Optimal Combination Of Therapies Research Articles

Fitting parameters and therapies of ODE tumor models with senescence and immune system

This work is devoted to introduce and study two quasispecies nonlinear ODE systems that model the behavior of tumor cell populations organized in different states. In the first model, replicative, senescent, extended lifespan, immortal and tumor cells are considered, while the second also includes immune cells. We fit the parameters regulating the transmission between states in order to approximate the outcomes of the models to a real progressive tumor invasion. After that, we study the identifiability of the fitted parameters, by using two sensitivity analysis methods. Then, we show that an adequate reduced fitting process (only accounting to the most identifiable parameters) gives similar results but saving computational cost. Three different therapies are introduced in the models to shrink (progressively in time) the tumor, while the replicative and senescent cells invade. Each therapy is identified to a dimensionless parameter. Then, we make a fitting process of the therapies’ parameters, in various scenarios depending on the initial tumor according to the time when the therapies started. We conclude that, although the optimal combination of therapies depends on the size of initial tumor, the most efficient therapy is the reinforcement of the immune system. Finally, an identifiability analysis allows us to detect a limitation in the therapy outcomes. In fact, perturbing the optimal combination of therapies under an appropriate therapeutic vector produces virtually the same results.

Management of Autoimmune Status Epilepticus.

Status epilepticus is a neurological emergency with increased morbidity and mortality. Urgent diagnosis and treatment are crucial to prevent irreversible brain damage. In this mini review, we will discuss the recent advances in the diagnosis and treatment of autoimmune status epilepticus (ASE), a rare form of the disorder encountered in the intensive care unit. ASE can be refractory to anticonvulsant therapy and the symptoms include subacute onset of short-term memory loss with rapidly progressive encephalopathy, psychiatric symptoms with unexplained new-onset seizures, imaging findings, CSF pleocytosis, and availability of antibody testing makes an earlier diagnosis of ASE possible. Neuroimmunomodulatory therapies are the mainstay in the treatment of ASE. The goal is to maximize the effectiveness of anticonvulsant agents and find an optimal combination of therapies while undergoing immunomodulatory therapy to reduce morbidity and mortality.

Factors Affecting Treatment Outcome in Elderly Head and Neck Cancer Patients: A Retrospective Pilot Study

BackgroundHead and neck cancer (HNC), the fifth most common cancer worldwide, is a complicated category of diseases comprised of cancers of the oral cavity, oropharynx, nasopharynx, hypopharynx, and larynx. Management of HNC can be very complex, with surgery, chemotherapy, and radiation therapy often used in combination to achieve optimal results. The optimal combination of therapies to maximize patient survival and post-treatment quality of life is yet unclear. Only some prognostic factors for HNC are relatively well understood, whereas others are affected by conflicting results of their significance. AimsThe present study will explore and attempt to clarify the prognostic factors affecting HNC patients, focusing specifically on patients aged 80 or older. MethodsA database of HNC patients treated at our center between 2006 and 2011 was generated in Mosaiq (an electronic patient record system); from this, a sample of patients aged 80 or older was selected randomly (n = 40). Various disease-, patient-, and treatment-related factors were collected from these records and compared against the patients' overall survival, disease-free status, rates of recurrence, and rates of radiation toxicity to determine which were significant prognostic indicators. ConclusionsDisease subsite was found to be a significant indicator of local recurrence (P = .049) and survival rate (P = .014), while anemia was related to poor disease-free status on follow-up (P = .017). Age was not significantly linked to any outcome measure. However, patients treated with palliative intent were significantly older (P = .012) despite not having higher stage disease, and only one radical patient (3.2%) failed to complete their treatment course. Follow-up data, quantitative toxicity data, and human papillomavirus and smoking status were either inconsistently collected or unavailable, identifying areas for improvement to better inform evidence-based practice.

Depression in cancer patients: Pathogenesis, implications and treatment (Review).

Depression is a common comorbidity in cancer cases, affecting >10% of patients. A cancer diagnosis is life-changing, and is a source of considerable psychological and emotional stress. Non-pathological sadness may be a normal response to a cancer diagnosis, however, stress beyond the coping mechanisms of patients may result in major depressive disorder. The current review, in addition to the obvious psychosocial elements of depression, explores its biological mechanisms, including tissue damage, inflammatory mediators and the chronic stress response, and how these immune and endocrine pathways may underlie depression in cancer. Possible iatrogenic causes of depression in cancer are also explored. There is a strong need to identify and treat depression in cancer patients in order to increase quality of life and reduce mortality. The most popular clinical and potential future biochemical screening tools for depression in cancer are briefly discussed. The interventions used will vary for every patient, but may include psychosocial therapies or pharmacotherapy; however, a paucity of research on the most effective management of depression in cancer means the optimal combination of therapies is unknown. Selection of antidepressants should be carefully considered, given the common side effects of chemotherapy (such as nausea), and the necessity to avoid serious interactions, including reducing the effectiveness of chemotherapeutic drugs. The possible link between the chronic stress response, which may predispose patients to depression, and the risk of mortality from cancer is also explored. The complex interactions between the endocrine, nervous and immune systems, which continue to be elucidated, may offer the opportunity for the development of more rapid and efficacious treatments for depression in cancer in the future.

The expanding armamentarium of drugs to aid sputum clearance: how should they be used to optimize care?

This review examines the evidence for use of agents that improve sputum clearance in cystic fibrosis. The basic defect in cystic fibrosis causes abnormal airway surface liquid leading to mucus plugging and subsequent infection and inflammation in the airways. Agents that improve clearance of secretions should improve lung function, reduce infective exacerbations and may enhance survival. There are two main varieties of mucoactive therapy, namely mucolytic therapy, which reduces viscosity in order to improve clearance, and hyperosmolar therapy, which increases the airway surface liquid volume and increases mucociliary clearance. The development of mannitol as a hyperosmolar agent in dry powder form has heightened the debate regarding the optimal approach to sputum clearance. The evidence for use of individual agents is discussed, as well as a practical approach to combining therapies. Dornase alfa, a mucolytic agent, and hypertonic saline and mannitol, both hyperosmolar agents, have all been shown to benefit patients with cystic fibrosis. The optimal combination of therapies has not been identified, but a combination of a hyperosmolar agent combined with a mucolytic provides the most logical approach to improving lung function and reducing exacerbations.

Assessing Response to Therapy in Idiopathic Pulmonary Arterial Hypertension: A Consensus Survey of Canadian Pulmonary Hypertension Physicians

Many treatment options are now available for patients with idiopathic pulmonary arterial hypertension (IPAH). Data regarding the optimal combination of therapies are lacking, as is consensus on how to assess response to therapy and when to change therapeutic regimens. To gather the opinions of Canadian pulmonary hypertension (PH) experts regarding standard practice in the care of IPAH patients after therapy is initiated. Canadian PH physicians were surveyed using short questionnaires to assess their opinions and practices in the care of IPAH patients. A Delphi forecasting approach was used to gain consensus among Canadian physicians on the most important clinical parameters to consider when assessing patients after the initiation of therapy. Twenty-six of 37 Canadian PH experts who were invited to participate completed the study. All endorsed the use of combination therapy for IPAH patients despite the lack of universal provincial coverage for this approach. By consensus, WHO functional class, 6 min walk distance and hospitalization for right heart failure were the most important clinical parameters. The most highly rated physical examination parameters were jugular venous pressure, peripheral edema, the presence of ascites and body weight. The overall approach to care of IPAH patients is similar across PH centres in Canada. A limited number of clinical and physical examination parameters were considered to be most important to reassess patients after therapy is initiated. These parameters, along with definition of threshold values, will facilitate the development of standard practice guidelines for IPAH patients in Canada.