Improving quality of care for cancer pain: an Italian five-year project

Background: cancer pain is still undertreated as for inappropriate use of opioids, as for reason related to other factors. To increase knowledge of cancer pain, the “Mario Negri” Institute promote a series of initiatives to improve the quality of care and patients’ outcomes. Methods: a series of activities were launched including literature review, clinical studies and training schemes. Results: literature reviews shown a prevalence of undertreatment ranged from 8% to 82% and a raw prevalence of BTcP (Breakthrough Cancer Pain) of 51%. In the outcome research study mean worst pain at baseline was 6.8, and 38.3% received a strong opioids. Prevalence of BTcP was 40.3%, and 33.9% of the patients were not receiving rescue therapy at the study inclusion. About analgesic effectiveness of oral and transdermal opioids (TD), treatments with TD were associated with a lower probability to switch (OR=0.83) and to drop out from the study (OR=0.68). Conclusions: the initiative, still ongoing, has allowed a) the creation of a unit for the study and evaluation of cancer pain, b) the production of clinical evidence about the epidemiology, quality and effects of cancer pain management in Italy, c) the design and promotion of a Randomized Controlled Trial to evaluate the effectiveness of four major opioids

Attachment, Self-Esteem and Shame in Emerging Adulthood

AbstractAttachment styles are critical to the organization and representation of self and for regulating emotions. 209students between the ages of 19 and 24 completed three self-report measures on attachment styles, self-esteem and feelings of shame. Males showed higher self-esteem and lower feelings of shame. In the entire sample, securely attached students reported a higher level of self-esteem and a lower level of shame than insecurely attached students. Moreover, this study showed a relationship between insecure attachment, low self-esteem and shame.The present study suggests the relevance of attachment styles and self-esteem for the understanding of feelings of shame among emerging adults.This can have important implications for the development of preventative measures to reduce the risk of a disorder

Pain management and outcomes in cancer patients: comparison between oncological and palliative sets of care

Background: medical oncologists and palliative care physicians have different tasks even if they play a similar role when coping with pain of their patients. In spite of this converging goal, oncologists and palliative care therapists can not have the same approach and impact in managing pain. This study analyzes how pain is treated and which outcomes derive from in 1 461 cancer patients separately cared by oncologists or palliative care physicians. Methods: data derive from an observational, multicentre, prospective, longitudinal study carried out in 110 Italian hospitals. After inclusion, the data were recorded weekly for a 28 days period of follow-up. Results: 876 patients (60%) were cared by oncologists and 585 (40%) by palliative care physicians. The two professional categories tended to similarly manage the drugs of WHO analgesic ladder, while rescue and adjuvant therapies were more frequently used by palliative care physicians. Opioids daily dose increased from 68.3 to 92.5 mg/day (Effect size=0.282) among oncologists and from 70.8 to 107.8 mg/day (Effect size=0.402) among palliative care physicians. The switch of opioids was applied in 12.3% and in 19.1% (p=0.1634), respectively. Pain intensity decreased in both groups but more strongly in the palliative context. The full responders patients were 50% in oncology wards and 58.9% in palliative care (p=0.0588). Conclusions: this study indicates how much oncologists and palliative care physicians differ in managing cancer pain. The observational nature of this study reflects the natural and unaffected choice of the professionals. As intrinsic limit the study only describes their behaviors without a stringent comparative evaluation

Anti-Invasive Activity of Bovine Lactoferrin against Listeria monocytogenes.

We have investigated the possible role of bovine lactoferrin in protecting the intestinal epithelium from bacterial infections, using as an in vitro model enterocyte-like cell lines HT-39 and Caco-2 infected with a food-borne pathogen, Listeria monocytogenes . When infection occurred in the presence of 1 mg/ml of bovine lactoferrin, in the form of apolactoferrin or iron- or manganese-saturated forms, the adhesion of bacteria to eukaryotk cells was unaffected, but the number of internalized bacteria was reduced by 42- to 125-fold. The possibility of a toxic effect of lactoferrin was excluded, because bovine lactoferrin was used at nonbactericidal and noncytotoxic concentrations

Parkinson's disease: autoimmunity and neuroinflammation

Parkinson's disease is a neurodegenerative disease that causes the death of dopaminergic neurons in the substantia nigra. The resulting dopamine deficiency in the basal ganglia leads to a movement disorder that is characterized by classical parkinsonian motor symptoms. Parkinson's disease is recognized as the most common neurodegenerative disorder after Alzheimer's disease. PD ethiopathogenesis remains to be elucidated and has been connected to genetic, environmental and immunologic conditions. The past decade has provided evidence for a significant role of the immune system in PD pathogenesis, either through inflammation or an autoimmune response. Several autoantibodies directed at antigens associated with PD pathogenesis have been identified in PD patients. This immune activation may be the cause of, rather than a response to, the observed neuronal loss. Parkinsonian motor symptoms include bradykinesia, muscular rigidity and resting tremor. The non-motor features include olfactory dysfunction, cognitive impairment, psychiatric symptoms and autonomic dysfunction. Microscopically, the specific degeneration of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies, which are brain deposits containing a substantial amount of α-synuclein, have been recognized. The progression of Parkinson's disease is characterized by a worsening of motor features; however, as the disease progresses, there is an emergence of complications related to long-term symptomatic treatment. The available therapies for Parkinson's disease only treat the symptoms of the disease. A major goal of Parkinson's disease research is the development of disease-modifying drugs that slow or stop the neurodegenerative process. Drugs that enhance the intracerebral dopamine concentrations or stimulate dopamine receptors remain the mainstay treatment for motor symptoms. Immunomodulatory therapeutic strategies aiming to attenuate PD neurodegeneration have become an attractive option and warrant further investigation

Warthin Tumor-Like Papillary Thyroid Carcinoma with a Minor Dedifferentiated Component: Report of a Case with Clinicopathologic Considerations

Warthin tumor-like papillary thyroid carcinoma is an uncommon variant of papillary thyroid carcinoma. We report a rare case of Warthin tumor-like variant of papillary thyroid carcinoma with a dedifferentiated component consisting of a solid tumor area composed of neoplastic cells with a spindle to tall cell morphology associated with marked nuclear pleomorphism, atypical mitoses, and foci of necrosis. Although our patient presented with a locally aggressive disease (T3 N1b Mo), she is disease-free without radioiodine therapy after a 23-month follow-up period. We emphasize that Warthin tumor-like papillary thyroid carcinoma, like other morphological variants of papillary carcinoma, may occasionally undergo dedifferentiation. As this component may be only focally detectable, we suggest an extensive sampling of all large-sized (>3 cm) papillary thyroid carcinoma. Recognition of any dedifferentiated component in a Warthin tumor-like papillary thyroid carcinoma should be reported, including its percentage, because it may reflect a more aggressive clinical course

Laryngeal sensitivity in patients with amyotrophic lateral sclerosis

Recent studies have shown the involvement of the sensory nervous system in patients with amyotrophic lateral sclerosis (ALS). The aim of our study was to investigate the correlation between the laryngeal sensitivity deficit and the type of ALS onset (bulbar or spinal) in a large series of 114 consecutive ALS patients. Participants were subdivided into two groups, bulbar and spinal ALS, according to the clinical onset of disease and submitted to a clinical and instrumental evaluation of swallowing, including a fiber-optic endoscopic evaluation of swallowing with sensory testing. Dysphagia severity was scored using the Penetration–Aspiration Scale (PAS) and the Pooling score (P-score). In addition, three patients with laryngeal sensitivity deficit were submitted to a laryngeal biopsy to assess the status of the sensory innervation. All patients showed a normal glottal closure during phonation and volitional cough. Fifty-six subjects (49%), 14 spinal- and 42 bulbar-onset ALS, showed dysphagia at the first clinical observation (PAS score >1; P-score >5). Dysphagia resulted more frequently in bulbar-onset ALS (P < 0.01). Thirty-eight (33%) patients had a sensory deficit of the larynx. The sensory deficit of the larynx was significantly more frequent in bulbar-onset ALS (P < 0.01). The sensory deficit of the larynx among dysphagic patients was also significantly more frequent in bulbar-onset ALS (P = 0.02). Several abnormalities were found in all three subjects who underwent a laryngeal biopsy: in one patient, no intraepidermal fiber was found; in the other two, the fibers showed morphological changes. Our observations are important to consider for assessment and management of dysphagia in patients with AL

Hydrocortisone malabsorption due to polyethylene glycols (Macrogol 3350) in a girl with congenital adrenal insufficiency.

BACKGROUND: Primary adrenal insufficiency is relatively rare in children and, if unrecognized, may present with cardiovascular collapse, making it a potentially life-threatening entity. CASE PRESENTATION: The proposita, 11 months old of age, was admitted for lethargy and severe dehydration. Blood pressure was 62/38 mm Hg, and biochemical measurements showed hyponatraemia, hypochloraemia, hyperkalaemia, and metabolic acidaemia. Renin activity was 1484 μU/mL; cortisol, 1.03 μg/dL (normal, 5-25 μg/dL); and corticotropin (ACTH), 4832 ng/L (normal, 9-52 ng/L). Adrenal deficiency was diagnosed, and replacement therapy with glucocorticoids and mineralocorticoids was initiated. After 40 days, ACTH was 797 ng/L. During follow-up, the patient started taking macrogol twice daily for constipation and experienced a significant increase in ACTH (3262 ng/L), which dropped to 648 ng/L when macrogol was stopped. After arbitrary reintroduction of macrogol, the child presented with hypoglycaemia, lethargy, weakness, and hypotonia; ACTH was 3145 ng/L. After again stopping macrogol, her ACTH was near normalized (323 ng/L). CONCLUSION: Hydrocortisone malabsorption may be caused by macrogol use. Because chronic constipation is frequently reported in children, the possibility that macrogol contributes to adrenal crisis should be taken in account

Allosterism vs. Orthosterism: Recent Findings and Future Perspectives on A2B AR Physio-Pathological Implications

The development of GPCR (G-coupled protein receptor) allosteric modulators has attracted increasing interest in the last decades. The use of allosteric modulators in therapy offers several advantages with respect to orthosteric ones, as they can fine-tune the tissue responses to the endogenous agonist. Since the discovery of the first A1 adenosine receptor (AR) allosteric modulator in 1990, several efforts have been made to develop more potent molecules as well as allosteric modulators for all adenosine receptor subtypes. There are four subtypes of AR: A1, A2A, A2B, and A3. Positive allosteric modulators of the A1 AR have been proposed for the cure of pain. A3 positive allosteric modulators are thought to be beneficial during inflammatory processes. More recently, A2A and A2B AR allosteric modulators have also been disclosed. The A2B AR displays the lowest affinity for its endogenous ligand adenosine and is mainly activated as a consequence of tissue damage. The A2B AR activation has been found to play a crucial role in chronic obstructive pulmonary disease, in the protection of the heart from ischemic injury, and in the process of bone formation. In this context, allosteric modulators of the A2B AR may represent pharmacological tools useful to develop new therapeutic agents. Herein, we provide an up-to-date highlight of the recent findings and future perspectives in the field of orthosteric and allosteric A2B AR ligands. Furthermore, we compare the use of orthosteric ligands with positive and negative allosteric modulators for the management of different pathological conditions