The etiology and management of intractable breathlessness in patients with advanced cancer: a systematic review of pharmacological therapy

Intractable breathlessness is a common, devastating symptom of advanced cancer causing distress and isolation for patients and families. In advanced cancer, breathlessness is complex and usually multifactorial and its severity unrelated to measurable pulmonary function or disease status. Therapeutic advances in the clinical management of dyspnea are limited and it remains difficult to treat successfully. There is growing interest in the palliation of breathlessness, and recent work has shown that a systematic, evidence-based approach by a committed multidisciplinary team can improve lives considerably. Where such care is lacking it may be owing to therapeutic nihilism in clinicians untrained in the management of chronic breathlessness and unaware that there are options other than endurance. Optimum management involves pharmacological treatment (principally opioids, occasionally oxygen and anxiolytics) and nonpharmacological interventions (including use of a fan, a tailor-made exercise program, and psychoeducational support for patient and family) with the use of parenteral opioids and sedation at the end of life when appropriate. Effective care centers on the patient's needs and goals. Priorities in breathlessness research include studies on: neuroimaging, the effectiveness of new interventions, the efficacy, safety, and dosing regimens of opioids, the contribution of deconditioning, and the effect of preventing or reversing breathlessness.     

Combined sub-threshold dosages of phenobarbital and low-frequency stimulation effectively reduce seizures in amygdala-kindled rats

Low-frequency stimulation (LFS) is a potential therapy utilized in patients who do not achieve satisfactory control of seizures with pharmacological treatments. Here, we investigated the interaction between anticonvulsant effects of LFS and phenobarbital (a commonly used medicine) on amygdala-kindled seizures in rats. Animals were kindled by electrical stimulation of basolateral amygdala in a rapid manner (12 stimulations/day). Fully kindled animals randomly received one of the three treatment choices: phenobarbital (1, 2, 3, 4 and 8 mg/kg; i.p.; 30 min before kindling stimulation), LFS (one or 4 packages contained 100 or 200 monophasic square wave pulses, 0.1-ms pulse duration at 1 Hz, immediately before kindling stimulation) or a combination of both (phenobarbital at 3 mg/kg and LFS). Phenobarbital alone at the doses of 1, 2 and 3 mg/kg had no significant effect on the main seizure parameters. LFS application always produced anticonvulsant effects unless applied with the pattern of one package of 100 pulses, which is considered as non-effective. All the seizure parameters were significantly reduced when phenobarbital (3 mg/kg) was administered prior to the application of the non-effective pattern of LFS. Phenobarbital (3 mg/kg) also increased the anticonvulsant actions of the effective LFS pattern. Our results provide an evidence of a positive cumulative anticonvulsant effect of LFS and phenobarbital, suggesting a potential combination therapy at sub-threshold dosages of phenobarbital and LFS to achieve a satisfactory clinical effect.     

Discovery of neurotrophic agents based on hydroxycinnamic acid scaffold

The number of people affected by neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease is rapidly increasing owing to the global increase in life expectancy. Small molecules with neurotrophic effects have great potential for management of these neurological disorders. In this study, different (C1–C12) alkyl ester derivatives of hydroxycinnamic acids (HCAs) were synthesized (a total of 30 compounds). The neurotrophic capacity of the test compounds was examined by measuring promotion of survival in serum‐deprived conditions and enhancement of nerve growth factor (NGF)‐induced neurite outgrowth in PC12 neuronal cells. p‐Coumaric, ferulic, and sinapic acids and their esters did not alter cell survival, while caffeic acid and all its alkyl esters, especially decyl and dodecyl caffeate, significantly promoted neuronal survival at 25 μm . Methyl, ethyl, propyl, and butyl caffeate esters also significantly enhanced NGF‐induced neurite outgrowth, among which the most effective ones were propyl and butyl esters, which at 5 μm led to 25‐ and 22‐fold increases in the number of neurites, respectively. The findings of the docking study suggested phosphatidylinositol 3‐kinase (PI3K) as the potential molecular target. In conclusion, our findings demonstrate that alkyl esters of caffeic acid can be useful as scaffolds for the discovery of therapeutic agents for neurodegenerative diseases.     

Effect of Zafirlukast on improving lung function in patients with chronic obstructive pulmonary diseases

Background

There is little evidence about the role of Zafirlukast (a highly selective LTD4 antagonist) in Chronic Obstructive Pulmonary Disease (COPD). The Zafirlukast can reduce the need for short-acting rescue β2 agonists, produce fewer exacerbations of asthma and increased quality of life as possible benefits treatment for asthma. The aim of our study was to evaluate the effects of Zafirlukast improvement of lung function in patients with COPD.

Methods

Twenty five patients with moderate to severe COPD, in stable phase of the disease, participated in this interventional, quasi-experimental study. All patients were received 40mg oral Zafirlukast per day for 2 weeks. Pulmonary function Test was performed both at the baseline and at the end of the study. Data were analyzed with paired t-test using SPSS v.16.

Results

The mean age of the patients was 67.29 (SD=5.56) years with the mean baseline for forced expiratory volume in first second (FEV₁) equal to 41.79% (SD=14.96) of predicted value. After 2 weeks, the mean improvements in forced vital capacity (FVC), FEV₁ and FEV₁/FVC were 4.75% (SD=13.18), 3.71% (SD=9.19) and 9.33(SD=27.08), respectively. Zafirlukast produced a non-significant (p>0.05) bronchodilation, with maximum mean increase in FEV₁ of 0.04 lit (3%) above baseline.

Conclusion

Results showed that Zafirlukast has no considerable bronchodilatory effect in COPD. Present study consisted of a very short treatment period and it is possible that the extension of this period could possibly have more effects. Additional larger studies are needed to verify the impact of leukoterien receptor antagonists on improving the lung function in COPD patients.     

Physicochemical and Biological Characterization of Pep‐1/Elastin Complexes

Transdermal drug delivery of proteins is challenging because the skin acts as a natural and protective barrier. Several techniques including using the cell‐penetrating peptides have been studied to increase the penetration of therapeutic proteins into and through the skin. Cell‐penetrating peptides facilitate and improve the transduction of large and hydrophilic cargo molecules through plasma membrane. We have recently reported an efficient skin delivery of elastin protein in complex with a cell‐penetrating peptide called Pep‐1. As the biophysical characteristics of cell‐penetrating peptide/protein complexes have been linked with their biological responses, in this study, we investigated biophysical properties of Pep‐1/elastin complexes (ratio 10:1) stored in three temperatures (?20 °C, 4 °C and 25 °C) by photon correlation spectroscopy, circular dichroism and isothermal denaturation. We also evaluated the ability of transduction of this complex into cells and skin tissue using both fluorescence microscopy and Kodak In‐Vivo FX Pro Imaging System.     

Current Considerations for Breast Reconstruction in Breast Cancer Patients

In the next year, approximately 250,000 women will be diagnosed with breast cancer in the United States [1]. The majority of these women will be recommended partial or total mastectomy as a component of their cancer treatment. The goal of breast reconstruction is to rebuild and/or reshape the breast mound to correct the mastectomy defect for physical and psychological reasons. There are a number of reconstructive options available to patients who desire breast reconstruction, including implant-based procedures, autologous tissue reconstructions, or a combination. Additionally, oncoplastic procedures are a recent advance in the field of breast-conserving therapies that further refines our ability to resect breast cancer while preserving the form of the breast. Because planning the reconstruction depends on the type of resection performed and the amount of tissue remaining after mastectomy, the breast surgeon, reconstructive surgeon, and the patient collectively should discuss reconstructive goals and how these can be achieved after the patient’s oncologic surgery.     

Validity and reliability of a nutrition screening tool in hospitalized patients

Objective

The British nutrition screening tool is a questionnaire designed to assess the nutrition status of hospitalized patients by nurses. The aim of this study was to evaluate the validity and reliability of this questionnaire in patients on admission to the hospital in Tehran.

Methods

For 6 mo, 446 patients aged over 18 y admitted to different wards of a general hospital were studied within the first 24 h of admission. A nutritionist undertook nutritional assessment in all patients to determine their nutritional status as an objective standard. Then a nurse completed the screening tool for patients. Results obtained using the screening tool were compared with those of the nutritional assessment to calculate the sensitivity, specificity, and predictive values. The interrater reliability of the tool was assessed by two nurses who completed the screening tool separately during the first 24 h following admission of each patient. It was also completed by a nurse within 2-d period of admission to test the intrarater reliability.

Results

Study participants included 229 women and 217 men with mean age of 49.5 ± 16.0 y. Sensitivity and specificity of the questionnaire were 86.7% (95% CI: 83.9-90.3%) and 61.7% (95% CI: 57.5-66.5%), respectively. Positive and negative predictive values were 79.1% (95% CI: 68.9-77.1%) and 73.1% (95% CI: 75.1-82.9), respectively. The sensitivity of the tool was over 80% for both genders, for all body mass index grades, and for data obtained from gastroenterology, transplant, oncology, and hematology wards. The interrater reliability of screening tool was interpreted as substantial, being k = 0.68 and k = 0.74 on both the first and second days, respectively. The intrarater reliability of the screening tool was also interpreted as substantial, being k = 0.77.

Conclusion

The nutrition screening tool is a simple, valid, and reliable tool that can be used by nurses to facilitate identification of patients requiring nutritional interventions.