Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Persistent organic pollutants and the incidence of type 2 diabetes in the CARLA and KORA cohort studies

Background: Associations between several persistent organic pollutants (POPs) and type 2 diabetes have been found in humans, but the relationship has rarely been investigated in the general population. The current nested case-control study examined internal exposure to polychlorinated biphenyls (PCB) and pesticides and the incidence of type 2 diabetes among participants of two population-based German cohort studies.Methods: We retrospectively selected 132 incident cases of type 2 diabetes and 264 age- and sex-matched controls from the CARdiovascular Living and Aging in Halle (CARLA) study (2002-2006, East Germany) and the Cooperative Health Research in the Region of Augsburg (KORA) study (1999-2001, South Germany) based on diabetes status at follow-up examinations in 2007-2010 and 2006-08, respectively (60% male, mean age 63 and 54 years). We assessed the association between baseline POP concentrations and incident diabetes by conditional logistic regression adjusted for cohort, BMI, cholesterol, alcohol, smoking, physical activity, and parental diabetes. Additionally, we examined effect modification by sex, obesity, parental diabetes and cohort.Results: In both cohorts, diabetes cases showed a higher BMI, a higher frequency of parental diabetes, and higher levels of POPs. We observed an increased chance for incident diabetes for PCB-138 and PCB-153 with an odds ratio (OR) of 1.50 (95%CI: 1.07-2.11) and 1.53 (1.15-2.04) per interquartile range increase in the respective POP. In addition, explorative results suggested higher OR for women and non-obese participants.Conclusions: Our results add to the evidence on diabetogenic effects of POPs in the general population, and warrant both policies to prevent human exposure to POPs and additional research on the adverse effects of more complex chemical mixtures

Neuropathic pain is not adequately treated in the older general population: results from the KORA F4 survey

Purpose: We evaluated the pharmacological treatment of distal sensorimotor polyneuropathy (DSPN) among older subjects from the general population. Methods: The study included subjects aged 61 to 82 years from the KORA F4 survey (2006-2008). DSPN was defined as the presence of bilaterally impaired foot-vibration perception and/or bilaterally impaired foot-pressure sensation. Pain intensity was assessed with the painDETECT questionnaire. Results: From the included 1076 older persons, 172 (16%) persons reported pain in the lower extremities and DSPN was present in 150 (14%) subjects. Forty-eight people with pain in the lower extremities reported DSPN. Only 38% of the subjects with DSPN reporting an average pain level of ≥4 during the past 4 weeks received medical treatment, predominantly nonsteroidal anti-inflammatory drugs (NSAIDs 20% and opioids 12%). The medication of choice for neuropathic pain, antidepressants, anticonvulsants, and opioids was relatively being underused. However, opioids and neuropathy preparations were prescribed preferably for subjects with painful DSPN. Conclusions: In the older general population, only a small proportion of subjects with painful DSPN receive analgesic pharmacotherapy. Although not recommended by guidelines for the treatment of neuropathic pain, NSAIDs were the most frequently used class of analgesic drugs

HURUF AL JAR FI QISHAH ANA AL MAUT AL QASIRAH LI TAUFIQ AL HAKIM : DIRASAH TAHLILIYAH NAHWIYAH

Dalam tata bahasa Arab, kata (kalimat dalam bahasa Arab) sebagai satuan terkecil bahasa, sebagaimana dalam bahasa yang lain dapat dikelompokkan menjadi tiga macam; pertama isim, fi’il dan huruf. Yang kemudian dapat lebih mudah untuk dipelajari namun, penulis dalam hal ini hanya akan sedikit membahas bagian yang terakhir yang berkaitan dengan huruf khusunya huruf jer. Pembahasan dalam skripsi ini mengkaji tentang Huruf Jer dalam cerpen “Akulah Kematian” karya Taufiq Hakim, dengan pendekatan ilmu Nahwu. Masalah yang dikemukakan dalam rumusan masalah ini meliputi dua hal yaitu; huruf jer apa saja yang terdapat dalam cerpen “Akulah Kematian” karya Taufiq Hakim dan apa saja makna huruf jer yang terdapat dalam cerpen “Akulah Kematian” karya Taufiq Hakim. Dalam pembahasan skripsi ini peneliti menggunakan ilmu nahwu sebagai pisau analisis dan ilmu kebahasaan sebagai pendekatannya. Peneliti mengambil beberapa teori nahwu dari buku-buku yang mudah dimengerti dalam penjelasannya seperti kitab Jamiud Durus. Adapun tujuan pembahasan ini adalah untuk mengungkap ilmu kebahasan yang terdapat dalam cerpen “Akulah Kematian” karya Taufiq Hakim, sedangkan metode penelitian yang dipakai adalah metode penelitian deskriptif kualitatif. Huruf Jer secara umum yang banyak dikemukakan oleh ahli nahwu berjumlah 20 huruf, sedangkan dalam cerpen “Akulah Kematian” karya Taufiq Hakim berjumlah 9 huruf yang terdiri dari (الباء، من، إلى، حتى، على، الكاف، عن، اللام، في) Adapun kesimpulan dalam penelitian ini bahwa di dalam cerpen “Akulah Kematian” terdapat 395 huruf jer, pertama: huruf jer berbentuk ba’ dengan makna ilshoq, mushohabah, as-sababiyyah wa at-ta’lil, at-ta’diyah, al-ist’la’, al-isti’anah, adz-dzhorfiyah, al-badal, al-‘iwadh. Harfu min dengan makna al-ibtida’ at-tab’iid, at-ta’kid, adz-dzorfiyah, dan makna ‘an. Harfu ila dengan makna al-intiha’, al-mushohabah, makna ‘inda. Huruf jer hatta dengan makna lil intiha’ ka ila. Huruf jer ‘an dengan makna almujawazah wal bu’du, makna min, dan makna ‘ala. Huruf jer ‘ala dengan makna al-isti’la’, makna min, makna ba’, makna ‘an, makna fi. Huruf jer fi dengan makna adz-dzorfiyah, al-muhohabah, al-isti’la’, dan makna ba. Huruf jer kaf dengan makna at-ta’lil, as-sababiyah, dan makna ‘ala. Huruf jer lam dengan makna al-isti’la’, al-milku, lamul-ikhtishah, as-sababiyah wat-ta’lil, sibhul-miku, dan taukid

Hazard Ratios (95% confidence intervals) for a future cardiovascular event¹ during follow-up in patients with the acute coronary syndrome, according to the number of chemokines (CCL3/MIP-1α, CCL5/RANTES and CCL18/PARC) in the highest tertile, Bad Nauheim ACS II registry.

<p>HR: hazard ratio; CI: confidence interval.</p>1<p>A cardiovascular event is defined as the occurrence of death, an acute myocardial infarction or an urgent revascularization procedure.</p>2<p>Adjusted for age, sex, diabetes, smoking, family history of cardiovascular disease and baseline levels of NT-proBNP, CK-MB and TnT.</p>3<p>All three chemokines concentrations in the lowest tertile.</p

Baseline characteristics and biomarker levels of the study population according to the occurrence of a cardiovascular event within six months of follow-up, Bad Nauheim ACS II registry.

<p>CVD: cardiovascular disease; AMI: acute myocardial infarction; TnT: Troponin T; CRP: C-Reactive Protein; NT-proBNP: N-terminal pro-Brain Natriuretic Peptide; CK-MB: Creatinine Kinase-MB; UAP: unstable angina pectoris; STEMI: ST-segment elevated myocardial infarction; NSTEMI: Non-ST-segment elevated myocardial infarction.</p>1<p>Presented as mean ± sd,</p>2<p>Presented as median (interquartile range),</p>3<p>Time of blood drawing since onset of symptoms,</p>4<p>based on values of 513 event free patients and 68 event patients,</p>5<p>based on values of 516 event free patients and 63 event patients,</p>6<p>based on values of 480 event free patients and 53 event patients.</p

Hazard Ratios (95% confidence intervals) for a fatal future cardiovascular event during follow-up in patients with the acute coronary syndrome, according to baseline levels of CCL3/MIP-1α, CCL5/RANTES and CCL18/PARC, Bad Nauheim ACS II registry.

<p>HR: hazard ratio; CI: confidence interval.</p>1<p>Tertile boundaries for CCL3/MIP-1α: 18.7–33.3 pg/ml, CCL5/RANTES: 16.2–134.15 ng/ml, CCL18/PARC: 43.0–70.9 ng/ml.</p>2<p>Adjusted for age, sex, diabetes, smoking, family history of cardiovascular disease and baseline levels of NT-proBNP, CK-MB and TnT.</p

Circulating Levels of Interleukin 1-Receptor Antagonist and Risk of Cardiovascular Disease: Meta-Analysis of Six Population-Based Cohorts

OBJECTIVE: Interleukin (IL)-1&beta; represents a key cytokine in the development of cardiovascular disease (CVD). IL-1&beta; is counter-regulated by IL-1 receptor antagonist (IL-1RA), an endogenous inhibitor. This study aimed to identify population-based studies on circulating IL-1RA and incident CVD in a systematic review, estimate the association between IL-1RA and incident CVD in a meta-analysis, and to test whether the association between IL-1RA and incident CVD is explained by other inflammation-related biomarkers in the MONICA/KORA Augsburg case-cohort study (Multinational Monitoring of Trends and Determinants in Cardiovascular Disease/Cooperative Health Research in the Region of Augsburg). APPROACH AND RESULTS: We performed a systematic literature search and identified 5 cohort studies on IL-1RA and incident CVD in addition to the MONICA/KORA Augsburg case-cohort study for a meta-analysis based on a total of 1855 CVD cases and 18 745 noncases with follow-up times between 5 and 16 years. The pooled standardized hazard ratio (95% confidence interval) for incident CVD was 1.11 (1.06-1.17) after adjustment for age, sex, anthropometric, metabolic, and lifestyle factors (P&lt;0.0001). There was no heterogeneity in effect sizes (I(2)=0%; P=0.88). More detailed analyses in the MONICA/KORA study showed that the excess risk for CVD was attenuated by &ge;10% after additional separate adjustment for serum levels of high-sensitivity C-reactive protein, IL-6, myeloperoxidase, soluble E-selectin, or soluble intercellular adhesion molecule-1. CONCLUSIONS: Serum IL-1RA levels were positively associated with risk of CVD after adjustment for multiple confounders in a meta-analysis of 6 population-based cohorts. This association may at least partially reflect a response to triggers inducing subclinical inflammation, oxidative stress, and endothelial activation