Risks of Antidepressant induced psychotic events in patients with depression and psychosis

The aim of this ‘literature review’-based argumentative paper has been to find out the risks of developing psychotic and depressive disorders in patients having been treated with antidepressants. In order to reach a resounding supposition, this literature review-based argumentative study had taken an incisive look into previous research works and meta-analysis, which in effect had underscored the risks of antidepressant-induced psychotic and depressive disorders in patients with depression as well as psychosis even as the protagonists of antidepressant drug classes could not be undermined given their upscaled magnitude of benefits. While following a probing interpretation of past studies, this might be demystified that antidepressants could lead to psychotic events and depressive disorders in patients of all age groups with children and young adults being more susceptible to develop psychosis. The psychotic episodes could even be developed during initial phase of treatments in patients suffering from depressive and psychotic disorders such as bipolar mood disorder, unipolar depression, major depressive disorders, mania, OCD (Obsessive Compulsive Disorder), delusional depression (psychotic depression), schizophrenia, schizoaffective disorders alongside multiple somatic symptoms among others as well. Concomitantly, with efficaciousness of antidepressants in major depressive disorder still remaining a subject to utter dubitability, different antidepressant drug classes were found to be associated with a considerable scale of adverse effects after carrying out protracted arguments on findings of evidence-based past studies, meta-analysis of previous researches and relevant clinical cases. Therefore, following a systematized approach towards past studies, this argumentative research has reached a coherent conclusion that antidepressants are likely to cause psychotic events and exaggeration of depressive disorders up to some extent in several cases. Hence, there is a stipulation of individual risk-benefit assessment and intricate history taking in patients being contemplated for antidepressant drugs alongside a close observation and follow-up in patients of all age groups after introducing antidepressant medications.

Utilization Rates of SGLT2 Inhibitors and GLP-1 Receptor Agonists and Their Facility-Level Variation Among Patients With Atherosclerotic Cardiovascular Disease and Type 2 Diabetes: Insights From the Department of Veterans Affairs

<i>Objective:</i> There is mounting evidence regarding the cardiovascular (CV) benefits of sodium-glucose cotransporter-2 inhibitors (SGLT2-Is) and glucagon like peptide-1 receptor agonists (GLP-1RAs) among patients with atherosclerotic cardiovascular disease (ASCVD) and type 2 diabetes (T2DM). There is paucity of data assessing real-world practice patterns for these drug classes. We aimed to assess utilization rates of these drug classes and facility-level variation in their utilization. <p> </p> <p><i>Research Design and Methods:</i> We used the nationwide Veterans Affairs (VA) healthcare system dataset from January 1, 2020 to December 31, 2020 and included patients with established ASCVD and T2DM. Among these patients, we assessed the use of SGLT2i and GLP-1RA and the facility-level variation in their utilization. Facility-level variation was computed using median rate ratios (MRR), a measure of likelihood that two random facilities differ in use of SGLT2i and GLP-1RA in patients with ASCVD and T2DM. </p> <p> </p> <p><i>Results:</i> Among 537,980 patients with ASCVD and T2DM across 130 VA facilities, 11.2% of patients received SGLT2i while 8.0% of patients received GLP-1RA. Patients receiving these cardioprotective glucose-lowering drug classes were on average younger and had a higher proportion of non-Hispanic Whites. Overall, median (10^th-90^th percentile) facility-level rates were 14.92% (9.31%-22.50%) for SGLT2i and 10.88% (4.44%-17.07%) for GLP-1RA. There was significant facility level variation among SGLT2-Is utilization - MRR_unadjusted (95% CI):1.41 (1.35-1.47) and MRR_adjusted (95% CI): 1.55 (1.46 – 1.63). Similar facility level variation was observed for utilization of GLP-1 RA – MRR_unadjusted (95% CI):1.34 (1.29-1.38) and MRR_adjusted(95% CI): 1.78 (1.65 – 1.90).</p> <p> </p> <p><i>Conclusions:</i> Overall utilization rates of SGLT2i and GLP-1RA among eligible patients are low with significantly higher residual facility-level variation in utilization of these drug classes. Our results suggest opportunities to optimize their use to prevent future adverse cardiovascular events among these patients. </p>

Utilization Rates of SGLT2 Inhibitors and GLP-1 Receptor Agonists and Their Facility-Level Variation Among Patients With Atherosclerotic Cardiovascular Disease and Type 2 Diabetes: Insights From the Department of Veterans Affairs

<i>Objective:</i> There is mounting evidence regarding the cardiovascular (CV) benefits of sodium-glucose cotransporter-2 inhibitors (SGLT2-Is) and glucagon like peptide-1 receptor agonists (GLP-1RAs) among patients with atherosclerotic cardiovascular disease (ASCVD) and type 2 diabetes (T2DM). There is paucity of data assessing real-world practice patterns for these drug classes. We aimed to assess utilization rates of these drug classes and facility-level variation in their utilization. <p> </p> <p><i>Research Design and Methods:</i> We used the nationwide Veterans Affairs (VA) healthcare system dataset from January 1, 2020 to December 31, 2020 and included patients with established ASCVD and T2DM. Among these patients, we assessed the use of SGLT2i and GLP-1RA and the facility-level variation in their utilization. Facility-level variation was computed using median rate ratios (MRR), a measure of likelihood that two random facilities differ in use of SGLT2i and GLP-1RA in patients with ASCVD and T2DM. </p> <p> </p> <p><i>Results:</i> Among 537,980 patients with ASCVD and T2DM across 130 VA facilities, 11.2% of patients received SGLT2i while 8.0% of patients received GLP-1RA. Patients receiving these cardioprotective glucose-lowering drug classes were on average younger and had a higher proportion of non-Hispanic Whites. Overall, median (10^th-90^th percentile) facility-level rates were 14.92% (9.31%-22.50%) for SGLT2i and 10.88% (4.44%-17.07%) for GLP-1RA. There was significant facility level variation among SGLT2-Is utilization - MRR_unadjusted (95% CI):1.41 (1.35-1.47) and MRR_adjusted (95% CI): 1.55 (1.46 – 1.63). Similar facility level variation was observed for utilization of GLP-1 RA – MRR_unadjusted (95% CI):1.34 (1.29-1.38) and MRR_adjusted(95% CI): 1.78 (1.65 – 1.90).</p> <p> </p> <p><i>Conclusions:</i> Overall utilization rates of SGLT2i and GLP-1RA among eligible patients are low with significantly higher residual facility-level variation in utilization of these drug classes. Our results suggest opportunities to optimize their use to prevent future adverse cardiovascular events among these patients. </p>

How I Treat Relapsed Multiple Myeloma

Despite recent advances multiple myeloma remains an incurable disease for most of the patients and initial remission will be followed by relapses requiring therapy. For many, there will be several remissions and relapses until resistance develops to all available therapies. With the introduction of several new agents, myeloma treatment has changed drastically and there are new options for the management of relapsed or refractory disease, including new drug classes with distinct mechanisms of action and cellular therapies. However, resistance to major drug classes used in first line remain the most critical factor for the choice of treatment at relapse. Continuous lenalidomide-based therapy is used extensively at first line and resistance to lenalidomide has become the key factor for the choice of salvage therapy. Daratumumab is increasingly used in first line and soon patients that relapse while on daratumumab will become a common challenge. Three-drug regimens are standard approach to manage relapsed disease. Adding drugs with new mechanisms of activity can improves outcomes and overcomes class resistance but, until now, while the biology is important, can offer only limited guidance for the choice of therapy.

Systematic analysis of drug-associated myocarditis reported in the World Health Organization pharmacovigilance database

While multiple pharmacological drugs have been associated with myocarditis, temporal trends and overall mortality have not been reported. Here we report the spectrum and main features of 5108 reports of drug-induced myocarditis, in a worldwide pharmacovigilance analysis, comprising more than 21 million individual-case-safety reports from 1967 to 2020. Significant association between myocarditis and a suspected drug is assessed using disproportionality analyses, which use Bayesian information component estimates. Overall, we identify 62 drugs associated with myocarditis, 41 of which are categorized into 5 main pharmacological classes: antipsychotics (n = 3108 reports), salicylates (n = 340), antineoplastic-cytotoxics (n = 190), antineoplastic-immunotherapies (n = 538), and vaccines (n = 790). Thirty-eight (61.3%) drugs were not previously reported associated with myocarditis. Antipsychotic was the first (1979) and most reported class (n = 3018). In 2019, the two most reported classes were antipsychotics (54.7%) and immunotherapies (29.5%). Time-to-onset between treatment start and myocarditis is 15 [interquartile range: 10; 23] days. Subsequent mortality is 10.3% and differs between drug classes with immunotherapies the highest, 32.5% and salicylates the lowest, 2.6%. These elements highlight the diversity of presentations of myocarditis depending on drug class, and show the emerging role of antineoplastic drugs in the field of drug-induced myocarditis.

Utilization Rates of SGLT2 Inhibitors and GLP-1 Receptor Agonists and Their Facility-Level Variation Among Patients With Atherosclerotic Cardiovascular Disease and Type 2 Diabetes: Insights From the Department of Veterans Affairs

OBJECTIVE There is mounting evidence regarding the cardiovascular benefits of sodium–glucose cotransporter 2 inhibitors (SGLT2-Is) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) among patients with atherosclerotic cardiovascular disease (ASCVD) and type 2 diabetes mellitus (T2DM). There is paucity of data assessing real-world practice patterns for these drug classes. We aimed to assess utilization rates of these drug classes and facility-level variation in their use. RESEARCH DESIGN AND METHODS We used the nationwide Veterans Affairs (VA) health care system data set from 1 January 2020 to 31 December 2020 and included patients with established ASCVD and T2DM. Among these patients, we assessed the use of SGLT2-I and GLP-1 RA and the facility-level variation in their use. Facility-level variation was computed using median rate ratios (MRR), a measure of likelihood that two random facilities differ in use of SGLT2i and GLP-1 RA in patients with ASCVD and T2DM. RESULTS Among 537,980 patients with ASCVD and T2DM across 130 VA facilities, 11.2% of patients received an SGLT2i while 8.0% of patients received a GLP-1 RA. Patients receiving these cardioprotective glucose-lowering drug classes were on average younger and had a higher proportion of non-Hispanic Whites. Overall, median (10th–90th percentile) facility-level rates were 14.92% (9.31–22.50) for SGLT2i and 10.88% (4.44–17.07) for GLP-1 RA. There was significant facility-level variation among SGLT2-Is use—MRRunadjusted: 1.41 (95% CI 1.35–1.47) and MRRadjusted: 1.55 (95% CI 1.46 –1.63). Similar facility-level variation was observed for use of GLP-1 RA—MRRunadjusted: 1.34 (95% CI 1.29–1.38) and MRRadjusted: 1.78 (95% CI1.65–1.90). CONCLUSIONS Overall utilization rates of SGLT2i and GLP-1 RA among eligible patients are low, with significantly higher residual facility-level variation in the use of these drug classes. Our results suggest opportunities to optimize their use to prevent future adverse cardiovascular events among these patients.

Duplication and overexpression of the genes encoding a beta 1,3-glucan synthase confer the intrinsic resistance to echinocandin in Mucor circinelloides

Procedures such as solid organ transplants and cancer treatments can leave many patients in an immunocompromised state resulting in an increased susceptibility to opportunistic diseases including fungal infections. Mucormycosis infections are continually emerging and pose a serious threat to immunocompromised patients. Currently there has been a sharp increase in mucormycosis cases as a secondary infection in patients battling SARS-CoV-2 infections. Mucorales fungi are notorious for presenting resistance to most antifungal drugs. The absence of effective means to treat these infections results in mortality rates approaching 100% in cases of disseminated infection. One of the most effective antifungal drug classes currently available are echinocandins. Echinocandins seem to be efficacious in treatment of many other fungal infections. Unfortunately, susceptibility testing has found that echinocandins have no to little effect on Mucorales. In this study, we found that the model Mucorales Mucor circinelloides genome carries three copies of the genes encoding for the echinocandin target protein β-(1,3)-D-glucan synthase (fksA, fksB, and fksC). Interestingly, we revealed that exposing M. circinelloides to micafungin significantly increased the expression of the fksA and fksB genes when compared to an untreated control. We further uncovered that the serine/threonine phosphatase calcineurin is responsible for the overexpression of fksA and fksB as deletion of calcineurin results in a decrease in expression of all three fks genes and a lower minimal inhibitory concentration (MIC) to micafungin. Taken together, this study demonstrates that the fks gene duplication and overexpression by calcineurin contribute to the intrinsic resistance to echinocandins in Mucor.

TRENDS IN PRESCRIPTION PATTERN IN MEDICAL INDIAN ICU AND IT’S IMPACT ON PATIENT OUTCOME

Objective: The objective of this study is to evaluate the trends in prescribing pattern in medical ICU concerning patient age, gender, past, and current illness along with comorbidities for the evasion of polypharmacy and to improve patient outcomes. Methods: A prospective analysis of the case records of patients admitted to the ICU of Yashoda hospital in India was carried out. Results: 120 patients were evaluated, consisting of 77% male patients. The mean±SD of age is 53.81±14.63. The majority of the study subjects belonged to the age group of 50-67 y (32%) Most common causes for admission to the ICU were Respiratory diseases and Stroke. Diabetes mellitus and Hypertension are the most common co-morbidities identified. The total number of drugs used were 1502 during this study period. The average number of drugs per prescription is 12. The range is between 2-30. The average number of antibiotics per prescription is 3. Commonly prescribed drug classes were the GI agents in 100% of patients, followed by antimicrobial agents (AMAs) in 95.8% of patients. About 42.5% of patients received 3 antibiotics per day. 55 potential drug-drug interactions were interpreted in 46 patients. 30(55%) were moderate interactions 25(45%) were major interactions, which were addressed. De-escalation of antibiotics was seen in 29% of patients while escalation in 13%. The death rate is only 5% in our ICU setting. Conclusion: This prescription pattern study can provide a framework for continuous prescription audit in the ICU

ESBL plasmids in Klebsiella pneumoniae: diversity, transmission, and contribution to infection burden in the hospital setting

Background Resistance to third-generation cephalosporins, often mediated by extended–spectrum beta–lactamases (ESBLs), is a considerable issue in hospital-associated infections as few drugs remain for treatment. ESBL genes are often located on large plasmids that transfer horizontally between strains and species of Enterobacteriaceae and frequently confer resistance to additional drug classes. While plasmid transmission is recognised to occur in the hospital setting, the frequency and impact of plasmid transmission on infection burden, compared to ESBL+ strain transmission, is not well understood. Methods We sequenced the genomes of clinical and carriage isolates of Klebsiella pneumoniae species complex from a year long hospital surveillance study to investigate ESBL burden and plasmid transmission in an Australian hospital. Long term persistence of a key transmitted ESBL+ plasmid was investigated via sequencing of ceftriaxone resistant isolates during four years of follow–up, beginning three years after the initial study. Results We found 25 distinct ESBL plasmids. One (Plasmid A, carrying blaCTX–M–15 in an IncF backbone similar to pKPN–307) was transmitted at least four times into different Klebsiella species/lineages and was responsible for half of all ESBL episodes during the initial one-year study period. Three of the Plasmid A–positive strains persisted locally 3–6 years later, and Plasmid A was detected in two additional strain backgrounds. Overall Plasmid A accounted for 21% of ESBL+ infections in the follow–up period. Conclusions Whilst ESBL plasmid transmission events were rare in this setting, they had a significant and sustained impact on the burden of ceftriaxone resistant and multidrug resistant infections.