disability, and consequences of snakebites.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7189/jogh.10.020415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719278PMC
December 2020

Efficacy and safety of pharmacological cachexia interventions: systematic review and network meta-analysis.

BMJ Support Palliat Care 2021 Mar 27;11(1):75-85. Epub 2020 Nov 27.

Department of Pharmacotherapy, University of Utah Health, Salt Lake City, Utah, USA

Aims: Randomised controlled trials (RCTs) demonstrated benefits of pharmacological interventions for cachexia in improving weight and appetite. However, comparative efficacy and safety are not available. We conducted a systematic review and network meta-analysis (NMA) to evaluate the relative efficacy and safety of pharmacological interventions for cachexia.

Methods: PubMed, EmBase, Cochrane, and ClinicalTrials.gov were searched for RCTs until October 2019. Key outcomes were total body weight (TBW) improvement, appetite (APP) score and serious adverse events. Two reviewers independently extracted data and assessed risk of bias. NMA was performed to estimate weight gain and APP score increase at 8 weeks, presented as mean difference (MD) or standardised MD with 95% CI.

Results: 80 RCTs (10 579 patients) with 12 treatments were included. Majority is patients with cancer (7220). Compared with placebo, corticosteroids, high-dose megestrol acetate combination (Megace_H_Com) (400 mg/day), medroxyprogesterone, high-dose megestrol acetate (Megace_H) (400 mg/day), ghrelin mimetic and androgen analogues (Androgen) were significantly associated with MD of TBW of 6.45 (95% CI 2.45 to 10.45), 4.29 (95% CI 2.23 to 6.35), 3.18 (95% CI 0.94 to 5.41), 2.66 (95% CI 1.47 to 3.85), 1.73 (95% CI 0.27 to 3.20) and 1.50 (95% CI 0.56 to 2.44) kg. For appetite improvement, Megace_H_Com, Megace_H and Androgen significantly improved standardised APP score, compared with placebo. There is no significant difference in serious adverse events from all interventions compared with placebo.

Conclusions: Our findings suggest that several pharmacological interventions have potential to offer benefits in treatment of cachexia especially Megace_H and short-term use corticosteroids. Nonetheless, high-quality comparative studies to compare safety and efficacy are warranted for better management of cachexia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjspcare-2020-002601DOI Listing
March 2021

Metabolic events associated with the use of antipsychotics in children, adolescents and young adults: a multinational sequence symmetry study.

Eur Child Adolesc Psychiatry 2020 Nov 13. Epub 2020 Nov 13.

School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, No.1, University Road, Tainan, 701, Taiwan.

It is known that younger patients treated with antipsychotics are at increased risk of metabolic events; however, it is unknown how this risk varies according to ethnicity, the class of antipsychotic and the specific product used, and by age group. We conducted a multinational sequence symmetry study in Asian populations (Hong Kong, Japan, Korea, Taiwan and Thailand) and non-Asian populations (Australia and Denmark) to evaluate the metabolic events associated with antipsychotics in both Asian and non-Asian populations, for typical and atypical antipsychotics, and by the subgroups of children and adolescents, and young adults. Patients aged 6-30 years newly initiating oral antipsychotic drugs were included. We defined a composite outcome for metabolic events which included dyslipidemia, hypertension and hyperglycemia. We calculated the sequence ratio (SR) by dividing the number of people for whom a medicine for one of the outcome events was initiated within a 12-month period after antipsychotic initiation by the number before antipsychotic initiation. This study included 346,904 antipsychotic initiators across seven countries. Antipsychotic use was associated with an increased risk of composite metabolic events with a pooled adjusted SR (ASR) of 1.22 (95% CI 1.00-1.50). Pooled ASRs were similar between Asian (ASR, 1.22; 95% CI 0.88-1.70) and non-Asian populations (ASR, 1.22; 95% CI 1.04-1.43). The pooled ASR for typical and atypical antipsychotics was 0.98 (95% CI 0.85-1.12) and 1.24 (95% CI 0.97-1.59), respectively. No difference was observed in the relative effect in children and adolescents compared to young adults. The risk of metabolic events associated with antipsychotics use was similar in magnitude in Asian and non-Asian populations despite the marked difference in drug utilization patterns.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00787-020-01674-6DOI Listing
November 2020

Real-World Comparative Effectiveness and Safety of Non-Vitamin K Antagonist Oral Anticoagulants vs. Warfarin in a Developing Country.

Clin Pharmacol Ther 2021 05 22;109(5):1282-1292. Epub 2020 Nov 22.

Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, UK.

We aimed to compare effectiveness and safety of the non-vitamin K antagonist oral anticoagulants (NOACs) vs. warfarin for stroke prevention in nonvalvular atrial fibrillation (NVAF) in a developing country where anticoagulation control with warfarin is suboptimal. A real-world study was conducted among patients with NVAF in Thailand receiving NOACs and warfarin from 9 hospitals during January 2012 to April 2018. Propensity-score weighting was used to balance covariates across study groups. Cox regression models were used to compare the risk of thromboembolism, major bleeding, and net adverse clinical events across matched cohorts. A total of 2,055 patients; 605, 604, 441, and 405 patients receiving warfarin, rivaroxaban, dabigatran, and apixaban, respectively, were included. Median (interquartile range) time in therapeutic range (TTR) for warfarin users was 49.5% (26.6%-70.3%). Compared with warfarin, NOACs were associated with a significant reduction in major bleeding either when analyzed as a group (adjusted hazard ratio (HR) (95% confidence interval (CI)) of 0.46 (0.34-0.62) or by each agent. Compared with warfarin users with poor TTR, apixaban (adjusted HR 0.48, 95% CI 0.26-0.86, P = 0.013) and dabigatran (adjusted HR 0.44, 95% CI 0.21-0.90, P = 0.025) were associated with a lower risk of thromboembolism, in addition to markedly lower risk of major bleeding. In a healthcare system where anticoagulation control with warfarin is suboptimal, use of NOACs was associated with a profound reduction in major bleeding. The effectiveness and safety advantages of NOACs were more pronounced compared with warfarin users with low TTR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cpt.2090DOI Listing
May 2021

Systematic review and network meta-analysis: efficacy of drugs for functional dyspepsia.

Aliment Pharmacol Ther 2021 01 16;53(1):8-21. Epub 2020 Sep 16.

School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Malaysia.

Background: Functional dyspepsia (FD) is a relapsing and remitting condition affecting between 5% and 10% of people. Efficacious therapies are available, but their relative efficacy is unknown.

Aim: To perform a systematic review with network meta-analysis to resolve this uncertainty.

Methods: We searched the medical literature through July 2020 for randomised controlled trials (RCTs) assessing efficacy of drugs for adults with FD, compared with each other, or placebo. Trials reported a dichotomous assessment of symptom status after completion of therapy. We pooled data using a random effects model. Efficacy was reported as a pooled relative risk (RR) of remaining symptomatic with a 95% confidence interval (CI) to summarise efficacy of each comparison tested. Relative ranking was assessed with surface under the cumulative ranking curve (SUCRA) probabilities.

Results: We identified 71 eligible RCTs (19 243 participants). Tricyclic antidepressants (TCAs) were ranked second for efficacy (RR of remaining symptomatic = 0.71; 95% CI 0.58-0.87, SUCRA 0.87), and first when only low risk of bias trials were included. Most RCTs that used TCAs recruited patients who were refractory to other drugs included in the network. Although sulpiride or levosulpiride were ranked first for efficacy (RR = 0.49; 95% CI 0.36-0.69, SUCRA 0.99), trial quality was low and only 86 patients received active therapy. TCAs were more likely to cause adverse events than placebo.

Conclusions: TCAs, histamine- receptor antagonists, standard- and low-dose proton pump inhibitors, sulpiride or levosulpiride, itopride and acotiamide were all more efficacious than placebo for FD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/apt.16072DOI Listing
January 2021

Systemic treatments for eczema: a network meta-analysis.

Cochrane Database Syst Rev 2020 09 14;9:CD013206. Epub 2020 Sep 14.

Department of Pharmacotherapy, College of Pharmacy, University of Utah, Salt Lake City, Utah, USA.

Background: Eczema is a common and chronic, relapsing, inflammatory skin disorder. It seriously impacts quality of life and economic outcomes, especially for those with moderate to severe eczema. Various treatments allow sustained control of the disease; however, their relative benefit remains unclear due to the limited number of trials directly comparing treatments.

Objectives: To assess the comparative efficacy and safety of different types of systemic immunosuppressive treatments for moderate to severe eczema using NMA and to generate rankings of available systemic immunosuppressive treatments for eczema according to their efficacy and safety.

Search Methods: We searched the following databases up to August 2019: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, and Embase.

Selection Criteria: All randomised controlled trials (RCTs) of systemic immunosuppressive agents for moderate to severe atopic eczema when compared against placebo or any other eligible eczema treatment.

Data Collection And Analysis: We synthesised data using pair-wise analysis and NMA to compare treatments and rank them according to their effectiveness. Effectiveness was assessed primarily by determining the proportion of participants who achieved at least 75% improvement in the Eczema Area and Severity Index (EASI75) and improvement in the Patient-Oriented Eczema Measure (POEM). Safety was evaluated primarily by considering the proportion of participants with serious adverse events (SAEs) and infection. We deemed short-term follow-up as ≤ 16 weeks and long-term follow-up as > 16 weeks. We assessed the certainty of the body of evidence from the NMA for these primary outcomes using six domains of CiNEMA grading.

Main Results: We included a total of 74 studies, with 8177 randomised participants. Approximately 55% of participants were male, with average age of 32 years (range 2 to 84 years), although age and gender were unreported for 419 and 902 participants, respectively. Most of the included trials were placebo controlled (65%), 34% were head-to-head studies (15% assessed the effects of different doses of the same drug), and 1% were multi-armed studies with both an active comparator and a placebo. All trials included participants with moderate to severe eczema, but 62% of studies did not separate data by severity; 38% of studies assessed only severe eczema. The total duration of included trials ranged from 2 weeks to 60 months, whereas treatment duration varied from a single dose (CIM331, KPL-716) to 60 months (methotrexate (MTX)). Seventy studies were available for quantitative synthesis; this review assessed 29 immunosuppressive agents from three classes of interventions. These included (1) conventional treatments, with ciclosporin assessed most commonly; (2) small molecule treatments, including phosphodiesterase (PDE)-4 inhibitors, tyrosine kinase inhibitors, and Janus kinase (JAK) inhibitors; and (3) biological treatments, including anti-CD31 receptors, anti-interleukin (IL)-22, anti-IL-31, anti-IL-13, anti-IL-12/23p40, anti-OX40, anti-TSLP, anti-CRTH2, and anti-immunoglobulin E (IgE) monoclonal antibodies, but most commonly dupilumab. Most trials (73) assessed outcomes at a short-term duration ranging from 2 to 16 weeks, whereas 33 trials assessed long-term outcomes, with duration ranging from 5 to 60 months. All participants were from a hospital setting. Fifty-two studies declared a source of funding, and of these, pharmaceutical companies funded 88%. We rated 37 studies as high risk; 21, unclear risk, and 16, low risk of bias, with studies most commonly at high risk of attrition bias. Network meta-analysis suggests that dupilumab ranks first for effectiveness when compared with other biological treatments. Dupilumab is more effective than placebo in achieving EASI75 (risk ratio (RR) 3.04, 95% confidence interval (CI) 2.51 to 3.69) and improvement in POEM score (mean difference 7.30, 95% CI 6.61 to 8.00) at short-term follow-up (high-certainty evidence). Very low-certainty evidence means we are uncertain of the effects of dupilumab when compared with placebo, in terms of the proportion of participants who achieve EASI75 (RR 2.59, 95% CI 1.87 to 3.60) at longer-term follow-up. Low-certainty evidence indicates that tralokinumab may be more effective than placebo in achieving short-term EASI75 (RR 2.54, 95% CI 1.21 to 5.34), but there was no evidence for tralokinumab to allow us to assess short-term follow-up of POEM or long-term follow-up of EASI75. We are uncertain of the effect of ustekinumab compared with placebo in achieving EASI75 (long-term follow-up: RR 1.17, 95% CI 0.40 to 3.45; short-term follow-up: RR 0.91, 95% CI 0.28 to 2.97; both very low certainty). We found no evidence on ustekinumab for the POEM outcome. We are uncertain whether other immunosuppressive agents that targeted our key outcomes influence the achievement of short-term EASI75 compared with placebo due to low- or very low-certainty evidence. Dupilumab and ustekinumab were the only immunosuppressive agents evaluated for longer-term EASI75. Dupilumab was the only agent evaluated for improvement in POEM during short-term follow-up. Low- to moderate-certainty evidence indicates a lower proportion of participants with SAEs after treatment with QAW039 and dupilumab compared to placebo during short-term follow-up, but low- to very low-certainty evidence suggests no difference in SAEs during short-term follow-up of other immunosuppressive agents compared to placebo. Evidence for effects of immunosuppressive agents on risk of any infection during short-term follow-up and SAEs during long-term follow-up compared with placebo was of low or very low certainty but did not indicate a difference. We did not identify differences in other adverse events (AEs), but dupilumab is associated with specific AEs, including eye inflammation and eosinophilia.

Authors' Conclusions: Our findings indicate that dupilumab is the most effective biological treatment for eczema. Compared to placebo, dupilumab reduces eczema signs and symptoms in the short term for people with moderate to severe atopic eczema. Short-term safety outcomes from clinical trials did not reveal new safety concerns with dupilumab. Overall, evidence for the efficacy of most other immunosuppressive treatments for moderate to severe atopic eczema is of low or very low certainty. Given the lack of data comparing conventional with newer biological treatments for the primary outcomes, there remains high uncertainty for ranking the efficacy and safety of conventional treatments such as ciclosporin and biological treatments such as dupilumab. Most studies were placebo-controlled and assessed only short-term efficacy of immunosuppressive agents. Further adequately powered head-to-head RCTs should evaluate comparative long-term efficacy and safety of available treatments for moderate to severe eczema.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/14651858.CD013206.pub2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128359PMC
September 2020

Aloe vera and health outcomes: An umbrella review of systematic reviews and meta-analyses.

Phytother Res 2021 Feb 14;35(2):555-576. Epub 2020 Sep 14.

Department of Pharmacotherapy, College of Pharmacy, University of Utah, Salt Lake City, Utah, USA.

This umbrella review aims to summarize the effects of Aloe vera on health outcomes and assess the strength of evidence. PubMed, Scopus, Embase, Cochrane database of systematic reviews, CINAHL, and AMED were searched from inception to October, 2019 for systematic reviews and meta-analyses of clinical trials that investigated the effects of Aloe vera on health outcomes. Two independent reviewers extracted data, assessed the methodological quality, and rated the credibility of evidence according to established criteria. Ten articles reporting 71 unique outcomes of Aloe vera were included. Of these, 47 (67%) were nominally statistically significant based on random-effects model (p ≤ .05). Only 3 outcomes were supported by highly suggestive evidence, whereas 42 outcomes were supported by weak evidence. The highly suggestive evidence supported benefits of Aloe vera in the prevention of second-degree infusion phlebitis (RR: 0.18, 95% CI: 0.10-0.32, p-value: 1.75 × 10 ) and chemotherapy-induced phlebitis based on overall incidence (OR: 0.13, 95% CI: 0.08-0.20, p-value: 9.68 × 10 ) and incidence of the second degree of severity (OR: 0.10, 95% CI: 0.07-0.14, p-value: 3.41 × 10 ). However, the majority of the evidence were limited by small sample size and poor methodological quality. Therefore, despite the overall favorable effect of Aloe vera, more robust studies are needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ptr.6833DOI Listing
February 2021

Prescriber compliance to direct oral anticoagulant labels and impact on outcomes in Thailand.

Br J Clin Pharmacol 2021 03 9;87(3):1390-1400. Epub 2020 Sep 9.

Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, UK.

Aims: This study aimed to evaluate the prescriber compliance to the approved labels of direct oral anticoagulants (DOACs) and impact of appropriateness of dosing on clinical outcomes.

Methods: A retrospective study was conducted using simple-stratified random sampling of adult patients receiving ≥6 months of DOACs for various indications during 2013-2017 in 10 tertiary care hospitals. Patients were classified into 3 dosing groups including approved dose, underdosing and overdosing based on the Thai Food and Drug Administration-approved labels. Cox proportional hazard models were used to evaluate the impact of different dosings on thromboembolic and bleeding events.

Results: From 1200 patients included in the data analysis, prescribing of DOACs was consistent with the approved indications in 1130 cases (94.2%) while 70 patients (5.8%) received DOACs despite having contraindications or with off-label usage. Among 1026 cases of dosing evaluation cohort, 688 patients (67.1%) received approved doses. There were 227 (21.9%) and 110 (10.7%) cases of underdosing and overdosing, respectively. Multivariate analysis showed that underdosing was associated with an increased risk of thromboembolism 3.023 (95% confidence interval [CI]: 1.291-7.080; P = .011) while overdosing was associated with an increased risk of bleeding requiring hospitalization (adjusted hazard ratio, 3.045; 95% CI, 1.501-6.178; P = .002) and Bleeding Academic Research Consortium type 2 or more (adjusted hazard ratio, 2.196; 95% CI, 1.083-4.452; P = .029).

Conclusion: Prescribers' compliance to approved indications were high. However, 1/3 of DOAC prescriptions were inconsistent with approved dosing. Dosing deviation was associated with an increase in adverse clinical outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bcp.14535DOI Listing
March 2021

Clinical burden associated with postsurgical complications in major cardiac surgeries in Asia-Oceania countries: A systematic review and meta-analysis.

J Card Surg 2020 Oct 2;35(10):2618-2626. Epub 2020 Aug 2.

Department of Pharmacotherapy, College of Pharmacy, University of Utah, Salt Lake City, Utah.

Background: Evidence on the burden of postsurgical complications is mainly from studies in western countries, and little is highlighted in the Asia-Oceania region. This study aimed to identify and compare the burden of postsurgical complications in major cardiac surgeries in Asia-Oceania countries.

Methods: A systematic search was performed in PubMed, Embase, and CENTRAL between January 2000 and July 2018. Inclusion criteria were: (a) observational studies or randomized control trials; (b) studied in coronary artery bypass graft (CABG) and/or heart valve procedures; (c) measured postsurgical clinical outcomes; and (d) conducted in Asia-Oceania countries. Pooled effects were calculated using a random-effects model.

Results: Of the 6032 articles screened, 472 studies with a total of 614 161 patients met the inclusion criteria. The pooled incidences (95% confidence interval) of hospital mortality and 30-day mortality were similar at 2.38% (2.16%-2.59%) and 2.33% (2.16%-2.50%), respectively. Length of stay (LOS) was 14.07 days (13.44-14.71 days). The incidence for atrial fibrillation (AF) and stroke/cerebrovascular accident (CVA) was 17.49% (15.99%-18.99%) and 1.64% (1.51%-1.78%), respectively. Below outcomes tended to be better in studies on CABG compared to heart valve procedures, including the incidence of hospital mortality (1.97%[1.75%-2.18%] vs 3.97% [3.29%-4.65%]), AF (16.47% [14.85%-18.10%] vs 21.98% [17.41%-26.54%]), stoke/CVA (1.51% [1n 37%-1.65%] vs 2.55% [2.07%-3.04%]), and mean LOS (days) (13.08 [12.51-13.65] vs 19.58 [16.72-22.45]). Similarly, all postsurgical complications tended to be higher in studies involving high-risk patients vs non-high-risk patients.

Conclusions: There are opportunities to improve clinical outcomes of patients with high surgical risks and those undertaking heart valve procedures, as they tend to have poorer survival and higher risk in developing postsurgical complications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jocs.14855DOI Listing
October 2020
-->