Referral Versus Embedded Palliative Care Consultation Among People Hospitalized With Heart Failure: A Report From a Single Center Pilot Program.

CONTEXT: Despite calls for integration into routine heart failure (HF) care, optimal palliative care delivery for people living with HF remains unclear. OBJECTIVES: Describe an innovative model of an embedded palliative care nurse practitioner (NP) within a HF team. Compare demographics and utilization among people hospitalized with HF receiving referral or embedded consultation. METHODS: Using an electronic health record-based palliative care registry, we conducted descriptive analyses and t-tests and χ2 tests, as appropriate, to examine bivariate associations between sociodemographic, clinical and utilization data of hospitalized people with HF receiving a traditional, referral-based palliative care consultation generated exclusively by the primary team vs. a novel, embedded-based consultation generated by collaboration between a palliative care NP and the advanced HF team at an urban, quaternary care academic medical center in New York City. RESULTS: During the study period from January 1, 2019-December 31, 2021, consultation volume nearly doubled with 363 consults from traditional referrals and an additional 317 consults from the newly embedded NP. People in the embedded group, as compared to referral, were younger (mean age: 60.1 vs. 71.9 years (2019); 59.2 vs. 70.4 (2020); 61.3 vs. 69.6 (2021), p-value < 0.001), more functional (median Karnofsky Performance Status: 40% vs. 30%, p-value = 0.01 (2019); 40% vs 20%, p-value < 0.0001 (2020); 40% vs. 20%, p-value = 0.02 (2021)), more likely had capacity to designate a medical decision maker (56.4% vs. 20.6%, p-value < 0.001 (2020); 76.3% vs. 49.5%, p-value < 0.001 (2021)), received earlier consultation (median days before discharge: 9.5 vs. 4 (2019); 11 vs. 5 (2020); 7 vs. 3 (2021), p-value ≤ 0.001), and more likely to discharge home (60% vs. 26%, p-value ≤ 0.001 (2019); 62.7% vs 20.6%, p-value ≤ 0.001 (2020); 42.3% vs. 28%, p-value = 0.03 (2021)). CONCLUSION: Hospitalized people living with advanced HF who received an embedded palliative care consult were younger, had higher functional status and less illness severity compared to those served by a traditional, referral-based consult.

Long-acting opioids and cardiovascular diseases: Help or hindrance!

Opioids are widely being used for chronic pain management, cough and diarrhea suppressants, anesthetic agents, and opioid de-addiction therapy. Opioid receptors, present in the central nervous system and peripheral tissues, are documented to regulate several cardiac functions through different signaling pathways. Long-acting opioids (LAO) have been successfully evaluated for their beneficial effects in various cardiovascular diseases viz. myocardial infarction, ischemic reperfusion injuries, atherosclerosis etc. However, on the other hand, several research studies pointed towards the harmful effects of LAOs which are mainly associated with QTc prolongation, torsade de pointes, ventricular arrhythmias, and cardiac arrest. This review shall familiarize readers with the benefits as well as the harmful effects of long-acting opioids in cardiovascular diseases. We have also provided an overview of cardiac opioid receptors, endogenous cardiac opioid peptides, and regulation of cardiovascular functions by central and cardiac opioid receptors.

Lessons Learned from an Embedded Palliative Care Model in the Medical Intensive Care Unit.

OBJECTIVE: To describe a physician (MD) and registered nurse (RN) led palliative care consultation team embedded in the medical intensive care unit (MICU). To compare patterns of palliative care consultation, and rates of goals of care documentation and in-ICU mortality before and after the implementation of the embedded team. CONTEXT: By embedding MD/RN palliative care team in the MICU, more critically ill patients with unmet palliative care needs could receive an earlier palliative care consultation. METHODS: In a retrospective cohort study of patients admitted to the MICU who received a palliative care consultation, we compared sociodemographic and clinical characteristics of patients who received a referral-based consultation (01/01/2019-06/30/2019) and those who received an embedded MD/RN consult (09/01/2019-02/28/2020). Using the electronic health record data, we compared palliative care consultation characteristics, rates of documentation of medical decision-maker and goals of care, and percentage of in-ICU mortality between the referral group and the embedded group. RESULTS: In a six-month period, 169 MICU patients received an embedded consultation, as compared to 52 MICU patients who received a referral-based consultation. As compared to the referral-based period, those patients who received an embedded consult were seen significantly earlier in hospitalization (median number of days from hospital admission to consult: 10 days [pre] vs. 3 days [embedded], P<0.001), more likely to have documentation of medical decision-makers (40% [pre] vs. 66% [embedded], P=0.002) and goals of care (37% [pre] vs. 71% [embedded], P<0.001) and less likely to die in the hospital (75% [pre] vs. 44% [embedded], P<0.001). CONCLUSIONS: After embedding a palliative care MD/RN team into the MICU, patients received earlier palliative care consultation, were more likely to have medical decision-maker and goals of care documented, and less likely to die in the hospital. Future work will examine how to adapt this model to other ICUs to improve palliative care access for critically ill patients broadly.

Comparison of Dosimetric Parameters and Clinical Outcomes in Inversely Planned Intensity-Modulated Radiotherapy (IMRT) and Field-in-Field Forward Planned IMRT for the Treatment of Breast Cancer.

Introduction Radiotherapy has been an important component of the multimodality approach to breast cancer treatment. Newer techniques like three-dimensional radiotherapy had led to better dose distribution over the target volume, with tissue inhomogeneity corrections. To improve the uniformity in dose distribution, a newer technique of intensity modulation was developed, namely, intensity-modulated radiotherapy (IMRT). The present study was designed to compare inverse planned IMRT (IP IMRT) and field-in-field forward planned IMRT (FP IMRT) in patients with breast cancer receiving post-modified radical mastectomy (MRM) adjuvant radiotherapy in terms of dosimetric parameters and clinical outcomes. Materials and methods Fifty patients with breast cancer who have undergone MRM and need adjuvant radiotherapy were randomly assigned in a 1:1 ratio into two groups (25 each) of IP IMRT and FP IMRT techniques. The prescribed dose was 50 Gy in 25 fractions over five weeks. In IP IMRT, five to seven tangential beams were used for the chest wall, nodal volumes were placed at suitable angles with beam optimization, and calculation was carried out by the analytical anisotropic algorithm. For FP IMRT, two opposing tangential fields were created in such a way to achieve uniform dose distribution to the planning target volume (PTV), minimizing hot spot regions, and limiting dose to the ipsilateral lung and contralateral breast. Multiple subfields were manually designed to boost the area not included in the dose cloud. The dosimetric parameters were compared for PTV, lungs, heart, left anterior descending coronary artery (LAD), opposite breast, and esophagus. Results The dosimetric parameters in terms of PTV are better for IP IMRT plans compared to FP IMRT plans (V95%: 92.3% vs 75.2%, p = 0.0001; D90%: 47.4 Gy vs 42.9 Gy, p = 0.0001; D95%: 44.9 Gy vs 37.1, p = 0.0004). The ipsilateral lung (V10Gy: 71.9% vs 41%, p = 0.00001; V20Gy: 42.14% vs 36.35%, p = 0.03; V40Gy: 17.31% vs 26.95%, p = 0.00004; Dmean: 20.91 Gy vs 17.88 Gy, p = 0.01) and contralateral lung (V5Gy: 31.8% vs 0.1%, p < 0.00001; V10Gy: 6.2% vs 0.08%, p = 0.0001) received statistically significant lesser doses in terms of low dose parameters in FP IMRT. In the heart, the dosimetric parameter V5 was significantly lower for FP IMRT (61.7% vs 9.7%, p = 0.00001) along with Dmean (10.92 Gy vs 4.01 Gy, p = 0.001). Similarly, LAD parameters showed comparable high dose volumes (V40Gy: 21.02% vs 16.26%; p = 0.29) in both groups and a trend toward reduction in mean dose (17.1% vs 9.2%; p = 0.05) in FP IMRT group, although low dose volumes were higher in IP IMRT group. In contralateral breast, doses in smaller volumes were better for FP IMRT plans (V0.5Gy: 59.7% vs 43.8%, p = 0.01; V0.6Gy: 54.07% vs 37.6%, p = 0.007; V1Gy: 40.9% vs 22.1%, p = 0.001; V2Gy: 28.7% vs 9.4%, p = 0.00003; V5Gy: 12.07% vs 4.2%, p = 0.0001). In esophagus, statistically significant lower doses were seen only in terms of Dmean (10.29 Gy vs 5.1 Gy; p = 0.03) with FP IMRT. No significant difference in terms of skin reactions and dysphagia was seen in both the groups. Conclusion Both IP IMRT and FP IMRT techniques have advantages and disadvantages, and the superiority of one technique over another cannot be established in this study. The decision for choosing one technique over another can also be based on various patient-related factors weighing the risk of loco-regional recurrences to that of manifesting radiation-induced sequelae.

Using Admission Karnofsky Performance Status as a Guide for Palliative Care Discharge Needs.

Objective: To examine the relationship between admission Karnofsky Performance Status (KPS) and discharge disposition. Background: Little is known about the relationship between functional status before hospitalization and discharge disposition. Methods: In a retrospective cohort study of patients seen by Mount Sinai Hospital Medicine Primary Palliative Care Program (HPPC), we used demographic and clinical data to compare discharge disposition by patients' functional status before admission into the hospital. Results: Overall, 596 patients received HPPC consults (286 [48%] female, mean age 68.4 years, median admission KPS 40% [requires hospital level care]). Of the 33 patients with a KPS ≥60% (unable to work) 30 (91%) were discharged home, whereas those 262 patients with KPS ≤30% (severely disabled) 52 (20%) were discharged home, 40 (15%) enrolled in hospice, 130 (49.5%) discharged to a facility, and 32 (12%) died in hospital. Conclusions: Worse functional status was associated with a hospice or facility discharge and better functional status was associated with discharge home. Key Message: This retrospective cohort study examined the relationship between KPS before hospital admission and discharge disposition in hospitalized seriously ill patients admitted to the hospital medicine service who received a HPPC consultation. The results suggest that those with a higher admission KPS (more functional) are more likely to be discharged home, whereas those with a lower KPS (less functional) are more likely to be discharged to a facility or hospice. KPS before hospital admission could guide palliative care resource allocation and discharge needs.

Therapeutic opportunities in colon cancer: Focus on phosphodiesterase inhibitors.

Despite novel technologies, colon cancer remains undiagnosed and 25% of patients are diagnosed with metastatic colon cancer. Resistant to chemotherapeutic agents is one of the major problems associated with treating colon cancer which creates the need to develop novel agents targeting towards newer targets. A phosphodiesterase is a group of isoenzyme, which, hydrolyze cyclic nucleotides and thereby lowers intracellular levels of cAMP and cGMP leading to tumorigenic effects. Many in vitro and in vivo studies have confirmed increased PDE expression in different types of cancers including colon cancer. cAMP-specific PDE inhibitors increase intracellular cAMP that leads to activation of effector molecules-cAMP-dependent protein kinase A, exchange protein activated by cAMP and cAMP gated ion channels. These molecules regulate cellular responses and exert its anticancer role through different mechanisms including apoptosis, inhibition of angiogenesis, upregulating tumor suppressor genes and suppressing oncogenes. On the other hand, cGMP specific PDE inhibitors exhibit anticancer effects through cGMP dependent protein kinase and cGMP dependent cation channels. Elevation in cGMP works through activation of caspases, suppression of Wnt/b-catenin pathway and TCF transcription leading to inhibition of CDK and survivin. These studies point out towards the fact that PDE inhibition is associated with anti-proliferative, anti-apoptotic and anti-angiogenic pathways involved in its anticancer effects in colon cancer. Thus, inhibition of PDE enzymes can be used as a novel approach to treat colon cancer. This review will focus on cAMP and cGMP signaling pathways leading to tumorigenesis and the use of PDE inhibitors in colon cancer.

In Silico Design, Synthesis and Bioactivity of N-(2, 4-Dinitrophenyl)-3-oxo- 3-phenyl-N-(aryl) Phenyl Propanamide Derivatives as Breast Cancer Inhibitors.

BACKGROUND: Breast cancer is a systemic disease which has challenged physicians worldwide as it is the most predominant cancer in women often leading to fatality. One of the types of treatment is chemotherapy which includes targeted oral or intravenous cancer-killing drugs. Treatment options are often limited to surgery and/or chemotherapy. OBJECTIVE: The discovery and design of new small molecule estrogen inhibitors is necessitated in order to circumvent the problem of drug-induced resistance in chemotherapy resulting in disease relapse. Chemoinformatics facilitates the design, selection and synthesis of new drug candidates for breast cancer by providing efficient in silico techniques for prediction of favourable ADMET properties, and structural descriptors to profile druggability of a compound. METHOD: Several molecules selected from docking studies were synthesized and evaluated for their biological activities on the MCF-7 (human breast cancer) cell line. RESULTS: These estrogen inhibitors displayed good inhibitory activity with high selectivity and hence can be further progressed as drug candidates effective against breast cancer. CONCLUSION: It is for the first time that N-(2, 4-dinitrophenyl)-3-oxo-3-phenyl-N-(aryl) phenylpropanamide derivatives were reported to be biological active as potential breast cancer inhibitors.

SMMRNA: a database of small molecule modulators of RNA.

We have developed SMMRNA, an interactive database, available at http://www.smmrna.org, with special focus on small molecule ligands targeting RNA. Currently, SMMRNA consists of ∼770 unique ligands along with structural images of RNA molecules. Each ligand in the SMMRNA contains information such as Kd, Ki, IC50, ΔTm, molecular weight (MW), hydrogen donor and acceptor count, XlogP, number of rotatable bonds, number of aromatic rings and 2D and 3D structures. These parameters can be explored using text search, advanced search, substructure and similarity-based analysis tools that are embedded in SMMRNA. A structure editor is provided for 3D visualization of ligands. Advance analysis can be performed using substructure and OpenBabel-based chemical similarity fingerprints. Upload facility for both RNA and ligands is also provided. The physicochemical properties of the ligands were further examined using OpenBabel descriptors, hierarchical clustering, binning partition and multidimensional scaling. We have also generated a 3D conformation database of ligands to support the structure and ligand-based screening. SMMRNA provides comprehensive resource for further design, development and refinement of small molecule modulators for selective targeting of RNA molecules.

Excitotoxicity: bridge to various triggers in neurodegenerative disorders.

Glutamate is one of the most prominent neurotransmitter in the body, present in over 50% of nervous tissue and plays an important role in neuronal excitation. This neuronal excitation is short-lived and is followed by depression. Multiple abnormal triggers such as energy deficiency, oxidative stress, mitochondrial dysfunction, calcium overload, etc can lead to aberration in neuronal excitation process. Such an aberration, serves as a common pool or bridge between abnormal triggers and deleterious signaling processes with which central neurons cannot cope up, leading to death. Excitotoxicity is the pathological process by which nerve cells are damaged and killed by excessive stimulation by neurotransmitters such as glutamate and similar substances. Such excitotoxic neuronal death has been implicated in spinal cord injury, stroke, traumatic brain injury, hearing loss and in neurodegenerative diseases of the central nervous system such as stroke, epilepsy, multiple sclerosis, Alzheimer disease, Amyltropic lateral sclerosis, Parkinson's disease, Huntington disease and alcohol withdrawal. This review mainly emphasizes the triggering events which sustain neuronal excitation, role of calcium, mitochondrial dysfunction, ROS, NO, chloride homeostasis and eicosanoids pathways. Further, a brief introduction about the recent research occurring in the treatment of various neurodegenerative diseases, including a summary of the presumed physiologic mechanisms behind the pharmacology of these disorders.

Development and Validation of HPTLC Method for the Estimation of Clotrimazole in Bulk drug and Tablet Formulation.

A simple, precise, accurate and rapid high performance thin layer chromatographic method has been developed and validated for the determination of clotrimazole in bulk drug and tablet dosage form. The stationary phase used was precoated silica gel 60F(254). The mobile phase used was a mixture of cyclohexane:toluene:methanol:triethyleamine (8:2:0.5:0.2 v/v/v/v). The detection of spot was carried out at 262 nm. The method was validated in terms of linearity, accuracy, precision and specificity. The calibration curve was found to be linear between 200 to 1000 ng/spot for clotrimazole. The limit of detection and the limit of quantification for clotrimazole were found to be 50 ng/spot and 200 ng/spot, respectively. The proposed method can be successfully used to determine the drug content of bulk drug and marketed formulation of tablet.