Higher Risk Of Adverse Events Research Articles

Efficacy of Duloxetine With Arthrocentesis in the Management of TMJ Internal Derangement.

Temporomandibular joint (TMJ) arthrocentesis is one of the most commonly used non-invasive surgical interventions in the treatment of refractory pain and dysfunction associated with internal derangement. Several adjunctive therapies have been used in combination with arthrocentesis in an attempt to increase its efficacy and long-term maintenance. Duloxetine is a selective serotonin and norepinephrine reuptake inhibitor which is used in different chronic pain conditions. This study aimed to assess the efficacy of duloxetine in combination with arthrocentesis compared with arthrocentesis alone. Twenty-eight patients with chronic TMJ pain were included and randomly allocated into 2 groups (control and study groups). The control group included patients who underwent TMJ arthrocentesis only, and the study group included patients who underwent arthrocentesis followed by giving duloxetine (30mg) orally twice daily for 3 months. Pain, maximum mouth opening, and level of anxiety and depression were assessed preoperatively and followed at regular intervals of 1 week, 1 month, 3 months, and 6 months postoperatively. Pain was significantly reduced in both groups at all postoperative intervals and was significantly lower in the study group than the control group at 6 months. Maximum mouth opening increased significantly in both groups, but the difference between them was not significant. Level of anxiety and depression was significantly decreased in both groups, with no statistically significant difference between them. The results of this study indicate that duloxetine in combination with arthrocentesis may provide effective and long-term pain control; however, its use is associated with a higher risk of adverse events.

Machine learning with electrocardiograms to optimize mortality risk stratification in patients with suspected acute coronary syndrome

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Heart, Lung, and Blood Institute (NHLBI) and National Center for Advancing Translational Sciences (NCATS). Background The importance of risk stratification in patients with suspected acute coronary syndrome (ACS) extends beyond diagnosis and immediate treatment. It influences the precision of care delivery and the allocation of resources to those at highest risk of adverse events. Purpose We sought to evaluate the prognostic value of electrocardiogram (ECG) feature-based machine learning models to risk-stratify long-term mortality in those with suspected ACS. Methods This was a multicenter prospective observational cohort study of consecutive, non-traumatic patients evaluated at the emergency department for suspected ACS. The derivation cohort included 4,015 patients from a University Medical Center (age 59±16 years, 47% women, 80% training with 10-fold cross-validation and 20% testing). Ascertainment of all-cause death was based on numerous data sources, including the Centers for Disease Control and Prevention’s National Death Index registry. We trained six machine learning methods for survival analysis using 73 morphological ECG features from presenting prehospital 10-second 12-lead ECGs. We used predicted risk scores in a variational Bayesian Gaussian mixture model to define three risk groups corresponding to low, moderate, and high-risk and compared the resulting classification performance against the HEART score. The external testing cohort included 3,095 patients from a University (age 59±15 years, 44% women). Results The mortality rate was 20.3% in the derivation cohort after an average follow-up period of 3.53 years (IQR 1.75 - 5.32). Extra Survival Trees outperformed other forecasting models during cross-validation. In the internal testing cohort, the derived risk groups were significantly predictive of survival (Kaplan-Meier log-rank test statistic = 121.14, p<0.001), outperforming the classification performance using the HEART score (Figure 1). Our machine learning-based risk stratification model detected >90% of death events missed by low-risk HEART score (Figure 2). Ruling-out the low-risk group, it achieved a negative predictive value of 93.4% with a sensitivity of 85.9% (compared to 89.0% and 75.0%, respectively, for the HEART score). This classification performance generalized well to our external testing cohort. Compared to those in the low-risk group, patients at moderate (OR = 3.62 [1.35-9.74]) and high (OR = 6.12 [2.38-15.75]) risk had significantly higher odds of 30-day cardiovascular death (n=109, 3.5%). Conclusions Using only features from the 10-second 12-lead ECG, we derived and externally validated a machine learning model that stratifies the mortality risk of patients during long-term follow up. This model outperformed current standard of care based on the HEART score. Future work should validate the potential of this decision-support tool in influencing treatment plans and resource allocation.Figure 1.Clustering performanceFigure 2.Sankey diagram

Predictors of Late Adverse Events in Patients with Surgically Treated Type I Aortic Dissection

Residual aortic dissection (AD) following DeBakey type I AD repair is associated with a high rate of adverse events that need additional intervention or surgery. This study aimed to identify clinical and early post-operative computed tomography (CT) imaging factors associated with adverse events in patients with type I AD after ascending aorta replacement. This single centre, retrospective cohort study included consecutive patients with type I AD who underwent ascending aorta replacement from January 2011 to December 2017 and post-operative CT within 3 months. The primary outcome was AD related adverse events, defined as AD related death and re-operation due to aortic aneurysm or impending rupture. The location and size of the primary intimal tears, aortic diameter, and false lumen status were evaluated. Regression analyses were performed to identify factors associated with AD related adverse events. A decision tree model was used to classify patients as high or low risk. Of 103 participants (55.43 ± 13.94 years; 49.5% males), 24 (23.3%) experienced AD related adverse events. In multivariable Cox regression analysis, connective tissue disease (hazard ratio [HR] 15.33; p < .001), maximum aortic diameter ≥ 40 mm (HR 4.90; p < .001), and multiple (three or more) intimal tears (HR 7.12; p < .001) were associated with AD related adverse events. The 3 year cumulative survival free from AD related events was lower in the high risk group with aortic diameter ≥ 40 mm and multiple intimal tears (41.7% vs. 90.9%; p < .001). Early post-operative CT findings indicating a maximum aortic diameter ≥ 40 mm and multiple intimal tears may predict a higher risk of adverse events. These findings suggest the need for careful monitoring and more vigilant management approaches in these cases.

Extraction of terminal ileal lipomas to cecum can facilitate endoscopic resection: A case series with video.

Large ileal lipomas over 2 cm can cause symptoms, that may require a resection. Due to the narrow lumen and thin walls of the ileum, endoscopic treatments can have a high risk of adverse events and require technical expertise, thus surgical resection is currently the mainstay of treatment. To overcome the technical challenges, we developed a novel method to endoscopically resect terminal ileal lipomas. The technique involves extracting the lesion into the cecum, which creates sufficient space to maneuver, and a better field of view. The lipoma is resected with endoscopic mucosal resection or endoscopic submucosal dissection. The appearance of the lipoma protruding out of the ileocecal valve resembles that of a tongue sticking out of the mouth, thus we named this the "tongue out technique". To assess the technical feasibility of this method, we retrospectively analyzed seven cases of terminal ileal lipoma that were endoscopically resected using the "tongue out technique" at NTT Medical Center Tokyo between January 2017 and October 2023. Technical success was 100% and en bloc resection was achieved in all cases. The median size was 31 (14-55) mm. Three cases were resected with endoscopic mucosal resection while endoscopic submucosal dissection was performed on the other four cases. There was one case of delayed post-endoscopic mucosal resection bleeding, which was caused by clip dislodgement. There were no perforations. No recurrence of the lipoma or associated symptoms have been observed. This new technique can allow more ileal lipomas to be treated with minimally invasive and organ-preserving endoscopic procedures.

Right heart strain in arrhythmogenic right ventricular cardiomyopathy: Implications for cardiovascular outcome.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by progressive myocardial dysfunction and associated with an increased risk of major cardiovascular events. To determine right heart strain (ventricular and atrial global longitudinal strain (RVGLS and RAGLS)) in patients with definite ARVC and its association with adverse events during follow-up. RVGLS and RAGLS were analysed in focused right heart apical views from 70 patients using TomTec ImageArena and association with a composite endpoint (sustained ventricular arrhythmia and cardiovascular death) was determined. Over a median follow-up duration of 4.9 years, 26 (37%) patients met the endpoint. RVGLS was significantly impaired in the event group (-11.5 [-13.3 - -10.2]%) versus the no-event group (-15.8 [-17.1 - -14.5]%, P < 0.001), and so was RAGLS (22.8 [21.4 - 27.4]% vs. 31.5 [25.1 - 39.6]%, respectively, P < 0.001). In Cox regression, RVGLS (HR 1.36, P < 0.001) and RAGLS (HR 0.92, P = 0.002) were associated with higher risk of adverse events. In multivariable Cox regression models, RVGLS and RAGLS remained independent of and were incremental to age, gender, and conventional RV parameters, and model fit was improved when RVGLS and RAGLS were applied together rather than alone. RVGLS and RAGLS are more impaired in patients with adverse events and associated with adverse events independent of age, gender, and conventional RV parameters. When RVGLS and RAGLS are applied together, prediction models are improved suggesting that right heart strain may form part of the echocardiographic routine protocol in patients with ARVC.

Opioid use and risks in liver transplant candidates and recipients.

Opioid use is extremely prevalent among cirrhosis and liver transplant (LT) patients, despite concerns regarding opioid-related risks in this population. While there are many theoretical risks of opioids in patients with hepatic dysfunction, there is limited evidence on the effect of opioid use on clinical outcomes in cirrhosis and pre- and post-LT patients specifically. As a result there is significant center-level variability in opioid-related practice and policies. The existing data-largely based on retrospective observational studies-does suggest that opioids are associated with increased health resource utilization pre- and post-LT, and that they may precipitate hepatic encephalopathy (HE) in patients with cirrhosis and increase risk of graft loss and death post-LT. The strongest predictor of opioid use post-LT is opioid use prior to transplant; thus, a focus on safe opioid use in the pre- and peri-transplant periods is essential for minimizing opioid-related harms. We describe three strategies to guide LT providers, including: 1) Improved characterization of pain, mental health symptoms, and opioid and polysubstance use; 2) Minimization of opioid prescriptions for those at highest risk of adverse events; and 3) Safe prescribing strategies for those who do use opioids and for management of opioid use disorder (OUD). Ultimately, our goal is to improve quality of life and transplant outcomes among cirrhosis and LT patients, particularly those living with concurrent pain, mental health, and substance use disorders.

Safety of subcutaneous immunotherapy with Novo-Helisen-Depot in the children: a retrospective analysis from a single center in Northern China.

Little is known about the safety of mite extract product Novo-Helisen Depot (NHD) as subcutaneous immunotherapy (SCIT) in the children with mite allergy especially immediate/late local reaction (LRs). We conducted a retrospective study analyzing the adverse events of the children undergoing subcutaneous immunotherapy with NHD. Adverse events included local and systemic adverse reactions (SRs) at the very early and late stage. The correlation of the basic characteristics, laboratory analysis results, LRs and SRs were analyzed. Two hundred and eighty-seven patients received at least 15 months of subcutaneous immunotherapy with NHD were included in the analysis. Skin-prick testing (SPT) results of D. pteronyssinus was associated with an increased risk of immediate LRs in build-up phase (OR = 1.53, 95% CI: 1.02, 2.37) and delayed LRs in maintenance phase (OR = 1.58, 95% CI: 1.05, 2.46), while SPT results of D. farinae was associated with an increased risk of SRs (OR = 3.22, 95% CI: 1.17, 10.00) and severe SRs (OR = 7.68, 95% CI: 1.13, 109.50). Serum IgE level of D. pteronyssinus was associated with an increased risk of SRs (OR = 1.01, 95% CI: 1.00, 1.03). Patients with both asthma and allergic rhinitis was associated with an increased risk of SR, and severe SRs (P < 0.05). NHD as SCIT is safe. The children with higher SPT level with D. farinae or D. pteronyssinus, higher serum IgE level of D. pteronyssinus, children with both asthma and allergic rhinitis, and the children with treatment interruption had higher risk of adverse events.

Patient-specific ascending aortic intervention criteria.

Ascending aortic aneurysms pose a different risk to each patient. We aim to provide personalized risk stratification for such patients based on sex, age, body surface area, and aneurysm location (root vs ascending). Root and ascending diameters, and adverse aortic events (dissection, rupture, death) of ascending thoracic aortic aneurysm patients were analyzed. Aortic diameter was placed in context vis-a-vis the normal distribution in the general population with similar sex, age, and BSA, by conversion to z scores. These were correlated of major adverse aortic events, producing risk curves with 'hinge points' of steep risk, constructed separately for the aortic root and mid ascending aorta. 1162 patients were included. Risk curves unveiled generalized thresholds of z = 4 for the aortic root, and z = 5 for the mid ascending aorta. These correspond to individualized thresholds of less than the standard criterion of 5.5 cm in the vast majority of patients. Indicative results include a 75 year-old typical male with 2.1 m2 body surface area, who was found to be at increased risk of adverse events if root diameter exceeds 5.15 cm, or mid ascending exceeds 5.27 cm. An automated calculator is presented which identifies patients at high risk of adverse events based on sex, age, height, weight, and root and ascending size. This analysis exploits a large sample of aneurysmal patients, demographic features of the general population, pre-dissection diameter, discrimination of root and supracoronary segments, and statistical tools to extract thresholds of increased risk tailor-made for each patient.

A practical guide to selecting and using new ulcerative colitis therapies.

Several new biologics (mirizikizumab) and small molecules (upadacitinib, ozanimod, etrasimod) are approved for the treatment of moderate-to-severe ulcerative colitis. To date, there are no head-to-head trials to guide positioning and use of these newer agents. From phase III clinical trials, in the biologic experienced patient, induction with ozanimod, etrasimod, and mirizikizumab had lower clinical remission rates, whereas upadacitinib's clinical remission rates remained similar. Indirect evidence using network meta-analysis suggests upadacitinib may be more efficacious than other advanced therapies for the treatment of ulcerative colitis in both the bio-naive and experienced patient. Upadacitinib was found to have the highest risk for adverse events. These newer agents add novel mechanisms of action to the expanding therapeutic armamentarium of advanced therapies to treat ulcerative colitis. Based on expert opinion and available data to date, we propose a practical guide on positioning of these new agents for the treatment of ulcerative colitis. In mild-to-moderate disease, one should consider using ozanimod or etrasimod as first-line agents. In moderate-to-severe disease, we favor using mirizikizumab as first-line agent. In patients who have failed an anti-tumor necrosis factor agent, upadacitinib or mirizikizumab should be considered using patient factors and safety to guide one's decision between these two agents.

Neonatal Outcomes of Early Term Versus Late-Term Births in a University Teaching Hospital in Lagos, Nigeria.

There is increasing evidence of an association between early term birth and adverse neonatal outcomes. However, there is a paucity of data on the true neonatal outcomes following term deliveries in lower-income countries, including Nigeria. This study compared the neonatal outcomes of early and late-term deliveries in a tertiary hospital in Lagos, Nigeria. This was a five-year retrospective cohort study of all term deliveries between January 2013 and December 2017. Data were obtained from the labour ward and neonatal ward admission registers and medical records of the hospital.Descriptive and inferential statistics were computed for all relevant data. Statistical significance was reported at a p-value < 0.05. Of the 1,001 deliveries reviewed and analysed for this study, 215 recorded adverse neonatal events, with a significantly higher proportion of these occurring in early term compared to late-term delivered pregnancies (75.8% versus 24.2%, p < 0.001).There was a statistically higher rate of NICU admission in early term neonates than in late-term neonates (14.3 versus 3.9%, p < 0.001). Respiratory complications were the most common adverse outcomes experienced by neonates in both groups. However, the early term neonates had a higher risk even when adjusted for sex, birth weight, and mode of delivery. Our study highlights the substantial impact of gestational age on neonatal outcomes, with early term neonates at a significantly higher risk of adverse events compared to late-term neonates. Strategies aimed at reducing the rates of elective early term induction of labour and caesarean deliveries may help minimize the occurrence of adverse neonatal outcomes in our setting.

Bispectral index monitoring for sedation in scheduled adult colonoscopy: A randomized controlled trial

BackgroundPatients should be closely monitored during procedures under sedation outside the operating room, but it is unclear which type of monitoring is best. We investigated the efficacy and safety of BIS monitoring vs conventional monitoring for sedation during colonoscopy. MethodsWe performed a double-blind clinical trial in 180 patients undergoing elective colonoscopy. Patients were randomized to 1) the BIS group or 2) a control group, in which sedation was monitored with a BIS monitor or the Ramsay Sedation Score, respectively. The primary outcome was the rate of sedation-induced adverse events in both groups. Secondary outcomes were the characteristics of patients who developed adverse events, and time during colonoscopy when these events occurred, propofol and remifentanil dosage, and patient satisfaction. ResultsUnivariate analysis showed fewer cardiopulmonary complications in the BIS group (41.11% vs 57.78% in controls; p = 0.02). Multivariate analysis found a significantly higher risk of adverse events in older patients (95% CI, 1.013–1.091; p = 0.0087) and in men (95% CI, 1.129–7.668; p = 0.0272). These events were observed at the hepatic flexure. No significant differences between propofol or remifentanil dosage, use of rescue medication, and patient satisfaction were observed between groups. ConclusionsOur data suggest that BIS monitoring during sedation in scheduled colonoscopies reduces adverse respiratory events. Although its routine use in sedation does not appear to be warranted, clinicians should take steps to identify patients with a higher risk of complications who might benefit from this type of monitoring.

Inappropriate Underdosing of Direct Oral Anticoagulants in Atrial Fibrillation Patients: Results from the START2-AF Registry.

Background: Direct oral anticoagulants (DOACs) are recommended for stroke prevention in non-valvular atrial fibrillation (NVAF) patients. We aimed to describe the prevalence of inappropriate DOACs dose prescription in the START2-AF Registry, the outcomes according to the appropriateness of the dosage, and the factors associated with inappropriate dose prescription. Methods: Patients' demographics and clinical data were prospectively collected as electronic files in an anonymous form on the website of the START2-Registry; DOACs dosage was determined to be appropriate when prescribed according to the European Heart Rhythm Association Guidelines. Results: We included 5943 NVAF patients on DOACs; 2572 (46.3%) were female patients. The standard dose (SD) was prescribed to 56.9% of patients and the low dose (LD) was prescribed to 43.1% of patients; 38.9% of all NVAF patients received an inappropriate LD DOAC and 0.3% received inappropriate SD. Patients treated with LD DOAC had a significantly higher rate of all bleedings (RR 1.5; 95% CI 1.2-2.0), major bleedings (RR 1.8; 95% CI 1.3-1.7), and mortality (RR 2.8; 95% CI 1.9-4.1) with respect to patients treated with SD DOAC. No difference was found among patients treated with appropriate and inappropriate LD regarding bleeding, thrombotic, and mortality rates. Age, body weight <60 kg, and renal failure were significantly associated with inappropriate LD DOAC prescription. Conclusions: Inappropriate LD DOACs in NVAF patients is not associated with a reduction in bleeding risk, nor with an increased thrombotic risk. Instead, it is associated with higher mortality rate, suggesting that, in clinical practice, underdosing is preferred for patients at particularly high risk for adverse events.

Treatment Efficacy of Plasmapheresis Versus Intravenous Immunoglobulin in Guillain-Barré Syndrome Management: A Systematic Review.

Guillain-Barré syndrome (GBS) is a rare and debilitating autoimmune disorder that affects the peripheral nervous system. Although the exact etiology of GBS is still unknown, it is thought to be triggered by a preceding gastrointestinal infection in most of the cases. Clinical manifestations include limb weakness, areflexia, and sensory loss that can further progress to neuromuscular paralysis affecting the respiratory, facial, and bulbar functions. Both plasmapheresis (PE) and intravenous immunoglobulin (IVIG) have shown effectiveness in the treatment of GBS, but it is still unclear which treatment approach is superior in terms of therapeutic efficacy. This systematic review acts per Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 guidelines. For appropriate studies and research, we searched PubMed, PubMed Central (PMC), Medical Literature Analysis and Retrieval System Online (MEDLINE), Science Direct, and Google Scholar. Screening of articles was performed based on relevance and inclusion and exclusion criteria. To check for bias, we used relevant quality appraisal tools. Initially, we found 2454 articles. After removing duplicates and irrelevant papers, we finalized 31 studies based on titles, abstracts, and reading entire articles. We excluded 14 studies because of poor quality; the remaining 17 papers were included in this review. IVIG is equally efficacious as PE in improving primary outcomes and secondary outcomes. IVIG showed a slight advantage over PE in reducing the need for mechanical ventilation (MV) and hospital stay duration. However, in children, PE demonstrated a slight edge in improving secondary outcomes. PE was associated with a slightly higher risk of adverse events and post-treatment worsening symptoms compared to IVIG. IVIG is considered more user-friendly with a significantly lower patient discontinuation rate than PE. IVIG treatment was found to be significantly more expensive than PE.

Intraoperative Hemodynamic Instability and Higher ASA Classification Increase the Risk of Developing Non-Surgical Complications following Orthopedic Surgeries.

(1) Background: Either pre-operative physical status or unstable hemodynamic changes has been reported to play a potential role in causing vital organ dysfunction. Therefore, we intended to investigate the impact of the American Society of Anesthesiologist (ASA) classification and intraoperative hemodynamic instability on non-surgical complications following orthopedic surgery. (2) Methods: We collected data on 6478 patients, with a mean age of 57.3 ± 16, who underwent orthopedic surgeries between 2018 and 2020. The ASA classification and hemodynamic data were obtained from an anesthesia database. Non-surgical complications were defined as a dysfunction of the vital organs. (3) Results: ASA III/IV caused significantly higher odds ratios (OR) of 17.49 and 40.96, respectively, than ASA I for developing non-surgical complications (p < 0.001). Non-surgical complications were correlated with a 20% reduction in systolic blood pressure (SBP), which was intraoperatively compared to the pre-operative baseline ((OR) = 1.38, p = 0.02). The risk of postoperative complications increased with longer durations of SBP < 100 mmHg, peaking at over 20 min ((OR) = 1.33, p = 0.34). (4) Conclusions: Extended intraoperative hypotension and ASA III/IV caused a significantly higher risk of adverse events occurring within the major organs. The maintenance of hemodynamic stability prevents non-surgical complications after orthopedic surgeries.

CAR T cells and T cells phenotype and function are impacted by glucocorticoid exposure with different magnitude.

Chimeric antigen receptor (CAR) T cell therapy is associated with high risk of adverse events. Glucocorticoids (GCs) are cornerstone in the management of high-grade cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Given the potentially deleterious effects of GCs on CAR T cells anti-tumor activity, increasing our understanding of GCs impact on CAR T cells is crucial. Using several CAR T cells i.e., CD19, mesothelin (MSLN)-CD28 and MSLN-41BB CAR T cells (M28z and MBBz), we compared phenotypical, functional, changes and anti-tumor activity between i) transduced CD19 CAR T cells with untransduced T cells, ii) M28z with MBBz CAR T cells induced by Dexamethasone (Dx) or Methylprednisolone (MP) exposures. Higher levels of GC receptor were found in less differentiated CAR T cells. Overall, Dx and MP showed a similar impact on CAR T cells. Compared to untreated condition, GCs exposure increased the expression of PD-1 and TIM-3 and reduced the expression of LAG3 and function of T cells and CAR T cells. GC exposures induced more exhausted (LAG3 + PD1 + TIM3 +) and dysfunctional (CD107a-INFγ-TNF-IL2-) untransduced T cells in comparison to CD19 CAR T cells. GC exposure impaired more CD4 + than CD8 + CD19 CAR T cells. GC exposures increased more PD-1 expression associated with reduced proliferative capacity and function of M28z as compared to MBBz CAR T cells. CAR T cells anti-tumor activity was greatly affected by repeated GC exposure but partly recovered within 48h after GCs withdrawal. In summary, GCs impacted phenotype and function of untransduced and CAR T cell with different magnitude. The nature of the CAR costimulatory domain influenced the magnitude of CAR T cell response to GCs.

(259) Comparison of Dapoxetine vs Paroxetine vs Clomipramine for Premature Ejaculation Patients

Abstract Introduction Premature ejaculation (PE) is a common male sexual dysfunction. The International Society for Sexual Medicine (ISSM) defines PE as the inability to delay ejaculation during all or nearly all vaginal penetrations with latency time before or within 1 minute of penetration for lifelong PE and within 3 minutes for acquired PE and negative personal consequences such as distress, bother, frustration. The introduction of Selective Serotonin reuptake inhibitors (SSRIs) and Tricyclic antidepressants (TCA) revolutionized the treatment of PE. However not many studies have compared the efficacy and safety of these drugs in a single study. Objective To compare the clinical efficacy and safety of Dapoxetine, Paroxetine, and Clomipramine for the oral pharmacotherapy of PE. Methods Men presenting with self-reported PE were evaluated with full medical/sexual history, comorbidities, focused physical examination, assessment for Erectile function, any investigations suggested by these findings. IELT was determined by stopwatch method for every intercourse attempt. IELT were recorded before and after using the above medications in each group. ISSM definition of PE formed basis of diagnosis. All patients were married potent men in a stable relationship for at least 6 months and possible sexual intercourse equal or greater than one per week. None of the patients had received other treatment for PE for at least 4 weeks before the start of the study. All subjects gave their written informed consent before entering the study. Standardized assessment measures such as validated questionnaires &amp; Patient Reported Outcomes (PRO) used as adjunct for assessment. Results 48 Patients with PE were recruited in this study. Patients were randomly assigned to receive 60 mg Dapoxetine ‘on-demand’(group 1, n = 24), or 20 mg Paroxetine daily (group 2, n = 12) or 50 mg Clomipramine (group 3, n = 12) orally daily during a 12-week period for each agent. After 12 weeks of treatment with Dapoxetine, Paroxetine and Clomipramine, the IELT was increased from the pretreatment mean of 35 seconds to 184 seconds, from 32 seconds to 178 seconds and from 34 seconds to 169 seconds, respectively (P = 0.01 in group 1 and 2,P = 0.02 in group 3). Baseline and 12-week mean intercourse satisfaction domain values of the IIEF were 10, 11, 10 and 14, 15, 13 in groups 1, 2, and 3 respectively. The mean number of coitus per week pretreatment and at 12-week treatment were 1.4, 1.3 and 1.3/week which rose to 2.4, 2.3 and 2.2 for Dapoxetine, Paroxetine and Clomipramine, respectively. The most common adverse effects of each drug were nausea, diarrhea, headache and perspiration. Conclusions Oral SSRIs &amp; TCA are safe and effective treatments for PE. Dapoxetine, although approved, does Not appear to be widely used; cost could be an issue. Its use can result in better QoL for the patient and their sexual partner. Paroxetine has the advantage of improving IELT with well-tolerated side effects. It has good efficacy in the treatment of PE. Higher dose of Clomipramine results in a longer IELT without higher risk of adverse events. Larger studies with different dosages and treatment regimens are required to yield more credible outcomes. Disclosure No.

Opioids for Acute Musculoskeletal Pain: A Systematic Review with Meta-Analysis.

To evaluate the efficacy of opioids for people with acute musculoskeletal pain against placebo. Systematic review and meta-analyses of randomised, placebo-controlled trials of opioid analgesics for acute musculoskeletal pain in any setting. The primary outcomes were pain and disability at the immediate timepoint (<24 h). Multiple databases were searched from their inception to February 22nd, 2023. Continuous outcomes were converted to a 0-100 scale. Dichotomous outcomes were presented as risk differences. Risk of bias and certainty of evidence was assessed. We located 17 trials (1 intravenous and 16 oral route of administration). For adults, high certainty evidence from 11 comparisons shows that oral opioids provide small benefits relative to placebo in the immediate term for pain (mean difference [MD] - 8.8 95% confidence interval [CI] -12.0 to -5.6). For disability, the difference is uncertain (MD -6.2, 95% CI -17.8 to 5.4). Opioid groups were at higher risk of adverse events (MD 14.3%, 95% CI 8.3-20.4%, very low certainty). There was moderate certainty evidence of a large effect of IV morphine on sciatica pain (MD -42.5, 95% CI -49.9 to -35.1, n = 197, 1 study). In paediatric populations, moderate certainty evidence from 3 trials shows that oral opioids probably do not provide benefit beyond that of placebo for pain (MD 6.1, 95% CI -1.7 to 12.8) and there was no evidence for disability. There was low certainty evidence that there may be no difference in adverse events (MD 10.4%, 95% CI -0.6 to 21.4%). Intravenous morphine likely offers benefits, but oral opioids may not provide clinically meaningful benefits. CRD42021249346.

Usability of the 4Ms Worksheet in the Emergency Department for Older Patients: A Qualitative Study.

Older adults often have multiple comorbidities; therefore, they are at high risk for adverse events after discharge. The 4Ms framework-what matters, medications, mentation, mobility-has been used in acute and ambulatory care settings to identify risk factors for adverse events in older adults, although it has not been used in the emergency department (ED). We aimed to determine whether 1)use of the 4Ms worksheet would help emergency clinicians understand older adult patients' goals of care and 2)use of the worksheet was feasible in the ED. We conducted a qualitative, descriptive study among patients aged ≥60years and emergency clinicians from January-June 2022. Patients were asked to fill out a 4Ms worksheet; following this, semi-structured interviews were conducted with patients and clinicians separately. We analysed data to create codes, which were divided into categories and sub-categories. A total of 20 older patients and 19 emergency clinicians were interviewed. We identified two categories based on our aims: understanding patient goals of care (sub-categories: clinician/ patient concordance; understanding underlying goals of care; underlying goals of care discrepancy) and use of 4Ms Worksheet (sub-categories: worksheet to discussion discrepancy; challenges using worksheet; challenge completing worksheet before discharge). Rates of concordance between patient and clinician on main concern/goal of care and underlying goals of care were 82.4% and 15.4%, respectively. We found that most patients and emergency clinicians agreed on the main goal of care, although clinicians often failed to elicit patients' underlying goal(s) of care. Additionally, many patients preferred to have the interviewer fill out the worksheet for them. There was often discrepancy between what was written and what was discussed with the interviewer. More research is needed to determine the best way to integrate the 4Ms framework within emergency care.

Aortic Elasticity and Cardiovascular Risk Stratification: A Narrative Review on the Current Understanding

Cardiovascular risk stratification is a cornerstone of preventive cardiology, aiming to identify individuals at a higher risk for adverse events. In line with this, aortic elastic properties have gained recognition as crucial indicators of vascular health and predictors of cardiovascular outcomes. This narrative review delves into the significance of aortic stiffness, compliance, and distensibility in risk assessment, shedding light on their associations with cardiovascular diseases, such as hypertension, atherosclerosis, and coronary artery disease. This review aims to provide an overview of the current knowledge regarding aortic elastic properties and their role in cardiovascular risk stratification. The exploration of potential mechanisms and clinical implications outlines the need for further research to establish precise links between aortic elasticity and cardiovascular risk. Furthermore, the integration of advanced imaging, genetic factors, and personalized medicine is suggested to refine risk assessment strategies and enhance patient care. Ultimately, this review underscores the importance of aortic elastic properties in cardiovascular risk prediction, opening avenues for future research and clinical application.

Monitorización del índice biespectral para sedación en colonoscopias electivas de pacientes adultos: ensayo controlado aleatorizado

BackgroundPatients should be closely monitored during procedures under sedation outside the operating room, but it is unclear which type of monitoring is best. We investigated the efficacy and safety of BIS monitoring vs conventional monitoring for sedation during colonoscopy. MethodsWe performed a double-blind clinical trial in 180 patients undergoing elective colonoscopy. Patients were randomized to 1)the BIS group or 2)a control group, in which sedation was monitored with a BIS monitor or the Ramsay Sedation Score, respectively. The primary outcome was the rate of sedation-induced adverse events in both groups. Secondary outcomes were the characteristics of patients who developed adverse events, and duration of colonoscopy when these events occurred, propofol and remifentanil dosage, and patient satisfaction. ResultsUnivariate analysis showed fewer cardiopulmonary complications in the BIS group (41.11% vs 57.78% in controls; P=.02). Multivariate analysis found a significantly higher risk of adverse events in older patients (95%CI: 1.013-1.091; P=.0087) and in men (95%CI: 1.129-7.668; P=.0272). These events were observed at the hepatic flexure. No significant differences between propofol or remifentanil dosage, use of rescue medication, and patient satisfaction were observed between groups. ConclusionsOur data suggest that BIS monitoring during sedation in scheduled colonoscopies reduces adverse respiratory events. Although its routine use in sedation does not appear to be warranted, clinicians should take steps to identify patients with a higher risk of complications who might benefit from this type of monitoring.