Periodisation Strategies: A Meta-Analysis Unravelling the Impact on Optimising Athletic Peak Performance.

The present study aimed to identify the impact of various periodisation approaches used in training athletes and to identify the effect size of the periodisation technique in improving athletes' peak performance before the main event. Inclusion criteria comprised recruitment of all those studies in which the effects of periodisation training were identified on athletes' peak performance. Various databases such as Google Scholar, Pedro, MEDLINE, Cochrane Library, EMBASE, and Web of Science were searched by independent reviewers using the MeSH terms including 'interval training', 'aerobic exercise', 'periodisation,' 'peak performance', and 'athletes'. A sample size of n = 121 participants included in six studies were analysed in which the effects of periodisation methods of training among athletes were estimated for improving their peak performance by assessing jump height and speed, pool effects in the form of random, and fixed effect model were provided to depict cumulative results of all the included studies. In achieving optimisation in athletes' peak performance, inculcating the concept of periodisation is a practical approach. While incorporating periodisation in training, models of training principles must be given ardent importance. Key Words: Exercise training, Sports, Athletes, Periodisation, Peak performance.

Drug repurposing: identification of SARS-CoV-2 potential inhibitors by virtual screening and pharmacokinetics strategies.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic caused global health, economic, and population loss. Variants of the coronavirus contributed to the severity of the disease and persistent rise in infections. This study aimed to identify potential drug candidates from fifteen approved antiviral drugs against SARS-CoV-2 (6LU7), SARS-CoV (5B6O), and SARS-CoV-2 spike protein (6M0J) using virtual screening and pharmacokinetics to gain insights into COVID-19 therapeutics. METHODOLOGY: We employed drug repurposing approach to analyze binding performance of fifteen clinically approved antiviral drugs against the main protease of SARS-CoV-2 (6LU7), SARS-CoV (5B6O), and SARS-CoV-2 spike proteins bound to ACE-2 receptor (6M0J), to provide an insight into the therapeutics of COVID-19. AutoDock Vina was used for docking studies. The binding affinities were calculated, and 2-3D structures of protein-ligand interactions were drawn. RESULTS: Rutin, hesperidin, and nelfinavir are clinically approved antiviral drugs with high binding affinity to proteins 6LU7, 5B6O, and 6M0J. These ligands have excellent pharmacokinetics, ensuring efficient absorption, metabolism, excretion, and digestibility. Hesperidin showed the most potent interaction with spike protein 6M0J, forming four H-bonds. Nelfinavir had a high human intestinal absorption (HIA) score of 0.93, indicating maximum absorption in the body and promising interactions with 6LU7. CONCLUSIONS: Our results indicated that rutin, hesperidin, and nelfinavir had the highest binding results against the proposed drug targets. The computational approach effectively identified SARS-CoV-2 inhibitors. COVID-19 is still a recurrent threat globally and predictive analysis using natural compounds might serve as a starting point for new drug development against SARS-CoV-2 and related viruses.

The Effectiveness of Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors on Cardiovascular Outcomes and All-Cause Mortality in Patients With Acute Coronary Syndrome: A Systematic Review and Meta-Analysis.

The aim of this systematic review and meta-analysis was to investigate the impact of early sodium-glucose cotransporter-2 (SGLT2) initiation on long-term cardiovascular outcomes and all-cause mortality among patients with acute coronary syndrome (ACS). For this study, we adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guideline. Two researchers independently performed a comprehensive literature search on PubMed, Embase, and the Cochrane Library, spanning from the inception of each database to February 24, 2023, without language limitations. The outcomes examined in this meta-analysis comprised major adverse cardiovascular events (MACE) (as defined by individual studies), all-cause mortality, cardiovascular mortality, stroke (ischemic and hemorrhagic), recurrent ACS, and hospitalization due to heart failure (HF). A total of nine studies were included in this meta-analysis. The pooled analysis of nine studies revealed a significant reduction in the risk of MACE, all-cause mortality, cardiovascular mortality, and cardiovascular-related hospitalizations among patients receiving SGLT2 inhibitors (SGLT2i) compared to those in the control group. Additionally, there was a trend toward a lower risk of recurrent ACS in the SGLT2i group, although this difference did not reach statistical significance. The findings of this study suggest a promising therapeutic effect of SGLT2 inhibitors in this population. Further research, particularly focusing on myocardial infarction (MI) patients, is warranted to validate these results and potentially revolutionize ACS management.

Comparison of the Effectiveness and Safety of Metoprolol and Diltiazem in Atrial Fibrillation With Rapid Ventricular Rate Patients: A Systematic Review and Meta-Analysis.

This study aims to assess the association between intravenous diltiazem and metoprolol in rate control for atrial fibrillation (AF) patients with rapid ventricular rate, focusing on rate control efficacy and hemodynamic adverse events. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, electronic searches were conducted in Embase, PubMed, and Cochrane Central Register of Controlled Trials (CENTRAL) until February 20, 2024. The primary outcome was achieving ventricular rate control < 110/min. Secondary outcomes included new hypotension (systolic blood pressure < 90 mm Hg) and bradycardia (heart rate < 60/min). Nineteen studies (three randomized controlled trials and 16 observational studies) were included in this meta-analysis. Pooled analysis showed intravenous metoprolol resulted in a 39% lower rate control attainment compared to diltiazem (OR: 0.61; 95% CI: 0.44 to 0.84; p = 0.002). There were no significant differences in bradycardia (OR: 0.51; 95% CI: 0.22 to 1.22; p = 0.13) or hypotension risk (OR: 1.08; 95% CI: 0.72 to 1.61; p = 0.72) between the two groups. Intravenous diltiazem demonstrated superior rate control efficacy compared to metoprolol in AF patients with rapid ventricular rate. However, no significant differences were observed in safety outcomes, namely, bradycardia and hypotension.

Comparison of Cardiovascular Outcomes and All-Cause Mortality Between Patients With and Without Epilepsy: A Systematic Review and Meta-Analysis of Observational Studies.

This meta-analysis aimed to assess the all-cause mortality and cardiovascular outcomes among patients diagnosed with epilepsy. The entire process of this systematic review and meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to ensure transparency and reporting completeness. A comprehensive search strategy was employed to identify relevant studies in electronic databases, including PubMed, Embase, and the Cumulative Index of Nursing and Allied Health Literature (CINAHL), from January 1, 2010, to January 15, 2024. Outcomes assessed in this meta-analysis included all-cause mortality, cardiovascular mortality, stroke, myocardial infarction, and arrhythmias. A total of 12 studies were included in this meta-analysis with a pooled sample size of 7,026,313. The majority of included studies were conducted in Taiwan (n=4). Our study revealed that individuals with epilepsy faced a higher risk of all-cause mortality, cardiovascular mortality, and stroke. Although there was a higher incidence of myocardial infarction and arrhythmias among epilepsy patients, this disparity did not reach statistical significance. There is a need for future research to explore the impact of epilepsy types, antiepileptic drugs, and lifestyle factors on cardiovascular outcomes.

Comparison of Risk of Stroke in Patients With and Without Depression: A Systematic Review and Meta-Analysis.

Individuals with depression face an elevated stroke risk, marked by an unfavorable prognosis. This meta-analysis aims to determine the impact of depression on stroke risk. The current meta-analysis was conducted using the guidelines established by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We selected studies through a systematic review of electronic databases, including PubMed, EMBASE, and CINAHL from January 2011 to January 2023. Google Scholar was utilized to identify supplementary studies. Furthermore, we scrutinized citation lists of reported articles for additional potential studies. Only English-language articles were included in the review. A total of 15 studies were included in this meta-analysis. The pooled sample size was 744,179. Sample size of the included studies ranged from 560 to 487,377. The pooled estimate of 15 studies showed that the risk of stroke was 1.47 times higher in individuals with depression compared to the individuals without depression, and the difference is statistically significant (RR: 1.47, 95% CI: 1.30 to 1.66, p-value<0.001). Age and hypertension emerged as significant predictors of stroke risk in depressed individuals identified through meta-regression. These findings underscore the importance of targeted preventive strategies for depression-related stroke risk, especially considering age-specific considerations and associated factors.

Integrating humanities in healthcare: a mixed-methods study for development and testing of a humanities curriculum for front-line health workers in Karachi, Pakistan.

Lady health workers (LHWs) provide lifesaving maternal and child health services to >60% of Pakistan's population but are poorly compensated and overburdened. Moreover, LHWs' training does not incorporate efforts to nurture attributes necessary for equitable and holistic healthcare delivery. We developed an interdisciplinary humanities curriculum, deriving its strengths from local art and literature, to enhance character virtues such as empathy and connection, interpersonal communication skills, compassion and purpose among LHWs. We tested the curriculum's feasibility and impact to enhance character strengths among LHWs.We conducted a multiphase mixed-methods pilot study in two towns of Karachi, Pakistan. We delivered the humanities curriculum to 48 LHWs via 12 weekly sessions, from 15 June to 2 September 2021. We developed a multiconstruct character strength survey that was administered preintervention and postintervention to assess the impact of the training. In-depth interviews were conducted with a subset of randomly selected participating LHWs.Of 48 participants, 47 (98%) completed the training, and 34 (71%) attended all 12 sessions. Scores for all outcomes increased between baseline and endline, with highest increase (10.0 points, 95% CI 2.91 to 17.02; p=0.006) observed for empathy/connection. LHWs provided positive feedback on the training and its impact in terms of improving their confidence, empathy/connection and ability to communicate with clients. Participants also rated the sessions highly in terms of the content's usefulness (mean: 9.7/10; SD: 0.16), the success of the sessions (mean: 9.7/10; SD: 0.17) and overall satisfaction (mean: 8.2/10; SD: 3.3).A humanities-based training for front-line health workers is a feasible intervention with demonstrated impact of nurturing key character strengths, notably empathy/connection and interpersonal communication. Evidence from this study highlights the value of a humanities-based training, grounded in local literature and cultural values, that can ultimately translate to improved well-being of LHWs thus contributing to better health outcomes among the populations they serve.

Comparison of Outcomes Between Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers in Patients With Myocardial Infarction: A Meta-Analysis.

Patients with acute myocardial infarction (AMI) are usually treated with angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARB). The aim of this meta-analysis is to compare outcomes between ACEi and ARB in patients with myocardial infarction (MI). This meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Three major online databases, including PubMed, EMBASE, and the Cochrane Library, were thoroughly searched to find studies comparing ACEi and ARB in patients with MI from January 1, 2000, onwards, without language or publication restrictions. Outcomes assessed in this meta-analysis included major adverse cardiovascular events (MACE), all-cause mortality, cardiovascular mortality, stroke, and hospitalization due to heart failure. A total of 16 studies were included in this meta-analysis. Pooled estimates showed no significant differences between the two groups in terms of MACE (risk ratio (RR): 1.03, 95% confidence interval (CI): 0.88-1.20), all-cause mortality (RR: 1.03, 95% CI: 0.88-1.20), cardiovascular mortality (RR: 1.00, 95% CI: 0.89-1.12), stroke (RR: 1.03, 95% CI: 0.80-1.32), and hospitalization due to heart failure (RR: 0.99, 95% CI: 0.90-1.09). These results suggest that ACEi and ARB have similar impacts on clinical outcomes across a broad spectrum of MI patients, reinforcing their roles in post-MI treatment.

Safety and Efficacy of Efpeglenatide in Patients With Type 2 Diabetes: A Meta-Analysis of Randomized Controlled Trials.

The aim of this study was to assess the efficacy and safety of efpeglenatide in patients with type 2 diabetes (T2D). The study was reported according to the 2020 guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Web of Science, PubMed, and Scopus databases were searched by two authors independently, with no restriction on language and year of publication, using the following key terms: (efpeglenatide) OR (glucagon-like peptide-1 receptor agonist) AND (type 2 diabetes) OR (diabetes) OR (T2DM) AND (HbA1c) OR (FSG) OR (fasting serum glucose) OR (weight) OR (bodyweight) OR (adverse events) OR (safety) OR (AE). Outcomes assessed in this meta-analysis included change in hemoglobin A1C (HbA1C) from baseline (%), change in weight from baseline (Kg), and change in fasting serum glucose (FSG) from baselines. For the safety analysis, we assessed total adverse events and gastrointestinal (GI) adverse events. A total of four studies fulfilled the inclusion and exclusion criteria and were included in this meta-analysis, encompassing six randomized controlled trials (RCTs). Compared with a control group, efpeglenatide lowered the HbA1c (mean difference (MD): -0.81, 95% confidence interval (CI): -1.01 to -0.60), body weight (MD: -1.15, 95% CI: -1.82 to -0.47), and FSG (MD: -0.98, 95% CI: -1.19 to -0.77). However, the risk of GI-related adverse events was significantly higher in the efpeglenatide group compared to the control group.

Evaluation of providers' assistive technology service delivery practices in Pakistan.

PURPOSE: Globally, one in three individuals needs at least one assistive product. The primary objective of this study was to conduct a survey of Pakistani rehabilitation service providers to determine what proportion provide assistive technology and if their characteristics (including geographical region, education, and experience) are associated with adherence to the service delivery process. The secondary objective was to determine if individuals that provide assistive technology adhere to a standard assistive technology service delivery process. The tertiary objective was to determine if the providers that adhered to a standard delivery process had characteristics that differed from the rest of the service providers. MATERIALS AND METHODS: An online survey composed of multiple-choice questions was distributed to physiotherapists, community-based healthcare workers, and related rehabilitation professions through a convenience sampling method. SPSS Statistics was used to develop correlation matrices to determine Pearson's coefficient of number of steps, education level, experience level and continuing education received. RESULTS: There were 71 respondents from 4 Pakistani provinces. 53.5% of respondents stated they provide assistive technology. There was participation in most steps of the service delivery process. There is weak correlation between number of steps and education level, number of steps and experience level, and number of steps and continuing education received. CONCLUSIONS: While the majority of respondents provide assistive technology, a significant proportion (46.5%) don't. This may suggest there is a need for additional advocacy and awareness raising of the benefits of and how to access assistive technology in Pakistan.

Implications for RehabilitationPakistan implemented a Rapid Assistive Technology Assessment and determined that only 22% of the population that needs an assistive device has had their needs met.From a relatively small sample, this study investigated if there is a presence of assistive technology service delivery in Pakistan and whether traditional education, experience, or continuing education promotes participation in the assistive technology service delivery process.This study found a presence of assistive technology service delivery in Pakistan, but found weak correlations between participation in the service delivery process with traditional education, experience, and continuing education.These findings suggest that there is room for additional advocacy and awareness training on assistive technology in Pakistan.

Comparison of Immediate Versus Staged Complete Revascularisation in Patients Presenting With Acute Coronary Syndrome and Multivessel Disease: A Meta-Analysis of Randomized and Non-randomized Studies.

Acute myocardial infarction is a critical medical condition that poses a significant health burden, leading to substantial morbidity. Despite advancements in medical care, managing this condition is challenging for patients and society. The preferred approach appears to be comprehensive multivessel revascularization, yet the optimal timing remains uncertain. This study aims to compare immediate complete revascularisation and stage complete vascularization in patients presenting with acute coronary syndrome (ACS) and multivessel coronary artery disease (MVD). The Preferred Reporting of Systematic Reviews and Meta-analysis (PRISMA) guidelines conducted the present meta-analysis. A comprehensive literature search was conducted using online databases, including PubMed, and EMBASE from 2010 onwards, to identify articles that compared cardiovascular outcomes between patients undergoing immediate and staged complete revascularization. We also searched Google Scholar for additional studies relevant to the present meta-analysis. The primary outcome assessed in this study was major adverse cardiovascular events (MACE). Secondary outcomes included all-cause mortality, cardiovascular mortality, myocardial infarction (MI), and revascularization. A total of 15 studies fulfilled pre-defined eligibility criteria and were included in the final analysis. Our analysis shows that staged revascularization is associated with improved outcomes in patients with ACS and multivessel CAD, including all-cause mortality and cardiovascular mortality, without increasing the risk of major adverse cardiovascular events, myocardial infarction, and the need for unplanned revascularization.

Nanoparticle Albumin­Bound Paclitaxel and Solvent-Based Paclitaxel as Chemotherapy Options for Patients With Advanced Gastric Cancer: A Systematic Review and Meta-Analysis.

The aim of this study is to assess and compare the effectiveness and safety of nanoparticle albumin-bound paclitaxel (nab-PTX) and solvent-based PTX (sb-PTX) as treatment options for advanced gastric cancer. This meta-analysis was reported according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. We carried out a comprehensive search of PubMed, Google Scholar, and EMBASE from inception to June 15, 2023. The search strategy included the following keywords: "Nanoparticle albumin-bound paclitaxel," "solvent-based paclitaxel," and "advanced gastric cancer," along with their synonyms and medical subject heading (MeSH) terms. In this meta-analysis, the primary outcome was the comparison of overall survival and progression-free survival between the two groups. For safety purposes, we compared the risk of hematological and non-hematological events between the two groups. Four studies were included in this meta-analysis enrolling 1052 patients (483 received nb-PTX and 569 received sb-PTX). In terms of efficacy, nab-PTX showed favorable trends in overall survival and progression-free survival, despite no statistically significant differences being reported. The subgroup meta-analysis showed that nab-PTX seemed to have a better effect on peritoneal metastasis compared to sb-PTX. Regarding safety, the number of patients with neutropenia and leucopenia was significantly higher in the nab-PTX group compared to the sb-PTX group. However, the difference was statistically insignificant. Future research should focus on conducting more robust studies to further validate these findings and establish a stronger evidence base for the use of nab-PTX in this patient population.

Comparison of Metacognitive Therapy Versus Cognitive Behavioral Therapy for Generalized Anxiety Disorder: A Meta-Analysis of Randomized Control Trials.

The aim of this meta-analysis is to compare the efficacy of meta-cognitive therapy (MCT) and cognitive behavioral therapy (CBT) in patients with generalized anxiety disorder (GAD). This study is reported according to the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A systematic electronic literature search was conducted on April 20, 2023, to find studies reporting on the efficacy of MCT for GAD. The search keywords included "Generalized anxiety disorders," "meta-cognitive therapy," "cognitive behavior therapy," and "randomized control trials.: The following databases were searched to find relevant articles: PubMed, PsychInfo, CINAHL, and SCOPUS. Outcomes assessed in the present meta-analysis included the change in the Penn State Worry Questionnaire (PSWQ) from baseline to completion of treatment and after two years of follow-up. The PSWQ measures the trait of worry in adults. Worry is regarded as a dominant feature of GAD. Secondary outcomes assessed in this meta-analysis included symptom severity using the Beck anxiety inventory (BAI). Change in BAI was scored from baseline to completion of treatment and after two years of follow-up. A total of three studies were included in this meta-analysis. The results show that patients treated with MCT had greater reductions in PSWQ and BAI scores post-treatment and after two years of treatment, as well as higher rates of recovery compared to those treated with CBT. These findings suggest that MCT is a promising approach for treating GAD and may have advantages over traditional CBT approaches.

Effect of Discontinuation of Renin Angiotensin-System Inhibitors in Patients With Advanced Chronic Kidney Disease: A Meta-Analysis.

Renin-angiotensin system inhibitors (RAS) inhibitors include angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme (ACE) inhibitors decrease proteinuria, progression of chronic kidney disease (CKD), and protect against heart failure hospitalizations and cardiovascular events. There is uncertainty about the appropriate time for discontinuing ARB and ACE inhibitor treatment in patients with low estimated glomerular filtration rate (eGFR). In the present meta-analysis, we examined the effect of RAS inhibitor discontinuation on clinical outcomes in patients with advanced CKD compared to the continuation of RAS inhibitors. Two authors conducted electronic database searches in PubMed, the Cochrane Library, and Excerpta Medica Database (EMBASE) for relevant studies published from the inception of the databases to March 15th, 2023, using the following combination of keywords or key terms: "Renin-angiotensin-system," "angiotensin-converting-enzyme inhibitors", "Angiotensin receptor blockers," and "advanced chronic kidney disease." Primary outcomes assessed in this meta-analysis included cardiovascular events. Secondary outcomes assessed included all-cause mortality and end-stage kidney disease (ESKD). A total of four studies were included in this meta-analysis. The pooled analysis showed that cardiovascular events were significantly higher in patients in the discontinuation group compared to the continuation group (HR: 1.38, 95% CI: 1.21-1.58), ESKD was also significantly higher in the discontinuation group (HR: 1.29, 95% CI: 1.18-1.41). No significant differences were reported between the two groups in all-cause mortality. In conclusion, our meta-analysis provides evidence that continuation of RAS inhibitors could be beneficial in patients with advanced CKD, as it is associated with less risk of cardiovascular events and ESKD.

Comparison of Effectiveness and Safety of Low-Dose Versus Standard-Dose Intravenous Recombinant Tissue Plasminogen Activator in Patients With Acute Ischemic Stroke: A Meta-Analysis.

The aim of the present meta-analysis is to compare the efficacy and safety of low-dose and standard-dose recombinant tissue plasminogen activators (r-tPA) in patients with acute ischemic stroke. The present meta-analysis was conducted according to the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines. We conducted a systematic search in PubMed, Embase, and the Cochrane Library to identify studies published between January 1, 2010, and January 31, 2023, using the following terms: "stroke," "alteplase," "doses," "efficacy," "tissue plasminogen activator," "r-tPA," and "safety." Primary efficacy outcomes included favorable outcomes (Modified Rankin Scale scores of 0-2), while secondary efficacy outcome was all-cause mortality at 90 days. Safety outcomes included asymptomatic intracerebral hemorrhage (ICH) and symptomatic ICH assessed using the National Institute of Neurological Disorders and Stroke (NINDS) study and the Safe Implementation of Thrombolysis in Stroke-Monitoring (SITS-MOST) study. We also compared parenchymal hematomas as safety outcome between the two groups defined by the authors themselves in their research. A total of 16 studies were included in the present meta-analysis. The meta-analysis did not report any significant difference between low-dose and standard-dose r-tPA in terms of mortality, symptomatic intracranial hemorrhage (SICH), asymptomatic ICH, and parenchymal hematomas. However, the favorable outcome was significantly greater in patients receiving a standard dose of r-tPA.

Continuous Infusion Versus Bolus Injection of Loop Diuretics for Patients With Congestive Heart Failure: A Meta-Analysis.

Loop diuretics continue to be a crucial component of pharmacological treatment, to eliminate extra fluid and enhance symptom control in acute decompensated heart failure (ADHF). Understanding the loop diuretics' more efficient form of administration would be very beneficial in improving the management of people's ADHF, resulting in a quicker resolution of symptoms and a notable decrease in morbidity. To assess the outcomes of intravenous continuous infusion with bolus injection of loop diuretics for patients with ADHF, this meta-analysis was carried out. The current meta-analysis was conducted as per the Cochrane Collaboration guidelines and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension (PRISMA) guidelines. A search was carried out on PubMed and EMBASE databases for studies comparing continuous infusion with intermittent bolus injection of furosemide in patients with congestive heart failure without restriction on the language of publication from 1 January 2001 to 31 July 2022. The primary outcome of the meta-analysis was all-cause mortality and loss of body weight (kg). Pre-defined secondary outcomes included length of hospital stay (LOS) in days, brain natriuretic peptide (BNP) reduction (pg/ml), number of patients with hypokalemia, and urine output at 24 hours (ml). A total of nine articles were included in this meta-analysis enrolling 713 patients. No significant difference was reported between patients who received intermittent bolus injections and continuous infusion of furosemide in regards to all-cause mortality, LOS, total urine output, the incidence of hypokalemia, and change in BNP. However, the reduction of body weight was greater in the continuous infusion group compared to bolus administration. In conclusion, in the current meta-analysis of nine randomized controlled trials (RCTs), continuous infusion of furosemide seemed to have a greater reduction of body weight. However, no significant difference was there in 24-hrs urine output. However, we cannot conclude that intravenous continuous infusion has a better diuretic effect compared to bolus administration.

Outcomes of Pigtail Catheter Placement versus Chest Tube Placement in Adult Thoracic Trauma Patients: A Systematic Review and Meta-Analysis.

INTRODUCTION: A debate currently exists regarding the efficacy of pigtail catheters vs chest tubes in the management of thoracic trauma. This meta-analysis aims to compare the outcomes of pigtail catheters vs chest tubes in adult trauma patients with thoracic injuries. METHODS: This systematic review and meta-analysis were conducted using PRISMA guidelines and registered with PROSPERO. PubMed, Google Scholar, Embase, Ebsco, and ProQuest electronic databases were queried for studies comparing the use of pigtail catheters vs chest tubes in adult trauma patients from database inception to August 15th, 2022. The primary outcome was the failure rate of drainage tubes, defined as requiring a second tube placement or VATS, unresolved pneumothorax, hemothorax, or hemopneumothorax requiring additional intervention. Secondary outcomes were initial drainage output, ICU-LOS, and ventilator days. RESULTS: A total of 7 studies satisfied eligibility criteria and were assessed in the meta-analysis. The pigtail group had higher initial output volumes vs the chest tube group, with a mean difference of 114.7 mL [95% CI (70.6 mL, 158.8 mL)]. Patients in the chest tube group also had a higher risk of requiring VATS vs the pigtail group, with a relative risk of 2.77 [95% CI (1.50, 5.11)]. CONCLUSIONS: In trauma patients, pigtail catheters rather than chest tubes are associated with higher initial output volume, reduced risk of VATS, and shorter tube duration. Considering the similar rates of failure, ventilator days, and ICU length-of-stay, pigtail catheters should be considered in the management of traumatic thoracic injuries. STUDY TYPE: Systematic Review and meta-analysis.

Rational polypharmacological targeting of FLT3, JAK2, ABL, and ERK1 suppresses the adaptive resistance to FLT3 inhibitors in AML.

Despite significant advancements in developing selective FMS-like tyrosine kinase 3 (FLT3) inhibitors, resistance to treatment is common even on continued therapy. Acquisition of on-target mutations or adaptation to MAPK, JAK2, and ABL signaling pathways drive treatment failure and disease relapse. Although combinatorial targeting of all escape routes in preclinical models demonstrated its efficacy, the clinical application is challenging owing to drug-drug interaction and differing pharmacokinetics of the inhibitors. We reasoned that selective polypharmacological targeting could lead to a durable response with reduced toxicity. A cell-based screening was carried out to identify inhibitors targeting FLT3, RAS-MAPK, BCR-ABL, and JAK2 to target the adaptive resistance observed with FLT3 inhibitors. Here, we show that pluripotin is an equipotent inhibitor of FLT3, BCR-ABL, and JAK2 in addition to inhibiting Ras-GAP and extracellular signal-regulated kinase 1 (ERK1). Structural modeling studies revealed that pluripotin is a type II kinase inhibitor that selectively binds with inactive conformations of FLT3, ABL, and JAK2. Pluripotin showed potent inhibitory activity on both mouse and human cells expressing FLT3ITD, including clinically challenging resistant mutations of the gatekeeper residue, F691L. Likewise, pluripotin suppressed the adaptive resistance conferred by the activation of RAS-MAPK pathways, BCR-ABL, and JAK2 signaling. Treatment with pluripotin curbed the progression of acute myeloid leukemia (AML) in multiple in vivo models including patient-derived primary AML cells in mouse xenotransplants. As a proof of concept, we demonstrate that targeted polypharmacological inhibition of key signaling nodes driving adaptive resistance can provide a durable response.

Analysis of Bicyclist Injuries and Fatalities in The United States: The Need for Effective & Sustainable Prevention Policies.

We aim to investigate nationwide and state trends of bicyclist injuries, fatalities, and associated costs amongst adult and pediatric populations to assess the need for effective and strategic interventions. An epidemiologic study was performed investigating the injury and fatality rate of bicyclists from 2010 to 2020. The fatality rate was higher in adults compared to pediatric bicyclists (0.36 vs. 0.12 per population of 100,000, P < .001), but pediatric bicyclists suffered higher rates of injury (246.19 vs. 102.11 per population of 100,000, P < .001). The medical cost of fatalities for adult bicyclists was $139.1 million compared to $9.0 million for pediatric bicyclists. Bicyclist fatality rates are significantly higher per capita for adult bicyclists. States including Florida, South Carolina, and Louisiana had the highest bicyclist fatalities per capita for both adults and children.

Analysis of Surgical Residents' Salaries and Associated Funding During Eight Residency Training Cycles: Toward Improving Future Residents' Benefits and Compensation.

INTRODUCTION: We aimed to investigate the trends in surgical residents' salaries across the nation and by region from 2014-2015 to 2021-2022 to identify areas for improvement in resident benefits and compensation. METHODS: This is a retrospective study investigating the trends in US medical resident salaries from 2014-2015 to 2021-2022. Residency salary was analyzed over time, by region, and between surgical specialties both unadjusted and adjusted for cost of living. Salary by surgical specialty was collected from available years 2014-2015 to 2019-2020. Trends in residency salaries were also compared to the trends in graduate medical education (GME) Medicare funding. RESULTS: The average resident salary/cost of living ratio did not significantly change over the study period (2014-2015: 0.96, 2020-2021, 0.96, P = 0.654). The South and Midwest had significantly higher average resident salaries than the Northeast (P < 0.001) and West (P < 0.001) after adjusting for the cost of living. The average total GME Medicare funding per resident increased significantly more than the average resident salary ($12,278 versus $4540, P < 0.001). The average general surgery resident salary (2014-2015: $57,000, 2019-2020: $61,500, Δ = $4500) increased significantly less than the average salary of all specialties (2014-2015: $51,586, 2019-2020: $57,191, Δ = $5605, P = 0.001). CONCLUSIONS: Residency salaries have increased marginally from 2014-2015 to 2021-2022 and remain below the average US cost of living. Residency salaries vary significantly between surgical specialties and by region. Discussions aimed at reformulating GME compensation that takes into consideration regional differences in cost of living are needed.