Economic preferences in the health setting. Three case studies concerning the needs of breast cancer patients, pain management in oncology and extreme end-of-life decisions

The thesis describes three studies concerning the role of the Economic Preference set investigated in the Global Preference Survey (GPS) in the following cases: 1) the needs of women with breast cancer; 2) pain undertreament in oncology; 3) legal status of euthanasia and assisted suicide. The analyses, based on regression techniques, were always conducted on the basis of aggregate data and revealed in all cases a possible role of the Economic Preferences studied, also resisting the concomitant effect of the other covariates that were considered from time to time. Regarding individual studies, the related conclusion are: 1) Economic Preferences appear to play a role in influencing the needs of women with breast cancer, albeit of non-trivial interpretation, statistically "resisting" the concomitant effect of the other independent variables considered. However, these results should be considered preliminary and need further confirmation, possibly with prospective studies conducted at the level of the individual; 2) the results show a good degree of internal consistency with regard to pro-social GPS scores, since they are all found to be non-statistically significant and united, albeit only weakly in trend, by a negative correlation with the % of pain undertreated patients. Sharper, at least statistically, is the role of Patience and Willingness to Take Risk, although of more complex empirical interpretation. 3) the results seem to indicate an obvious role of Economic Preferences, however difficult to interpret empirically. Less evidence, at least on the inferential level, emerged, however, regarding variables that, based on common sense, should play an even more obvious role than Economic Preferences in orienting attitudes toward euthanasia and assisted suicide, namely Healthcare System, Legal Origin, and Kinship Tightness; striking, in particular, is the inability to prove a role for the dominant religious orientation even with a simple bivariate analysis.

Influence of Electromagnetic Fields On Biological Signalling: An Experimental and Theoretical Approach

The primary goals of this study were to develop a cell-free in vitro assay for the assessment of nonthermal electromagnetic (EMF) bioeffects and to develop theoretical models in accord with current experimental observations. Based upon the hypothesis that EMF effects operate by modulating Ca2+/CaM binding, an in vitro nitric oxide (NO) synthesis assay was developed to assess the effects of a pulsed radiofrequency (PRF) signal used for treatment of postoperative pain and edema. No effects of PRF on NO synthesis were observed. Effects of PRF on Ca2+/CaM binding were also assessed using a Ca2+-selective electrode, also yielding no EMF Ca2+/CaM binding. However, a PRF effect was observed on the interaction of hemoglobin (Hb) with tetrahydrobiopterin, leading to the development of an in vitro Hb deoxygenation assay, showing a reduction in the rate of Hb deoxygenation for exposures to both PRF and a static magnetic field (SMF). Structural studies using pyranine fluorescence, Gd3+ vibronic sideband luminescence and attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy were conducted in order to ascertain the mechanism of this EMF effect on Hb. Also, the effect of SMF on Hb oxygen saturation (SO2) was assessed under gas-controlled conditions. These studies showed no definitive changes in protein/solvation structure or SO2 under equilibrium conditions, suggesting the need for real-time instrumentation or other means of observing out-of-equilibrium Hb dynamics. Theoretical models were developed for EMF transduction, effects on ion binding, neuronal spike timing, and dynamics of Hb deoxygenation. The EMF sensitivity and simplicity of the Hb deoxygenation assay suggest a new tool to further establish basic biophysical EMF transduction mechanisms. If an EMF-induced increase in the rate of deoxygenation can be demonstrated in vivo, then enhancement of oxygen delivery may be a new therapeutic method by which clinically relevant EMF-mediated enhancement of growth and repair processes can occur.

The role of Proteasome in the development, maintenance and management of Chronic Pain

In chronic pain, opioids represent the gold standard analgesics, but their use is hampered by the development of several side effects, as development of analgesic tolerance and opioid-induced hyperalgesia. Evidence showed that many molecular mechanisms (changes in opioid receptors, neurotransmitter release, and glia/microglia activation) are involved in their appearance, as well as in chronic pain. Recently, a crucial role has been proposed for oxidative stress and proteasome in chronic pain and in treatment-related side effects. To better elucidate these aspects, the aim of this PhD thesis was to investigate the effects of opioids on cell oxidative stress, antioxidant enzymatic machinery and proteasome expression and activity in vitro. Also, the involvement of proteasome in the development of chronic pain conditions was investigated utilizing an experimental model of oxaliplatin-induced neuropathy (OXAIN), in vivo. Data showed that morphine, fentanyl, buprenorphine and tapentadol alter differently ROS production. The ROS increasing effect of morphine is not shared by the other opioids, suggesting that the different pharmacological profile could influence this parameter. Moreover, these drugs produced different alterations of β2trypsin-like and β5chymotrypsin-like activities. In fact, while morphine and fentanyl increased the proteolytic activity after prolonged exposure, a different picture was observed for buprenorphine and tapentadol, suggesting that the level of MOR agonism could be strongly related with proteasome activation. In vivo studies revealed that rats treated with oxaliplatin showed a significant increase in β5, in the thalamus (TH) and somatosensory cortex (SSCx). Moreover, a selective up-regulation of β5 and LMP7 subunit gene expression was assessed in the SSCx. Furthermore, our study revealed that oprozomib, a selective β5 inhibitor normalized the spinal prodynorphin gene expression upregulation induced by oxaliplatin, and reverted mechanical/thermal allodynia and mechanical hyperalgesia in oxaliplatin-treated rats. These results underline the role of proteasome in the OXAIN and suggest new pharmacological targets to counteract it.

Colic surgery in the equine patient: novel biomarkers, postoperative management, microbiotal influence and epidemiological analysis on the italian territory

The aim of this work was to investigate novel diagnostic and prognostic tools, postoperative treatments and epidemiologic factors impacting the outcome of surgical cases of colic. To make a more accurate diagnosis and establish a prognosis, several biomarkers have been investigated in colic patients. In this study we evaluated peritoneal PCT and blood ADMA and SDMA in SIRS positive and negative colic patients to be used as prognostic biomarkers. Our results highlighted the limits of these biomarkers in detection and the lack of specificity. In fact PCT was not detectable and even if ADMA and SDMA significantly increased in colic horses, they are not diagnostic nor prognostic markers for SIRS. Fluid therapy has been described to be crucial for the outcome of colic patients, nevertheless no guidelines have been established. Overhydration was the common practice in post surgical management. We compared cases with an extended fluid therapy protocol and cases with a restricted protocol. Results showed that survival rate and postoperative complications were similar between the groups, despite costs being significantly lower in the restricted group. The possible correlation between intestinal microbiota and colics has gained interest. In this study, cecal and colonic content from horses undergoing laparotomy were collected, and the microbiota analized. Results showed some differences in microbiota between discharged and non discharged patients, and between strangulating and non strangulating types of colic, that might suggest some influence of hind gut microbiota on the disease. A multicentric study involving three veterinary teaching hospitals on the italian territory was conducted investigating factors affecting postoperative survival and complications in colics. Results showed that the influence of age, PCV, TPP, blood lactate, reflux, type of disease, type of lesion, presence of anastomosis, duration of surgery and surgeons, were in line with literature. Amount of crystalloids used could affected the outcome.

Psychological characterization of hypertensive patients: associations with adherence to pharmacological treatment and self-management

Introduction: The role of psychosocial factors in the onset and progression of essential hypertension has been object of a large body of literature, yet findings appear to be controversial. Aims: We assessed the predictive role of psychosomatic syndromes, affective symptomatology, psychological reactance, psychological distress, well-being and quality of life on adherence to antihypertensive medications, lifestyle behaviors, hypertension severity and absolute cardiovascular risk grading, as well as their temporal stability at 1-year follow-up, in a sample of hypertensive patients. In addition, we aimed to validate the Italian version of the Hong Psychological Reactance Scale (HPRS). Methods: Eighty consecutive hypertensive outpatients treated with antihypertensive medications were compared to 80 controls. Psychosocial variables were assessed using clinical interviews and self-rating questionnaires at baseline and at 1-year follow-up. Cardiac parameters were also collected. One-hundred and fifty individuals from general population provided data for the HPRS validation. Results: Hypertensive patients reported significantly higher levels of psychological distress and lower levels of psychological well-being at baseline compared to controls. Among hypertensive patients, allostatic overload (AO) was the most frequently reported psychosomatic syndrome at baseline. Patients with AO displayed significantly greater levels of psychological distress and lower levels of well-being and quality of life than those without. Further, patients with illness denial were significantly more likely to report poor adherence to pharmacological treatment and, as well as those with higher levels of affective symptomatology, were less likely to follow a balanced diet. At follow-up, patients displayed significantly higher levels of well-being and lower levels of stress, mental pain and quality of life. Conclusions: Findings suggest the clinical relevance of psychosocial factors and psychosomatic syndromes in the progression of hypertension, with important implications for its management. As to the Italian validation of the HPRS, results support previous findings, even though a confirmatory factor analysis should be carried out.