Patient Population Research Articles

Comparative Evaluation of Mortality Predictors in Trauma Patients: A Prospective Single-center Observational Study Assessing Injury Severity Score Revised Trauma Score Trauma and Injury Severity Score and Acute Physiology and Chronic Health Evaluation II Scores.

This prospective cohort study aimed to compare the predictive accuracy of outcome (survival/death) among trauma patients using various prognostic scores. Over 3 months, 240 trauma patients in a tertiary care hospital were assessed for demographic details, trauma characteristics, vital signs, Glasgow coma scale, arterial blood gas values, and lab markers. Injury severity score (ISS), revised trauma score (RTS), trauma and injury severity score (TRISS), and acute physiology and chronic health evaluation II (APACHE II) were applied at admission, 24 hours, and 48 hours post-admission. Road traffic accidents (55.83%) were the primary cause of trauma, followed by falls (33.75%) and violence (10.41%). The all-cause mortality rate was 23.33%, with 34.16% requiring ICU admission. Head injuries (65.83%) were both the most frequent injury site and cause of mortality. Analysis indicated that APACHE II outperformed other scores in predicting outcomes, with ISS following closely. The study concludes that trauma severity correlates with ICU admission and mortality, emphasizing APACHE II as a superior predictor, particularly for traumatic brain injuries leading to ICU admission and mortality. This study contributes to the existing body of knowledge by addressing the gap in comparing prognostic abilities among scoring systems for trauma patients. The unexpected superiority of APACHE II suggests its potential as a valuable tool in predicting outcomes in this specific patient population. Gupta J, Kshirsagar S, Naik S, Pande A. Comparative Evaluation of Mortality Predictors in Trauma Patients: A Prospective Single-center Observational Study Assessing Injury Severity Score Revised Trauma Score Trauma and Injury Severity Score and Acute Physiology and Chronic Health Evaluation II Scores. Indian J Crit Care Med 2024;28(5):475-482.

Cannabidiol-enriched oil for adult patients with drug-resistant epilepsy: Prospective clinical and electrophysiological study.

Cannabidiol-enriched oil (CBDO) is being used increasingly to improve seizure control in adult patients with drug-resistant epilepsy (DRE), despite the lack of large-scale studies supporting its efficacy in this patient population. We aimed to assess the effects of add-on CBDO on seizure frequency as well as on gait, cognitive, affective, and sleep-quality metrics, and to explore the electrophysiological changes in responder and non-responder DRE patients treated with add-on CBDO. We prospectively recruited adult DRE patients who were treated with add-on CBDO. Patients were evaluated prior to treatment and following 4 weeks of a maintenance daily dose of ≈260 mg CBD and ≈12 mg Δ9-tetrahydrocannabinol (THC). The outcome measures included seizure response to CBDO (defined as ≥50% decrease in seizures compared to pre-CBDO baseline), gait testing, Montreal Cognitive Assessment (MoCA), Hospital Anxiety and Depression Scale (HADS), and sleep-quality questionnaire assessments. Patients underwent electroencephalography (EEG) recording during rest as well as event-related potentials (ERPs) during visual Go/NoGo task while sitting and while walking. Nineteen patients were recruited, of which 16 finished pre- and post-CBDO assessments. Seven patients (43.75%) were responders demonstrating an average reduction of 82.4% in seizures, and nine patients (56.25%) were non-responders with an average seizure increase of 30.1%. No differences in demographics and clinical parameters were found between responders and non-responders at baseline. However, responders demonstrated better performance in the dual-task walking post-treatment (p = .015), and correlation between increase in MoCA and seizure reduction (r = .810, p = .027). Post-CBDO P300 amplitude was lower during No/Go-sitting in non-responders (p = .028) and during No/Go-walking in responders (p = .068). CBDO treatment can reduce seizures in a subset of patients with DRE, but could aggravate seizure control in a minority of patients; yet we found no specific baseline clinical or electrophysiological characteristics that are associated with response to CBDO. However, changes in ERPs in response to treatment could be a promising direction to better identify patients who could benefit from CBDO treatment.

Impact of Risk Stratification in Patients With Diabetes Mellitus in a Health System Specialty Pharmacy Setting.

Background: Integrated pharmacist care into health systems results in significant A1c reduction and improved outcomes in patients with diabetes. However, little is known about the adoption of Health System Specialty Pharmacy (HSSP) chronic disease management (CDM) services within diabetes clinics. Risk stratification is proven to enhance care in various patient populations. Objective: The objective of this study is to describe how the implementation of risk stratification in the HSSP setting results in optimized patient outcomes in diabetes. Method: This is a retrospective descriptive study reporting the results of expanding the HSSP care model to implement risk stratified CDM services for patients with diabetes. A total of 285 patients were enrolled in the HSSP CDM pharmacy services and were stratified into high- or low-risk groups. Results: Eighty-eight patients were stratified as high-risk with an average baseline A1c of 11.47% and a most recent average of 8.84%. The remaining 285 patients were stratified into the low-risk group. Their average baseline A1c was 7.48% and the last recorded average A1c was 7.15%. Patients not enrolled in HSSP CDM services (N = 100) had a lower reduction in average A1c compared to patients enrolled in the program. Conclusion: Patients stratified into high- and low-risk groups had greater reductions in A1c compared to patients who did not use HSSP CDM services. These results showcase the success of risk stratification and demonstrate the impact HSSP has on patients needing CDM services and outlines a strategy to provide the greatest impact in a high-volume patient population.

Enhancement of anti-PD-L1 antibody plus anlotinib efficacy due to downregulation of PD-L1 in the micro-conduit endothelium within the tumor: a randomized double-blind trial.

The possible enhancing effect of anlotinib on programmed death receptor ligand (PD-L1) antibody and the efficacy-predicting power of PD-L1 in micro-conduit endothelium, including lymphatic endothelial cells (LECs) and blood endothelial cells (BECs), were determined to identify patients who would benefit from this treatment. PD-L1 positivity in LECs, BECs, and tumor cells (TCs) was assessed using paraffin sections with multicolor immunofluorescence in an investigator's brochure clinical trial of TQB2450 (PD-L1 antibody) alone or in combination with anlotinib in patients with non-small cell lung cancer. Progression-free survival (PFS) with different levels of PD-L1 expression was compared between the two groups. Among 75 patients, the median PFS (mPFS) was longer in patients who received TQB2450 with anlotinib [10 and 12 mg (161 and 194 days, respectively)] than patients receiving TQB2450 alone (61 days) [hazard ratio (HR)10 mg = 0.390 (95% confidence interval {CI}, 0.201-0.756), P = 0.005; HR12 mg = 0.397 (0.208-0.756), P = 0.005]. The results were similar among 58 patients with high PD-L1 expression in LECs and TCs [159 and 209 vs. 82 days, HR10 mg = 0.445 (0.210-0.939), P = 0.034; HR12 mg = 0.369 (0.174-0.784), P = 0.009], and 53 patients with high PD-L1 expression in BECs and TCs [161 and 209 vs. 41 days, HR10 mg = 0.340 (0.156-0.742), P = 0.007; HR12 mg = 0.340 (0.159-0.727), P = 0.005]. No differences were detected in the mPFS between the TQB2450 and combination therapy groups in 13 low/no LEC-expressing and 18 low/no BEC-expressing PD-L1 cases. Mono-immunotherapy is not effective in patients with high PD-L1 expression in LECs and/or BECs. Anlotinib may increase efficacy by downregulating PD-L1 expression in LECs and/or BECs, which is presumed to be a feasible marker for screening the optimal immune patient population undergoing anti-angiogenic therapy.

Use of Patient-Centered Technology and Digital Interventions in Pediatric and Adult Patients with Hematologic Malignancies.

As society continues to advance in technology, it is important to address how this advancement can impact and enhance patient care. The purpose of this review is to identify patient-centered technology currently available for adult and pediatric patients with and those having survived hematologic malignancies. Given that patients with hematologic malignancies often have to adhere to strenuous medication regimens, coordinate care with many different providers, manage symptoms associated with treatment, and manage late effects associated with survivorship, they would benefit greatly from patient-centered technology aimed at decreasing these burdens. This review found various available digital interventions for this patient population and focuses on an overview of commercially available smartphone applications, patient portals, and technology for remote monitoring. In summary, many digital interventions exist for use in the medical care of oncology patients. The incorporation of these interventions can allow for more personalized medical care, better organization of treatment plans by caregivers at home, and easy delivery of accurate medical information.

Preoperative Physical Therapy is Associated with Decreased Length of Stay and Improved Postoperative Mobility in Patients with Sarcopenia Undergoing Adult Spinal Deformity Surgery.

Retrospective cohort study. To determine the relationship between preoperative physical therapy (PT) and postoperative mobility, adverse events (AEs), and length of stay (LOS) among patients with low normalized total psoas area (NTPA) undergoing ASD surgery. Sarcopenia as defined by low NTPA has been shown to predict poor perioperative outcomes following adult spinal deformity (ASD) surgery. However, there is limited evidence correlating the benefits of PT within the sarcopenic patient population. NTPA was analyzed at the L3 and L4 mid-vertebral body on preoperative magnetic resonance imaging (MRI). Receiver operating characteristic (ROC) curve analysis was used to determine gender-specific NTPA cut-off values for predicting perioperative AEs. Patients were categorized as having low NTPA if both L3 and L4 NTPA were below these cut-off values. Perioperative outcomes were compared between patients with low NTPA that underwent documented formal PT within 6 months prior to ASD surgery with those that did not. 103 patients (42 males, 61 females) met criteria for low NTPA for inclusion in the study, of which 42 underwent preoperative PT and 61 did not. The preoperative PT group had a shorter LOS (111.2±37.5 vs. 162.1±97.0h, P<0.001), higher ambulation distances (feet) on postoperative day (POD) 1 (61.7±50.3 vs. 26.1±69.0, P<0.001), POD 2 (113.2±81.8 vs. 62.1±73.1, P=0.003), and POD 3 (126.0±61.2 vs. 91.2±72.6, P=0.029), and lower rates of total AEs (31.0% vs. 54.1%, P=0.003) when excluding anemia requiring transfusion. Multivariable analysis found preoperative PT to be the most significant predictor of decreased LOS (OR 0.32, P=0.013). Sarcopenic patients may benefit from formal preoperative PT prior to undergoing ASD surgery to improve early postoperative mobility, decrease AEs, and decrease LOS. 3.

Lack of Prognostic Value of T-Wave Alternans for Implantable Cardioverter-Defibrillator Benefit in Primary Prevention.

New methods to identify patients who benefit from a primary prophylactic implantable cardioverter-defibrillator (ICD) are needed. T-wave alternans (TWA) has been shown to associate with arrhythmogenesis of the heart and sudden cardiac death. We hypothesized that TWA might be associated with benefit from ICD implantation in primary prevention. In the EU-CERT-ICD (European Comparative Effectiveness Research to Assess the Use of Primary Prophylactic Implantable Cardioverter-Defibrillators) study, we prospectively enrolled 2327 candidates for primary prophylactic ICD. A 24-hour Holter monitor reading was taken from all recruited patients at enrollment. TWA was assessed from Holter monitoring using the modified moving average method. Study outcomes were all-cause death, appropriate shock, and survival benefit. TWA was assessed both as a contiguous variable and as a dichotomized variable with cutoff points <47 μV and <60 μV. The final cohort included 1734 valid T-wave alternans samples, 1211 patients with ICD, and 523 control patients with conservative treatment, with a mean follow-up time of 2.3 years. TWA ≥60 μV was a predicter for a higher all-cause death in patients with an ICD on the basis of a univariate Cox regression model (hazard ratio, 1.484 [95% CI, 1.024-2.151]; P=0.0374; concordance statistic, 0.51). In multivariable models, TWA was not prognostic of death or appropriate shocks in patients with an ICD. In addition, TWA was not prognostic of death in control patients. In a propensity score-adjusted Cox regression model, TWA was not a predictor of ICD benefit. T-wave alternans is poorly prognostic in patients with a primary prophylactic ICD. Although it may be prognostic of life-threatening arrhythmias and sudden cardiac death in several patient populations, it does not seem to be useful in assessing benefit from ICD therapy in primary prevention among patients with an ejection fraction of ≤35%.

Identifying Giant Cell Arteritis patients with higher risk of relapse and vascular events: a cluster analysis.

Giant cell arteritis (GCA) is one of the most common large vessel (LVV) vasculitis and is associated with a high risk of relapse and cardiovascular complications. Improving risk stratification remains a significant issue in this patient population. We aimed to perform a cluster analysis among GCA to identify clusters and evaluate their prognostic value. In a multicenter cohort study, we performed hierarchical cluster analysis on the factor analysis of mixed data coordinates results with 283 GCA patients' characteristics to generate clusters and assess incidence of relapse, cardiovascular events and death. Three clusters were identified: "Vascular relapsing profile" (23.0%), "Typical GCA profile" (47.7%), and "Ophthalmologic elderly profile" (29.3%). The "Vascular relapsing profile" cluster included younger patients with more frequent relapses and cardiovascular events, particularly thoracic aortic aneurysms. The "Typical GCA profile" was the largest, with classic cranial manifestations and frequently associated polymyalgia rheumatica. The "Ophthalmologic elderly profile" had the oldest patients with more visual loss and the highest mortality rate. Our findings underline the varied prognostic landscape within GCA, emphasizing the poor cardiovascular prognosis of younger patients with LV involvement and the higher mortality among elderly patients. This reinforces the need for further research regarding the screening of aortic abnormalities and whether those patients might benefit from intensive treatment with biotherapy and cardiovascular risk factors management.

HPV overtakes smoking as the leading cause of oropharyngeal cancer in Ireland: experience of a head and neck surgery tertiary referral centre.

Worldwide, the incidence of oropharyngeal squamous cell carcinoma (OPSCC) caused by human papillomavirus (HPV), a sexually transmitted virus, is increasing. This increase has yet to be demonstrated in an Irish cohort. To evaluate the number of OPSCC presentations locally, to stratify cases by HPV status and to estimate if any changes in the patient population had occurred over a 10-year period. A STROBE-compliant, retrospective evaluation of patients with OPSCC at St James's Hospital between 2012 and 2022 was performed. Patients with non-SCC histology, undocumented HPV status and residual or recurrent tumours were excluded. We included 294 patients with a mean age of 60.4years (95% CI 59.2-61.5years) and 175 (59.5%) patients had HPV+ OPSCC. The number of new OPSCC diagnoses increased from 115 patients (39.1%) between 2012 and 2016 to 179 patients (60.9%) between 2017 and 2021. This was associated with an increased proportion of HPV-linked OPSCC (50.4% 2012-2016 vs. 65.4% 2017-2021, p = 0.011). Over time, more patients had a functionally limiting comorbidity (p = 0.011). The mean age of HPV+ OPSCC cases increased by 3.6years (p = 0.019). Patients with HPV+ OPSCC had greater 2-year OS (83.9% vs. 54.9%; p < 0.001) and 2-year DFS (73.5% vs. 45.6%; p < 0.001). The 2-year OS and DFS did not change over time for HPV+ or HPV- patients. In our institution, the number of patients with OPSCC is increasing due to an escalation in cases associated with HPV. Population-level interventions such as vaccination programs may alter the current increase in the incidence of these tumours.

Intracranial arterial calcification in patients with unruptured and ruptured intracranial aneurysms.

Arterial calcification is thought to protect against rupture of intracranial aneurysms, but studies in a representative population of intracranial aneurysm patients have not yet been performed. The aim was to compare the prevalence of aneurysm wall calcification and intracranial carotid artery calcification (ICAC) between patients with an unruptured intracranial aneurysm (UIA) and a ruptured intracranial aneurysm (RIA). We matched 150 consecutive UIA patients to 150 RIA patients on age and sex. Aneurysm wall calcification and ICAC were quantified on non-contrast enhanced computed tomography images with the modified Agatston score. We compared the prevalence of aneurysm wall calcification, ICAC, and severe ICAC (defined as a modified Agatston score in the fourth quartile) between UIA and RIA patients using univariate and multivariate conditional logistic regression models adjusted for aneurysm characteristics and cardiovascular risk factors. Aneurysm wall calcification was more prevalent in UIA compared to RIA patients (OR 5.2, 95% CI: 2.0-13.8), which persisted after adjustment (OR 5.9, 95% CI: 1.7-20.2). ICAC prevalence did not differ between the two groups (crude OR 0.9, 95% CI: 0.5-1.8). Severe ICAC was more prevalent in UIA patients (OR 2.0, 95% CI: 1.1-3.6), but not after adjustment (OR 1.0, 95% CI: 0.5-2.3). Aneurysm wall calcification but not ICAC was more prevalent in UIAs than in RIAs, which corresponds to the hypothesis that calcification may protect against aneurysmal rupture. Aneurysm wall calcification should be further assessed as a predictor of aneurysm stability in prospective cohort studies. Calcification of the intracranial aneurysm wall was more prevalent in unruptured than ruptured intracranial aneurysms after adjustment for cardiovascular risk factors. Calcification may therefore protect the aneurysm against rupture, and aneurysm wall calcification is a candidate predictor of aneurysm stability. Aneurysm wall calcification was more prevalent in patients with unruptured than ruptured aneurysms, while internal carotid artery calcification was similar. Aneurysm wall calcification but not internal carotid artery calcification is a candidate predictor of aneurysm stability. Cohort studies are needed to assess the predictive value of aneurysm wall calcification for aneurysm stability.

Blind versus endoscopy-guided postpyloric feeding tube placement in adults with ischemic stroke: A retrospective cohort study.

This study compared the one-time success rate of blind and endoscopy-guided postpyloric feeding tube placement after implementing a comprehensive nursing scheme of intestinal blind placement for patients with ischemic stroke. This retrospective cohort study included 179 patients with blind bedside placement and 118 with endoscopy-guided placement. The primary outcome was the one-time success rate of radiologically confirmed postpyloric placement. The secondary endpoints included the position of the tube tip, length of insertion, time of placement, and expenses. The safety endpoints were the incidence of complications caused by placement. The results showed that the method of tube placement did not significantly affect the outcome of the first tube placement (odds ratio [OR] = 0.41; 95% CI = 0.137-1.207; P = 0.105). Compared with endoscopy-guided placement, blind placement was half the cost. We also found that a history of abdominal surgery (OR = 0.003; 95% CI = 0.000-0.059; P < 0.001) and longer intensive care unit (ICU) days (OR = 0.94; 95% CI = 0.903-0.981; P = 0.004) were inversely associated with the one-time success rate. Our study suggested that blind intestinal feeding tube placement has an equivalent one-time success rate compared with endoscopy-guided placement in hospitalized patients with ischemic stroke if operators can be trained well. However, the expenses of endoscopy-guided placement were twice those of blind bedside methods. We also found that patients with abdominal surgery history and longer ICU stay were more likely to fail at the first placement. Further research is needed to replicate our single-center observations in a larger population of patients.

Prognostic value of visual IMPeTUs criteria and metabolic tumor burden at baseline [18F]FDG PET/CT in patients with newly diagnosed multiple myeloma

Background2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) positron emission tomography combined with low-dose computed tomography (PET/CT) can be used at diagnosis to identify myeloma-defining events and also provides prognostic factors. The aim of this study was to assess the prognostic significance of baseline [18F]FDG PET/CT visual IMPeTUs (Italian myeloma criteria for PET Use)-based parameters and/or total metabolic tumor volume (TMTV) in a single-center population of patients with newly diagnosed multiple myeloma (NDMM) eligible for transplantation.MethodsPatients with MM who underwent a baseline [18F]FDG PET/CT were retrospectively selected from a large internal database of the University Hospital of Liege (Liege, Belgium). Initially, all PET/CT images were visually analyzed using IMPeTUs criteria, followed by delineation of TMTV using a semi-automatic lesion delineation workflow, including [18F]FDG-positive MM focal lesions (FL) with an absolute SUV threshold set at 4.0. In a first step, to ensure PET/CT scans accurate reporting, the agreement between two nuclear medicine physicians with distinct experience was assessed. In the second step, univariable and multivariable analyses were conducted to determine the prognostic significance of [18F]FDG PET/CT parameters on progression free survival (PFS) and overall survival (OS), respectively.ResultsA total of 40 patients with NDMM were included in the study. The observers agreement in the analysis [18F]FDG PET/CT images was substantial for the presence of spine FL, extra spine FL, at least one fracture and paramedullary disease (Cohen’s kappa 0.79, 0.87, 0.75 and 0.64, respectively). For the presence of skull FL and extramedullary disease the agreement was moderate (Cohen’s kappa 0.56 and 0.53, respectively). Among [18F]FDG PET/CT parameters, a high number of delineated volumes of interest (VOI) using the SUV4.0 threshold was the only independent prognostic factor associated with PFS [HR (95% CI): 1.03 (1.004–1.05), P = 0.019] while a high number of FL (n > 10; F group 4) was the only independent prognostic factor associated with OS [HR (95% CI): 19.10 (1.90–191.95), P = 0.01].ConclusionOur work confirms the reproducibility IMPeTUs criteria. Furthermore, it demonstrates that a high number of FL (n > 10; IMPeTUs F group 4), reflecting a high [18F]FDG-avid tumor burden, is an independent prognostic factor for OS. The prognostic value of the TMTV delineated using a SUV4.0 threshold was not significant. Nevertheless, the count of delineated [18F]FDG-avid lesions VOI using a SUV4.0 threshold was an independent prognostic factor for PFS.

Evaluating the between-day reliability and likelihood of change of a test battery incorporating vastus lateralis muscle thickness, ankle-brachial pressure index, maximal voluntary torque, and six-minute walk test in patients with claudication.

The study aims to evaluate the between-day reliability of a proposed test battery for patients with claudication that can be used for monitoring the effectiveness of exercise interventions and other therapeutic strategies tailored to this patient population. Twenty-five men with claudication were recruited. The test battery consisted of the Vastus Lateralis muscle thickness (VL-MT), ankle-brachial pressure index (ABI), unilateral isometric knee extension maximal voluntary torque (MVT) and 6-minute walk test (6MWT). A single investigator conducted the tests for each patient on two separate testing sessions (T1 and T2) 5-7days apart. Good to excellent reliability was observed for VL-MT (ICC = 0.95, 95% LOA = ±3.10mm, SEM = 0.81mm), ABI (ICC = 0.97, 95% LOA = ±0.10, SEM = 0.02), MVT (ICC = 0.97, 95% LOA = ±24.0N·m, SEM = 6.31N·m), 6MWT distance (ICC = 0.99, 95% LOA = ±39.6m, SEM = 11.0m), 6MWT time to claudication (ICC = 0.99, 95% LOA = ±30.8s, SEM = 7.8s), and 6MWT ratings of pain (ICC = 0.87, 95% LOA = ±2.4 CR-10+, SEM = 0.7 CR-10+ ). Analysis derived from reliability data indicates a change of 1.4mm for VL-MT, 0.14 for ABI, 12N·m for MVT, 25m for 6MWT distance, 15s for 6MWT time to claudication and 1 CR-10+ for 6MWT ratings of pain is required to be interpreted as the minimum 'likely' change (76% chance). The test battery provides a reliable assessment of patients with claudication and can be widely used to evaluate the effects of exercise programmes and other therapeutic interventions. For the individual, changes in VL-MT, ABI, MVT, and 6MWT greater than the minimum likely change as a result of an exercise programme or an intervention are likely changes and less influenced by error associated with the test.

Role of Cyp2c19 Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention.

Identification of a reliable discriminatory test to accurately stratify patient responses to antiplatelet therapy following coronary revascularization has become increasingly desirable to optimize therapeutic efficacy and safety. The expansion of platelet function testing to include genotype assessment has been an evolutionary journey, initially fraught with confounding results. However, more recent and rigorous data analysis suggests that genotype testing- guided, tailored antiplatelet therapy may hold promise in optimizing treatment of patients after coronary intervention. Current evidence increasingly supports the use of genotype guided CYP2C19 testing to better match the post coronary intervention patient with the most efficacious and least risky antiplatelet inhibitor. The risk stratification of poor, intermediate, and good metabolizers of these drugs with such testing promises to yield clinical dividends in terms of morbidity, mortality and cost control, in this growing patient population.

Intraperitoneal pharmacokinetics of systemic oxaliplatin, 5-fluorouracil and bevacizumab in patients with colorectal peritoneal metastases

BackgroundPeritoneal metastases (PM) commonly occur in colorectal cancer patients. Systemic chemotherapy yields poor outcomes for these patients. It is hypothesised that traditional systemic chemotherapy is not very effective for this patient population. This study investigates to what extent systemic anti-cancer therapy crosses the peritoneal barrier. MethodsIn a Phase I study, eighteen patients received systemic oxaliplatin, 5-FU, and bevacizumab. Plasma and peritoneal fluid samples were collected to measure drug concentrations. A non-compartmental analysis determined the Area Under the Curve (AUC) for oxaliplatin and 5-FU in both matrices. Intraperitoneal (IP) and intravenous (IV) exposure ratios were calculated, along with the bevacizumab concentration IP/IV ratio. The relationship between tumour load and IP/IV ratios and the correlation between the IP/IV ratios of different treatments were assessed statistically. ResultsA total of 438 5-FU samples and 578 oxaliplatin samples were analysed in plasma and peritoneal fluid. Bevacizumab was quantified with 17 measurements in plasma and 15 measurements IP. Median IP/IV ratios were 0.143, 0.352 and 0.085 for 5-FU, oxaliplatin and bevacizumab, respectively. Oxaliplatin exhibited a longer IP half-life than 5-FU. A correlation was found between oxaliplatin and bevacizumab IP/IV ratios (R=0.69, p=0.01). No statistical correlations were found between the other investigated drugs. ConclusionsOur findings indicate that only a small percentage of systemically administered anti-cancer treatment reaches the IP cavity, questioning their efficacy against PM. This strengthens the hypothesis for repeated intraperitoneal chemotherapy to reach adequate anti-cancer drug levels.

Liquid foam improves potency and safety of gene therapy vectors

Interest in gene therapy medicines is intensifying as the first wave of gene-correcting drugs is now reaching patient populations. However, efficacy and safety concerns, laborious manufacturing protocols, and the high cost of the therapeutics are still significant barriers in gene therapy. Here we describe liquid foam as a vehicle for gene delivery. We demonstrate that embedding gene therapy vectors (nonviral or viral) in a methylcellulose/xanthan gum-based foam formulation substantially boosts gene transfection efficiencies in situ, compared to liquid-based gene delivery. We further establish that our gene therapy foam is nontoxic and retained at the intended target tissue, thus minimizing both systemic exposure and targeting of irrelevant cell types. The foam can be applied locally or injected to fill body cavities so the vector is uniformly dispersed over a large surface area. Our technology may provide a safe, facile and broadly applicable option in a variety of clinical settings.

Digital phenotyping data and anomaly detection methods to assess changes in mood and anxiety symptoms across a transdiagnostic clinical sample.

Clinical assessment of mood and anxiety change often relies on clinical assessment or self-reported scales. Using smartphone digital phenotyping data and resulting markers of behavior (e.g., sleep) to augment clinical symptom scores offers a scalable and potentially more valid method to understand changes in patients' state. This paper explores the potential of using a combination of active and passive sensors in the context of smartphone-based digital phenotyping to assess mood and anxiety changes in two distinct cohorts of patients to assess the preliminary reliability and validity of this digital phenotyping method. Participants from two different cohorts, each n = 76, one with diagnoses of depression/anxiety and the other schizophrenia, utilized mindLAMP to collect active data (e.g., surveys on mood/anxiety), along with passive data consisting of smartphone digital phenotyping data (geolocation, accelerometer, and screen state) for at least 1 month. Using anomaly detection algorithms, we assessed if statistical anomalies in the combination of active and passive data could predict changes in mood/anxiety scores as measured via smartphone surveys. The anomaly detection model was reliably able to predict symptom change of 4 points or greater for depression as measured by the PHQ-9 and anxiety as measured for the GAD-8 for both patient populations, with an area under the ROC curve of 0.65 and 0.80 for each respectively. For both PHQ-9 and GAD-7, these AUCs were maintained when predicting significant symptom change at least 7 days in advance. Active data alone predicted around 52% and 75% of the symptom variability for the depression/anxiety and schizophrenia populations respectively. These results indicate the feasibility of anomaly detection for predicting symptom change in transdiagnostic cohorts. These results across different patient groups, different countries, and different sites (India and the US) suggest anomaly detection of smartphone digital phenotyping data may offer a reliable and valid approach to predicting symptom change. Future work should emphasize prospective application of these statistical methods.

Impact of patient navigation on time from diagnosis to treatment in an urban safety net lung cancer patient population

Impact of patient navigation on time from diagnosis to treatment in an urban safety net lung cancer patient population

Vancomycin: An analysis and evaluation of eight population pharmacokinetic models for clinical application in general adult population.

Based on the recent guidelines for vancomycin therapeutic drug monitoring (TDM), the area under the curve to minimum inhibitory concentration ratio was to be employed combined with the usage of population pharmacokinetic (popPK) model for dosing adaptation. Yet, deploying these models in a clinical setting requires an external evaluation of their performance. This study aimed to evaluate existing vancomycin popPK models from the literature for the use in TDM within the general patient population in a clinical setting. The models under external evaluation were chosen based on a review of literature covering vancomycin popPK models developed in general adult populations. Patients' data were collected from Charles-Le Moyne Hospital (CLMH). The external evaluation was performed with NONMEM® (v7.5). Additional analyses such as evaluating the impact of number of samples on external evaluation, Bayesian forecasting, and a priori dosing regimen simulations were performed on the best performing model. Eight popPK models were evaluated with an independent dataset that included 40 patients and 252 samples. The model developed by Goti and colleagues demonstrated superior performance in diagnostic plots and population predictive performance, with bias and inaccuracy values of 0.251% and 22.7%, respectively, and for individual predictive performance, bias and inaccuracy were -4.90% and 12.1%, respectively. When limiting the independent dataset to one or two samples per patient, the Goti model exhibited inadequate predictive performance for inaccuracy, with values exceeding 30%. Moreover, the Goti model is suitable for Bayesian forecasting with at least two samples as prior for the prediction of the next trough concentration. Furthermore, the vancomycin dosing regimen that would maximize therapeutic targets of area under the curve to minimum inhibitory concentration ratio (AUC24/MIC) and trough concentrations (Ctrough) for the Goti model was 20 mg/kg/dose twice daily. Considering the superior predictive performance and potential for Bayesian forecasting in the Goti model, future research aims to test its applicability in clinical settings at CLMH, both in a priori and a posteriori scenario.

The Role of Antidepressants in a Malignancy Patient with Palliative Care: A Systematic Literature Review

Background: Depression is a common complication in malignancy patients, and can worsen their quality of life and prognosis. Palliative care aims to improve the quality of life of patients with life-limiting illnesses, and antidepressants are often used in this context. Methods: This systematic review was conducted to evaluate the effectiveness of antidepressants in malignancy patients with palliative care. A literature search was conducted in three databases: PubMed, Cochrane, and ScienceDirect. Search terms included “Antidepressants,” “Malignancies,” and “Palliatives.” Results: Two studies met inclusion criteria: First study: Randomized controlled clinical trial evaluating the effectiveness of mirtazapine compared with escitalopram in malignant patients with depression. The results showed that mirtazapine was more effective in improving quality of life and reducing depressive symptoms compared with escitalopram. Second study: a study evaluating the effectiveness of antidepressants in elderly malignancy patients with depression. The results suggest that antidepressants may be effective in reducing depressive symptoms and improving quality of life, but further research is needed to confirm their effectiveness and safety. Conclusion: Available evidence suggests that antidepressants may be effective in treating depression in malignancy patients with palliative care. However, further research is needed to identify the most effective and safe antidepressants for this patient population.