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  1. Naing C, Racloz V, Whittaker MA, Aung K, Reid SA, Mak JW, et al.
    PLoS ONE, 2013;8(12):e78819.
    PMID: 24312446 DOI: 10.1371/journal.pone.0078819
    This study aimed to synthesize available evidence on the efficacy of dihydroartemisinin-piperaquine (DHP) in treating uncomplicated Plasmodium vivax malaria in people living in endemic countries.
    Matched MeSH terms: Drug Therapy, Combination/adverse effects; Drug Therapy, Combination/methods
  2. Leong CF, Cheong SK, Fadilah SA
    Med. J. Malaysia, 1999 Dec;54(4):517-9.
    PMID: 11072473
    A 56-year-old Chinese lady with valvular heart disease and atrial fibrillation was referred to us from a private hospital for further management of autoimmune haemolytic anaemia. Physical examination and laboratory investigations did not support the diagnosis of haemolytic anaemia. However, direct antiglobulin test (DAT) was strongly positive with anti-IgG and negative with anti-C3d. There was also mild anaemia and reticulocytosis, which was attributable to persistent haematuria. The DAT became positive after commencing Unasyn and cessation was associated with decreasing reactivity of the positive DAT. We believe that the positive DAT in this patient was most likely due to the Unasyn therapy.
    Matched MeSH terms: Drug Therapy, Combination/adverse effects*
  3. Bukhsh A, Goh BH, Lee LH, Khan TM
    J Infect Public Health, 2017 02 10;10(5):692-693.
    PMID: 28209323 DOI: 10.1016/j.jiph.2016.09.012
    Matched MeSH terms: Drug Therapy, Combination/methods
  4. Loh SP
    Med. J. Malaysia, 1993 Jun;48(2):207-10.
    PMID: 8350797
    Eight patients underwent major gynaecological operations. Their post-operative analgesia was provided by epidural buprenorphine 0.15 mg and bupivacaine 0.5%. The efficacy and side-effects of this combination were assessed. All patients had satisfactory analgesia ranging in duration from 10 hours to greater than 36 hours after a single dose injection. No significant side-effect was noted.
    Matched MeSH terms: Drug Therapy, Combination
  5. Ng, B.K., Lim, P.S., Ng, Y.L., Kew, T.Y., Abdul Kadir, A.K., Hatta, M.
    MyJurnal
    Primary malignant melanoma of the vagina is rare but aggressive. Various treatment options include surgery and adjuvant therapy has been advocated but the outcome remained unpredictable. Standard treatment protocol is yet to be established. We report a case of 54-year-old, Para 4+1, with malignant melanoma of the vagina. She underwent wide local excision but the surgical margin was not clear of malignant cells, hence adjuvant radiotherapy was given. Combination chemotherapy was initiated subsequently as her disease disseminated. She succumbed later due to septicaemic shock. The treatment options for vaginal melanoma were reviewed.
    Matched MeSH terms: Drug Therapy, Combination
  6. Fazal SA, Khan M, Nishi SE, Alam F, Zarin N, Bari MT, et al.
    Endocr Metab Immune Disord Drug Targets, 2018 Feb 13;18(2):98-109.
    PMID: 29141572 DOI: 10.2174/1871530317666171114122417
    BACKGROUND AND OBJECTIVE: Rheumatoid arthritis (RA) is a predominant inflammatory autoimmune disorder. The incidence and prevalence of RA is increasing with considerable morbidity and mortality worldwide. The pathophysiology of RA has become clearer due to many significant research outputs during the last two decades. Many inflammatory cytokines involved in RA pathophysiology and the presence of autoantibodies are being used as potential biomarkers via the use of effective diagnostic techniques for the early diagnosis of RA. Currently, several disease-modifying anti-rheumatic drugs are being prescribed targeting RA pathophysiology, which have shown significant contributions in improving the disease outcomes.

    DISCUSSION: Even though innovations in treatment strategies and monitoring are helping the patients to achieve early and sustained clinical and radiographic remission, the high cost of drugs and limited health care budgets are restricting the easy access of RA treatment. Both direct and indirect high cost of treatment are creating economic burden for the patients and affecting their quality of life.

    CONCLUSION: The aim of this review is to describe the updated concept of RA pathophysiology and highlight current diagnostic tools used for the early detection as well as prognosis - targeting several biomarkers of RA. Additionally, we explored the updated treatment options with side effects besides discussing the global economic burden.
    Matched MeSH terms: Drug Therapy, Combination/adverse effects; Drug Therapy, Combination/economics; Drug Therapy, Combination/trends
  7. HIV-CAUSAL Collaboration, Ray M, Logan R, Sterne JA, Hernández-Díaz S, Robins JM, et al.
    AIDS, 2010 Jan 02;24(1):123-37.
    PMID: 19770621 DOI: 10.1097/QAD.0b013e3283324283
    OBJECTIVE: To estimate the effect of combined antiretroviral therapy (cART) on mortality among HIV-infected individuals after appropriate adjustment for time-varying confounding by indication.

    DESIGN: A collaboration of 12 prospective cohort studies from Europe and the United States (the HIV-CAUSAL Collaboration) that includes 62 760 HIV-infected, therapy-naive individuals followed for an average of 3.3 years. Inverse probability weighting of marginal structural models was used to adjust for measured confounding by indication.

    RESULTS: Two thousand and thirty-nine individuals died during the follow-up. The mortality hazard ratio was 0.48 (95% confidence interval 0.41-0.57) for cART initiation versus no initiation. In analyses stratified by CD4 cell count at baseline, the corresponding hazard ratios were 0.29 (0.22-0.37) for less than 100 cells/microl, 0.33 (0.25-0.44) for 100 to less than 200 cells/microl, 0.38 (0.28-0.52) for 200 to less than 350 cells/microl, 0.55 (0.41-0.74) for 350 to less than 500 cells/microl, and 0.77 (0.58-1.01) for 500 cells/microl or more. The estimated hazard ratio varied with years since initiation of cART from 0.57 (0.49-0.67) for less than 1 year since initiation to 0.21 (0.14-0.31) for 5 years or more (P value for trend <0.001).

    CONCLUSION: We estimated that cART halved the average mortality rate in HIV-infected individuals. The mortality reduction was greater in those with worse prognosis at the start of follow-up.

    Matched MeSH terms: Drug Therapy, Combination/mortality
  8. Basri DF, Xian LW, Abdul Shukor NI, Latip J
    Biomed Res Int, 2014;2014:461756.
    PMID: 24783205 DOI: 10.1155/2014/461756
    Stilbenoids have been considered as an alternative phytotherapeutic treatment against methicillin-resistant Staphylococcus aureus (MRSA) infection. The combined effect of ε-viniferin and johorenol A with the standard antibiotics, vancomycin and linezolid, was assessed against MRSA ATCC 33591 and HUKM clinical isolate. The minimum inhibitory concentration (MIC) value of the individual tested compounds and the fractional inhibitory concentration index (FICI) value of the combined agents were, respectively, determined using microbroth dilution test and microdilution checkerboard (MDC) method. Only synergistic outcome from checkerboard test will be substantiated for its rate of bacterial killing using time-kill assay. The MIC value of ε -viniferin against ATCC 33591 and johorenol A against both strains was 0.05 mg/mL whereas HUKM strain was susceptible to 0.1 mg/mL of ε-viniferin. MDC study showed that only combination between ε-viniferin and vancomycin was synergistic against ATCC 33591 (FICI 0.25) and HUKM (FICI 0.19). All the other combinations (ε-viniferin-linezolid, johorenol A-vancomycin, and johorenol A-linezolid) were either indifferent or additive against both strains. However, despite the FICI value showing synergistic effect for ε-viniferin-vancomycin, TKA analysis displayed antagonistic interaction with bacteriostatic action against both strains. As conclusion, ε-viniferin can be considered as a bacteriostatic stilbenoid as it antagonized the bactericidal activity of vancomycin. These findings therefore disputed previous report that ε-viniferin acted in synergism with vancomycin but revealed that it targets similar site in close proximity to vancomycin's action, possibly at the bacterial membrane protein. Hence, this combination has a huge potential to be further studied and developed as an alternative treatment in combating MRSA in future.
    Matched MeSH terms: Drug Therapy, Combination/methods
  9. De Britto RL, Vanamail P, Sankari T, Vijayalakshmi G, Das LK, Pani SP
    Trop Biomed, 2015 Jun;32(2):198-209.
    PMID: 26691247 MyJurnal
    Till today, there is no effective treatment protocol for the complete clearance of Wuchereria bancrofti (W.b) infection that causes secondary lymphoedema. In a double blind randomized control trial (RCT), 146 asymptomatic W. b infected individuals were randomly assigned to one of the four regimens for 12 days, DEC 300 mg + Doxycycline 100 mg coadministration or DEC 300 mg + Albendazole 400 mg co-administration or DEC 300 mg + Albendazole 400 mg sequential administration or control regimen DEC 300 mg and were followed up at 13, 26 and 52 weeks post-treatment for the clearance of infection. At intake, there was no significant variation in mf counts (F(3,137)=0.044; P=0.988) and antigen levels (F(3,137)=1.433; P=0.236) between the regimens. Primary outcome analysis showed that DEC + Albendazole sequential administration has an enhanced efficacy over DEC + Albendazole co-administration (80.6 Vs 64.7%), and this regimen is significantly different when compared to DEC + doxycycline co-administration and control (P<0.05), in clearing microfilaria in 13 weeks. Secondary outcome analysis showed that, all the trial regimens were comparable to control regimen in clearing antigen (F(3, 109)=0.405; P=0.750). Therefore, DEC + Albendazole sequential administration appears to be a better option for rapid clearance of W. b microfilariae in 13 weeks time. (Clinical trials.gov identifier - NCT02005653).
    Matched MeSH terms: Drug Therapy, Combination/methods
  10. Ti TK, Yong NK
    Med. J. Malaysia, 1974 Mar;28(3):165-70.
    PMID: 4278036
    Matched MeSH terms: Drug Therapy, Combination*
  11. Yang SK, Yusoff K, Mai CW, Lim WM, Yap WS, Lim SE, et al.
    Molecules, 2017 Nov 04;22(11).
    PMID: 29113046 DOI: 10.3390/molecules22111733
    Combinatory therapies have been commonly applied in the clinical setting to tackle multi-drug resistant bacterial infections and these have frequently proven to be effective. Specifically, combinatory therapies resulting in synergistic interactions between antibiotics and adjuvant have been the main focus due to their effectiveness, sidelining the effects of additivity, which also lowers the minimal effective dosage of either antimicrobial agent. Thus, this study was undertaken to look at the effects of additivity between essential oils and antibiotic, via the use of cinnamon bark essential oil (CBO) and meropenem as a model for additivity. Comparisons between synergistic and additive interaction of CBO were performed in terms of the ability of CBO to disrupt bacterial membrane, via zeta potential measurement, outer membrane permeability assay and scanning electron microscopy. It has been found that the additivity interaction between CBO and meropenem showed similar membrane disruption ability when compared to those synergistic combinations which was previously reported. Hence, results based on our studies strongly suggest that additive interaction acts on a par with synergistic interaction. Therefore, further investigation in additive interaction between antibiotics and adjuvant should be performed for a more in depth understanding of the mechanism and the impacts of such interaction.
    Matched MeSH terms: Drug Therapy, Combination/methods
  12. Mazlan-Kepli W, Dawson J, Berry C, Walters M
    Heart, 2019 01;105(1):67-74.
    PMID: 30030335 DOI: 10.1136/heartjnl-2018-313148
    OBJECTIVE: To assess whether cardiovascular events are increased after cessation of dual antiplatelet therapy (DAPT) following acute coronary syndrome (ACS) and to explore predictors for recurrent events after DAPT cessation during long-term follow-up.

    METHODS: We did a retrospective observational cohort study. We included consecutive people with ACS who were discharged from Scottish hospitals between January 2008 and December 2013 and who received DAPT after discharge followed by antiplatelet monotherapy. The rates of cardiovascular events were assessed during each 90-day period of DAPT treatment and 90-day period after stopping DAPT. Cardiovascular events were defined as a composite of death, ACS, transient ischaemic attack or stroke. Cox regression was used to identify predictors of cardiovascular events following DAPT cessation.

    RESULTS: 1340 patients were included (62% male, mean age 64.9 (13.0) years). Cardiovascular events occurred in 15.7% (n=211) during the DAPT period (mean DAPT duration 175.1 (155.3) days) and in 16.7% (n=188) following DAPT cessation (mean of 2.7 years follow-up). Independent predictors for a cardiovascular event following DAPT cessation were age (HR 1.07; 95% CI 1.05 to 1.08; p<0.001), DAPT duration (HR 0.997; 95% CI 0.995 to 0.998; p<0.001) and having revascularisation therapy during the index admission (HR 0.58; 95% CI 0.39 to 0.85; p=0.005).

    CONCLUSIONS: The rate of cardiovascular events was not significantly increased in the early period post-DAPT cessation compared with later periods in this ACS population. Increasing age, DAPT duration and lack of revascularisation therapy were associated with increased risk of cardiovascular events during long-term follow-up after DAPT cessation.

    Matched MeSH terms: Drug Therapy, Combination/methods
  13. Moayyedi P, Eikelboom JW, Bosch J, Connolly SJ, Dyal L, Shestakovska O, et al.
    Gastroenterology, 2019 08;157(2):403-412.e5.
    PMID: 31054846 DOI: 10.1053/j.gastro.2019.04.041
    BACKGROUND & AIMS: Antiplatelets and anticoagulants are associated with increased upper gastrointestinal bleeding. We evaluated whether proton pump inhibitor therapy could reduce this risk.

    METHODS: We performed a 3 × 2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease. Participants were randomly assigned to groups given pantoprazole 40 mg daily or placebo, as well as rivaroxaban 2.5 mg twice daily with aspirin 100 mg once daily, rivaroxaban 5 mg twice daily, or aspirin 100 mg alone. The primary outcome was time to first upper gastrointestinal event, defined as a composite of overt bleeding, upper gastrointestinal bleeding from a gastroduodenal lesion or of unknown origin, occult bleeding, symptomatic gastroduodenal ulcer or ≥5 erosions, upper gastrointestinal obstruction, or perforation.

    RESULTS: There was no significant difference in upper gastrointestinal events between the pantoprazole group (102 of 8791 events) and the placebo group (116 of 8807 events) (hazard ratio, 0.88; 95% confidence interval [CI], 0.67-1.15). Pantoprazole significantly reduced bleeding of gastroduodenal lesions (hazard ratio, 0.52; 95% confidence interval, 0.28-0.94; P = .03); this reduction was greater when we used a post-hoc definition of bleeding gastroduodenal lesion (hazard ratio, 0.45; 95% confidence interval, 0.27-0.74), although the number needed to treat still was high (n = 982; 95% confidence interval, 609-2528).

    CONCLUSIONS: In a randomized placebo-controlled trial, we found that routine use of proton pump inhibitors in patients receiving low-dose anticoagulation and/or aspirin for stable cardiovascular disease does not reduce upper gastrointestinal events, but may reduce bleeding from gastroduodenal lesions. ClinicalTrials.gov ID: NCT01776424.

    Matched MeSH terms: Drug Therapy, Combination/adverse effects; Drug Therapy, Combination/methods
  14. Rahman NH, Hashim A
    Emerg Med J, 2011 Oct;28(10):861-5.
    PMID: 21098799 DOI: 10.1136/emj.2009.085019
    This study aimed to determine the effectiveness of propofol as an alternative agent for procedural sedation and analgesia (PSA) in the emergency department (ED) and to make a comparison between two different sedative (propofol vs midazolam) drugs used in combination with fentanyl.
    Matched MeSH terms: Drug Therapy, Combination/methods
  15. Hamidah A, Rizal AM, Nordiah AJ, Jamal R
    Singapore Med J, 2008 Jan;49(1):26-30.
    PMID: 18204765
    We evaluated piperacillin-tazobactam in association with amikacin in the initial empirical therapy of febrile neutropenic children.
    Matched MeSH terms: Drug Therapy, Combination*
  16. Goh KL, Parasakthi N, Chuah SY, Cheah PL, Lo YL, Chin SC
    Aliment. Pharmacol. Ther., 1997 Dec;11(6):1115-8.
    PMID: 9663838
    OBJECTIVES: To determine and compare the efficacy and tolerability of two 1-week regimen comprising omeprazole, clarithromycin and amoxycillin or metronidazole in the eradication of Helicobacter pylori, and to determine the influence of bacterial resistance to metronidazole and clarithromycin on the outcome of treatment.

    PATIENTS AND METHODS: Patients with unequivocal evidence of H. pylori infection based on culture, histology and rapid urease test of both antrum and corpus biopsies were recruited for the study. The study was a randomized, investigator-blind, comparative study. Patients received either omeprazole 20 mg o.m., clarithromycin 250 mg b.d. and amoxycillin 500 mg b.d. (OAC) or omeprazole 20 mg o.m., metronidazole 400 mg b.d. and clarithromycin 250 mg b.d. (OMC) for 1 week. Patients were assessed for successful eradication, which was defined as absence of bacteria in all tests (culture, histology and urease test on both antral and corpus biopsies), at least 4 weeks after completion of therapy.

    RESULTS: Eighty-two patients were recruited for the study. Eradication rates on intention-to-treat analysis were--OAC: 36/41 (87.8%, 95% CI: 73.8, 95.9); OMC: 33/41 (80.5%, 95% CI: 65.1, 91.2). On per protocol analysis were--OAC: 36/40 (90%, 95% CI: 76.3, 97.2); OMC: 32/38 (84.2%, 95% CI: 68.7, 94.0). All side-effects encountered were mild and no patient discontinued treatment because of intolerance to medications. The most common side-effects were altered taste (OAC 31.7%, OMC 53.7%) and lethargy (OAC 14.6%, OMC 19.5%). Pre-treatment metronidazole resistance was encountered in 34/63 (54.0%) patients. No bacterial strains were found with primary resistance to clarithromycin. Metronidazole resistance did not significantly affect eradication rates. Emergence of resistance to clarithromycin was not seen post-therapy.

    CONCLUSIONS: Both the OAC and the OMC regimens were convenient and well-tolerated treatments for H. pylori. However, eradication rates were lower than anticipated.

    Matched MeSH terms: Drug Therapy, Combination/adverse effects
  17. Goh KL, Parasakthi N, Chuah SY, Toetsch M
    Eur J Gastroenterol Hepatol, 1997 Nov;9(11):1091-5.
    PMID: 9431900
    OBJECTIVES: To determine the efficacy of a three times daily (t.i.d.) versus a twice daily (b.i.d.) regimen of combination amoxycillin and metronidazole and famotidine in the eradication of Helicobacter pylori and the influence of metronidazole resistance on the outcome of treatment.

    PATIENTS: Patients selected had unequivocal evidence of H. pylori infection based on the urease test, culture and histology and had either peptic ulcer disease or non-ulcer dyspepsia.

    DESIGN: The study was a comparative and double-blind study and patients were randomized to receive either amoxycillin 750 mg t.i.d. and metronidazole 500 mg t.i.d. for 12 days or amoxycillin 1000 mg b.i.d. and metronidazole 500 mg b.i.d. for 12 days. Both groups also received famotidine 40 mg for 6 weeks.

    MAIN OUTCOME MEASURE: Patients were assessed for successful eradication, defined as absence of bacteria in all tests, at least 4 weeks after completion of antibiotic therapy by repeat gastroscopy.

    RESULTS: One hundred and twenty-nine patients were recruited for the study. Two patients defaulted follow-up, two patients were withdrawn from the study and six patients were found to be non-compliant with medications. The eradication rates of the t.i.d. regimen was higher than the b.i.d. regimen (per protocol (PP) analysis: 83.3% (50/60) vs. 76.3% (45/59), P=0.337; intention-to-treat (ITT) analysis: 78.5% (51/65) vs. 75.0% (48/64), P=0.642). Seventy-five patients had pre-treatment cultures checked for metronidazole resistance, 33 (44.0%) were found to be resistant. Acquired resistance occurred in 3/40 (7.5%) patients. Eradication rates of metronidazole-sensitive and metronidazole-resistant patients: t.i.d. regimen - 100% (17/17) and 88.2% (15/17), b.i.d. regimen - 19/21 (90.5%) and 11/15 (73.3%). Side effects were reported in up to 70% of patients but were mild and tolerable in the majority. Two patients were withdrawn from the study because of a fixed drug eruption in one and generalized macular rash in the other.

    CONCLUSION: Combination amoxycillin and metronidazole is effective in eradicating H. pylori. There was a tendency for the t.i.d. regimen to be better than the b.i.d. regimen and for metronidazole-resistant infections to be associated with a lower eradication rate but these differences did not reach statistical significance.

    Matched MeSH terms: Drug Therapy, Combination/adverse effects
  18. Ni H, Moe S, Soe Z, Myint KT, Viswanathan KN
    Cochrane Database Syst Rev, 2018 Dec 11;12:CD011594.
    PMID: 30536566 DOI: 10.1002/14651858.CD011594.pub2
    BACKGROUND: Several dual bronchodilator combinations of long-acting beta2-agonist (LABA) and long-acting muscarinic antagonist (LAMA) have been approved for treatment of stable chronic obstructive pulmonary disease (COPD). The current GOLD (Global Initiative for Chronic Obstructive Lung Disease) recommendations suggest the use of LABA/LAMA combinations in people with group B COPD with persistent symptoms, group C COPD with further exacerbations on LAMA therapy alone and group D COPD with or without inhaled corticosteroids (ICS). Fixed-dose combination (FDC) of aclidinium/formoterol is one of the approved LABA/LAMA therapies for people with stable COPD.

    OBJECTIVES: To assess the efficacy and safety of combined aclidinium bromide and long-acting beta2-agonists in stable COPD.

    SEARCH METHODS: We searched the Cochrane Airways Group Specialised Register (CAGR), ClinicalTrials.gov, World Health Organization (WHO) trials portal, United States Food and Drug Administration (FDA) and manufacturers' websites as well as the reference list of published trials up to 12 October 2018.

    SELECTION CRITERIA: Parallel-group randomised controlled trials (RCTs) assessing combined aclidinium bromide and LABAs in people with stable COPD.

    DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane for data collection and analysis. The primary outcomes were exacerbations requiring a short course of an oral steroid or antibiotic, or both; quality of life measured by a validated scale and non-fatal serious adverse events (SAEs). Where the outcome or study details were not reported, we contacted the study investigators or pharmaceutical company trial co-ordinators (or both) for missing data.

    MAIN RESULTS: We identified RCTs comparing aclidinium/formoterol FDC versus aclidinium, formoterol or placebo only. We included seven multicentre trials of four to 52 weeks' duration conducted in outpatient settings. There were 5921 participants, whose mean age ranged from 60.7 to 64.7 years, mostly men with a mean smoking pack-years of 46.4 to 61.3 of which 43.9% to 63.4% were current smokers. They had a moderate-to-severe degree of COPD with a mean postbronchodilator forced expiratory volume in one second (FEV1) between 50.5% and 61% of predicted normal and the baseline mean FEV1 of 1.23 L to 1.43 L. We assessed performance and detection biases as low for all studies whereas selection, attrition and reporting biases were either low or unclear.FDC versus aclidiniumThere was no evidence of a difference between FDC and aclidinium for exacerbations requiring steroids or antibiotics, or both (OR 0.95, 95% CI 0.71 to 1.27; 2 trials, 2156 participants; moderate-certainty evidence); quality of life measured by St George's Respiratory Questionnaire (SGRQ) total score (MD -0.92, 95% CI -2.15 to 0.30); participants with significant improvement in SGRQ score (OR 1.17, 95% CI 0.97 to 1.41; 2 trials, 2002 participants; moderate-certainty evidence); non-fatal SAE (OR 1.19, 95% CI 0.79 to 1.80; 3 trials, 2473 participants; moderate-certainty evidence); hospital admissions due to severe exacerbations (OR 0.62, 95% CI 0.29 to 1.29; 2 trials, 2156 participants; moderate-certainty evidence) or adverse events (OR 0.95, 95% CI 0.76 to 1.18; 3 trials, 2473 participants; moderate-certainty evidence). Compared with aclidinium, FDC improved symptoms (Transitional Dyspnoea Index (TDI) focal score: MD 0.37, 95% CI 0.07 to 0.68; 2 trials, 2013 participants) with a higher chance of achieving a minimal clinically important difference (MCID) of at least one unit improvement (OR 1.34, 95% CI 1.11 to 1.62; high-certainty evidence); the number needed to treat for an additional beneficial outcome (NNTB) being 14 (95% CI 9 to 39).FDC versus formoterolWhen compared to formoterol, combination therapy reduced exacerbations requiring steroids or antibiotics, or both (OR 0.78, 95% CI 0.62 to 0.99; 3 trials, 2694 participants; high-certainty evidence); may decrease SGRQ total score (MD -1.88, 95% CI -3.10 to -0.65; 2 trials, 2002 participants; low-certainty evidence; MCID for SGRQ is 4 units); increased TDI focal score (MD 0.42, 95% CI 0.11 to 0.72; 2 trials, 2010 participants) with more participants attaining an MCID (OR 1.30, 95% CI 1.07 to 1.56; high-certainty evidence) and an NNTB of 16 (95% CI 10 to 60). FDC lowered the risk of adverse events compared to formoterol (OR 0.78, 95% CI 0.65 to 0.93; 5 trials, 3140 participants; high-certainty evidence; NNTB 22). However, there was no difference between FDC and formoterol for hospital admissions, all-cause mortality and non-fatal SAEs.FDC versus placeboCompared with placebo, FDC demonstrated no evidence of a difference in exacerbations requiring steroids or antibiotics, or both (OR 0.82, 95% CI 0.60 to 1.12; 2 trials, 1960 participants; moderate-certainty evidence) or hospital admissions due to severe exacerbations (OR 0.55, 95% CI 0.25 to 1.18; 2 trials, 1960 participants; moderate-certainty evidence), although estimates were uncertain. Quality of life measure by SGRQ total score was significantly better with FDC compared to placebo (MD -2.91, 95% CI -4.33 to -1.50; 2 trials, 1823 participants) resulting in a corresponding increase in SGRQ responders who achieved at least four units decrease in SGRQ total score (OR 1.72, 95% CI 1.39 to 2.13; high-certainty evidence) with an NNTB of 7 (95% CI 5 to 12). FDC also improved symptoms measured by TDI focal score (MD 1.32, 95% CI 0.96 to 1.69; 2 studies, 1832 participants) with more participants attaining at least one unit improvement in TDI focal score (OR 2.51, 95% CI 2.02 to 3.11; high-certainty evidence; NNTB 4). There were no differences in non-fatal SAEs, adverse events and all-cause mortality between FDC and placebo.Combination therapy significantly improved trough FEV1 compared to aclidinium, formoterol or placebo.

    AUTHORS' CONCLUSIONS: FDC improved dyspnoea and lung function compared to aclidinium, formoterol or placebo, and this translated into an increase in the number of responders on combination treatment. Quality of life was better with combination compared to formoterol or placebo. There was no evidence of a difference between FDC and monotherapy or placebo for exacerbations, hospital admissions, mortality, non-fatal SAEs or adverse events. Studies reported a lower risk of moderate exacerbations and adverse events with FDC compared to formoterol; however, larger studies would yield a more precise estimate for these outcomes.

    Matched MeSH terms: Drug Therapy, Combination/methods
  19. Ram M R, Teh X, Rajakumar T, Goh KL, Leow AHR, Poh BH, et al.
    J. Antimicrob. Chemother., 2019 01 01;74(1):11-16.
    PMID: 30403784 DOI: 10.1093/jac/dky401
    Objectives: Eradication of Helicobacter pylori is influenced by susceptibility to antimicrobial agents, elevated bacterial load and degree of acid inhibition, which can be affected by genotypes of drug-metabolizing enzymes [cytochrome P450 (CYP) 2C19 polymorphism]. Theoretically, the choice and dose of proton pump inhibitor may also influence the suppression of H. pylori infection. The CYP2C19 genotype has recently been found to have an impact on peptic ulcer healing, H. pylori eradication and therapeutic efficacy of proton pump inhibitors.

    Methods: Here, we investigated the impact of the CYP2C19 genotype polymorphism and the success of triple therapy (fluoroquinolones/metronidazole/clarithromycin) on antibiotic-resistant strains in eradicating H. pylori in human subjects with non-ulcer dyspepsia (NUD), in human subjects with peptic ulcer disease (PUD) and in asymptomatic human subjects (positive and negative for H. pylori infection).

    Results: Based on the CYP2C19 genotypes, determined by Droplet Digital PCR (ddPCR) analysis, we found 11.2%, 62.5% and 26.3% corresponding to rapid metabolizers, intermediate metabolizers and poor metabolizers, respectively. However, we did not find any significant effect for homozygous ABCB1 or CYP2C19*2 and CYP2C19*3 alleles. We detected several participants heterozygous for both ABCB1 and CYP2C19*2, CYP2C19*3 and CYP2C19*17 loci. The participants heterozygous for both ABCB1 and CYP2C19*2 and *3 loci should be defined as intermediate and poor metabolizers according to the haplotype analysis in the NUD, PUD and asymptomatic subjects.

    Conclusions: Consequently, fluoroquinolones/metronidazole/clarithromycin-based triple therapies can be used to eradicate H. pylori infection, if one does not know the CYP2C19 genotype of the patient.

    Matched MeSH terms: Drug Therapy, Combination/methods
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