First-line Intervention Research Articles

Efficacy comparison of immune combination therapies in subgroups for advanced hepatocellular carcinoma patients: Systematic review and network meta-analysis.

There is a lack of precision in the immunotherapy strategy tailored for patients exhibiting diverse clinical characteristics. This study aims to employ a rigorous network meta-analysis (NMA) approach to systematically evaluate the effectiveness of immune-combination therapies among patients with advanced hepatocellular carcinoma, taking into account their varying clinico-characteristics. Studies were retrieved from PubMed, Embase, Cochrane Library, and Web of Science databases. The included first-line phase III studies were categorized into three types: immunotherapy combined with anti-angiogenetic agents, immunotherapy combined with tyrosine kinase inhibitors, and dual immunotherapy, with sorafenib serving as the control group. The primary endpoint used to assess efficacy was overall survival (OS), facilitating a comparative analysis among the three treatment modalities. Furthermore, subgroup analyses were conducted to evaluate the varying effectiveness for patients with diverse clinico-characteristics. Secondary outcome measures included progression-free survival, objective response rate, and toxicity assessment. A total of 6 studies were included in the NMA, encompassing a cohort of 3840 patients. The results revealed that immunotherapy combined with anti-angiogenetic agents exhibited a significantly enhanced therapeutic effect in terms of improving OS compared to sorafenib (HR = 0.61, 95% CrI, 0.42-0.90). Furthermore, based on various clinicopathological features, this combination therapy demonstrated superior OS responses in specific patient subgroups: BCLC C (HR = 0.63, 95% CrI, 0.42-0.93), ECOG 1 (HR = 0.57, 95% CrI, 0.36-0.91), with extrahepatic spread (EHS) (HR = 0.59, 95% CrI, 0.37-0.92), alpha fetoprotein (AFP)<400ng/ml (HR = 0.56, 95% CrI, 0.33-0.94) and viral hepatitis positivity (HR = 0.56, 95% CrI, 0.39-0.77) (especially HBV (HR = 0.58, 95% CrI, 0.40-0.85)). Importantly, the advantage of this combination therapy was even more pronounced in patients with viral hepatitis positivity. Also, the adverse events associated with immunotherapy combined with antiangiogenic drugs were moderate. Immunotherapy combined with anti-angiogenetic agents could represent the most effective first-line intervention for achieving improved OS, particularly in patients with viral hepatitis positivity.

Neurobiology of Obsessive-Compulsive Disorder from Genes to Circuits: Insights from Animal Models.

Obsessive-compulsive disorder (OCD) is a chronic, severe psychiatric disorder that has been ranked by the World Health Organization as one of the leading causes of illness-related disability, and first-line interventions are limited in efficacy and have side-effect issues. However, the exact pathophysiology underlying this complex, heterogeneous disorder remains unknown. This scenario is now rapidly changing due to the advancement of powerful technologies that can be used to verify the function of the specific gene and dissect the neural circuits underlying the neurobiology of OCD in rodents. Genetic and circuit-specific manipulation in rodents has provided important insights into the neurobiology of OCD by identifying the molecular, cellular, and circuit events that induce OCD-like behaviors. This review will highlight recent progress specifically toward classic genetic animal models and advanced neural circuit findings, which provide theoretical evidence for targeted intervention on specific molecular, cellular, and neural circuit events.

Sustained Release Therapies with the Prostaglandin Analogues Intracameral Implants.

The travoprost intracameral implant was recently approved by the US Food and Drug Administration for sustained release medical treatment of open-angle glaucoma in the USA. The approval represents a substantial and progressive step forward in the area of sustained-release glaucoma therapy. Topical intraocular pressure-lowering medications for the treatment of glaucoma are faced with a host of challenges for long-term and usually lifelong care. A changing paradigm in glaucoma management involves first-line interventions with laser modalities, micro-invasive surgeries, and sustained-release treatment platforms. Future needs in the area of sustained-release therapy include a non-prostaglandin drug delivery platform and longer-term treatments that do not require surgical reintervention.

Epidermal Growth Factor Receptor Targeting in Colorectal Carcinoma: Antibodies and Patient-Derived Organoids as a Smart Model to Study Therapy Resistance.

Colorectal cancer (CRC) is the second leading cause of cancer-related death worldwide. Therefore, the need for new therapeutic strategies is still a challenge. Surgery and chemotherapy represent the first-line interventions; nevertheless, the prognosis for metastatic CRC (mCRC) patients remains unacceptable. An important step towards targeted therapy came from the inhibition of the epidermal growth factor receptor (EGFR) pathway, by the anti-EGFR antibody, Cetuximab, or by specific tyrosine kinase inhibitors (TKI). Cetuximab, a mouse-human chimeric monoclonal antibody (mAb), binds to the extracellular domain of EGFR thus impairing EGFR-mediated signaling and reducing cell proliferation. TKI can affect the EGFR biochemical pathway at different steps along the signaling cascade. Apart from Cetuximab, other anti-EGFR mAbs have been developed, such as Panitumumab. Both antibodies have been approved for the treatment of KRAS-NRAS wild type mCRC, alone or in combination with chemotherapy. These antibodies display strong differences in activating the host immune system against CRC, due to their different immunoglobulin isotypes. Although anti-EGFR antibodies are efficient, drug resistance occurs with high frequency. Resistant tumor cell populations can either already be present before therapy or develop later by biochemical adaptations or new genomic mutations in the EGFR pathway. Numerous efforts have been made to improve the efficacy of the anti-EGFR mAbs or to find new agents that are able to block downstream EGFR signaling cascade molecules. Indeed, we examined the importance of analyzing the anti-EGFR antibody-drug conjugates (ADC) developed to overcome resistance and/or stimulate the tumor host's immunity against CRC growth. Also, patient-derived CRC organoid cultures represent a useful and feasible in vitro model to study tumor behavior and therapy response. Organoids can reflect tumor genetic heterogeneity found in the tissue of origin, representing a unique tool for personalized medicine. Thus, CRC-derived organoid cultures are a smart model for studying the tumor microenvironment and for the preclinical assay of anti-EGFR drugs.

An exploration of having social media influencers deliver a first-line digital intervention to improve body image among adolescent girls: A qualitative study

Social media influencers are popular among adolescents and could offer a unique way to reach young people at scale with body image interventions. This study explored girls’ and influencers’ views on having influencers deliver body image interventions through vlogs (video blogs) and to gain insight into their preferred format, content, and views on factors that encourage engagement with vlogs. Twenty-one UK based participants were recruited. Three online focus groups were conducted with adolescent girls (n = 16) aged 14–18 years and one with influencers (n = 5) aged 24–33 years, who had a collective following of over 1.5 million subscribers across social media platforms. Data were analysed using reflexive thematic analysis and four themes were generated: Choosing an influencer whose messages and core values are aligned with the topic of body image; the importance of influencer authenticity and personal experience; collaborating on content creation with mental health professionals; and the need for long-form (i.e., 10–20 min) content to address serious topics. Findings suggest having influencers deliver body image interventions to young people could be a useful approach. Results highlight the need to engage with end users from the outset of intervention development to increase the likelihood of intervention effectiveness and engagement.

Expert opinion on screening, diagnosis and management of diabetic peripheral neuropathy: a multidisciplinary approach.

The proposed expert opinion aimed to address the current knowledge on conceptual, clinical, and therapeutic aspects of diabetic peripheral neuropathy (DPN) and to provide a guidance document to assist clinicians for the best practice in DPN care. The participating experts consider the suspicion of the disease by clinicians as a key factor in early recognition and diagnosis, emphasizing an improved awareness of the disease by the first-admission or referring physicians. The proposed "screening and diagnostic" algorithm involves the consideration of DPN in a patient with prediabetes or diabetes who presents with neuropathic symptoms and/or signs of neuropathy in the presence of DPN risk factors, with careful consideration of laboratory testing to rule out other causes of distal symmetric peripheral neuropathy and referral for a detailed neurological work-up for a confirmative test of either small or large nerve fiber dysfunction in atypical cases. Although, the first-line interventions for DPN are currently represented by optimized glycemic control (mainly for type 1 diabetes) and multifactorial intervention (mainly for type 2 diabetes), there is a need for individualized pathogenesis-directed treatment approaches for DPN. Alpha-lipoic acid (ALA) seems to be an important first-line pathogenesis-directed agent, given that it is a direct and indirect antioxidant that works with a strategy targeted directly against reactive oxygen species and indirectly in favor of endogenous antioxidant capacity for improving DPN conditions. There is still a gap in existing research in the field, necessitating well-designed, robust, multicenter clinical trials with sensitive endpoints and standardized protocols to facilitate the diagnosis of DPN via a simple and effective algorithm and to track progression of disease and treatment response. Identification of biomarkers/predictors that would allow an individualized approach from a potentially disease-modifying perspective may provide opportunities for novel treatments that would be efficacious in early stages of DPN, and may modify the natural course of the disease. This expert opinion document is expected to increase awareness among physicians about conceptual, clinical, and therapeutic aspects of DPN and to assist them in timely recognition of DPN and translating this information into their clinical practice for best practice in the management of patients with DPN.

Facilitators, barriers and support needs to GLA:D exercise adherence – a mixed method study

BackgroundKnee and hip osteoarthritis (OA) are among the most common musculoskeletal joint diseases worldwide. International guidelines recommend exercise and education as first-line interventions for their management. The Good Life with osteoArthritis Denmark (GLA:D) programme aims to achieve self-management using group exercise and education sessions. It also encourages participants to stay physically active and perform GLA:D exercises (GE) twice weekly after programme end. This study investigated the participants’ self-reported level of physical activity (PA) and self-reported adherence to the GE between five and 17 months after completion of the GLA:D programme and also explored the barriers, facilitators and support needs to achieve long-term adherence to GE.MethodsA mixed method study using an exploratory sequential design was performed. A qualitative phase, involving semi-structured interviews and a focus group, led to the development of a questionnaire on participants’ level of PA, as well as ratings of the barriers, facilitators and support needs for the achievement of long-term adherence to GE. In a second quantitative phase, the survey was conducted online with former GLA:D participants from Switzerland. Descriptive statistical analysis and a group comparison between adherent and non-adherent participants to the GE were performed using Fisher’s exact test, odds ratio, and confidence interval.ResultsEleven former GLA:D participants attended the interviews and focus group, and former GLA:D participants (30% response rate) participated in the survey. Of these, 84% (n = 285) reported to reach the recommended level of PA and 53% (n = 178) GE adherence. The top barrier to GE adherence was no/little self-discipline to perform GE (40%, n = 112) and the top facilitator was GE are easy to perform (93%, n = 300). The top 3 items regarding support needs to enhance GE adherence were a shortened version (max. 30 min) of the GE home programme (75%, n = 255), monthly continuation of small GE groups under GLA:D physiotherapists’ supervision (65%, n = 221), and monitoring with regular testing of individual progress (65%, n = 221).ConclusionsThe top barriers and facilitators should be considered by those responsible for the GLA:D programme and may need to be specifically addressed during and after the programme. The development of a shortened version of the GLA:D programme, a post-GLA:D group, and monitoring with regular testing seem crucial for enhancing GE adherence.Clinical Trial Registrationnot applicable.

Artificial neural networks analysis predicts long-term fistula function in hemodialysis patients following percutaneous transluminal angioplasty

Kidney failure is particularly common in the United States, where it affects over 700,000 individuals. It is typically treated through repeated sessions of hemodialysis to filter and clean the blood. Hemodialysis requires vascular access, in about 70% of cases through an arteriovenous fistula (AVF) surgically created by connecting an artery and vein. AVF take 6 weeks or more to mature. Mature fistulae often require intervention, most often percutaneous transluminal angioplasty (PTA), also known as fistulaplasty, to maintain the patency of the fistula. PTA is also the first-line intervention to restore blood flow and prolong the use of an AVF, and many patients undergo the procedure multiple times. Although PTA is important for AVF maturation and maintenance, research into predictive models of AVF function following PTA has been limited. Therefore, in this paper we hypothesize that based on patient-specific information collected during PTA, a predictive model can be created to help improve treatment planning. We test a set of rich, multimodal data from 28 patients that includes medical history, AVF blood flow, and interventional angiographic imaging (specifically excluding any post-PTA measurements) and build deep hybrid neural networks. A hybrid model combining a 3D convolutional neural network with a multi-layer perceptron to classify AVF was established. We found using this model that we were able to identify the association between different factors and evaluate whether the PTA procedure can maintain primary patency for more than 3 months. The testing accuracy achieved was 0.75 with a weighted F1-score of 0.75, and AUROC of 0.75. These results indicate that evaluating multimodal clinical data using artificial neural networks can predict the outcome of PTA. These initial findings suggest that the hybrid model combining clinical data, imaging and hemodynamic analysis can be useful to treatment planning for hemodialysis. Further study based on a large cohort is needed to refine the accuracy and model efficiency.

Beyond Obesity and Overweight: The Clinical Assessment and Treatment of Excess Body Fat in Children : Part 1 - Insulin Resistance as the Root Cause of Pediatric Obesity.

Pediatric obesity and comorbidities related to insulin resistance continue to be a growing public health crisis. If lifestyle measures are unsuccessful, pharmacological and surgical interventions are offered. In this paper, we describe the driving force of the obesity crisis: hyperinsulinemia and the development of insulin resistance. We give historical background of key policy issues which have contributed to this pandemic as well as the physiologic mechanisms of insulin resistance. The prevalence of obesity will continue to rise unless the root cause of hyperinsulinemia is addressed. Current research on insulin resistance demonstrates that a decreased consumption of carbohydrates is an effective first-line dietary intervention for the treatment of obesity and related metabolic diseases. Evidence shows it is safe and beneficial. A low-carbohydrate eating pattern can be helpful to address pediatric obesity. However, there must be policy guardrails in place to ensure that this is a sustainable and viable option for children and their families. There must be a change in the nutritional environment to help individuals battle the chronic disease of obesity.

Beyond Obesity and Overweight: the Clinical Assessment and Treatment of Excess Body Fat In Children : Part 2 - the Prescription of Low-Carbohydrate Eating as the First Approach.

Pediatric obesity and comorbidities related to insulin resistance continue to be a growing public health crisis. If lifestyle measures are unsuccessful, pharmacological and surgical interventions are offered. In this paper, we describe the driving force of the obesity crisis: hyperinsulinemia and the development of insulin resistance. We give historical background of key policy issues which have contributed to this pandemic as well as the physiologic mechanisms of insulin resistance. The prevalence of obesity will continue to rise unless the root cause of hyperinsulinemia is addressed. Current research on insulin resistance demonstrates that a decreased consumption of carbohydrates is an effective first-line dietary intervention for the treatment of obesity and related metabolic diseases. Evidence shows it is safe and beneficial. A low-carbohydrate eating pattern can be helpful to address pediatric obesity. However, there must be policy guardrails in place to ensure that this is a sustainable and viable option for children and their families. There must be a change in the nutritional environment to help individuals battle the chronic disease of obesity.

Acute Cholangitis GRADE II–III. The View of an Interventional Radiologist

Aim of study To evaluate the safety and efficacy of percutaneous transhepatic cholangiostomy (PTC) as a first-line intervention in the treatment of patients with acute cholangitis (AC) Grade II–III (TG 13/18).Material and methods The results of treatment of 42 patients with AC Grade II–III, who underwent PTC, were analyzed. The criteria for non-inclusion were the presence in patients of destructive cholecystitis and (or) acute pancreatitis, AC due to proximal block of the bile ducts, regardless of etiology, as well as the presence of cholangiogenic liver abscesses. Literature data were used as reference results of the use of endoscopic techniques. AC was diagnosed and its severity was determined in accordance with the diagnostic criteria TG 13/18. The control points of the study were the frequency of post-manipulation complications associated with PTC, as well as the immediate efficacy of cholangiostomy, assessed by the dynamics of Grade-status within 24 and 48 hours.Results In all 42 patients, PTC was technically successful. Major complications that might require a change in treatment tactics (significant hemobilia, bile peritonitis, bleeding into the abdominal cavity) were not observed. Two complications occurred: subcapsular hematoma (2.4%) and right-sided pleurisy (2.4%). When assessing the dynamics of Grade status, its significant decrease was found in the group of patients with initial Grade III after 24 hours (from 16 to 9 hours) and 48 hours (from 9 to 4 hours). In patients with initial Grade II status, in three cases it worsened to Grade III, which still persisted in one patient even in 48 hours. There was no in-hospital mortality in the examined patients.Conclusion Antegrade endobiliary intervention for acute cholangitis involves performing real-time monitored biliary decompression. Experience with the use of percutaneous interventions does not confirm the high risk and frequency of post-manipulation complications in comparison with endoscopic retrogradeprocedures. It seems obvious that there is a need for and the possibility of choosing both retrograde and antegrade methods of emergency biliary decompression in the arsenal of treatment for patients with acute cholangitis.

Healing wounded trees: clinicians' perspectives on treatment of complex posttraumatic stress disorder.

While treatment guidelines agree on the first-line interventions for the treatment of posttraumatic stress disorder (PTSD), there is an ongoing debate between experts regarding the treatment of complex posttraumatic stress disorder (C-PTSD). As scientific research is slowly emerging, different treatment approaches are used in clinical practice This article aims to provide a set of treatment options for C-PTSD in adult survivors of repeated exposure to severe violence and abuse, both in childhood and later on in life. The developmental-contextual perspective on mental health forms the basis of this approach. This perspective is elaborated using the tree metaphor. Then, several treatment strategies are suggested. The presented strategies are a combination of the existing evidence-based approaches for the treatment of PTSD and personality disorders. They target psychological damage in survivors while taking their developmental trajectories and ecological environments into consideration. The treatment model presented is based on longstanding clinical practice and it may be a promising framework for treating C-PTSD. However, it still needs to be scientifically examined for acceptability and effectiveness.

Effect of Fluid and Caffeine Management on Quality of Life in Older Women with Overactive Bladder in Rural Korea: A Pilot Study.

This study aimed to investigate the effectiveness of the simplified intervention, consisting of fluid and caffeine management alone in older women with overactive bladder symptoms. A quasi-experimental pretest-posttest design was used. Rural, community-dwelling older women were recruited at four senior centers in South Korea. Of the 63 participants initially enrolled, 34 met the inclusion criteria. One group (n = 15) used fluid and caffeine management alone (FM), and the other group (n = 12) used a combination of fluid and caffeine management and pelvic floor muscle training (FM+PFMT). Urinary symptom-specific health-related quality of life was measured using the Korean version of KHQ. Sleep quality was measured using the Pittsburgh Sleep Quality Index. After the intervention, participants were assessed 4 and 8 weeks. A linear mixed model was used for the analysis. The mean age of the participants was 74.44 ± 5.67 years. Among the nine domains of KHQ, impact on life and physical limitations decreased significantly in both groups, without significant between-group differences. Sleep/energy increased in both groups, and the scores in the FM+PFMT group were significantly improved. The number of micturition episodes per day and the quality of sleep did not differ significantly between the two groups. A simplified intervention, consisting of fluid and caffeine management alone can be considered as the first-line intervention to improve health-related quality of life in rural, community-dwelling, older women with overactive bladder symptoms. Healthcare providers should consider providing a relatively simple, but equally effective intervention to maximize the adherence and effectiveness.

The Role of Pharmaceutical Innovation in Clinical Practice Guidelines for Chronic Diseases.

Over the last 25 years, clinical practice guidelines have emerged as a means to standardize and improve care. As pharmaceutical innovations develop, guidelines are updated to incorporate new interventions. However, the extent to which pharmacotherapies are represented as treatment options in guideline recommendations has not been well elucidated. This study aimed to quantify the role pharmacotherapy has played in clinical practice guidelines across a range of chronic diseases over the past 20 years. Clinical practice guidelines published from 2000 to 2021 were identified for five chronic diseases: ischemic heart disease (IHD), non-small cell lung cancer (NSCLC), chronic obstructive pulmonary disease (COPD), Alzheimer's disease (AD), and type 2 diabetes (T2D). Guidelines were reviewed and data on treatment recommendations were collected, including the type of intervention, line of therapy, and, for pharmacotherapies, year of regulatory approval and year of inclusion in guidelines. In total, 92 clinical practice guidelines were reviewed. Among the 184 discrete recommended interventions across the five disease areas, 146 (79.3%) were pharmacotherapies, 21 (11.4%) were behavioral modifications, 6 (3.3%) were surgical interventions, and 11 (6%) were other interventions. Across guidelines, when a line of therapy was specified, behavioral modifications and pharmacotherapies were most frequently recommended as first-line interventions, whereas surgical interventions were more often recommended for subsequent lines of treatment. The time from regulatory approval of novel pharmacotherapies to inclusion in guideline recommendations varied considerably by disease area and geography. Across the reviewed disease areas, behavioral interventions and pharmacotherapies are shown to be critical components of clinical practice. Over the last 20 years, novel pharmaceutical innovations have been incorporated into clinical practice guideline recommendations; however, with varying speeds of adoption. Given the increasing pace of pharmacologic innovation, timely updates of clinical practice guidelines are critical to evolving the standard of care and practicing evidence-based medicine.

Access to psychological treatment for chronic cancer-related pain in Sweden.

Cancer-related pain (CRP) is among the most frequent collateral effects of cancer, with chronic CRP, lasting at least 3 months, affecting >40% of cancer survivors. Evidence-based treatments, including pain-focused cognitive behavioral therapy (CBT), are available, but it appears that cancer patients/survivors are often poorly informed about CRP or the potential benefits of CBT for such pain. This study examined current experience of Swedish cancer patients/survivors in relation to CRP. Participants (N = 276; 83% female; mean age = 55.5 years, SD = 11.9) were recruited to an online survey via cancer websites in Sweden, and they provided information about their history of chronic CRP and whether they received information about or treatment for CRP from a healthcare professional. Participants had a history of breast (36%), gynecological (12%), lung (10%), colon (8%), and other forms of cancer (36%). A majority (74%) reported a history of chronic CRP and being prescribed analgesic medications (70%). Less than half (47%) received information from their healthcare provider about the risk of CRP and only 13% with chronic CRP received psychological treatment, and of these, only 33% received CBT. Among those receiving psychological treatment for chronic CRP, satisfaction rates were moderate, reported as an average of 6 on a 0-10 scale (standard deviation 2.6). Greater efforts are needed to raise awareness among cancer patients/survivors and healthcare providers about the risk of CRP and evidence-based interventions, including CBT, the first-line intervention for chronic pain. These efforts will need to be matched with increases in treatment capacity, particularly pain-focused CBT.

A Rare Case of Hairy Cell Leukemia with COVID Infection: A Case Report

Abstract Hairy cell leukemia (HCL) is a distinct subset of chronic lymphoid leukemia, presents with unique features, including the characteristic "hairy" projections seen in neoplastic B cells. We reported a case on hairy cell leukemia (HCL), emphasizing the challenges posed by this rare hematological malignancy, especially in the context of concurrent health crises such as the COVID-19 pandemic. This malignancy, though uncommon, necessitates comprehensive diagnostic methodologies, such as peripheral blood studies, flow cytometry, and bone marrow biopsy. Treatment strategies for HCL involve tailored approaches based on symptomatic presentations. Purine analogs, cladribine and pentostatin, stand as first-line interventions, showcasing efficacy in inducing and sustaining remission. However, the prolonged immunosuppression resulting from these treatments warrants vigilant monitoring for potential infectious complications. Emerging therapies, such as the BRAF inhibitor vemurafenib, provide additional options for refractory or progressive cases. The post-treatment phase demands meticulous follow-up, with an emphasis on regular blood work assessments by an oncology nurse and primary care physician. Our case further highlights the need for heightened awareness among healthcare professionals, particularly in the post-COVID-19 phase, where persistent symptoms led to the discovery of an underlying hematological disorder. Keywords: Hairy cell leukemia, Evan syndrome, Covid-19.

Effects of Endotracheal Epinephrine on Pharmacokinetics and Survival in a Swine Pediatric Cardiac Arrest Model.

The aim of this study was to compare the endotracheal tube (ET) and intravenous (IV) administration of epinephrine relative to concentration maximum, time to maximum concentration, mean concentration over time (MC), area under the curve, odds, and time to return of spontaneous circulation (ROSC) in a normovolemic pediatric cardiac arrest model. Male swine weighing 24-37 kg were assigned to 4 groups: ET (n = 8), IV (n = 7), cardiopulmonary resuscitation (CPR) + defibrillation (CPR + Defib) (n = 5), and CPR only (n = 3). Swine were placed arrest for 2 minutes, and then CPR was initiated for 2 minutes. Epinephrine (0.1 mg/kg) for the ET group or 0.01 mg/kg for the IV was administered every 4 minutes or until ROSC. Defibrillation started at 3 minutes and continued every 2 minutes for 30 minutes or until ROSC for all groups except the CPR-only group. Blood samples were collected over a period of 5 minutes. The MC of plasma epinephrine for the IV group was significantly higher at the 30- and 60-second time points (P = 0.001). The ET group had a significantly higher MC of epinephrine at the 180- and 240-second time points (P < 0.05). The concentration maximum of plasma epinephrine was significantly lower for the ET group (195 ± 32 ng/mL) than for the IV group (428 ± 38 ng/mL) (P = 0.01). The time to maximum concentration was significantly longer for the ET group (145 ± 26 seconds) than for the IV group (42 ± 16 seconds) (P = 0.01). No significant difference existed in area under the curve between the 2 groups (P = 0.62). The odds of ROSC were 7.7 times greater for the ET versus IV group. Time to ROSC was not significantly different among the IV, ET, and CPR + Defib groups (P = 0.31). Based on the results of this study, the ET route of administration should be considered a first-line intervention.

Clinical impact of KRAS mutations in metastatic pancreatic ductal adenocarcinoma (PDAC).

619 Background: Mutations in the KRAS oncogene occur in most PDAC and lead to the activation of the KRAS protein. Little is known about the differential impact of KRAS mutations on the outcomes of patients receiving standard of care cytotoxic treatments for metastatic disease. KRAS inhibitors are emerging as promising options for this disease and understanding the impact of distinct KRAS mutations in patient outcomes is needed. Methods: This study used the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database from 5,369 patients. Adult patients with diagnosis of metastatic PDAC who received at least one line of systemic therapy and had sufficient data available were included in this analysis. Median time to next treatment (TTNT) and overall survival (OS) time were calculated for three common first-line treatments and KRAS mutations. TTNT and OS were calculated for each permutation of treatment and each KRAS mutation. Hazard ratios (HR) were generated for each KRAS mutation and treatment, accounting for potentially confounding variables. Results: Of the 5,369 patients, 2,472 met the inclusion/exclusion criteria. G12C had the shortest median OS (7.5 mo) and G12R had the longest (9.1 mo). Overall, KRAS mutation-positive patients had a median OS of 8.6 mo, compared to 11.7 mo for KRAS Wild Type (WT) patients. A Cox Proportional Hazard analysis of OS across KRAS mutation status found that G12C, G12V, G12D, and Other Non G12/13 KRAS had significantly higher HR than KRAS WT. A comparison of the three common first-line interventions for metastatic PDAC showed that FOLFIRINOX had the longest median TTNT (5.3 mo) and the longest OS (10.2 mo), while Gemcitabine had the shortest TTNT (2.6 mo) and OS (5.9 mo). A Cox Proportional Hazard analysis of OS across all patients found that Gemcitabine and Gemcitabine with Nabpaclitaxel had significantly higher HR than FOLFIRINOX. FOLFIRINOX had the longest TTNT in the G12C, G12V, G12D, G12R, and other non-G12/G13 KRAS groups (see table). Conclusions: Our data suggest that FOLFIRINOX has a longer TTNT than other first-line regimens for KRAS G12C, G12V, G12D, and G12R. KRAS G12C was associated with the shortest OS among common KRAS mutations.[Table: see text]

A cross sectional study exploring the relationship of self-reported physical activity with function, kinesiophobia, self-efficacy and quality of life in an Asian population seeking care for knee osteoarthritis

BackgroundPhysical activity is a guideline-recommended first-line intervention for people with knee osteoarthritis. Physical activity levels, and its potential correlates, is underexplored in Asian populations with knee osteoarthritis.MethodsParticipants enrolled in a longitudinal study in Singapore self-reported physical activity (UCLA activity score), function (Knee Osteoarthritis Outcome Score [KOOS-12]), kinesiophobia (Brief fear of movement [BFOM]), self-efficacy (ASES-8), and quality of life (EQ-5D-5 L). One-Way ANOVA was used to test the difference in outcomes between UCLA categories, while ordinal logistic regression was used to identify the associated factors to physical activity level.ResultsSeventy-three percent of all enrolled participants (n = 311/425) reported either inactivity or low physical activity (median 4, IQR 3–5). Significant, weak, positive correlations were observed be-tween UCLA activity score and either KOOS-12 (Spearman’s rho: 0.1961; p < 0.001), ASES-8 (0.1983; p = 0.004), or EQ-5D-5 L (0.2078; p < 0.001). A significant, weak, negative correlation was observed between physical activity and BFOM (-0.2183; p < 0.001). Significant differences in function between groups (moderate vs. inactive or low physical activity) were not clinically important. Participants with obesity, from the eldest age category (i.e. ≥75), or who identified as Malay or female, were less physically active than those with a healthy BMI, below the age of 54, or who identified as Chinese or male, respectively.ConclusionHealthcare professionals in Asia should be aware of the large proportion of people with knee osteoarthritis who are either inactive or have low physical activity levels. Screening for, and offering interventions to promote, physical activity and its correlates should be prioritised.

Isolated Tubercular Epididymitis: A 10-Year Series

Introduction: Genitourinary tuberculosis (TB) is considered a common form of extrapulmonary TB, being second only to lymph node tuberculosis, which is the most common site. Isolated TB of the epididymis is rare, and diagnosis of epididymal TB can be challenging. In this study, we report our series of isolated TB of the epididymis. Materials &amp; Methods: We retrospectively collected the outpatient and inpatient records of histologically confirmed epididymal tuberculosis. Data including age, clinical presentation, examination findings, and diagnostic tests were reviewed and analyzed. Results: A total of 56 patients were diagnosed to have isolated tuberculosis of the epididymis during the 10-year study period. The mean age was 33 years. The clinical presentation included a hard nodule in the epididymis (100%), hydrocele in 16 (28.5%), posterior scrotal sinus in 6 (10.7%), and sensitivity in 14 (25%) and fever in 3 (5.3%). Four (7.1%) patients had bilateral epididymal nodules, 30 (53.5%) had left-sided, and 22 (39.2%) had right-sided involvement. Scrotal exploration and epididymal biopsy were performed in 16 (28.5%), and unilateral epididymectomy was performed in 40 (71.4%). The histopathological examination revealed a typical tubercular granuloma in all these patients. All patients were put on anti-TB drugs. Conclusions: Isolated TB of the epididymis is a rare disease. Treatment with anti-TB drugs remains the first-line intervention in all cases. Surgery is indicated in cases of failure of pharmacological treatment or the development of complications.