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  1. Article ; Online: Efficacy and safety of selinexor for patients with relapsed and refractory multiple myeloma: A meta-analysis.

    Shafei, Laila / Bashir, Shaima / Chan, Esther W / Abushanab, Dina / Hamad, Anas / Al-Badriyeh, Daoud

    Current problems in cancer

    2024  Volume 50, Page(s) 101076

    Abstract: Purpose: Selinexor is a first-in-class, oral selective-inhibitor-of-nuclear-export, granted accelerated approval by FDA (2019) for relapsed and refractory multiple myeloma (RRMM). We sought to quantitatively summarize the selinexor efficacy and safety ... ...

    Abstract Purpose: Selinexor is a first-in-class, oral selective-inhibitor-of-nuclear-export, granted accelerated approval by FDA (2019) for relapsed and refractory multiple myeloma (RRMM). We sought to quantitatively summarize the selinexor efficacy and safety in RRMM.
    Methods: We searched PubMed, EMBASE, CENTRAL, clinicaltrial.gov, and google scholar, until May 2023, studies about selinexor use in RRMM. The outcome measures of interest were primarily efficacy outcomes, in addition to safety outcomes. Random-effect model analyses were performed, at statistical significance of P<0.05, using the RevMan software.
    Results: Meta-analyses of eleven included clinical trials yielded a significant 56.21% overall clinical benefit, 46.91% overall response, 4.89% complete response, 23.41% very good partial response, 24.68% partial response, and 28.06% stable disease rates with selinexor. Due to safety reasons, selinexor caused significant increase in discontinuation rate, 16.80%. Subgroup analyses demonstrated higher efficacy with selinexor plus dexamethasone and proteasome inhibitor combinations than with selinexor alone. The multiple myeloma type, high cytogenetic risk, refractory state, and advanced disease state did not affect performance. Risk of selection, performance, and detection biases were unclear in the included trials.
    Conclusion: Selinexor led to significant positive responses with an acceptable safety profile in RRMM patients, despite higher rates of safety-related discontinuations. Selinexor-based combinations further enhanced response.
    Language English
    Publishing date 2024-03-26
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 441816-5
    ISSN 1535-6345 ; 0147-0272
    ISSN (online) 1535-6345
    ISSN 0147-0272
    DOI 10.1016/j.currproblcancer.2024.101076
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  2. Article ; Online: Cost-Effectiveness of Direct Oral Anticoagulants in Patients With Nonvalvular Atrial Fibrillation in Hong Kong.

    Peng, Kuan / Li, Yihua / Chan, Esther W / Wong, Ian C K / Li, Xue

    Value in health regional issues

    2023  Volume 36, Page(s) 51–57

    Abstract: Objectives: The emergence of direct oral anticoagulants (DOACs) has revolutionized the prevention of stroke related to nonvalvular atrial fibrillation (NVAF). Several DOACs are available on the market, while the cost-effectiveness comparison among DOACs ...

    Abstract Objectives: The emergence of direct oral anticoagulants (DOACs) has revolutionized the prevention of stroke related to nonvalvular atrial fibrillation (NVAF). Several DOACs are available on the market, while the cost-effectiveness comparison among DOACs and vitamin K antagonist (warfarin) in NVAF management in Hong Kong market remains scarce. The objective of this study was to assess the cost-effectiveness of DOACs and warfarin from a Hong Kong public institutional perspective to inform formulary listing decisions.
    Methods: A previously developed Markov model was adapted to simulate the lifetime disease progression of a hypothetical cohort of 1000 patients. Net monetary costs, quality-adjusted life-year (QALY), and incremental cost-effectiveness ratio were computed for the following competing alternatives: warfarin, apixaban (5 mg twice daily), dabigatran (110 mg or 150 mg twice daily), and rivaroxaban (20 mg once daily). Probabilistic sensitivity analyses were conducted to address study uncertainties.
    Results: In base-case results, all DOACs were associated with greater QALYs improvements and lower costs than warfarin. Rivaroxaban, apixaban, dabigatran 150 mg, dabigatran 110 mg, and warfarin resulted in net costs US dollar (USD) 8088, USD 8240, USD 8566, USD 8653, and USD 16 363 and net QALY 5.87, 6.017, 6.022, 5.98, and 5.829, respectively. In probabilistic sensitivity analysis, the probabilities of warfarin, rivaroxaban 20 mg, dabigatran 110 mg, dabigatran 150 mg, and apixaban 5 mg being cost-effective of 2000 iterations were 0%, 0%, 29.4%, 33.2%, and 37.4%, respectively.
    Conclusion: Apixaban was the most cost-effective option compared with other DOACs and warfarin in the management of NVAF; this conclusion is consistent under all the tested uncertainty scenarios.
    MeSH term(s) Humans ; Warfarin/therapeutic use ; Atrial Fibrillation/complications ; Atrial Fibrillation/drug therapy ; Rivaroxaban/therapeutic use ; Dabigatran/therapeutic use ; Cost-Benefit Analysis ; Hong Kong ; Anticoagulants
    Chemical Substances Warfarin (5Q7ZVV76EI) ; Rivaroxaban (9NDF7JZ4M3) ; Dabigatran (I0VM4M70GC) ; Anticoagulants
    Language English
    Publishing date 2023-04-06
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2679127-4
    ISSN 2212-1102 ; 2212-1099
    ISSN (online) 2212-1102
    ISSN 2212-1099
    DOI 10.1016/j.vhri.2023.02.003
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    Zs.A 6969: Show issues Location:
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  3. Article ; Online: Proton pump inhibitors associated with severe COVID-19 among two-dose but not three-dose vaccine recipients.

    Cheung, Ka Shing / Yan, Vincent K C / Ye, Xuxiao / Hung, Ivan F N / Chan, Esther W / Leung, Wai K

    Journal of gastroenterology and hepatology

    2024  

    Abstract: Background and aim: Proton pump inhibitors (PPIs) may increase the risk of COVID-19 among non-vaccinated subjects via various mechanisms, including gut dysbiosis. We aimed to investigate whether PPIs also affect the clinical outcomes of COVID-19 among ... ...

    Abstract Background and aim: Proton pump inhibitors (PPIs) may increase the risk of COVID-19 among non-vaccinated subjects via various mechanisms, including gut dysbiosis. We aimed to investigate whether PPIs also affect the clinical outcomes of COVID-19 among vaccine recipients.
    Methods: This was a territory-wide cohort study of 3 272 286 vaccine recipients (aged ≥ 18 years) of ≥ 2 doses of either BNT162b2 or CoronaVac. Exclusion criteria included prior gastrointestinal surgery, immunocompromised status, and prior COVID-19. The primary outcome was COVID-19, and secondary outcomes included COVID-19-related hospitalization and severe infection (composite of intensive care unit admission, ventilatory support, and/or death). Covariates include age, sex, the Charlson Comorbidity Index, comorbidities, and concomitant medication use. Subjects were followed from index date (first dose of vaccination) until outcome occurrence, death, additional dose of vaccination, or March 31, 2022. Exposure was pre-vaccination PPI use (any prescription within 90 days before the index date). Propensity score (PS) matching and a Poisson regression model were used to estimate the adjusted incidence rate ratio (aIRR) of outcomes with PPI use.
    Results: Among 439 154 PS-matched two-dose vaccine recipients (mean age: 65.3 years; male: 45.7%) with a median follow-up of 6.8 months (interquartile range: 2.6-7.9), PPI exposure was associated with a higher risk of COVID-19 (aIRR: 1.08; 95% confidence interval [95% CI]: 1.05-1.10), hospitalization (aIRR: 1.20; 95% CI: 1.08-1.33), and severe infection (aIRR: 1.57; 95% CI: 1.24-1.98). Among 188 360 PS-matched three-dose vaccine recipients (mean age: 62.5 years; male: 49.0%; median follow-up: 9.1 months [interquartile range: 8.0-10.9]), PPIs were associated with higher infection risk (aIRR: 1.11; 95% CI: 1.08-1.15) but not other outcomes.
    Conclusions: Although PPI use was associated with a higher COVID-19 risk, severe infection was limited to two-dose but not three-dose vaccine recipients.
    Language English
    Publishing date 2024-05-05
    Publishing country Australia
    Document type Journal Article
    ZDB-ID 632882-9
    ISSN 1440-1746 ; 0815-9319
    ISSN (online) 1440-1746
    ISSN 0815-9319
    DOI 10.1111/jgh.16601
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  4. Article ; Online: Trends in PCSK9 inhibitor utilization in the United States, Europe, and other countries: An analysis of international sales data.

    Blais, Joseph Edgar / Wei, Yue / Knapp, Martin / Wong, Ian C K / Wei, Li / Chan, Esther W

    American heart journal

    2022  Volume 248, Page(s) 13–20

    MeSH term(s) Antiviral Agents ; Commerce ; Europe ; Humans ; Proprotein Convertase 9 ; United States
    Chemical Substances Antiviral Agents ; PCSK9 protein, human (EC 3.4.21.-) ; Proprotein Convertase 9 (EC 3.4.21.-)
    Language English
    Publishing date 2022-03-01
    Publishing country United States
    Document type Letter
    ZDB-ID 80026-0
    ISSN 1097-6744 ; 0002-8703
    ISSN (online) 1097-6744
    ISSN 0002-8703
    DOI 10.1016/j.ahj.2022.02.008
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  5. Article: Antibiotic Use Prior to COVID-19 Vaccine Is Associated with Higher Risk of COVID-19 and Adverse Outcomes: A Propensity-Scored Matched Territory-Wide Cohort.

    Cheung, Ka Shing / Yan, Vincent K C / Lam, Lok Ka / Ye, Xuxiao / Hung, Ivan F N / Chan, Esther W / Leung, Wai K

    Vaccines

    2023  Volume 11, Issue 8

    Abstract: Background: ...

    Abstract Background:
    Language English
    Publishing date 2023-08-08
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2703319-3
    ISSN 2076-393X
    ISSN 2076-393X
    DOI 10.3390/vaccines11081341
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  6. Article ; Online: Evolving Trends in Consumption of Direct Oral Anticoagulants in 65 Countries/Regions from 2008 to 2019.

    Yan, Vincent K C / Li, Hang-Long / Wei, Li / Knapp, Martin R J / Wong, Ian C K / Chan, Esther W

    Drugs

    2023  Volume 83, Issue 4, Page(s) 315–340

    Abstract: Background: Direct oral anticoagulants (DOACs) have been increasingly utilised over warfarin. However, little is known about the relative consumption trends and costs of each DOAC at the global level.: Methods: An ecological study using ... ...

    Abstract Background: Direct oral anticoagulants (DOACs) have been increasingly utilised over warfarin. However, little is known about the relative consumption trends and costs of each DOAC at the global level.
    Methods: An ecological study using pharmaceutical sales data from IQVIA-MIDAS database was used to estimate consumption and cost of individual DOACs in 65 countries from 2008 to 2019. Consumption was estimated from the volume of DOACs sold, expressed as defined-daily-dose/1000-inhabitants/day (DDDTID). Compound and absolute annual growth rates were reported to quantify consumption changes over time. Costs were estimated as manufacturer price per day-of-therapy.
    Results: Global consumption of dabigatran, rivaroxaban, apixaban and edoxaban were 0.31, 1.05, 1.08 and 0.78 DDDTID, respectively, in Q2-2019, compared to 0.23, 0.54, 0.21 and 0.03 in Q2-2015, with highest consumption in Western Europe, Northern Europe and Oceania (18.2, 14.07, 13.14 DDDTID). In most countries (46/65, 70%), rivaroxaban contributed to most DOAC consumption (35%-100%), whereas dabigatran accounted for less than one-third. Edoxaban accounted for < 20% of the total in Northern America and Europe but contributed significant proportions in Japan (28.58%) and South Korea (31.37%). Longer median time-to-adoption from FDA approval for apixaban and edoxaban was observed. Costs of all DOACs were ~2-4 times higher in the USA, Puerto Rico and Thailand than in other countries.
    Conclusions: Regional differences exist in consumption pattern and trends of individual DOACs over the past decade. Consumption of rivaroxaban and apixaban overtook dabigatran in most countries, whereas use of edoxaban remains limited except in East Asian countries. The USA pays higher prices for DOACs than other countries.
    MeSH term(s) Humans ; Rivaroxaban/therapeutic use ; Dabigatran/therapeutic use ; Anticoagulants/therapeutic use ; Stroke/drug therapy ; Atrial Fibrillation/drug therapy ; Pyridones/therapeutic use ; Administration, Oral
    Chemical Substances edoxaban (NDU3J18APO) ; Rivaroxaban (9NDF7JZ4M3) ; Dabigatran (I0VM4M70GC) ; Anticoagulants ; Pyridones
    Language English
    Publishing date 2023-02-25
    Publishing country New Zealand
    Document type Journal Article
    ZDB-ID 120316-2
    ISSN 1179-1950 ; 0012-6667
    ISSN (online) 1179-1950
    ISSN 0012-6667
    DOI 10.1007/s40265-023-01837-0
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    Zs.A 762: Show issues Location:
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  7. Article ; Online: Effects of empagliflozin on liver fat in patients with metabolic dysfunction-associated steatotic liver disease without diabetes mellitus: A randomized, double-blind, placebo-controlled trial.

    Cheung, Ka Shing / Ng, Ho Yu / Hui, Rex Wan Hin / Lam, Lok Ka / Mak, Lung Yi / Ho, Yuen Chi / Tan, Jing Tong / Chan, Esther W / Seto, Wai Kay / Yuen, Man Fung / Leung, Wai K

    Hepatology (Baltimore, Md.)

    2024  

    Abstract: Background and aims: We investigated whether empagliflozin reduces hepatic steatosis in patients with metabolic dysfunction-associated steatotic liver disease without diabetes mellitus.: Approach and results: This was an investigator-initiated, ... ...

    Abstract Background and aims: We investigated whether empagliflozin reduces hepatic steatosis in patients with metabolic dysfunction-associated steatotic liver disease without diabetes mellitus.
    Approach and results: This was an investigator-initiated, double-blind, randomized, placebo-controlled trial recruiting adult subjects from the community. Eligible subjects without diabetes mellitus (fasting plasma glucose < 7 mmol/L and HbA1c < 6.5%) who had magnetic resonance imaging-proton density fat fraction (MRI-PDFF) ≥ 5% were randomly allocated to receive empagliflozin 10 mg daily or placebo (1:1 ratio) for 52 weeks (end of treatment, EOT). MRI-PDFF was conducted at baseline and EOT. The primary outcome was the difference in change of MRI-PDFF between the 2 groups at EOT. Secondary outcomes were hepatic steatosis resolution (MRI-PDFF < 5%), alanine aminotransferase drop ≥ 17 U/L, MRI-PDFF decline ≥ 30%, a combination of both, and changes of anthropometric and laboratory parameters at EOT. All outcomes were based on intention-to-treat analysis. Of 98 recruited subjects (median age: 55.7 y [IQR:49.5-63.4]; male:54 [55.1%]), 97 (empagliflozin:49, placebo:48; median MRI-PDFF:9.7% vs 9.0%) had MRI-PDFF repeated at EOT. The Empagliflozin group had a greater reduction in median MRI-PDFF compared to the placebo group (-2.49% vs. -1.43%; p = 0.025), with a nonsignificant trend of resolution of hepatic steatosis (44.9% vs. 28.6%; p = 0.094). There was no significant difference in alanine aminotransferase drop ≥ 17 U/L (16.3% vs. 12.2%; p = 0.564), MRI-PDFF drop ≥ 30% (49.0% vs. 40.8%; p = 0.417), and composite outcome (8.2% vs. 8.2%; p = 1.000). Empagliflozin group had a greater drop in body weight (-2.7 vs. -0.2 kg), waist circumference (-2.0 vs. 0 cm), fasting glucose (-0.3 vs. 0 mmol/L), and ferritin (-126 vs. -22 pmol/L) (all p < 0.05).
    Conclusions: Empagliflozin for 52 weeks reduces hepatic fat content in subjects with nondiabetic metabolic dysfunction-associated steatotic liver disease. (ClinicalTrials.gov Identifier: NCT04642261).
    Language English
    Publishing date 2024-03-27
    Publishing country United States
    Document type Journal Article
    ZDB-ID 604603-4
    ISSN 1527-3350 ; 0270-9139
    ISSN (online) 1527-3350
    ISSN 0270-9139
    DOI 10.1097/HEP.0000000000000855
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    Zs.A 1660: Show issues Location:
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  8. Article ; Online: SABINA + Hong Kong: a territory wide study of prescribing trends and outcomes associated with the use of short-acting β2 agonists in the Chinese population.

    Fung, Lydia Wy / Yan, Vincent Kc / Kwan, Christine / Kwok, W C / Lam, David Cl / McDonald, Christine F / Bloom, Chloe I / Wong, Ian Ck / Chan, Esther W

    BMC pulmonary medicine

    2024  Volume 24, Issue 1, Page(s) 232

    Abstract: Background: Excessive use of short-acting β2 agonists (SABA) in patients with asthma continues to be a notable concern due to its link to higher mortality rates. Global relevance of SABA overuse in asthma management cannot be understated, it poses ... ...

    Abstract Background: Excessive use of short-acting β2 agonists (SABA) in patients with asthma continues to be a notable concern due to its link to higher mortality rates. Global relevance of SABA overuse in asthma management cannot be understated, it poses significant health risk to patients with asthma and imposes burden on healthcare systems. This study, as part of global SABINA progamme, aimed to describe the prescribing patterns and clinical outcomes associated with SABA use in the Chinese population.
    Methods: Retrospective cohort study was conducted using anonymized electronic healthcare records of Clinical Data Analysis and Reporting System (CDARS) from Hong Kong Hospital Authority (HA). Patients newly diagnosed with asthma between 2011 and 2018 and aged ≥12 years were included, stratified by SABA use (≤2, 3-6, 7-10, or ≥11 canisters/year) during one-year baseline period since asthma diagnosis date. Patients were followed up from one-year post-index until earliest censoring of events: outcome occurrence and end of study period (31 December 2020). Cox proportional regression and negative binomial regression were used to estimate the mortality risk and frequency of hospital admissions associated with SABA use respectively, after adjusting for age, sex, Charlson Comorbidity Index (CCI), and inhaled corticosteroid (ICS) dose. Outcomes include all-cause, asthma-related, and respiratory-related mortality, frequency of hospital admissions for any cause, and frequency of hospital admissions due to asthma.
    Results: 17,782 patients with asthma (mean age 46.7 years, 40.8% male) were included and 59.1% of patients were overusing SABA (≥ 3 canisters per year). Each patient was prescribed a median of 5.61 SABA canisters/year. SABA overuse during baseline period was associated with higher all-cause mortality risk compared to patients with ≤2 canisters/year. Association was dose-dependent, highest risk in those used ≥11 canisters/year (adjusted hazard ratio: 1.42, 95% CI: 1.13, 1.79) and 3-6 canisters/year (adjusted hazard ratio: 1.22, 95% CI: 1.00, 1.50). Higher SABA prescription volume associated with increased frequency of hospital admissions with greatest risk observed in 7-10 canisters/year subgroup (adjusted rate ratio: 4.81, 95% CI: 3.66, 6.37).
    Conclusions: SABA overuse is prevalent and is associated with increased all-cause mortality risk and frequency of hospital admissions among the patients with asthma in Hong Kong.
    MeSH term(s) Humans ; Hong Kong/epidemiology ; Male ; Female ; Asthma/drug therapy ; Retrospective Studies ; Middle Aged ; Adult ; Adrenergic beta-2 Receptor Agonists/therapeutic use ; Adrenergic beta-2 Receptor Agonists/administration & dosage ; Practice Patterns, Physicians'/statistics & numerical data ; Practice Patterns, Physicians'/trends ; Aged ; Young Adult ; Adolescent ; Hospitalization/statistics & numerical data ; East Asian People
    Language English
    Publishing date 2024-05-14
    Publishing country England
    Document type Journal Article
    ZDB-ID 2059871-3
    ISSN 1471-2466 ; 1471-2466
    ISSN (online) 1471-2466
    ISSN 1471-2466
    DOI 10.1186/s12890-024-03038-1
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  9. Article ; Online: Inconsistent Safety Outcome Reporting in Randomized Clinical Trials of COVID-19 Vaccines Complicates Informed Medical Decisions.

    Blais, Joseph E / Wei, Yue / Chui, Celine S L / Chan, Esther W / Wong, Ian C K

    Drug safety

    2021  Volume 44, Issue 11, Page(s) 1121–1123

    MeSH term(s) COVID-19 Vaccines/adverse effects ; Decision Making ; Humans ; Publishing/standards ; Randomized Controlled Trials as Topic/standards ; Research Design/standards ; Research Report/standards ; SARS-CoV-2
    Chemical Substances COVID-19 Vaccines
    Language English
    Publishing date 2021-08-17
    Publishing country New Zealand
    Document type Editorial ; Research Support, Non-U.S. Gov't
    ZDB-ID 1018059-x
    ISSN 1179-1942 ; 0114-5916
    ISSN (online) 1179-1942
    ISSN 0114-5916
    DOI 10.1007/s40264-021-01108-5
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    Zs.A 2127: Show issues Location:
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  10. Article ; Online: Proton pump inhibitors and myocardial infarction: an application of active comparators in a self-controlled case series.

    Chui, Celine S L / Cheung, Ka Shing / Brown, Jeremy P / Douglas, Ian J / Wong, Ian C K / Chan, Esther W / Wong, Angel Y S

    International journal of epidemiology

    2022  Volume 52, Issue 3, Page(s) 899–907

    Abstract: Background: Previous studies investigating potential cardiovascular adverse events of acid-suppressing drugs are susceptible to protopathic bias and confounding. We aimed to investigate the association between short-term risk of myocardial infarction ( ... ...

    Abstract Background: Previous studies investigating potential cardiovascular adverse events of acid-suppressing drugs are susceptible to protopathic bias and confounding. We aimed to investigate the association between short-term risk of myocardial infarction (MI) and proton pump inhibitors (PPIs) using a self-controlled case series (SCCS) with an active comparator.
    Methods: We conducted a SCCS using a population-wide database from Hong Kong from 2003-2014. Adult with ≥1 outpatient oral PPI prescription or H2 receptor antagonist (H2RA) and MI during the observation period were included. We used both simple ratio and effect modifier approaches to SCCS with active comparators to obtain comparator adjusted estimates.
    Results: A total of 2802 and 1889 people with MI who had exposure to PPIs and H2RA were included respectively. We observed a higher risk of MI during days 1-14 following the start of PPI prescription (Incidence rate ratio (IRR): 2.30, 95% confidence interval (CI): 1.76-3.00) versus baseline. Similarly, we observed a higher risk of MI during days 1-14 following the start of H2RA prescription (IRR: 2.46, 95%CI: 1.92-3.16) versus baseline. In the novel SCCS analyses, comparator adjusted estimates were 0.93 (95%CI: 0.57-1.30) and 0.83 (95%CI: 0.58-1.20) during days 1-14 in simple ratio and effect modifier approach, respectively.
    Conclusions: We observed no difference in risk of MI associated with PPIs compared with baseline using H2RA as the active comparator. The elevated risk of MI associated with PPIs is likely due to protopathic bias. More studies are required to explore the feasibility of using active comparators in SCCS to address protopathic bias in addition to confounding.
    MeSH term(s) Adult ; Humans ; Proton Pump Inhibitors/adverse effects ; Myocardial Infarction/chemically induced ; Myocardial Infarction/epidemiology ; Histamine H2 Antagonists/adverse effects ; Hong Kong
    Chemical Substances Proton Pump Inhibitors ; Histamine H2 Antagonists
    Language English
    Publishing date 2022-10-21
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 187909-1
    ISSN 1464-3685 ; 0300-5771
    ISSN (online) 1464-3685
    ISSN 0300-5771
    DOI 10.1093/ije/dyac196
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