Displaying publications 61 - 80 of 292 in total

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  1. Patel V, Collazo Lorduy A, Stern A, Fahmy O, Pinotti R, Galsky MD, et al.
    Bladder cancer (Amsterdam, Netherlands), 2017 Apr 27;3(2):121-132.
    PMID: 28516157 DOI: 10.3233/BLC-170108
    Background: Cisplatin-based combination chemotherapy is standard treatment for metastatic urothelial carcinoma; however, the vast majority of patients experience disease progression. As systemic therapy alone is rarely curative for the treatment of metastatic urothelial cancer, not only are new therapies needed but also refinement of general treatment principles. Herein, we conducted a systematic review and meta-analysis to explore the role of metastasectomy in metastatic urothelial carcinoma. Methods: We conducted a systematic review of the literature regarding local treatment for metastatic urothelial carcinoma. An online electronic search of the PubMed/MEDLINE and EMBASE databases was performed to identify peer-reviewed articles. All procedures were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Information was then extracted including number of patients, gender, the site of the primary urothelial tumor, site of metastasis, chemotherapy before or after metastasectomy, overall survival (OS), and disease specific survival (DSS) after metastasectomy. A meta-analysis was performed with those studies with sufficient survival data to obtain pooled overall survival. The article quality was assessed using the Cochrane Handbook "risk of bias" tool. Results: Seventeen out of 3963 articles were eligible for review between 1990-2015, including a total of 412 patients. The mean time to recurrence after metastasectomy was 14.25 months. The overall survival from time of metastasectomy ranged from 2 to 60 months. Pooled analyses of studies reported survival data revealed an improved overall survival for patients treated with metastasectomy compared with non-surgical treatment of metastatic lesions (HR 0.63; 95% CI, 0.49-0.81). All, except for three studies, were retrospective and non-randomized, leading to a high risk of bias associated with patient selection, patient attrition, and reporting. Such high potential of selection bias may lead to higher OS than expected. Additionally, treatment and outcome details reported across studies was highly variable. Conclusions: Limited conclusions can be drawn from the available literature exploring the role of metastasectomy in the management of metastatic urothelial cancer due to lack of uniform reporting elements and multiple sources of bias particularly related to a lack of prospective randomized trials. As a subset of patients treated with metastasectomy achieve durable disease control, this approach may be considered for select patients.
    Matched MeSH terms: Drug Therapy, Combination
  2. Hasan SS, Bahari MB, Babar ZU, Ganesan V
    Singapore Med J, 2010 Jan;51(1):21-7.
    PMID: 20200771
    INTRODUCTION: The primary purpose of this study was to evaluate the utilisation pattern and seizure outcome of newer and older antiepileptic drugs in paediatric clinical practice in a Malaysian hospital setting.
    METHODS: Over a two-month period, all paediatric epilepsy patients from Penang General Hospital, Malaysia who were diagnosed according to the classification of the International League Against Epilepsy were followed up prospectively, and the patients' information was gathered with the help of a validated data collection form. This included demographic characteristics, monotherapy and polytherapy of antiepileptic drugs, as well as the number of seizures experienced.
    RESULTS: Partial seizures, including complex and simple partial seizures (47.2 percent), followed by generalised seizures (40 percent), were the most common seizure types found in this study. An average of 1.51 antiepileptic drugs per patient was prescribed, with 54.3 percent of the patients on monotherapy and 45.7 percent on polytherapy. Overall, sodium valproate was the most frequently prescribed antiepileptic drug (36.8 percent), followed by carbamazepine (30.2 percent) and lamotrigine (10.4 percent). Carbamazepine was the most frequently prescribed monotherapy (28.6 percent), followed by sodium valproate (17.1 percent). The newer antiepileptic drugs were also found to be used as monotherapy in 7.2 percent of the cases. Moreover, a significant difference was observed between the older and newer antiepileptic drugs in terms of the number of seizures experienced (p=0.027). Most (75 percent) of the seizure-free patients were on carbamazepine monotherapy.
    CONCLUSION: Monotherapy was the most frequently used remedy in all forms of epilepsy. Overall, sodium valproate was the most commonly used drug, while carbamazepine was found to be more frequently used as monotherapy. There was a significant difference found between the older and newer antiepileptic drugs, with 87.5 percent of seizure-free patients on older antiepileptic drugs.

    Study site: all paediatric epilepsy patients from Penang General Hospital
    Matched MeSH terms: Drug Therapy, Combination
  3. Lee LM, Gendeh BS
    Med J Malaysia, 2003 Mar;58(1):17-20.
    PMID: 14556322
    Allergic rhinitis causes an impairment of the mucociliary function in the nose. It is hoped that treatment of perennial allergic rhinitis would be able to revert mucociliary function to normal. This study aims to compare pre and post treatment mucociliary transport time in 3 different treatment modalities. Ninety-two newly diagnosed patients with allergic rhinitis were randomised into 3 groups and started on different treatment regimes. At the end of 8 weeks, the group treated with only intranasal beclomethasone showed some, though not significant, improvement in the mucociliary function. There were no changes in the mucociliary function in the other two groups treated with beclomethasone and loratidine or loratidine alone.

    Study site: ENT clinic in Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM)
    UKM
    Matched MeSH terms: Drug Therapy, Combination
  4. Keat CH, Ghani NA
    Asian Pac J Cancer Prev, 2013;14(12):7701-6.
    PMID: 24460356
    BACKGROUND: In a prospective cohort study of antiemetic therapy conducted in Malaysia, a total of 94 patients received low emetogenic chemotherapy (LEC) with or without granisetron injections as the primary prophylaxis for chemotherapy-induced nausea and vomiting (CINV). This study is a retrospective cost analysis of two antiemetic regimens from the payer perspective.

    MATERIALS AND METHODS: This cost evaluation refers to 2011, the year in which the observation was conducted. Direct costs incurred by hospitals including the drug acquisition, materials and time spent for clinical activities from prescribing to dispensing of home medications were evaluated (MYR 1=$0.32 USD). As reported to be significantly different between two regimens (96.1% vs 81.0%; p=0.017), the complete response rate of acute emesis which was defined as a patient successfully treated without any emesis episode within 24 hours after LEC was used as the main indicator for effectiveness.

    RESULTS: Antiemetic drug acquisition cost per patient was 40.7 times higher for the granisetron-based regimen than for the standard regimen (MYR 64.3 vs 1.58). When both the costs for materials and clinical activities were included, the total cost per patient was 8.68 times higher for the granisetron-based regimen (MYR 73.5 vs 8.47). Considering the complete response rates, the mean cost per successfully treated patient in granisetron group was 7.31 times higher (MYR 76.5 vs 10.5). The incremental cost-effectiveness ratio (ICER) with granisetron-based regimen, relative to the standard regimen, was MYR 430.7. It was found to be most sensitive to the change of antiemetic effects of granisetron-based regimen.

    CONCLUSIONS: While providing a better efficacy in acute emesis control, the low incidence of acute emesis and high ICER makes use of granisetron as primary prophylaxis in LEC controversial.

    Matched MeSH terms: Drug Therapy, Combination
  5. Tweed CD, Wills GH, Crook AM, Amukoye E, Balanag V, Ban AYL, et al.
    Int J Tuberc Lung Dis, 2021 Apr 01;25(4):305-314.
    PMID: 33762075 DOI: 10.5588/ijtld.20.0513
    BACKGROUND: Treatment for TB is lengthy and toxic, and new regimens are needed.METHODS: Participants with pulmonary drug-susceptible TB (DS-TB) were randomised to receive: 200 mg pretomanid (Pa, PMD) daily, 400 mg moxifloxacin (M) and 1500 mg pyrazinamide (Z) for 6 months (6Pa200MZ) or 4 months (4Pa200MZ); 100 mg pretomanid daily for 4 months in the same combination (4Pa100MZ); or standard DS-TB treatment for 6 months. The primary outcome was treatment failure or relapse at 12 months post-randomisation. The non-inferiority margin for between-group differences was 12.0%. Recruitment was paused following three deaths and not resumed.RESULTS: Respectively 4/47 (8.5%), 11/57 (19.3%), 14/52 (26.9%) and 1/53 (1.9%) DS-TB outcomes were unfavourable in patients on 6Pa200MZ, 4Pa200MZ, 4Pa100MZ and controls. There was a 6.6% (95% CI -2.2% to 15.4%) difference per protocol and 9.9% (95%CI -4.1% to 23.9%) modified intention-to-treat difference in unfavourable responses between the control and 6Pa200MZ arms. Grade 3+ adverse events affected 68/203 (33.5%) receiving experimental regimens, and 19/68 (27.9%) on control. Ten of 203 (4.9%) participants on experimental arms and 2/68 (2.9%) controls died.CONCLUSION: PaMZ regimens did not achieve non-inferiority in this under-powered trial. An ongoing evaluation of PMD remains a priority.
    Matched MeSH terms: Drug Therapy, Combination
  6. 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
  7. Hasan MS, Tan JK, Chan CYW, Kwan MK, Karim FSA, Goh KJ
    J Orthop Surg (Hong Kong), 2018 7 31;26(3):2309499018789529.
    PMID: 30058437 DOI: 10.1177/2309499018789529
    BACKGROUND: Drugs used in anesthesia can affect somatosensory evoked potential (SSEP) monitoring, which is used routinely for intraoperative monitoring of spinal cord integrity during spinal surgery.

    OBJECTIVE: The objective of this study was to determine whether combined total intravenous anesthesia (TIVA) technique with propofol/remifentanil is associated with less SSEP suppression when compared to combined volatile agent desflurane/remifentanil anesthesia during corrective scoliosis surgery at a comparable depth of anesthesia.

    DESIGN: It is a randomized controlled trial.

    SETTING: The study was conducted at the Single tertiary University Hospital during October 2014 to June 2015.

    PATIENTS: Patients who required SSEP and had no neurological deficits, and were of American Society of Anesthesiologist I and II physical status, were included. Patients who had sensory or motor deficits preoperatively and significant cardiovascular and respiratory disease were excluded. A total of 72 patients were screened, and 67 patients were randomized and allocated to two groups: 34 in desflurane/remifentanil group and 33 in TIVA group. Four patients from desflurane/remifentanil group and three from TIVA group were withdrawn due to decrease in SSEP amplitude to <0.3 µV after induction of anesthesia. Thirty patients from each group were analyzed.

    INTERVENTIONS: Sixty-seven patients were randomized to receive TIVA or desflurane/remifentanil anesthesia.

    MAIN OUTCOME MEASURES: The measurements taken were the amplitude and latency of SSEP monitoring at five different time points during surgery: before and after the induction of anesthesia, at skin incision, at pedicle screw insertion, and at rod insertion.

    RESULTS: Both anesthesia techniques, TIVA and desflurane/remifentanil, resulted in decreased amplitude and increased latencies of both cervical and cortical peaks. The desflurane/remifentanil group had a significantly greater reduction in the amplitude ( p = 0.004) and an increase in latency ( p = 0.002) of P40 compared with the TIVA group. However, there were no differences in both amplitude ( p = 0.214) and latency ( p = 0.16) in cervical SSEP between the two groups.

    CONCLUSIONS: Compared with TIVA technique, desflurane/remifentanil anesthesia caused more suppression in cortical SSEP, but not in cervical SSEP, at a comparable depth of anesthesia.

    Matched MeSH terms: Drug Therapy, Combination
  8. Qua CS, Manikam J, Goh KL
    J Dig Dis, 2010 Aug;11(4):244-8.
    PMID: 20649738 DOI: 10.1111/j.1751-2980.2010.00445.x
    OBJECTIVE:
    To re-examine the efficacy and tolerability of 1-week proton pump inhibitor triple therapy as a first-line Helicobacter pylori (H. pylori) eradication therapy.

    METHODS:
    Consecutive participants with a positive rapid urease test during an outpatient upper endoscopy were included. All participants were given pantoprazole 40 mg b.i.d., amoxycillin 1 g b.i.d. and clarithromycin 500 mg b.i.d. for 1 week. They were asked to return after 1 week to report any side effects related to the medications and to check for compliance. Successful eradication was defined by negative (13)C-urea breath test at least 4 weeks after the completion of therapy.

    RESULTS:
    A total of 191 patients were recruited into the study, of whom 81 were male (42.4%) and 110 female (57.6%), with a mean age of 55.6 (range 21-88) years. Overall 26 patients (13.6%) defaulted follow up and five patients were not compliant (taking less than 85%) with the medications. Per-protocol and intention-to-treat eradication rates were 84.4% (95% CI: 78.6-89.9%) and 71.2% (95% CI: 64.5-77.6%), respectively. Overall 68 participants (42.5%) reported no side effects, followed by 58 (36.3%) with a taste disturbance, 16 (10.0%) with epigastric pain, 15 (9.4%) with diarrhea, 13 (8.1%) with nausea or vomiting, 12 (7.5%) with loss of appetite, nine (5.6%) with dizziness and two (1.3%) with an allergic skin rash, none of which was severe.

    CONCLUSION:
    The current regime using pantoprazole, amoxycillin and clarithromycin is highly tolerable and effective and should continue to be recommended as a first-line therapy for H. pylori eradication in our setting.
    Matched MeSH terms: Drug Therapy, Combination
  9. Hwong-Ruey Leow A, Chang JV, Goh KL
    Helicobacter, 2020 Oct;25(5):e12723.
    PMID: 32713104 DOI: 10.1111/hel.12723
    BACKGROUND & AIMS: We compared a high-dose dual therapy (HDDT) with rabeprazole and amoxicillin and compared it with a standard triple therapy (STT) with rabeprazole, amoxicillin, and clarithromycin for 2 weeks for H pylori eradication in treatment naïve patients.

    METHODS: H pylori-positive patients were randomly assigned to either a rabeparzole (Pariet) 20 mg b.i.d., amoxicillin (Ospamox) 1 g b.i.d. and clarithromycin (Klacid) 500 mg b.i.d. for 14 days or rabeprazole (Pariet) 20 mg q.i.d., amoxicillin (Ospamox) 1 g q.i.d. also for 14 days. Eradication was tested for by the C13 -UBT at least 4 weeks after the completion of therapy.

    RESULTS: H pylori was eradicated in 86.2% of patients (81/94) (95% CI: 77.8-91.7) in the STT group compared with 92.8% (90/97) (95% CI: 85.9-96.5) in the HDDT group on ITT analysis. On PP analysis, H pylori was eradicated in 91.0% of patients (81/89) (95% CI: 83.3-95.4) in the STT group compared with 93.8% (90/96) (95% CI: 87.0-97.1) in the HDDT group. Side effects were few although many patients in the STT arm complained of bitter taste. The HDDT arm was well tolerated by patients.

    CONCLUSIONS: The HDDT gave a high eradication rate comparable to the STT for 2 weeks and was a well-tolerated regimen for H pylori eradication.

    Matched MeSH terms: Drug Therapy, Combination
  10. Parasakthi N, Goh KL
    Am J Gastroenterol, 1995 Mar;90(3):519.
    PMID: 7872306
    Matched MeSH terms: Drug Therapy, Combination
  11. Zou D, Goh KL
    J Gastroenterol Hepatol, 2017 Jun;32(6):1152-1159.
    PMID: 28024166 DOI: 10.1111/jgh.13712
    Both proton pump inhibitors (PPIs) and clopidogrel are widely prescribed in the Asia-Pacific population. PPIs are the mainstay therapeutic agents for prophylaxis against aspirin gastropathy and for acid-related disorders including gastroesophageal reflux disease. They are also co-prescribed with oral anticoagulant agents and with dual-antiplatelet therapy for the treatment and prevention of gastrointestinal bleeding. Clopidogrel belongs to the drug class of thienopyridines and is currently the most widely prescribed oral anticoagulant agent either alone or in combination with aspirin. Platelet inhibition by clopidogrel is prone to significant inter-individual variability and is believed to be affected by several factors such as genetics and drug-drug interactions. Since it was first reported in 2009, the potential for drug-drug interactions between PPIs and clopidogrel has remained headline news, and its significance in clinical practice is the subject of an ongoing debate. For East Asian patients in particular, the clinical relevance of the interaction between PPIs and clopidogrel remains unclear because of conflicting data, as well as underrepresentation of East Asian subjects in landmark trials. Increased CYP2C19 genetic polymorphisms in individuals from Asia-Pacific countries only fuel the confusion. Recent studies in East Asian cohorts suggests that the potential of PPIs to attenuate the efficacy of clopidogrel could be minimized by the use of newer PPIs with weaker affinity for the CYP2C19 isoenzyme, namely, pantoprazole, dexlansoprazole, and rabeprazole. This review aims to help clinicians choose the most appropriate PPI for co-prescription with clopidogrel in patients from Asia-Pacific countries.
    Matched MeSH terms: Drug Therapy, Combination
  12. Mahachai V, Vilaichone RK, Pittayanon R, Rojborwonwitaya J, Leelakusolvong S, Maneerattanaporn M, et al.
    J Gastroenterol Hepatol, 2018 Jan;33(1):37-56.
    PMID: 28762251 DOI: 10.1111/jgh.13911
    Helicobacter pylori (H. pylori) infection remains to be the major cause of important upper gastrointestinal diseases such as chronic gastritis, peptic ulcer, gastric adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma. H. pylori management in ASEAN: the Bangkok consensus report gathered key opinion leaders for the region to review and evaluate clinical aspects of H. pylori infection and to develop consensus statements, rationales, and grades of recommendation for the management of H. pylori infection in clinical practice in ASEAN countries. This ASEAN Consensus consisted of 34 international experts from 10 ASEAN countries, Japan, Taiwan, and the United States. The meeting mainly focused on four issues: (i) epidemiology and disease association; (ii) diagnostic tests; (iii) management; and (iv) follow-up after eradication. The final results of each workshop were presented for consensus voting by all participants. Statements, rationale, and recommendations were developed from the available current evidence to help clinicians in the diagnosis and treatment of H. pylori and its clinical diseases.
    Matched MeSH terms: Drug Therapy, Combination
  13. Guan R
    Med J Malaysia, 2005 Jul;60 Suppl B:28-33.
    PMID: 16108170
    Four to 6 months of conventional interferon alpha (IFN-alpha) (5MU daily or 10MU three times weekly) resulted in HBeAg loss in approximately 33% of HBeAg positive patients (controls: 12%). Longer treatment duration improved HBeAg seroconversion. Children with chronic HBV infection and high ALT respond to IFN-a at similar rates. Good end-of-treatment (ET) biochemical and virological response were also achieved with IFN-alpha in HBeAg negative, HBV-DNA positive hepatitis patients. Sustained response (SR) however, was disappointing, but improved with longer duration of treatment: (10-15% SR with 4/6 months treatment: 30% SR with 24 months treatment). Weekly pegylated IFN-alpha2a (PegIFN-alpha2a) for 24 weeks gave a significantly higher HBeAg conversion rate (33%) than conventional IFN-alpha2a (25%). Fifty-two weeks of PegIFN-alpha2b gave a sustained HBeAg loss in 35% patients and HBeAg seroconversion in 29% patients. Similar results were obtained with 48 weeks of weekly PegIFN-alpha2a. PegIFN-alpha2a monotherapy was found to be superior to lamivudine monotherapy in affecting a 6-month SR (normal ALTs and HBV DNA < 20,000 copies/mL) in HBeAg negative/anti-HBe positive chronic hepatitis B patients. There is a tendency for IFN-a and lamivudine combination to result in better sustained response than lamivudine monotherapy. This tendency is also observed with PegIFN-a and lamivudine combination although the combination did not appear to be better than PegIFN-alpha monotherapy. IFN induced HBeAg seroconversion is durable, could increase over time and resulted in better overall survival and survival free of hepatic decompensation or hepatocellular cancer. The main advantage of IFN-a therapy is that a course of finite duration may achieve sustained off-therapy response in a proportion of both HBeAg positive and HBeAg negative chronic hepatitis B patients. However, IFN treatment is usually associated with side-effects, especially flu-like symptoms, fatigue, neutropenia, thrombocytopenia and depression. These are usually tolerable but may require dose modification and premature cessation of treatment (5%). Interferon therapy induced hepatitis flares may lead to decompensation in patients with cirrhosis and can be dangerous in patients with decompensated liver function despite dose reduction.
    Matched MeSH terms: Drug Therapy, Combination
  14. Koh KT, Teh CL, Cheah CK, Ling GR, Yong MC, Hong HC, et al.
    Reumatismo, 2016 Sep 09;68(2):90-6.
    PMID: 27608797 DOI: 10.4081/reumatismo.2016.872
    The objective of this study was to compare the tolerability of methotrexate in two different regimes of folic acid (FA) supplementation in rheumatoid arthritis (RA). We performed a multicenter, cross-sectional observational cohort study on 240 RA patients with 120 patients each in 5 mg of FA weekly and 30 mg of FA weekly supplementation. There were no significant differences for side effects (14.2 versus 22.5%, P=0.523) and discontinuation of methotrexate (3.6 versus 13.3%, P=0.085). RA patients given 5 mg of FA weekly supplementation had a lower disease activity score 28 compared to 30 mg of FA weekly supplementation [3.44 (1.10) versus 3.85 (1.40), P=0.014]. FA supplementation of 5 mg per week and 30 mg per week was associated with similar tolerability of methotrexate in RA patients.
    Matched MeSH terms: Drug Therapy, Combination
  15. Tan BE, Lim AL, Kan SL, Lim CH, Tsang EEL, Ch'ng SS, et al.
    Rheumatol Int, 2017 Oct;37(10):1719-1725.
    PMID: 28695274 DOI: 10.1007/s00296-017-3772-8
    The effect of biologic disease modifying anti-rheumatic drugs (bDMARDs) in treating rheumatoid arthritis (RA) in real-world clinical practice remains unknown in Southeast Asia. We aimed to assess the efficacy and safety of bDMARDs among Malaysian RA patients treated in routine clinical practice. A retrospective medical chart review of RA patients from 11 government hospitals were conducted from January 2003 to January 2014. A standardized questionnaire was used to abstract patient's demographic, clinical and treatment data. Level of disease activity was measured by DAS28 collected at baseline, 3, 6 and 12 months. Three hundred and one patients were available for analysis, mean age 41 (SD, 10.8) years, mean RA duration 12.3 (SD, 6.9) years and 98% had history of two or more conventional-synthetic DMARDs. There were 467 bDMARD courses prescribed with mean bDMARDs duration use of 12.9 months (SD 14.7). Tumour necrosis factor alpha inhibitors were the most common prescribed bDMARDs (77.1%), followed by Tocilizumab (14.6%) and Rituximab (8.4%). We observed significant improvement in mean DAS28 values from baseline to 3, 6 and 12 months (p 
    Matched MeSH terms: Drug Therapy, Combination
  16. del Amo J, Moreno S, Bucher HC, Furrer H, Logan R, Sterne J, et al.
    Clin Infect Dis, 2012 May;54(9):1364-72.
    PMID: 22460971 DOI: 10.1093/cid/cis203
    BACKGROUND: The lower tuberculosis incidence reported in human immunodeficiency virus (HIV)-positive individuals receiving combined antiretroviral therapy (cART) is difficult to interpret causally. Furthermore, the role of unmasking immune reconstitution inflammatory syndrome (IRIS) is unclear. We aim to estimate the effect of cART on tuberculosis incidence in HIV-positive individuals in high-income countries.

    METHODS: The HIV-CAUSAL Collaboration consisted of 12 cohorts from the United States and Europe of HIV-positive, ART-naive, AIDS-free individuals aged ≥18 years with baseline CD4 cell count and HIV RNA levels followed up from 1996 through 2007. We estimated hazard ratios (HRs) for cART versus no cART, adjusted for time-varying CD4 cell count and HIV RNA level via inverse probability weighting.

    RESULTS: Of 65 121 individuals, 712 developed tuberculosis over 28 months of median follow-up (incidence, 3.0 cases per 1000 person-years). The HR for tuberculosis for cART versus no cART was 0.56 (95% confidence interval [CI], 0.44-0.72) overall, 1.04 (95% CI, 0.64-1.68) for individuals aged >50 years, and 1.46 (95% CI, 0.70-3.04) for people with a CD4 cell count of <50 cells/μL. Compared with people who had not started cART, HRs differed by time since cART initiation: 1.36 (95% CI, 0.98-1.89) for initiation <3 months ago and 0.44 (95% CI, 0.34-0.58) for initiation ≥3 months ago. Compared with people who had not initiated cART, HRs <3 months after cART initiation were 0.67 (95% CI, 0.38-1.18), 1.51 (95% CI, 0.98-2.31), and 3.20 (95% CI, 1.34-7.60) for people <35, 35-50, and >50 years old, respectively, and 2.30 (95% CI, 1.03-5.14) for people with a CD4 cell count of <50 cells/μL.

    CONCLUSIONS: Tuberculosis incidence decreased after cART initiation but not among people >50 years old or with CD4 cell counts of <50 cells/μL. Despite an overall decrease in tuberculosis incidence, the increased rate during 3 months of ART suggests unmasking IRIS.

    Matched MeSH terms: Drug Therapy, Combination
  17. Yusuf S, Lonn E, Pais P, Bosch J, López-Jaramillo P, Zhu J, et al.
    N Engl J Med, 2016 May 26;374(21):2032-43.
    PMID: 27039945 DOI: 10.1056/NEJMoa1600177
    BACKGROUND: Elevated blood pressure and elevated low-density lipoprotein (LDL) cholesterol increase the risk of cardiovascular disease. Lowering both should reduce the risk of cardiovascular events substantially.
    METHODS: In a trial with 2-by-2 factorial design, we randomly assigned 12,705 participants at intermediate risk who did not have cardiovascular disease to rosuvastatin (10 mg per day) or placebo and to candesartan (16 mg per day) plus hydrochlorothiazide (12.5 mg per day) or placebo. In the analyses reported here, we compared the 3180 participants assigned to combined therapy (with rosuvastatin and the two antihypertensive agents) with the 3168 participants assigned to dual placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, and the second coprimary outcome additionally included heart failure, cardiac arrest, or revascularization. The median follow-up was 5.6 years.
    RESULTS: The decrease in the LDL cholesterol level was 33.7 mg per deciliter (0.87 mmol per liter) greater in the combined-therapy group than in the dual-placebo group, and the decrease in systolic blood pressure was 6.2 mm Hg greater with combined therapy than with dual placebo. The first coprimary outcome occurred in 113 participants (3.6%) in the combined-therapy group and in 157 (5.0%) in the dual-placebo group (hazard ratio, 0.71; 95% confidence interval [CI], 0.56 to 0.90; P=0.005). The second coprimary outcome occurred in 136 participants (4.3%) and 187 participants (5.9%), respectively (hazard ratio, 0.72; 95% CI, 0.57 to 0.89; P=0.003). Muscle weakness and dizziness were more common in the combined-therapy group than in the dual-placebo group, but the overall rate of discontinuation of the trial regimen was similar in the two groups.
    CONCLUSIONS: The combination of rosuvastatin (10 mg per day), candesartan (16 mg per day), and hydrochlorothiazide (12.5 mg per day) was associated with a significantly lower rate of cardiovascular events than dual placebo among persons at intermediate risk who did not have cardiovascular disease. (Funded by the Canadian Institutes of Health Research and AstraZeneca; ClinicalTrials.gov number, NCT00468923.).
    Note: Malaysia is a study site (Author: Yusoff K)
    Matched MeSH terms: Drug Therapy, Combination
  18. Lonn EM, Bosch J, López-Jaramillo P, Zhu J, Liu L, Pais P, et al.
    N Engl J Med, 2016 May 26;374(21):2009-20.
    PMID: 27041480 DOI: 10.1056/NEJMoa1600175
    BACKGROUND: Antihypertensive therapy reduces the risk of cardiovascular events among high-risk persons and among those with a systolic blood pressure of 160 mm Hg or higher, but its role in persons at intermediate risk and with lower blood pressure is unclear.
    METHODS: In one comparison from a 2-by-2 factorial trial, we randomly assigned 12,705 participants at intermediate risk who did not have cardiovascular disease to receive either candesartan at a dose of 16 mg per day plus hydrochlorothiazide at a dose of 12.5 mg per day or placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke; the second coprimary outcome additionally included resuscitated cardiac arrest, heart failure, and revascularization. The median follow-up was 5.6 years.
    RESULTS: The mean blood pressure of the participants at baseline was 138.1/81.9 mm Hg; the decrease in blood pressure was 6.0/3.0 mm Hg greater in the active-treatment group than in the placebo group. The first coprimary outcome occurred in 260 participants (4.1%) in the active-treatment group and in 279 (4.4%) in the placebo group (hazard ratio, 0.93; 95% confidence interval [CI], 0.79 to 1.10; P=0.40); the second coprimary outcome occurred in 312 participants (4.9%) and 328 participants (5.2%), respectively (hazard ratio, 0.95; 95% CI, 0.81 to 1.11; P=0.51). In one of the three prespecified hypothesis-based subgroups, participants in the subgroup for the upper third of systolic blood pressure (>143.5 mm Hg) who were in the active-treatment group had significantly lower rates of the first and second coprimary outcomes than those in the placebo group; effects were neutral in the middle and lower thirds (P=0.02 and P=0.009, respectively, for trend in the two outcomes).
    CONCLUSIONS: Therapy with candesartan at a dose of 16 mg per day plus hydrochlorothiazide at a dose of 12.5 mg per day was not associated with a lower rate of major cardiovascular events than placebo among persons at intermediate risk who did not have cardiovascular disease. (Funded by the Canadian Institutes of Health Research and AstraZeneca; ClinicalTrials.gov number, NCT00468923.).
    Note: Malaysia is a study site (Author: Yusoff K)
    Matched MeSH terms: Drug Therapy, Combination
  19. Wan KS, Moy FM, Mohd Yusof K, Mustapha FI, Mohd Ali Z, Hairi NN
    PLoS One, 2020;15(10):e0240531.
    PMID: 33035261 DOI: 10.1371/journal.pone.0240531
    BACKGROUND: Clinical inertia can lead to poor glycemic control among type 2 diabetes patients. However, there is paucity of information on clinical inertia in low- and middle-income countries including Malaysia. This study aimed to determine the time to treatment intensification among T2D patients with HbA1c of ≥7% (≥53 mmol/mol) in Malaysian public health clinics. The proportion of patients with treatment intensification and its associated factors were also determined.

    MATERIAL AND METHODS: This was a five-year retrospective open cohort study using secondary data from the National Diabetes Registry. The study setting was all public health clinics (n = 47) in the state of Negeri Sembilan, Malaysia. Time to treatment intensification was defined as the number of years from the index year until the addition of another oral antidiabetic drug or initiation of insulin. Life table survival analysis based on best-worst case scenarios was used to determine the time to treatment intensification. Discrete-time proportional hazards model was fitted for the factors associated with treatment intensification.

    RESULTS: The mean follow-up duration was 2.6 (SD 1.1) years. Of 7,646 patients, the median time to treatment intensification was 1.29 years (15.5 months), 1.58 years (19.0 months) and 2.32 years (27.8 months) under the best-, average- and worst-case scenarios respectively. The proportion of patients with treatment intensification was 45.4% (95% CI: 44.2-46.5), of which 34.6% occurred only after one year. Younger adults, overweight, obesity, use of antiplatelet medications and poorer HbA1c were positively associated with treatment intensification. Patients treated with more oral antidiabetics were less likely to have treatment intensification.

    CONCLUSION: Clinical inertia is present in the management of T2D patients in Malaysian public health clinics. We recommend further studies in lower- and middle-income countries to explore its causes so that targeted strategies can be developed to address this issue.

    Matched MeSH terms: Drug Therapy, Combination
  20. 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
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