GAMBARAN KLINIS SINDROM KORONER AKUT BERDASARKAN STATUS GULA DARAH DI RSUD Dr. SOETOMO SURABAYA

Sindrom Koroner Akut (SKA) merupakan penyebab utama morbiditas dan mortalitas di dunia, termasuk Indonesia. SKA merupakan kumpulan gejala akibat iskemia miokardium karena terdapat penyumbatan pada arteri koronaria. Penyumbatan tersebut sebagian besar disebabkan oleh terbentuknya plak aterosklerosis. Salah satu faktor risiko terbentuknya plak aterosklerosis adalah gangguan metabolisme glukosa. Di sisi lain, gangguan metabolisme glukosa dapat terjadi pada penyakit akut dan kritis, sindroma koroner akut adalah salah satu dari antaranya. Tujuan penelitian ini adalah untuk mengetahui karakteristik penderita SKA berdasarkan kadar gula darah acak ketika masuk rumah sakit RSUD Dr. Soetomo Surabaya. Penelitian ini menggunakan data rekam medis penderita SKA yang masuk rumah sakit pada periode Januari - Desember 2013 di Intensive Cardiac Care Unit (ICCU) RSUD Dr. Soetomo Surabaya. Metode sampling yang digunakan adalah total sampling, dimana jumlah sampel yang diperoleh yaitu 62 sampel. Data yang diperoleh kemudian dianalisis dengan metode statistik deskriptif. Dari penelitian dapat disimpulkan bahwa 72,6% penderita SKA mengalami hiperglikemia. Hiperglikemia terjadi pada penderita berjenis kelamin laki-laki dan berusia lebih dari 55 tahun. Gejala nyeri dada spesifik lebih banyak dikeluhkan pada penderita hiperglikemik (66,7%) daripada normoglikemia (47,1%). Diagnosa akhir ST-Elevation Myocardium Infarction (STEMI) lebih banyak daripada Non ST-Elevation Myocardium Infarction (NSTEMI) baik pada hiperglikemia (97,8% banding 2,2%) maupun normoglikemia (82,4% banding 17,6%). Riwayat penyakit diabetes mellitus tipe 2 lebih banyak didapatkan pada penderita SKA dengan hiperglikemik (53,3%) daripada normoglikemia (11,8%). Komplikasi ketika perawatan lebih banyak terjadi pada penderita SKA dengan hiperglikemia (1,2 komplikasi/penderita) daripada normoglikemia (1,17 komplikasi/penderita), dengan komplikasi organ jantung yang paling banyak terjadi, yaitu 64,4% pada hiperglikemia dan 58,8% pada normoglikemia. Lama rawat penderita SKA dengan hiperglikemia lebih lama daripada normoglikemia (7,81 ± 2,71 hari banding 6,67 ± 1,03 hari). Penderita SKA dengan hiperglikemia lebih banyak yang meninggal daripada penderita SKA normoglikemia

Survey Among Medical Students During COVID-19 Lockdown: The Online Class Dilemma

Background: In view of COVID-19 lockdown in India, many colleges started online classes. This study aimed to evaluate the attitudes of, and the factors affecting, medical students attending online classes during lockdown. Methods: We designed an online questionnaire with open-ended, close-ended, and Likert scale questions. Links to the questionnaires were shared with the medical students who have attended at least one online class during the COVID-19 lockdown period. Respondents were 1061 participants from 30 medical colleges from the states of Kerala and Tamil Nadu in India. Results: The majority of students – 94% (955/1016) – used smartphones to attend online classes. ZOOM/ Skype – by 57.1% (580/1016) – and Google platforms – by 54.4% (553/1016) – were commonly used. Learning at leisure – 44.5% (452/1016) – was the top reason why students liked online classes, whereas network problems – 85.8% (872/1016) – was the top reason why students disliked them. Lack of sufficient interaction – 61.1% (621/1016) was another reason why students disliked online learning. More than half the participants – 51.7% (526/1016) – did not want to continue online classes after COVID-19 lockdown. More students – 55% (558/1016) – favored regular classes than online classes. Conclusion: Students in our survey did not seem favorably disposed to online classes. Network problems experienced by students should be addressed. Furthermore, teachers should try to make the classes more interactive and educational institutions should address the problems pointed out by the students in order to make online classes more effective in the future

Fragment-based discovery of a new class of inhibitors targeting mycobacterial tRNA modification.

Translational frameshift errors are often deleterious to the synthesis of functional proteins and could therefore be promoted therapeutically to kill bacteria. TrmD (tRNA-(N(1)G37) methyltransferase) is an essential tRNA modification enzyme in bacteria that prevents +1 errors in the reading frame during protein translation and represents an attractive potential target for the development of new antibiotics. Here, we describe the application of a structure-guided fragment-based drug discovery approach to the design of a new class of inhibitors against TrmD in Mycobacterium abscessus. Fragment library screening, followed by structure-guided chemical elaboration of hits, led to the rapid development of drug-like molecules with potent in vitro TrmD inhibitory activity. Several of these compounds exhibit activity against planktonic M. abscessus and M. tuberculosis as well as against intracellular M. abscessus and M. leprae, indicating their potential as the basis for a novel class of broad-spectrum mycobacterial drugs

Mycobacterial genomics and structural bioinformatics: opportunities and challenges in drug discovery.

Of the more than 190 distinct species of Mycobacterium genus, many are economically and clinically important pathogens of humans or animals. Among those mycobacteria that infect humans, three species namely Mycobacterium tuberculosis (causative agent of tuberculosis), Mycobacterium leprae (causative agent of leprosy) and Mycobacterium abscessus (causative agent of chronic pulmonary infections) pose concern to global public health. Although antibiotics have been successfully developed to combat each of these, the emergence of drug-resistant strains is an increasing challenge for treatment and drug discovery. Here we describe the impact of the rapid expansion of genome sequencing and genome/pathway annotations that have greatly improved the progress of structure-guided drug discovery. We focus on the applications of comparative genomics, metabolomics, evolutionary bioinformatics and structural proteomics to identify potential drug targets. The opportunities and challenges for the design of drugs for M. tuberculosis, M. leprae and M. abscessus to combat resistance are discussed

Conflicting Climate Change Frames in a Global Field of Media Discourse

Reducing global emissions will require a global cosmopolitan culture built from detailed attention to conflicting national climate change frames (interpretations) in media discourse. The authors analyze the global field of media climate change discourse using 17 diverse cases and 131 frames. They find four main conflicting dimensions of difference: validity of climate science, scale of ecological risk, scale of climate politics, and support for mitigation policy. These dimensions yield four clusters of cases producing a fractured global field. Positive values on the dimensions show modest association with emissions reductions. Data-mining media research is needed to determine trends in this global field.Peer reviewe

The SCIDOTS Project: Evidence of benefits of an integrated tobacco cessation intervention in tuberculosis care on treatment outcomes

<p>Abstract</p> <p>Background</p> <p>There is substantial evidence to support the association between tuberculosis (TB) and tobacco smoking and that the smoking-related immunological abnormalities in TB are reversible within six weeks of cessation. Therefore, connecting TB and tobacco cessation interventions may produce significant benefits and positively impact TB treatment outcomes. However, no study has extensively documented the evidence of benefits of such integration. SCIDOTS Project is a study from the context of a developing nation aimed to determine this.</p> <p>Methods</p> <p>An integrated TB-tobacco intervention was provided by trained TB directly observed therapy short-course (DOTS) providers at five chest clinics in Malaysia. The study was a prospective non-randomized controlled intervention using quasi-experimental design. Using Transtheoretical Model approach, 120 eligible participants who were current smokers at the time of TB diagnosis were assigned to either of two treatment groups: conventional TB DOTS plus smoking cessation intervention (integrated intervention or SCIDOTS group) or conventional TB DOTS alone (comparison or DOTS group). At baseline, newly diagnosed TB patients considering quitting smoking within the next 30 days were placed in the integrated intervention group, while those who were contemplating quitting were assigned to the comparison group. Eleven sessions of individualized cognitive behavioral therapy with or without nicotine replacement therapy were provided to each participant in the integrated intervention group. The impacts of the novel approach on biochemically validated smoking cessation and TB treatment outcomes were measured periodically as appropriate.</p> <p>Results</p> <p>A linear effect on both 7-day point prevalence abstinence and continuous abstinence was observed over time in the intervention group. At the end of 6 months, patients who received the integrated intervention had significantly higher rate of success in quitting smoking when compared with those who received the conventional TB treatment alone (77.5% vs. 8.7%; p < 0.001). Furthermore, at the end of TB treatment (6 months or later), there were significantly higher rates of treatment default (15.2% vs. 2.5%; p = 0.019) and treatment failure (6.5% vs. 0%; p = 0.019) in the DOTS group than in the SCIDOTS group.</p> <p>Conclusion</p> <p>This study provides evidence that connecting TB-tobacco treatment strategy is significant among TB patients who are smokers. The findings suggest that the integrated approach may be beneficial and confer advantages on short-term outcomes and possibly on future lung health of TB patients who quit smoking. This study may have important implications on health policy and clinical practice related to TB management among tobacco users.</p

Assessing Tuberculosis Case Fatality Ratio: A Meta-Analysis

Background: Recently, the tuberculosis (TB) Task Force Impact Measurement acknowledged the need to review the assumptions underlying the TB mortality estimates published annually by the World Health Organization (WHO). TB mortality is indirectly measured by multiplying estimated TB incidence with estimated case fatality ratio (CFR). We conducted a meta-analysis to estimate the TB case fatality ratio in TB patients having initiated TB treatment. Methods: We searched for eligible studies in the PubMed and Embase databases through March 4(th) 2011 and by reference listing of relevant review articles. Main analyses included the estimation of the pooled percentages of: a) TB patients dying due to TB after having initiated TB treatment and b) TB patients dying during TB treatment. Pooled percentages were estimated using random effects regression models on the combined patient population from all studies. Main Results: We identified 69 relevant studies of which 22 provided data on mortality due to TB and 59 provided data on mortality during TB treatment. Among HIV infected persons the pooled percentage of TB patients dying due to TB was 9.2% (95% Confidence Interval (CI): 3.7%-14.7%) and among HIV uninfected persons 3.0% (95% CI: 21.2%-7.4%) based on the results of eight and three studies respectively providing data for this analyses. The pooled percentage of TB patients dying during TB treatment was 18.8% (95% CI: 14.8%-22.8%) among HIV infected patients and 3.5% (95% CI: 2.0%-4.92%) among HIV uninfected patients based on the results of 27 and 19 studies respectively. Conclusion: The results of the literature review are useful in generating prior distributions of CFR in countries with vital registration systems and have contributed towards revised estimates of TB mortality This literature review did not provide us with all data needed for a valid estimation of TB CFR in TB patients initiating TB treatmen

CYP2C19 Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention in Diverse Clinical Settings.

Background Studies have demonstrated increased risk of major atherothrombotic events in CYP2C19 loss-of-function (LOF) variant carriers versus non-carriers treated with clopidogrel after percutaneous coronary intervention (PCI). We sought to evaluate real-world outcomes with the clinical implementation of CYP2C19-guided antiplatelet therapy after PCI. Methods and Results Data from 9 medical centers where genotyping was performed in the setting of PCI were included. Alternative therapy with prasugrel or ticagrelor was recommended for patients with a CYP2C19 LOF variant. The primary outcome was the composite of major atherothrombotic events (all-cause death, myocardial infarction, ischemic stroke, stent thrombosis, or hospitalization for unstable angina) within 12 months following PCI. Moderate or severe/life-threatening bleeding within 12 months was a secondary outcome. Among 3342 patients, 1032 (31%) were LOF carriers, of whom 571/1032 (55%) were treated with alternative therapy. In LOF carriers, the rate of major atherothrombotic events was lower in patients treated with alternative therapy versus clopidogrel (adjusted HR, 0.56; 95% CI 0.39-0.82). In those without a LOF allele, no difference was observed (adjusted HR, 1.07; 95% CI 0.71-1.60). There was no difference in bleeding with alternative therapy versus clopidogrel in either LOF carriers or those without a LOF allele. Conclusions Real-world data demonstrate lower atherothrombotic risk in CYP2C19 LOF carriers treated with alternative therapy versus clopidogrel and similar risk in those without a LOF allele treated with clopidogrel or alternative therapy. These data suggest that PCI patients treated with clopidogrel should undergo genotyping so that CYP2C19 LOF carriers can be identified and treated with alternative therapy

Impact of the CYP2C19*17 Allele on Outcomes in Patients Receiving Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention.

Genotyping for CYP2C19 no function alleles to guide antiplatelet therapy after percutaneous coronary intervention (PCI) improves clinical outcomes. Although results for the increased function CYP2C19*17 allele are also reported, its clinical relevance in this setting remains unclear. A collaboration across nine sites examined antiplatelet therapy prescribing and clinical outcomes in 3,342 patients after implementation of CYP2C19-guided antiplatelet therapy. Risk of major atherothrombotic and bleeding events over 12 months after PCI were compared across cytochrome P450 2C19 isozyme (CYP2C19) metabolizer phenotype and antiplatelet therapy groups by proportional hazards regression. Clopidogrel was prescribed to a similar proportion of CYP2C19 normal (84.5%), rapid (82.9%), and ultrarapid metabolizers (80.6%) (P = 0.360). Clopidogrel-treated normal metabolizers (20.4 events/100 patient-years; adjusted hazard ratio (HR) 1.00, 95% confidence interval (CI), 0.75-1.33, P = 0.993) and clopidogrel-treated rapid or ultrarapid metabolizers (19.1 events/100 patient-years; adjusted HR 0.95, 95% CI, 0.69-1.30, P = 0.734) exhibited no difference in major atherothrombotic events compared with patients treated with prasugrel or ticagrelor (17.6 events/100 patient-years). In contrast, clopidogrel-treated intermediate and poor metabolizers exhibited significantly higher atherothrombotic event risk compared with prasugrel/ticagrelor-treated patients (adjusted HR 1.56, 95% CI, 1.12-2.16, P = 0.008). When comparing clopidogrel-treated rapid or ultrarapid metabolizers to normal metabolizers, no difference in atherothrombotic (adjusted HR 0.97, 95% CI, 0.73-1.29, P = 0.808) or bleeding events (adjusted HR 1.34, 95% CI, 0.83-2.17, P = 0.224) were observed. In a real-world setting of genotype-guided antiplatelet therapy, the CYP2C19*17 allele did not significantly impact post-PCI prescribing decisions or clinical outcomes. These results suggest the CYP2C19 *1/*17 and *17/*17 genotypes have limited clinical utility to guide antiplatelet therapy after PCI