Displaying publications 1 - 20 of 291 in total

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  1. Bujanda L, Nyssen OP, Ramos J, Bordin DS, Tepes B, Perez-Aisa A, et al.
    Am J Gastroenterol, 2024 Apr 01;119(4):646-654.
    PMID: 37983769 DOI: 10.14309/ajg.0000000000002600
    INTRODUCTION: Antibiotic resistance is one of the main factors that determine the efficacy of treatments to eradicate Helicobacter pylori infection. Our aim was to evaluate the effectiveness of first-line and rescue treatments against H. pylori in Europe according to antibiotics resistance.

    METHODS: Prospective, multicenter, international registry on the management of H. pylori (European Registry on H. pylori Management). All infected and culture-diagnosed adult patients registered in the Spanish Association of Gastroenterology-Research Electronic Data Capture from 2013 to 2021 were included.

    RESULTS: A total of 2,852 naive patients with culture results were analyzed. Resistance to clarithromycin, metronidazole, and quinolones was 22%, 27%, and 18%, respectively. The most effective treatment, regardless of resistance, were the 3-in-1 single capsule with bismuth, metronidazole, and tetracycline (91%) and the quadruple with bismuth, offering optimal cure rates even in the presence of bacterial resistance to clarithromycin or metronidazole. The concomitant regimen with tinidazole achieved an eradication rate of 99% (90/91) vs 84% (90/107) with metronidazole. Triple schedules, sequential, or concomitant regimen with metronidazole did not achieve optimal results. A total of 1,118 non-naive patients were analyzed. Resistance to clarithromycin, metronidazole, and quinolones was 49%, 41%, and 24%, respectively. The 3-in-1 single capsule (87%) and the triple therapy with levofloxacin (85%) were the only ones that provided encouraging results.

    DISCUSSION: In regions where the antibiotic resistance rate of H. pylori is high, eradication treatment with the 3-in-1 single capsule, the quadruple with bismuth, and concomitant with tinidazole are the best options in naive patients. In non-naive patients, the 3-in-1 single capsule and the triple therapy with levofloxacin provided encouraging results.

    Matched MeSH terms: Drug Therapy, Combination
  2. Farhani S, Sulizah S, Siti Khalimah R, Jasrinjeet Kaur K, Nur Hidayah Z, Nur Athirah R, et al.
    Med J Malaysia, 2024 Jan;79(1):68-73.
    PMID: 38287760
    INTRODUCTION: Studies showed that vildagliptin can lower HbA1c levels by 0.8%-1%. However, there is limited data looking at vildagliptin use among suburban populations. The efficacy of vildagliptin use may differ among different populations, especially those with low socio-economic status. Thus, this study aimed to assess the HbA1c reduction after vildagliptin initiation, treatment patterns and the reason for its initiation among patients with type 2 diabetes mellitus attending outpatient clinics in Kuala Selangor District, Selangor.

    MATERIALS AND METHODS: This is a cross-sectional, retrospective study design. All patients who received vildagliptin in the Pharmacy Integrated Health System (PHIS) registry database from 2016 to 2021 were included as study samples. The exclusion criteria were being less than 18 years old and having type 1 diabetes mellitus. Patients' medical records were retrieved after sampling, and data were collected. One medical record was missing, thus SPSS analysis were performed on 144 vildagliptin users.

    RESULTS: In total, 84 females (58.3%) and 60 males (41.7%) with a mean age of 62.1 (±10.1) years were analysed in this study. Mean HbA1c pre-therapy was 8.5 ± 2.1%; while posttherapy 6 months demonstrated a mean HbA1c of 7.9 ± 1.8%. Use of vildagliptin alone or as an adjunct was associated with a mean reduction of 0.6% in HbA1c (p = 0.01). Factors influencing this HbA1c reduction were advancing age, specifically individuals aged 62 years and older (p = 0.02), patients who are already receiving insulin therapy (p=0.00) and those who express a willingness to commence insulin treatment during the counselling session prior to initiating the treatment plan (p = 0.00). Reasons for vildagliptin initiation documented by prescribers were non-insulin acceptance (n = 59, 40.97%), frequent hypoglycaemia (n = 6, 4.1%) and non-compliance with medications (n = 23, 15.9%). There was no association between demographic, medical background and reason for starting vildagliptin variables and HbA1c reduction (p < 0.001).

    CONCLUSION: This study showed that initiating vildagliptin alone or as an adjunct therapy significantly reduced HbA1c and is beneficial for uncontrolled diabetes patients. While advancing age, concurrent administration of insulin and the patients' willingness to accept insulin treatment prior to the commencement of therapy were the factors that influenced HbA1c reduction among patients receiving vildagliptin therapy, we recommend primary care providers prioritise all of the significant variables discovered before initiating vildagliptin for their patients.

    Matched MeSH terms: Drug Therapy, Combination
  3. Quach DT, Vilaichone RK, Luu MN, Lee YY, Ang TL, Miftahussurur M, et al.
    Helicobacter, 2023 Dec;28(6):e13018.
    PMID: 37634226 DOI: 10.1111/hel.13018
    BACKGROUND: Multidrug-resistant Helicobacter pylori strains are emerging in Southeast Asia. This study evaluates the region's real-world practice in H. pylori management.

    MATERIALS AND METHODS: Physicians who managed H. pylori eradication in daily practice across 10 Southeast Asian countries were invited to participate in an online questionnaire, which included questions about the local availability of antimicrobial susceptibility tests (ASTs) and their preferred eradication regimens in real-world practice. An empiric regimen was considered inappropriate if it did not follow the local guidelines/consensus, particularly if it contained antibiotics with a high reported resistance rate or was recommended not to be empirically used worldwide.

    RESULTS: There were 564 valid responses, including 314 (55.7%) from gastroenterologists (GIs) and 250 (44.3%) from non-GI physicians. ASTs were unavailable in 41.7%. In countries with low and intermediate clarithromycin resistance, the most common first-line regimen was PAC (proton pump inhibitor [PPI], amoxicillin, clarithromycin) (72.7% and 73.2%, respectively). Regarding second-line therapy, the most common regimen was bismuth-based quadruple therapy, PBMT (PPI, bismuth, metronidazole, tetracycline) (50.0% and 59.8%, respectively), if other regimens were used as first-line treatment. Concomitant therapy (PPI, amoxicillin, clarithromycin, metronidazole) (30.5% and 25.9%, respectively) and PAL (PPI, amoxicillin, levofloxacin) (22.7% and 27.7%, respectively) were favored if PBMT had been used as first-line treatment. In countries with high clarithromycin resistance, the most common first-line regimen was PBMT, but the utilization rate was only 57.7%. Alarmingly, PAC was prescribed in 27.8% of patients, ranking as the second most common regimen, and its prescription rate was higher in non-GI physicians than GI physicians (40.1% vs. 16.2%, p 

    Matched MeSH terms: Drug Therapy, Combination
  4. Ismail NI, Nawawi KNM, Hsin DCC, Hao KW, Mahmood NRKN, Chearn GLC, et al.
    Helicobacter, 2023 Dec;28(6):e13017.
    PMID: 37614081 DOI: 10.1111/hel.13017
    BACKGROUND: Despite multiple therapy regimens, the decline in the Helicobacter pylori eradication rate poses a significant challenge to the medical community. Adding Lactobacillus reuteri probiotic as an adjunct treatment has shown some promising results. This study aims to investigate the efficacy of Lactobacillus reuteri DSM 17648 in H. pylori eradication and its effect in ameliorating gastrointestinal symptoms and adverse treatment effects.

    MATERIALS AND METHODS: This randomized, double-blinded, placebo-controlled trial involved treatment-naïve H. pylori-positive patients. Ninety patients received standard triple therapy for 2 weeks before receiving either a probiotic or placebo for 4 weeks. The posttreatment eradication rate was assessed via a 14 C urea breath test in Week 8. The Gastrointestinal Symptom Rating Scale (GSRS) questionnaire and an interview on treatment adverse effects were conducted during this study.

    RESULTS: The eradication rate was higher in the probiotic group than in the placebo group, with a 22.2% difference in the intention-to-treat analysis (91.1% vs. 68.9%; p = 0.007) and 24.3% difference in the per-protocol analysis (93.2% vs. 68.9%; p = 0.007). The probiotic group showed significant pre- to post-treatment reductions in indigestion, constipation, abdominal pain, and total GSRS scores. The probiotic group showed significantly greater reductions in GSRS scores than the placebo group: indigestion (4.34 ± 5.00 vs. 1.78 ± 5.64; p = 0.026), abdominal pain (2.64 ± 2.88 vs. 0.89 ± 3.11; p = 0.007), constipation (2.34 ± 3.91 vs. 0.64 ± 2.92; p = 0.023), and total score (12.41 ± 12.19 vs. 4.24 ± 13.72; p = 0.004). The probiotic group reported significantly fewer adverse headache (0% vs. 15.6%; p = 0.012) and abdominal pain (0% vs. 13.3%; p = 0.026) effects.

    CONCLUSIONS: There was a significant increase in H. pylori eradication rate and attenuation of symptoms and adverse treatment effects when L. reuteri was given as an adjunct treatment.

    Matched MeSH terms: Drug Therapy, Combination
  5. Jonaitis P, Nyssen OP, Saracino IM, Fiorini G, Vaira D, Pérez-Aísa Á, et al.
    Sci Rep, 2023 Oct 11;13(1):17235.
    PMID: 37821503 DOI: 10.1038/s41598-023-43287-4
    The prevalence of Helicobacter pylori remains high in the older population. Specific age-related peculiarities may impact the outcomes of H. pylori treatment. The aim of the study was to evaluate the diagnostics and effectiveness of H. pylori eradication between the younger and older European populations. "European Registry on H. pylori Management (Hp-EuReg)" data from 2013 to 2022 were analyzed. Patients were divided into older (≥ 60 years) and younger (18-59 years) groups. Modified intention-to-treat (mITT) and per-protocol (PP) analysis was performed. 49,461 patients included of which 14,467 (29%) were older-aged. Concomitant medications and penicillin allergy were more frequent among the older patients. Differences between younger and older populations were observed in treatment duration in first-line treatment and in proton pump inhibitors (PPIs) doses in second-line treatment. The overall incidence of adverse events was lower in the older adults group. The overall first-line treatment mITT effectiveness was 88% in younger and 90% in the older patients (p 
    Matched MeSH terms: Drug Therapy, Combination
  6. Lim KY, Khoo CS, Rajah R, Tan HJ, Tajurudin FW
    Med J Malaysia, 2023 Sep;78(5):635-638.
    PMID: 37775491
    INTRODUCTION: Epilepsy is a neurological disease with high global prevalence. Almost one-third of epilepsy patients continue having seizures despite adequate treatment. Perampanel has been widely used in the Western countries as an adjunctive therapy for both generalized and focal seizures. Owing to its high cost, the use of perampanel is limited in our country.

    MATERIALS AND METHODS: We conducted a descriptive, retrospective study among epilepsy patients treated with perampanel. We aimed to assess the efficacy and safety of perampanel as an adjunctive in our hospital.

    RESULTS AND CONCLUSIONS: From our cohort of 25 patients, most of the patients were either on one or three anti-seizure medications (ASMs) prior to initiation of perampanel. Perampanel was added in 88% of them due to persistent seizures. Twenty-two (88%) patients experienced reduction in seizure frequency. 12% experienced mild side effects, which were leg cramps, hyponatremia and drowsiness. Only 1 patient stopped perampanel due to its side effects.

    CONCLUSION: Perampanel is a well-tolerated ASM that should be widely used as an adjunctive. More studies with regards to its efficacy and safety involving more centres are encouraged in Malaysia.

    Matched MeSH terms: Drug Therapy, Combination
  7. Tan BE, Wong PY, Baibhav B, Thakkar S, Azhar AZ, Rao M, et al.
    Curr Probl Cardiol, 2023 Aug;48(8):101174.
    PMID: 35341798 DOI: 10.1016/j.cpcardiol.2022.101174
    Current guidelines recommend 6-12 months of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) followed by aspirin monotherapy indefinitely. We aimed to assess the efficacy and safety of clopidogrel vs aspirin in the post-PCI population after completing DAPT. We systematically searched 5 electronic databases to identify studies comparing clopidogrel with aspirin following completion of DAPT after PCI. We pooled outcomes for major adverse cardiac events (MACE), cardiac death, all-cause death, major bleeding, myocardial infarction (MI), and stroke. We included 5 studies with 13,850 patients, of whom 5601 (40.4%) received clopidogrel. Mean follow-up was 12-36 months. All patients received drug-eluting stents. Duration of DAPT before antiplatelet monotherapy was 1-18 months. Clopidogrel was associated with reductions in MACE (Risk ratio [RR] 0.77, 95% confidence interval [CI] 0.65-0.91), any stroke (RR 0.51; 95% confidence interval [CI] 0.35-0.76), ischemic stroke (RR 0.55; 95% CI 0.32-0.94), and hemorrhagic stroke (RR 0.24; 95% CI 0.09-0.68) when compared with aspirin. Cardiac death (RR 0.87; 95% CI 0.53-1.41), all-cause death (RR 1.06; 95% CI 0.81-1.39), major bleeding (RR 0.74; 95% CI 0.43-1.29), MI (RR 1.01; 95% CI 0.64-1.60), repeat revascularization (RR 0.88; 95% CI 0.71-1.09), target vessel revascularization (RR 0.76; 95% CI 0.52-1.13), and stent thrombosis (RR 0.96; 95% CI 0.35-2.59) were not significantly different among groups. Compared with aspirin, clopidogrel was associated with reductions in MACE and stroke (ischemic and hemorrhagic) following DAPT completion after PCI. There were no significant differences in mortality, major bleeding, MI, and repeat revascularization between groups.
    Matched MeSH terms: Drug Therapy, Combination
  8. Younossi ZM, Yu ML, Yilmaz Y, Alswat KA, Buti M, Fernandez MIC, et al.
    J Viral Hepat, 2023 Apr;30(4):335-344.
    PMID: 36601668 DOI: 10.1111/jvh.13800
    Chronic hepatitis B (CHB) infection is one of the most common causes of cirrhosis and liver cancer worldwide. Our aim was to assess clinical and patient-reported outcome (PRO) profile of CHB patients from different regions of the world using the Global Liver Registry. The CHB patients seen in real-world practices are being enrolled in the Global Liver Registry. Clinical and PRO (FACIT-F, CLDQ, WPAI) data were collected and compared to baseline data from CHB controls from clinical trials. The study included 1818 HBV subjects (48 ± 13 years, 58% male, 14% advanced fibrosis, 7% cirrhosis) from 15 countries in 6/7 Global Burden of Disease super-regions. The rates of advanced fibrosis varied (3-24%). The lowest PRO scores across multiple domains were in HBV subjects from the Middle East/North Africa (MENA), the highest - Southeast/East and South Asia. Subjects with advanced fibrosis had PRO impairment in 3 CLDQ domains, Activity of WPAI (p  0.10). The clinico-demographic portrait of CHB patients varies across regions of the world and enrollment settings. Advanced fibrosis and non-hepatic comorbidities are independently associated with PRO impairment in CHB patients.
    Matched MeSH terms: Drug Therapy, Combination
  9. Eikelboom JW, Bosch J, Connolly SJ, Tyrwitt J, Fox KAA, Muehlhofer E, et al.
    Eur Heart J Cardiovasc Pharmacother, 2022 Dec 02;8(8):786-795.
    PMID: 35383832 DOI: 10.1093/ehjcvp/pvac023
    AIMS: To describe outcomes of patients with chronic coronary artery disease (CAD) and/or peripheral artery disease (PAD) enrolled in the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) randomized trial who were treated with the combination of rivaroxaban 2.5 mg twice daily and aspirin 100 mg once daily during long-term open-label extension (LTOLE).

    METHODS AND RESULTS: Of the 27 395 patients enrolled in COMPASS, 12 964 (mean age at baseline 67.2 years) from 455 sites in 32 countries were enrolled in LTOLE and treated with the combination of rivaroxaban and aspirin for a median of 374 additional days (range 1-1191 days). During LTOLE, the incident events per 100 patient years were as follows: for the primary outcome [cardiovascular death, stroke, or myocardial infarction (MI)] 2.35 [95% confidence interval (CI) 2.11-2.61], mortality 1.87 (1.65-2.10), stroke 0.62 (0.50-0.76), and MI 1.02 (0.86-1.19), with CIs that overlapped those seen during the randomized treatment phase with the combination of rivaroxaban and aspirin. The incidence rates for major and minor bleeding were 1.01 (0.86-1.19) and 2.49 (2.24-2.75), compared with 1.67 (1.48-1.87) and 5.11 (95% CI 4.77-5.47), respectively, during the randomized treatment phase with the combination.

    CONCLUSION: In patients with chronic CAD and/or PAD, extended combination treatment for a median of 1 year and a maximum of 3 years was associated with incidence rates for efficacy and bleeding that were similar to or lower than those seen during the randomized treatment phase, without any new safety signals.

    Matched MeSH terms: Drug Therapy, Combination
  10. Younossi ZM, Yu ML, El-Kassas M, Esmat G, Castellanos Fernández MI, Buti M, et al.
    J Viral Hepat, 2022 Nov;29(11):1015-1025.
    PMID: 36036096 DOI: 10.1111/jvh.13741
    Cure of chronic hepatitis C (CHC) can lead to improvement of health-related quality of life and other patient-reported outcomes (PROs). While extensive PRO data for CHC patients who were enrolled in clinical trials are available, similar data for patients seen in real-world practices are scarce. Our aim was to assess PROs of CHC patients enrolled from real-world practices from different regions and to compare them with those enrolled in clinical trials. CHC patients seen in clinical practices and not receiving treatment were enrolled in the Global Liver Registry (GLR). Clinical and PRO (FACIT-F, CLDQ-HCV, WPAI) data were collected and compared with the baseline data from CHC patients enrolled in clinical trials. N = 12,171 CHC patients were included (GLR n = 3146, clinical trial subjects n = 9025). Patients were from 30 countries from 6 out of 7 Global Burden of Disease (GBD) super-regions. Compared with clinical trial enrollees, patients from GLR were less commonly enrolled from High-Income GBD super-region, older, more commonly female, less employed, had more type 2 diabetes, anxiety and clinically overt fatigue but less cirrhosis (all p  0.05). In conclusion, hepatitis C patients seen in the real-world practices have PRO impairment driven by fatigue and psychiatric comorbidities.
    Matched MeSH terms: Drug Therapy, Combination
  11. Krishnan K, Law ZK, Minhas JS, Bath PM, Robinson TG, Sprigg N, et al.
    Clin Med (Lond), 2022 Sep;22(5):449-454.
    PMID: 36507812 DOI: 10.7861/clinmed.2021-0597
    Acute stroke is the leading cause of disability in the UK and a leading cause of mortality worldwide. The majority of patients with ischaemic stroke present with minor deficits or transient ischaemic attack (TIA), and are often first seen by patient-facing clinicians. Urgent evaluation and treatment are important as many patients are at high risk of major vascular events and death within hours to days after the index event. This narrative review summarises the evidence on four antiplatelet treatments for non-cardioembolic stroke prevention: aspirin, clopidogrel, dipyridamole and ticagrelor. Each of these drugs has a unique mechanism and has been tested as a single agent or in combination. Aspirin, when given early is beneficial and short-term treatment with aspirin and clopidogrel has been shown to be more effective in high-risk TIA / minor stroke. This review concludes by highlighting gaps in evidence, including scope for future trials that could potentially change clinical practice.
    Matched MeSH terms: Drug Therapy, Combination
  12. Papot E, Jacoby S, Arlinda D, Avihingsanon A, Azwa I, Borok M, et al.
    HIV Res Clin Pract, 2022 Jul 19;23(1):37-46.
    PMID: 35938597
    A rapidly changing landscape of antiretrovirals and their procurement at scale has permitted the evaluation of new optimised second-line antiretroviral therapy (ART) in low- and middle-income countries. D2EFT is an open-label randomised controlled non-inferiority phase IIIB/IV trial in people living with HIV-1 (PWH) whose first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART is failing. At inception, it compared a standard of care of boosted darunavir with two nucleos(t)ide reverse transcriptase inhibitors (NRTIs) to the novel NRTI-sparing regimen of boosted darunavir with dolutegravir. Implemented in 2017, participating sites were across Africa, Asia and Latin America. Around the time of implementation, the World Health Organization updated its treatment guidelines and recommended scaling up tenofovir disoproxil fumarate-lamivudine-dolutegravir (TLD). This situation pushed D2EFT investigators to consider the impact of the roll-out of TLD on the D2EFT research question. The protocol team agreed it was important to study TLD in second-line when an NNRTI regimen was failing, and focused on options to expedite the work by studying the question within the existing trial and network. All key issues (statistical, programmatic and financial) were reviewed to assess the benefits and risks of adding a third arm to the ongoing study, as opposed to developing a new randomised clinical trial with the same control arm and within the same network. The development of a new trial was deemed to be longer than adding a third arm, and to create a challenging situation with two competing clinical trials at the same sites which would slow down recruitment and impair both trials. On the other hand, adding a third arm would be demanding in terms of operationalisation, increased sample size and statistical biases to control. The optimal strategy was deemed to be the addition of a third arm, arriving retrospectively at a simplified multi-arm multi-stage clinical trial design to achieve statistical validity. The D2EFT study maintains additional value in a quickly evolving second-line ART strategy allowed by the progress in global access to ART.
    Matched MeSH terms: Drug Therapy, Combination
  13. Tew MP, Tan PC, Saaid R, Hong JGS, Omar SZ
    Int J Gynaecol Obstet, 2022 Mar;156(3):508-515.
    PMID: 33890319 DOI: 10.1002/ijgo.13718
    OBJECTIVE: To evaluate the impact of preemptive metformin on the level of glycosylated hemoglobin (HbA1c) at 36 weeks of pregnancy in women with gestational diabetes mellitus controlled by diet change (GDMA1).

    METHODS: A randomized, double-blind, placebo-controlled trial was performed in a university hospital. Women with GDMA1 were recruited at 16-30 weeks of pregnancy and randomized to oral metformin 500 mg twice daily or identical placebo tablets to delivery. Level of HbA1c was taken at recruitment and at 36 weeks of pregnancy. The primary outcome was the change in level of HbA1c at recruitment and 36 weeks of pregnancy.

    RESULTS: Data from 106 participants were analyzed. The level of HbA1c during pregnancy increased significantly with a mean increase of 0.20% ± 0.31% (P 

    Matched MeSH terms: Drug Therapy, Combination
  14. Domnic G, Jeng-Yeou Chear N, Abdul Rahman SF, Ramanathan S, Lo KW, Singh D, et al.
    J Ethnopharmacol, 2021 Oct 28;279:114391.
    PMID: 34224811 DOI: 10.1016/j.jep.2021.114391
    ETHNOPHARMACOLOGICAL RELEVANCE: Mitragyna speciosa (Korth.) or kratom is a medicinal plant indigenous to Southeast Asia. The leaf of M. speciosa is used as a remedy in pain management including cancer related pain, in a similar way as opioids and cannabis. Despite its well-known analgesic effect, there is a scarce of information on the cancer-suppressing potential of M. speciosa and its active constituents.

    AIM OF THE STUDY: To assess the potential applicability of M. speciosa alkaloids (mitragynine, speciociliatine or paynantheine) as chemosensitizers for cisplatin in Nasopharyngeal carcinoma (NPC) cell lines.

    MATERIALS AND METHODS: The cytotoxic effects of the extracts, fractions and compounds were determined by conducting in vitro cytotoxicity assays. Based on the cytotoxic screening, the alkaloid extract of M. speciosa exhibited potent inhibitory effect on the NPC cell line NPC/HK1, and therefore, was chosen for further fractionation and purification. NPC cell lines NPC/HK1 and C666-1 were treated with combinations of cisplatin and M. speciosa alkaloids combinations in 2D monolayer culture. The effect of cisplatin and mitragynine as a combination on cell migration was tested using in vitro wound healing and spheroid invasion assays.

    RESULTS: In our bioassay guided isolation, both methanolic and alkaloid extracts showed mild to moderate cytotoxic effect against the NPC/HK1 cell line. Both NPC cell lines (NPC/HK1 and C666-1) were insensitive to single agent and combination treatments of the M. speciosa alkaloids. However, mitragynine and speciociliatine sensitized the NPC/HK1 and C666-1 cells to cisplatin at ~4- and >5-fold, respectively in 2D monolayer culture. The combination of mitragynine and cisplatin also significantly inhibited cell migration of the NPC cell lines. Similarly, the combination also of mitragynine and cisplatin inhibited growth and invasion of NPC/HK1 spheroids in a dose-dependent manner. In addition, the spheroids did not rapidly develop resistance to the drug combinations at higher concentrations over 10 days.

    CONCLUSION: Our data indicate that both mitragynine and speciociliatine could be potential chemosensitizers for cisplatin. Further elucidation focusing on the drug mechanistic studies and in vivo studies are necessary to support delineate the therapeutic applicability of M. speciosa alkaloids for NPC treatment.

    Matched MeSH terms: Drug Therapy, Combination
  15. WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group, Shankar-Hari M, Vale CL, Godolphin PJ, Fisher D, Higgins JPT, et al.
    JAMA, 2021 Aug 10;326(6):499-518.
    PMID: 34228774 DOI: 10.1001/jama.2021.11330
    IMPORTANCE: Clinical trials assessing the efficacy of IL-6 antagonists in patients hospitalized for COVID-19 have variously reported benefit, no effect, and harm.

    OBJECTIVE: To estimate the association between administration of IL-6 antagonists compared with usual care or placebo and 28-day all-cause mortality and other outcomes.

    DATA SOURCES: Trials were identified through systematic searches of electronic databases between October 2020 and January 2021. Searches were not restricted by trial status or language. Additional trials were identified through contact with experts.

    STUDY SELECTION: Eligible trials randomly assigned patients hospitalized for COVID-19 to a group in whom IL-6 antagonists were administered and to a group in whom neither IL-6 antagonists nor any other immunomodulators except corticosteroids were administered. Among 72 potentially eligible trials, 27 (37.5%) met study selection criteria.

    DATA EXTRACTION AND SYNTHESIS: In this prospective meta-analysis, risk of bias was assessed using the Cochrane Risk of Bias Assessment Tool. Inconsistency among trial results was assessed using the I2 statistic. The primary analysis was an inverse variance-weighted fixed-effects meta-analysis of odds ratios (ORs) for 28-day all-cause mortality.

    MAIN OUTCOMES AND MEASURES: The primary outcome measure was all-cause mortality at 28 days after randomization. There were 9 secondary outcomes including progression to invasive mechanical ventilation or death and risk of secondary infection by 28 days.

    RESULTS: A total of 10 930 patients (median age, 61 years [range of medians, 52-68 years]; 3560 [33%] were women) participating in 27 trials were included. By 28 days, there were 1407 deaths among 6449 patients randomized to IL-6 antagonists and 1158 deaths among 4481 patients randomized to usual care or placebo (summary OR, 0.86 [95% CI, 0.79-0.95]; P = .003 based on a fixed-effects meta-analysis). This corresponds to an absolute mortality risk of 22% for IL-6 antagonists compared with an assumed mortality risk of 25% for usual care or placebo. The corresponding summary ORs were 0.83 (95% CI, 0.74-0.92; P 

    Matched MeSH terms: Drug Therapy, Combination
  16. Bosch J, Lonn EM, Dagenais GR, Gao P, Lopez-Jaramillo P, Zhu J, et al.
    Stroke, 2021 08;52(8):2494-2501.
    PMID: 33985364 DOI: 10.1161/STROKEAHA.120.030790
    Background and Purpose: The HOPE-3 trial (Heart Outcomes Prevention Evaluation–3) found that antihypertensive therapy combined with a statin reduced first stroke among people at intermediate cardiovascular risk. We report secondary analyses of stroke outcomes by stroke subtype, predictors, treatment effects in key subgroups.

    Methods: Using a 2-by-2 factorial design, 12 705 participants from 21 countries with vascular risk factors but without overt cardiovascular disease were randomized to candesartan 16 mg plus hydrochlorothiazide 12.5 mg daily or placebo and to rosuvastatin 10 mg daily or placebo. The effect of the interventions on stroke subtypes was assessed.

    Results: Participants were 66 years old and 46% were women. Baseline blood pressure (138/82 mm Hg) was reduced by 6.0/3.0 mm Hg and LDL-C (low-density lipoprotein cholesterol; 3.3 mmol/L) was reduced by 0.90 mmol/L on active treatment. During 5.6 years of follow-up, 169 strokes occurred (117 ischemic, 29 hemorrhagic, 23 undetermined). Blood pressure lowering did not significantly reduce stroke (hazard ratio [HR], 0.80 [95% CI, 0.59–1.08]), ischemic stroke (HR, 0.80 [95% CI, 0.55–1.15]), hemorrhagic stroke (HR, 0.71 [95% CI, 0.34–1.48]), or strokes of undetermined origin (HR, 0.92 [95% CI, 0.41–2.08]). Rosuvastatin significantly reduced strokes (HR, 0.70 [95% CI, 0.52–0.95]), with reductions mainly in ischemic stroke (HR, 0.53 [95% CI, 0.37–0.78]) but did not significantly affect hemorrhagic (HR, 1.22 [95% CI, 0.59–2.54]) or strokes of undetermined origin (HR, 1.29 [95% CI, 0.57–2.95]). The combination of both interventions compared with double placebo substantially and significantly reduced strokes (HR, 0.56 [95% CI, 0.36–0.87]) and ischemic strokes (HR, 0.41 [95% CI, 0.23–0.72]).

    Conclusions: Among people at intermediate cardiovascular risk but without overt cardiovascular disease, rosuvastatin 10 mg daily significantly reduced first stroke. Blood pressure lowering combined with rosuvastatin reduced ischemic stroke by 59%. Both therapies are safe and generally well tolerated.

    Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00468923.

    Matched MeSH terms: Drug Therapy, Combination
  17. Andrieux-Meyer I, Tan SS, Thanprasertsuk S, Salvadori N, Menétrey C, Simon F, et al.
    Lancet Gastroenterol Hepatol, 2021 Jun;6(6):448-458.
    PMID: 33865507 DOI: 10.1016/S2468-1253(21)00031-5
    BACKGROUND: In low-income and middle-income countries, affordable direct-acting antivirals are urgently needed to treat hepatitis C virus (HCV) infection. The combination of ravidasvir, a pangenotypic non-structural protein 5A (NS5A) inhibitor, and sofosbuvir has shown efficacy and safety in patients with chronic HCV genotype 4 infection. STORM-C-1 trial aimed to assess the efficacy and safety of ravidasvir plus sofosbuvir in a diverse population of adults chronically infected with HCV.

    METHODS: STORM-C-1 is a two-stage, open-label, phase 2/3 single-arm clinical trial in six public academic and non-academic centres in Malaysia and four public academic and non-academic centres in Thailand. Patients with HCV with compensated cirrhosis (Metavir F4 and Child-Turcotte-Pugh class A) or without cirrhosis (Metavir F0-3) aged 18-69 years were eligible to participate, regardless of HCV genotype, HIV infection status, previous interferon-based HCV treatment, or source of HCV infection. Once daily ravidasvir (200 mg) and sofosbuvir (400 mg) were prescribed for 12 weeks for patients without cirrhosis and for 24 weeks for those with cirrhosis. The primary endpoint was sustained virological response at 12 weeks after treatment (SVR12; defined as HCV RNA <12 IU/mL in Thailand and HCV RNA <15 IU/mL in Malaysia at 12 weeks after the end of treatment). This trial is registered with ClinicalTrials.gov, number NCT02961426, and the National Medical Research Register of Malaysia, NMRR-16-747-29183.

    FINDINGS: Between Sept 14, 2016, and June 5, 2017, 301 patients were enrolled in stage one of STORM-C-1. 98 (33%) patients had genotype 1a infection, 27 (9%) had genotype 1b infection, two (1%) had genotype 2 infection, 158 (52%) had genotype 3 infection, and 16 (5%) had genotype 6 infection. 81 (27%) patients had compensated cirrhosis, 90 (30%) had HIV co-infection, and 99 (33%) had received previous interferon-based treatment. The most common treatment-emergent adverse events were pyrexia (35 [12%]), cough (26 [9%]), upper respiratory tract infection (23 [8%]), and headache (20 [7%]). There were no deaths or treatment discontinuations due to serious adverse events related to study drugs. Of the 300 patients included in the full analysis set, 291 (97%; 95% CI 94-99) had SVR12. Of note, SVR12 was reported in 78 (96%) of 81 patients with cirrhosis and 153 (97%) of 158 patients with genotype 3 infection, including 51 (96%) of 53 patients with cirrhosis. There was no difference in SVR12 rates by HIV co-infection or previous interferon treatment.

    INTERPRETATION: In this first stage, ravidasvir plus sofosbuvir was effective and well tolerated in this diverse adult population of patients with chronic HCV infection. Ravidasvir plus sofosbuvir has the potential to provide an additional affordable, simple, and efficacious public health tool for large-scale implementation to eliminate HCV as a cause of morbidity and mortality.

    FUNDING: National Science and Technology Development Agency, Thailand; Department of Disease Control, Ministry of Public Health, Thailand; Ministry of Health, Malaysia; UK Aid; Médecins Sans Frontières (MSF); MSF Transformational Investment Capacity; FIND; Pharmaniaga; Starr International Foundation; Foundation for Art, Research, Partnership and Education; and the Swiss Agency for Development and Cooperation.

    Matched MeSH terms: Drug Therapy, Combination
  18. Damanhuri NS, Kumolosasi E, Omar MS, Razak AFA, Mansor AH
    Daru, 2021 Jun;29(1):13-22.
    PMID: 33405191 DOI: 10.1007/s40199-020-00377-2
    BACKGROUND: P-glycoprotein (P-gp) is an Adenosine triphosphate (ATP) dependent drug-efflux pump which is located abundantly in the stomach and protects the gut mucosa from xenobiotic.

    OBJECTIVE: The purpose of this study was to investigate the influence of P-gp modulation on the efficacy of treatment regimen.

    METHOD: P-gp modulation in rats was performed by using P-gp inducer (150 mg/kg rifampicin) and P-gp inhibitor (10 mg/kg cyclosporine A) for 14 days prior to be infected with Helicobacter pylori (H. pylori). The rats were further divided into groups, which were normal control, vehicle control, antibiotics and omeprazole, antibiotics only and omeprazole only for another 2 weeks of treatment. The ulcer formation and P-gp expression were determined by using macroscopic evaluation and western blot analysis, respectively.

    RESULTS: The highest P-gp expression was shown in the induced P-gp rats (2.00 ± 0.68) while the lowest P-gp expression was shown in the inhibited P-gp rats (0.45 ± 0.36) compared to the normal P-gp rats. In all groups, the rats which were infected with H. pylori, had a significant increase (p 

    Matched MeSH terms: Drug Therapy, Combination
  19. Tang ASO, Wong QY, Yeo ST, Ting IPL, Lee JTH, Fam TL, et al.
    Am J Case Rep, 2021 May 26;22:e931655.
    PMID: 34038399 DOI: 10.12659/AJCR.931655
    BACKGROUND Leprosy is an infection caused by Mycobacterium leprae. An extensive literature search did not reveal many reports of melioidosis in association with leprosy. CASE REPORT A 22-year-old woman, who was diagnosed with multibacillary leprosy, developed dapsone-induced methemoglobinemia and hemolytic anemia, complicated by melioidosis. Methemoglobinemia was treated with methylene blue and vitamin C. Two weeks of ceftazidime was initiated to treat melioidosis, and the patient was discharged on amoxicillin/clavulanic acid and doxycycline as melioidosis eradication therapy. However, she developed drug-induced hypersensitivity. Trimethoprim/sulfamethoxazole, as an alternative treatment for melioidosis eradication, was commenced and was successfully completed for 12 weeks. During the fifth month of multidrug therapy, the patient developed type II lepra reaction with erythema nodosum leprosum reaction, which was treated with prednisolone. Leprosy treatment continued with clofazimine and ofloxacin, and complete resolution of skin lesions occurred after 12 months of therapy. CONCLUSIONS Our case highlighted the challenges posed in managing a patient with multibacillary leprosy with multiple complications. Clinicians should be aware that dapsone-induced methemoglobinemia and hemolysis might complicate the treatment of leprosy. Our case also highlighted the safety and efficacy of combining ofloxacin and clofazimine as a leprosy treatment regimen in addition to gradual steroid dose titration in the presence of type II lepra reaction.
    Matched MeSH terms: Drug Therapy, Combination
  20. Das S, Kar A, Manna S, Mandal S, Mandal S, Das S, et al.
    Sci Rep, 2021 05 11;11(1):9946.
    PMID: 33976269 DOI: 10.1038/s41598-021-89295-0
    Artemisinin is the frontline fast-acting anti-malarial against P. falciparum. Emergence and spread of resistant parasite in eastern-India poses a threat to national malaria control programs. Therefore, the objective of our study is to evaluate the artesunate-sulfadoxine-pyrimethamine efficacy in Central India. 180 monoclonal P. falciparum-infected patients received standard ASSP therapy during August 2015-January 2017, soon after diagnosis and monitored over next 42-days. Artemisinin-resistance was assessed through in-vivo parasite clearance half-life (PC1/2), ex-vivo ring-stage survivability (RSA), and genome analysis of kelch13 and other candidate gene (pfcrt, pfmdr1, pfatpase 6, pfdhfr and pfdhps). Of 180 P. falciparum positive patients, 9.5% showed increased PC1/2 (> 5.5 h), among them eleven isolates (6.1%) showed reduced sensitivity to RSA. In 4.4% of cases, parasites were not cleared by 72 h and showed prolonged PC1/2(5.6 h) (P 
    Matched MeSH terms: Drug Therapy, Combination/methods
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