Pain, symptoms and therapy satisfaction in adult oncologic patients at admission to palliative care: An Italian prospective, multicenter, observational study.

BACKGROUND: Pain in cancer patients is a complex clinical problem. Pain is systematically assessed and treated during palliative care, but little is known about how it is addressed before starting palliative care. AIM: This study primarily analyzed pain, symptoms, ongoing therapy at patients' admittance to the palliative care unit, and the relationships between pain and tumor, comorbidities, performance status and quality of life (QoL). Notably, patient satisfaction with the received antalgic therapy was assessed. METHODS: A multicentric, prospective, observational study was conducted in seven Italian palliative centers. The population consisted of adult cancer patients admitted to specialist palliative care units in hospice and home care. RESULTS: The sample consisted of 476 patients. Ninety-three patients reported moderate pain of 4.0 and worst pain of 5.9 at the initial medical examination. The pain was high, and QoL was lower in breakthrough pain. The pain was lower in older subjects when it was discontinuous and when it was also treated with corticosteroids. A total of 61% of the patients were unsatisfied with the prescribed pain therapy. CONCLUSIONS: Before the beginning of palliative care, physicians do not manage pain adequately. We support the idea that palliative care is not only intended for the last days of life but must be started early and simultaneously with oncological treatments. All that, in our opinion, is often ignored, and we hope that our study could have a positive influence and that the study results stimulate further research in this area with in-depth studies.

Adherence to ESMO guidelines on cancer pain management and their applicability to specialist palliative care centers: An observational, prospective, and multicenter study.

INTRODUCTION: Pain management in late-stage cancer patients is a complex clinical problem. The historical guidelines were from the World Health Organization (WHO). Recently, ESMO produced guidelines consistent with 52 recommendations applicable to the entire period of disease since the pain appears. AIM: To evaluate the appropriateness and applicability of ESMO guidelines (EGL) in advanced cancer patients admitted to palliative care. METHOD: An observational, prospective, multicentric study conducted by specialist palliative care centers on cancer patients in the advanced stage. The 52 recommendations were divided into eight macro areas. The adherence levels were expressed as a percentage for each recommendation and have been broken down as high (>75%), medium (50%-75%), and low (<50%). In the case of not adhering to a recommendation, the comment was "not applicable" (NA) or not evaluable (NE). RESULTS: Four hundred seventy-six patients were enrolled in the study. Thirty-five recommendations were considered NA or NE, especially because their application took too long to achieve clinical results, given the condition of the patients. Some interesting opinions on the choice of drugs emerged. At the end of the study, pain dropped from 5.0 to 2.6, patients' satisfaction increased from 3.3 to 4.6, and quality of life improved from 4.4 to 5.5. CONCLUSIONS: Palliative physicians' adherence to EGL was medium. The main contribution of this study was to evaluate their applicability and clinical results in far-advanced patients assisted by palliative care. The selection of useful recommendations and expert opinions can make a contribution to clinical practice.

Protein concentration and mitochondrial content in the gastrocnemius predicts mortality rates in patients with peripheral arterial disease.

OBJECTIVE: This study evaluated the hypothesis that protein concentration and mitochondrial content in gastrocnemius biopsies from patients with peripheral arterial disease (PAD) predict mortality rates. BACKGROUND: PAD patients experience advancing myopathy characterized by mitochondrial dysfunction, myofiber degradation, and fibrosis in their ischemic legs, along with increased mortality rates. METHODS: Samples from the gastrocnemius of PAD patients were used for all analyses. Protein concentration was normalized to muscle wet weight, and citrate synthase activity (standard measure of mitochondrial content in cells) was normalized to muscle wet weight and protein concentration. Protein and citrate synthase data were grouped into tertiles and 5-year, all-cause mortality for each tertile was determined with Kaplan-Meier curves and compared by the modified Peto-Peto test. A Cox-regression model for each variable controlled for the effects of clinical characteristics. RESULTS: Of the 187 study participants, 46 died during a mean follow-up of 23.0 months. Five-year mortality rate was highest for patients in the lowest tertile of protein concentration. Mortality was lowest for patients in the middle tertile of citrate synthase activity when normalized to either muscle wet weight or protein concentration. The mortality hazard ratios (HRs) from the Cox analysis were statistically significant for protein concentration normalized to muscle wet weight (lowest vs middle tertile; HR = 2.93; P = 0.008) and citrate synthase normalized to protein concentration (lowest vs middle tertile; HR = 4.68; P = 0.003; and lowest vs highest tertile; HR = 2.36; P = 0.027). CONCLUSIONS: Survival analysis of a contemporaneous population of PAD patients identifies protein and mitochondrial content of their gastrocnemius as predictors of mortality rate.

Features and organization of Pain Centers in the Lazio Region, Italy, in 2011.

BACKGROUND: Evidence on pain management highlights the importance of a multidisciplinary approach in order to achieve optimal therapeutic results. Such programs can be guaranteed by the Centers for Pain Management (CPMs), in which multidisciplinary teams are able to provide advanced and specialized activities for the assessment, diagnosis and treatment of chronic benign pain. To date, information related to healthcare supply and the organizational structure of these centers in Italy is incomplete. The aim of this paper was to provide an overview of the healthcare network of the CPMs in the Lazio region. METHODS: A descriptive survey was conducted in all the 37 CPMs existing in the Lazio region in 2011 of which 28 participated. RESULTS: CPMs were located either in Universities or in public or private hospital facilities. They included a clinic, a Day Hospital service, Day surgery and day-beds. CPMs were managed by anaesthesiologists who, in most instances, did not work in a multidisciplinary team. The number of other health professionals available, such as nurses, psychologists and physiotherapists, was limited. CPMs mainly provided drug therapy, Complementary Alternative Medicine (CAM) and complex interventional treatments. The median waiting time was 30 days. The clinics were not homogeneously distributed in the region with a higher concentration in Rome (56%), followed by other provinces of the Lazio region (26%) and the province of Rome (18%). Clearly, Rome was the city which offered the greatest range of healthcare services and the highest number of consultations with patients, which significantly differed from those of the other areas (χ²=19.6 p<0.01). CONCLUSIONS: In 2011, the availability of CPMs was not equally distributed throughout the territory, and there was an over-utilization of the facilities in Rome and an under-utilization in the provincial areas. Moreover, this study showed a lack of a multi-professional approach to chronic pain management.

[Modalities for access to networks of palliative care and pain management in Lazio: level of information for health personnel aware of the Policlinico Tor Vergata]. / Modalità per l'accesso alle reti di cure palliative e terapia del dolore nel Lazio: grado di informazione del personale sanitario del Policlinico Tor Vergata.

Law no. 38 of 2010 introduces for the first time protection for access to Palliative Care and Pain Management. It was interesting to evaluate the level of knowledge among health care workers at the Policlinico Tor Vergata, procedures relating to such access through the administration of a questionnaire. The questionnaire divided into a general part and the two sections (A and B) The general part concerns the health operator respect to age, gender, profession, and his role within the operating unit of the hospital. The section A and B, is to understand if the operator knows Palliative Care, and Pain Therapy, as he became aware of the two arguments, and if they have been addressed during the university courses he attended. The analysis of the data examined show a general confusion distributed evenly among all professionals. Is greater knowledge of pain therapy compared to Palliative Care.

Pressure ulcers in cancer palliative care patients.

Terminally ill cancer patients are considered at high risk for pressure ulcers because of their clinical condition. However, in Italy, data about pressure ulcers and their prevalence are insufficient. This paper reports a study on pressure ulcers incidence and prevalence in a population of oncology patients cared for in an Italian palliative care service. A retrospective analysis of 414 clinical records of patients admitted over 6 months showed a prevalence of pressure ulcers of 22.9% and an incidence of 6.7%. Karnofsky Performance Scale Index scores, age and length of the stay were significantly related to the pressure sore development. These results support the need to focus attention on pressure ulcers prevention and treatment in terminally ill cancer patients, and to further define specific guidelines aimed at warranting patients' comfort and quality of life.

Design and bioevaluation of a 32P-patch for brachytherapy of skin diseases.

The purpose of this study was to design and evaluate a 32P patch for brachytherapy of skin diseases. We employed Phosphoric-32P-acid and Chromic 32P-phosphate in combination with natural rubber or silicone to produce the patches. Stability studies in vitro to evaluate the leakage of radioactivity, autoradiographic studies to evaluate homogeneity and shielding, as well as therapeutic efficacy in an animal model of skin cancer of the selected 32P patch were performed. The 32P-silicone-patch demonstrated its safety for external application. Tumor growth was arrest and complete regressions of tumors were seen in some other cases with 40 Gy applied in a single-dose scheme. In conclusion, the 32P-silicone-patch is easy to prepare and use in the treatment of skin diseases.

Assessment of indoor climate of Mogila Abbey in Kraków (Poland) and the application of the analogues method to predict microclimate indoor conditions.

The microclimatic monitoring of the historic church of Mogila Abbey (Kraków, Poland) was carried out to study the impact of the environmental parameters on the organic and hygroscopic artworks. Specific indexes were proposed to objectively assess the quality of time series of temperature (T), relative humidity (RH), and carbon dioxide (CO2) before applying the exploratory data analysis. The series were used to define the historic environmental conditions as stated in the European Standard EN 15757:2010 and with the use of the climate evaluation chart (CEC). It was found that the percentage of time in which T and RH values are within the allowable limits of the ASHRAE (2011) Class B is more than 85 %. This means that, for about 15 % of the time, there is a high risk of mechanical damage to highly vulnerable objects mainly due to the RH variability. The environment at the chancel resulted moister than that at the cornice, and the fungal growth is possible. In addition, the time-weighted preservation index (TWPI) is computed to evaluate the life expectancy of the objects, taking into account the environmental conditions of the site under study. The method of analogues, developed to predict the evolution of a system given observations of the past and without the knowledge of any equation among variables, was proposed and applied to the time series of temperature, relative humidity, and carbon dioxide with a 1-h sampling time to avoid the influence of the autocorrelation.

Variability among polysulphone calibration curves.

Within an epidemiological study regarding the correlation between skin pathologies and personal ultraviolet (UV) exposure due to solar radiation, 14 field campaigns using polysulphone (PS) dosemeters were carried out at three different Italian sites (urban, semi-rural and rural) in every season of the year. A polysulphone calibration curve for each field experiment was obtained by measuring the ambient UV dose under almost clear sky conditions and the corresponding change in the PS film absorbance, prior and post exposure. Ambient UV doses were measured by well-calibrated broad-band radiometers and by electronic dosemeters. The dose-response relation was represented by the typical best fit to a third-degree polynomial and it was parameterized by a coefficient multiplying a cubic polynomial function. It was observed that the fit curves differed from each other in the coefficient only. It was assessed that the multiplying coefficient was affected by the solar UV spectrum at the Earth's surface whilst the polynomial factor depended on the photoinduced reaction of the polysulphone film. The mismatch between the polysulphone spectral curve and the CIE erythemal action spectrum was responsible for the variability among polysulphone calibration curves. The variability of the coefficient was related to the total ozone amount and the solar zenith angle. A mathematical explanation of such a parameterization was also discussed.

A canopy layer model and its application to Rome.

An urban canopy layer model based on four energy balance equations at ground level and at building level was developed to simulate and describe the urban climate and the heat storage in an urban setting. Thermal and radiative characteristics of urban and rural surfaces as well as atmospheric parameters related to the general synoptic conditions were used as data input. In addition, buildings were modelled as parallelepipeds and the hysteresis of materials was taken into account. The model provides as output skin temperature of buildings, air temperature and humidity within the canopy layer and hence the mean surface temperature and the air temperature at 2 m above surface. The latter parameter was used for the comparison with in situ temperature observations. The model was applied to Rome in radiative summer and winter episodes. The results, which agree with observations, show that the Urban Heat Island (UHI) is a nocturnal phenomenon, present both in winter (the greatest difference between urban and rural temperatures is about 2 degrees C) and summer (the temperature difference is about 5 degrees C), mainly resulting from the urban geometry and the thermal properties of materials. The anthropogenic heat does not play an important role in the UHI development. A monthly nocturnal behaviour of temperature differences between urban and surrounding rural areas shows that the maximum mean value of 4.2 degrees C occurs in August. Moreover, the parks in the city centre, where temperatures are lower, define two distinct heat islands, east and west.

[SOSIA classification of the frail elderly in nursing homes of region of Lombardy]. / La Classificazione SOSIA degli anziani ospiti delle residenze sanitario-assistenziali lombarde.

Since 2001, the region of Lombardy has accreditated nursing homes named R.S.A. "Residenza Sanitario-Assistenziale", which make up Italy's principal RSA network with the annual turnover of approximately 60,000 people. The most noteworthy element of the reform introduced is a concentration on resident's frailty rather than disability. This is assessed by using SOSIA, a form for intermediate observation of assistance. Residents are classified into eight classes of frailty, called isofrailty classes of SOSIA, which are differentiated by how compromised their motor and cognitive skills are, and by the presence of comorbidity. The study presents the methodology used to identify and estimate cut-offs of three indicators employed in SOSIA classification. It also discusses their characteristics versus other evaluation systems, such as Resource Utilization Group RUG-III and Autonomie Gerontologique--Groupes Iso-Resources AGGIR.

Inhibition of human bone marrow-derived stem cell colony formation (CFU-E, BFU-E, and CFU-GM) following in vitro exposure to organophosphates.

Cholinergic toxicity of organophosphate insecticides is regarded as the principal health hazard associated with both human and animal exposures. Recent studies indicate that these pesticides may have important effects on both the immune and hematopoietic systems. In the present study, human bone marrow cells were exposed in vitro to paraoxon and malaoxon (the primary metabolites of parathion and malathion). These compounds produced dose-dependent depression of colony formation by erythrocyte (burst-forming units-erythroid [BFU-E] and colony-forming units-erythroid [CFU-E]) and granulocyte-macrophage progenitors (colony-forming units-granulocyte-macrophage [CFU-GM]). CFU-E colony formation was reduced 15%-57%, by both paraoxon and malaoxon, in the range of 10(-8)-10(-5) M. No effects were seen at 10(-9) and 10(-10) M. Colony formation by BFU-E was reduced 15%-75%, at 10(-9)-10(-5) M organophosphate (OP), then returned to normal at 10(-10) M OP. In comparison to CFU-E, BFU-E appeared to be more sensitive to the suppressive action of OPs. Numbers of CFU-GM colonies were reduced 16%-59% in the range of 10(-9)-10(-5) M OP, then returned to normal at 10(-10) M OP. Choline chloride added to marrow cultures (final concentration, 10 mM) enhanced CFU-GM colony formation at all concentrations of paraoxon and malaoxon. Our results provide a rationale for assessing hematologic parameters in occupationally exposed individuals, and indicate the need to determine both the mechanism and the environmental health consequences of the observed hematopoietic effects.

Spontaneous and coherent anti-Stokes Raman spectroscopy of human gastrocnemius muscle biopsies in CH-stretching region for discrimination of peripheral artery disease.

Peripheral Artery Disease (PAD) is a common manifestation of atherosclerosis, characterized by lower leg ischemia and myopathy in association with leg dysfunction. In the present study, Spontaneous and coherent anti-Stokes Raman scattering (CARS) spectroscopic techniques in CH-stretching spectral region were evaluated for discriminating healthy and diseased tissues of human gastrocnemius biopsies of control and PAD patients. Since Raman signatures of the tissues in the fingerprint region are highly complex and CH containing moieties are dense, CH-stretching limited spectral range was used to classify the diseased tissues. A total of 181 Raman spectra from 9 patients and 122 CARS spectra from 12 patients were acquired. Due to the high dimensionality of the data in Raman and CARS measurements, principal component analysis (PCA) was first performed to reduce the dimensionality of the data (6 and 9 principal scores for Raman and CARS, respectively) in the CH-stretching region, followed by a discriminant function analysis (DFA) to classify the samples into different categories based on disease severity. The CH2 and CH3 vibrational signatures were observed in the Raman and CARS spectroscopy. Raman and CARS data in conjunction with PCA-DFA analysis were capable of differentiating healthy and PAD gastrocnemius with an accuracy of 85.6% and 78.7%, respectively.

Serum glucagon after arginine infusion in aged and young subjects.

In 12 aged nondiabetic subjects, 10 aged diabetic subjects, and 6 young nondiabetic subjects the glucose, insulin, glucagon and growth hormone responses to the intravenous administration of arginine were studied. A prompt increase in the levels of blood glucose, serum insulin and serum glucagon was observed, but the glucose and glucagon peaks were significantly higher in the aged nondiabetic and diabetic subjects. Growth hormone secretion did not differ between the nondiabetic aged and young subjects. These findings suggest the hypothesis that glucose intolerance in old age is due to increased release of glucagon.

Solar UV dose patterns in Italy.

Since 1992 solar ultraviolet (UV) spectral irradiance (290-325 nm) has been measured at two Italian stations of Rome (urban site) and Ispra (semirural site) using Brewer spectrophotometry. The data collected under all sky conditions, are compared with the output of a sophisticated radiative transfer model (System for Transfer of Atmospheric Radiation--STAR model). The STAR multiple scattering scheme is able to cope with all physical processes relevant to the UV transfer through the atmosphere. The experience so far acquired indicates that, in spite of the unavoidable uncertainties in the input parameters (ozone, aerosol, surface albedo, pressure, temperature, relative humidity, cloud cover), measured and computed clear sky iradiances are in reasonable agreement. The STAR model is applied to build up the solar UV geographic patterns in Italy: the daily dose in the range 290-325 nm is computed at about 70 sites where a thorough and homogeneous climatology is available. For each month the concept of an idealized "standard day" is introduced and the surface distribution of solar UV field determined. The map of solar UV patterns for Italy, available for the first time, meets the study requirements in the field of skin and eye epidemiology, as well as in other investigations dealing with the impact of UV on the biosphere. The results are interpreted in terms of atmospheric and meteorological parameters modulating UV radiation reaching the ground.

Parathion-induced suppression of humoral immunity in inbred mice.

Numbers of IgM plaque-forming cells (PFC) were reduced by 65% in C57Bl/6 mice given parathion 2 days after immunization with sheep red blood cells (SRBC). The immunosuppressive dose (16 mg/kg, p.o.) caused signs of cholinergic poisoning and 20% mortality. Survivors appeared to have recovered fully from the cholinergic crisis at the time of immunologic assay. However, these animals had reduced tissue cholinesterase (ChE) activities and decreased numbers of nucleated spleen cells. Immunosuppression was apparent on day 4 but not on day 3 or days 5-8 of the primary IgM response. Reduction of serum hemagglutinin titers coincided with reduction of the number of splenic PFC. A lower dose of insecticide (4 mg/kg, p.o.) did not produce signs of poisoning and was not immunosuppressive. The number of 8-day IgG PFC was reduced by 45% when parathion (16 mg/kg, p.o.) was given 6 days after immunization, but not when parathion was given 2 days after immunization. The data suggest that cholinergic stimulation and/or the associated toxic chemical stress may be involved in parathion-induced immunosuppression.

Inhibition of interleukin-2-stimulated enhancement of human natural killer (NK) cell activity by carbaryl, an anticholinesterase insecticide.

The potency of the anticholinesterase (antiCHE) insecticides as serine hydrolase inhibitors, and evidence for serine hydrolase activity in interleukin-2 (IL2) signalling suggest that the natural killer (NK) cell may be a target for dysregulation by antiCHE insecticides. NK cells are large granular lymphocytes (LGL) that respond to IL2 by proliferating and increasing their cytolytic efficiency. In the present study, we assessed the effects of carbaryl (CA, an antiCHE insecticide) and alpha-naphthol (NA, the major metabolite of CA) on both target cell killing per se and IL2 enhancement of target cell killing by human NK cells. Human LGL, collected from the peripheral blood of normal donors, were cultured for 4 days with human recombinant IL2 (HRIL2), then assayed by a 51Chromium (51Cr) release assay for lytic activity against human K562 cells. When added at the beginning of the culture period, CA inhibited enhancement of cytolytic efficiency in a concentration-dependent manner; at concentrations (0.5 and 5.0 microM) compatible with no cholinergic toxicity. Reduction of the effector/target cell (E/T) ratio in the 51Cr release assay markedly enhanced the observed inhibition by CA. In one experiment, inhibition increased from 6% to 20%, 17% to 35%, and 53% to 73% at 0.5, 5.0, and 50 microM CA, respectively, when E/T was reduced from 10:1 to 2.5:1. This result is consistent with reduced cytolytic efficiency of individual NK cells exposed to CA. NA had no effect at 0.5 or 5.0 microM but caused some inhibition at 50 microM. Neither CA nor NA produced LGL death. When CA or NA was added directly to the 51Cr release assay, inhibition was not observed. The mechanism of inhibition of IL2-stimulated enhancement of target cell killing is not yet known, however, the results are consistent with impairment of IL2 signalling, by CA.

Circadian rhythms in the aged: a review.

After a review of the fundamental concepts on chronobiology, the importance of circadian rhythms in the aged was examined on the basis of the data obtained in animals and humans, including personal observations on over 40 blood constituents. During ageing there are significant modifications of circadian rhythms, with frequent diminution of amplitude and a shift of acrophase. The biological, clinical and therapeutic implications of these findings are discussed.

[Circadian rhythms and aging]. / Ritmi circadiani ed invecchiamento.

The cosinor method was used to study the circadian variations in 36 haematic parameters in apparently healthy elderly subjects. A nyctohemeral cycle was evident in most cases. Differences in the means and range of IgA, IgG and antithrombin III rhythms compared to those of younger adults were noted. On the whole, the circadian system of the elderly is very similar to that of adults.

[Proteinuria in the aged]. / La proteinuria negli anziani.

The Authors for a better knowledge of the senile kidney have studied the urinary proteins of a group of elderly people resident in a geriatric institute. For instance they have noted the percentage of proteinuria in the urine of 313 patients (M and F) with various pathology, making also an electrophoresis of the urinary proteins. They put in evidence that the subjects with proteinuria were older than others, without proteinuria, and noted the high incidence of the infectious diseases of the urinary tract in these patients. In a second time the urine of 247 apparently healthy elderly people has been studied. Through an accurate examination (that is comprehensive of some serum parameters and a comparison with subjects without proteinuria) the Authors discussed a way of growing old defined "with biological trouble".