Antidepressant Use During Pregnancy

There are no studies that have shown any antidepressant to be absolutely safe for use during any stage of pregnancy. The use of selective serotonin reuptake inhibitors (SSRIs) or tricyclic antidepressants (TCAs) during pregnancy does not increase the risk of congenital malformations or miscarriage. (Strength of Recommendation [SOR]: B, based on limited-quality, patient-oriented evidence.) The use of SSRIs or TCAs during pregnancy may increase the risk of preterm birth, low birth weight, respiratory distress, and neonatal convulsions, without obvious subsequent adverse neurodevelopmental outcomes. (SOR: B, based on limited-quality, patient-oriented evidence.

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

Micronuclei and chromosomal aberrations in healthy tobacco chewers and controls: A study from Gujarat, India

Background: Tobacco chewing is attributed to oral cancer. Prediction of cancer development by genotoxicity analysis is a major challenge to identify tobacco users at greater risk. Therefore, present study aimed to analyze tobacco related genotoxic effects in chewers monitoring micronuclei (MN) and chromosome aberrations (CA). The biomarkers were compared with non chewer to (i) predict risk for genotoxicity, (ii) estimate synergistic effect of tobacco exposure with level of biomarkers, and (iii) identify best cellular site of measurements for genotoxicity assessment. Methods: Healthy tobacco chewers (n=47); and controls (n=48) were enrolled in the study. The peripheral blood lymphocyte and exfoliated buccal mucosa cells were studied for CA and micro nucleated cell count (MNC) respectively. An arbitrary unit was obtained for Lifetime Tobacco Exposure (LTE) using frequency/day multiplied by duration of years of tobacco use. Data were analyzed using SPSS statistical software. Results: MNC was significantly higher (p=0.001) in chewers than controls. CA was higher in chewers than controls. MNC can differentiate higher tobacco exposure in chewers than CA. Controls having MNC above cutoff level have greater risk of genotoxic exposition (95% C.I.; 1.462-23.26, p=0.012). Conclusion: The present study concludes that MNC is a better surrogate biomarker to predict genotoxicity than CA for tobacco exposure and DNA damage index in tobacco chewers

Detection of derivative 9 deletion by BCR-ABL fluorescence in-situ hybridization signal pattern to evaluate treatment response in CML patients

Background: To evaluate prognostic effect of submicroscopic deletions involving breakage and fusion points of the derivative chromosome 9 and 22 in chronic myeloid leukemia in untreated patients and their follow up samples to correlate with disease outcome. Methods: The study included 78 pretreatment (PT) samples from CML patients and 90 follow-up samples, classified as complete responders (CR, n=33), nonresponders (NR, n =54), and partial responder (PR, n=3) depending on the treatment status of the follow-up samples. Karyotype analysis was performed on metaphases obtained through short term cultures of bone marrow and blood. Detection of BCR-ABL fusion gene was performed using dual color dual fusion (D-FISH) translocation probes. Results: BCR-ABL fusion gene detection by D-FISH showed ABL-BCR deletion on derivative 9 in 47.8% of nonresponders which was higher as compared to pretreatment (11%). Mix D-FISH signal pattern was found in around 20% of pretreatment and non-responder samples. Average interval from chronic phase to blast crisis and accelerated phase was respectively 3.5 and 18 months and accelerated to blast crisis was 16.5 months from the time of diagnosis. The follow-up duration of 31 patients responded to therapy was significantly higher (p=0.0001) as compared to 45 patients who did not respond to therapy. Variant D-FISH signal pattern was seen at the time of diagnosis in patient who responded to therapy as well as those patients who did not respond to therapy. Conclusion: This is the first study from India reporting deletion in ABL, BCR, or ABL-BCR on derivative 9 did not correlate with response to therapy