Impact of intensity and timing of integrated home palliative cancer care on end-of-life hospitalization in Northern Italy.

PURPOSE: The Veneto Region implemented a novel integrated home-based palliative cancer care (HPCC) program embedded in primary care. We examined the impact of timing and intensity of this program on the quality of end-of-life (EOL) care. METHODS: We selected adult cancer patients died in the Veneto Region between March and December 2013, excluding those died from haematological malignancies as well as the very elderly (85+ years). We retrieved the claim-based data on hospitalization and homecare visits, and defined two observation windows: 90 to 16 days before death to examine intensity of HPCC exposure, and the last 15 days of life to examine EOL outcomes, including hospital death, any hospital stay for medical reasons and hospital stay ≥7 days for medical reasons. Multivariate analysis was conducted using a Poisson model. RESULTS: Among the 2211 adults who died of solid tumours and received 1+ homecare visits during the exposure period, 1077 (48.7%), 552 (25.0%) and 582 (26.3%) had 0.1-1.9, 2-3.9 and 4+ homecare visits/week, respectively. The median duration between an HPCC home visit and death was 92 days (IQR 42-257 days). Hospital death occurred in 856 (38.7%) patients, while 1087 (49.2%) and 556 (25.1%) had a hospital stay and a hospital stay ≥7 days during the exposure period, respectively. In the multivariate analysis, a greater intensity of integrated HPCC (4+ visits/week) was significantly associated with a lower risk of hospital death (relative risk [RR] = 0.67, 0.59-0.76), any hospital stay (RR = 0.69, 0.62-0.77) and hospital stay ≥7 days for medical reasons (RR = 0.59, 0.49-0.71). A late activation (≤30 days before death) of HPCC was also associated with increased both hospital stay (RR = 1.26, 0.11-1.42) and hospital stay ≥7 days (RR = 1.25, 1.01-1.54). CONCLUSIONS: A greater HPCC program intensity reduces the risk of hospital death and hospital stay in the end-of-life. An early activation of this program can contribute to improve these EOL outcomes.

Prevalence of diabetes across different immigrant groups in North-eastern Italy.

BACKGROUND AND AIMS: Type 2 diabetes, one of the most important non-communicable diseases, represents a major health problem worldwide. Immigrants may contribute relevantly to the increase in diabetes. The aim of the study was to investigate variability in diabetes prevalence across different immigrant groups in the Veneto Region (northeastern Italy). METHODS AND RESULTS: Diabetic subjects on January 2013 were identified by record linkage of hospital discharge records, drug prescriptions, and exemptions from medical charges for diabetes. Immigrant groups were identified based on citizenship. Age-standardized prevalence rates were obtained for residents aged 20-59 years by the direct method, taking the whole regional population as reference. Prevalence rate ratios (RR) with 95% Confidence Intervals (CI) were computed with respect to Italian citizens. Among residents aged 20-59 years, 45280 Italian and 7782 foreign subjects affected by diabetes were identified. Prevalence rates were highest among immigrants from South-East Asia, RR 4.9 (CI 4.7-5.1) among males, and 7.6 (7.2-8.1) among females, followed by residents from both North and Sub-Saharan Africa. Citizens from Eastern Europe (the largest immigrant group) showed rates similar to Italians. Most South-Asian patients aged 20-39 years were not insulin-treated, suggesting a very high risk of early onset type 2 diabetes in this ethnic group. CONCLUSION: Large variations in diabetes prevalence by ethnicity should prompt tailored strategies for primary prevention, diabetes screening, and disease control. An increased demand for prevention and health care in selected population groups should guide appropriate resource allocation.

Meta-analysis: adherence to colorectal cancer screening and the detection rate for advanced neoplasia, according to the type of screening test.

BACKGROUND: A variety of tests have been proposed for colorectal cancer (CRC), giving rise to uncertainty regarding the optimal approach. The efficacy and effectiveness of different tests are related to both screened participation and the detection rate. AIM: To perform a meta-analysis on adherence and detection rates of CRC screening tests. METHODS: Relevant publications were identified by MEDLINE/EMBASE and other databases for the period 1999-2012. A previous systematic review was used for the period before 1966-1999. RCTs and controlled studies including a direct comparison of the uptake rates among different options for CRC screening were included. Adherence and detection rates for advanced neoplasia and cancer were extracted. Risk for bias was ascertained according to CONSORT guidelines. Forrest plots were produced based on random-effect models. RESULTS: Fourteen studies provided data on 197 910 subjects. Endoscopic strategies were associated with a lower participation (RR: 0.67, 95% CI: 0.56, 0.80) rate, but a higher detection rate of advanced neoplasia (RR: 3.21, 95% CI: 2.38, 4.32) compared with faecal tests. FIT was superior to g-FOBT with regard to both adherence (RR: 1.16, 95% CI 1.03, 1.30) and detection of advanced neoplasia (RR: 2.28, 95% CI 1.68, 3.10) and cancer (RR: 1.96, 95% CI: 1.2, 3.2). CONCLUSION: The superior accuracy of endoscopy compared with faecal tests minimised any impact of the participation rate in determining the detection rate of advanced neoplasia in a screening setting.

How to increase uptake in oncologic screening: a systematic review of studies comparing population-based screening programs and spontaneous access.

BACKGROUND: Cervical, breast and colorectal cancer (CRC) screenings are universally recommended interventions. High coverage of the target population represents the most important factor in determining their success. This systematic review aimed at assessing the effectiveness of population-based screening programs in increasing coverage compared to spontaneous access. METHODS: Electronic databases and national and regional websites were searched. We included all studies on interventions aimed at increasing screening participation published between 1999 and 2009; for those published before, we consulted the Jepson et al. review (2000). We compared spontaneous access (including no intervention) vs population-based screening programs actively inviting the target population. Among the latter, we compared GP-based vs invitation letter-based interventions. RESULTS: The invitation letter vs no intervention showed significantly more participation (RR=1.60 95%CI 1.33-1.92; RR=1.52 95%CI 1.28-1.82; RR=1.15 95%CI 1.12-1.19, for breast, cervical and CRC screenings, respectively). GP-based interventions, although more heterogeneous, showed a significant effect when compared with no intervention for breast (RR=1.74 95%CI 1.25-2.43), but not for cervical and CRC. No significant differences were found between invitation letter-based and GP-based organization (RR=0.99 95%CI 0.94-1.05; RR=1.08 95%CI 0.99-1.17, for breast and cervical cancer, respectively). CONCLUSION: Population-based programs are more effective than spontaneous screening in obtaining higher testing uptake. Both invitation letter-based and GP-based programs are effective.

Interventions for the interruption or reduction of the spread of respiratory viruses.

BACKGROUND: Viral epidemics or pandemics such as of influenza or severe acute respiratory syndrome (SARS) pose a significant threat. Antiviral drugs and vaccination may not be adequate to prevent catastrophe in such an event. OBJECTIVES: To systematically review the evidence of effectiveness of interventions to interrupt or reduce the spread of respiratory viruses (excluding vaccines and antiviral drugs, which have been previously reviewed). SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2006, Issue 4); MEDLINE (1966 to November 2006); OLDMEDLINE (1950 to 1965); EMBASE (1990 to November 2006); and CINAHL (1982 to November 2006). SELECTION CRITERIA: We scanned 2300 titles, excluded 2162 and retrieved the full papers of 138 trials, including 49 papers of 51 studies. The quality of three randomised controlled trials (RCTs) was poor; as were most cluster RCTs. The observational studies were of mixed quality. We were only able to meta-analyse case-control data. We searched for any interventions to prevent viral transmission of respiratory viruses (isolation, quarantine, social distancing, barriers, personal protection and hygiene). Study design included RCTs, cohort studies, case-control studies, cross-over studies, before-after, and time series studies. DATA COLLECTION AND ANALYSIS: We scanned the titles, abstracts and full text articles using a standardised form to assess eligibility. RCTs were assessed according to randomisation method, allocation generation, concealment, blinding, and follow up. Non-RCTs were assessed for the presence of potential confounders and classified as low, medium, and high risk of bias. MAIN RESULTS: The highest quality cluster RCTs suggest respiratory virus spread can be prevented by hygienic measures around younger children. Additional benefit from reduced transmission from children to other household members is broadly supported in results of other study designs, where the potential for confounding is greater. The six case-control studies suggested that implementing barriers to transmission, isolation, and hygienic measures are effective at containing respiratory virus epidemics. We found limited evidence that the more uncomfortable and expensive N95 masks were superior to simple surgical masks. The incremental effect of adding virucidals or antiseptics to normal handwashing to decrease respiratory disease remains uncertain. The lack of proper evaluation of global measures such as screening at entry ports and social distancing prevent firm conclusions about these measures. AUTHORS' CONCLUSIONS: Many simple and probably low-cost interventions would be useful for reducing the transmission of epidemic respiratory viruses. Routine long-term implementation of some of the measures assessed might be difficult without the threat of a looming epidemic.

Transdermal estroprogestins versus transdermal estrogen plus oral dihydrogesterone replacement in menopause.

We studied 18 early (6 to 36 months) postmenopausal patients with a mean age of 51 years (47-53), who had never undergone hormone replacement therapy before and had no contraindications to hormone replacement. All cases of menopause were spontaneous. The treatment consisted in the continuous transdermal administration of 17-beta-estradiol (50 microg/daily) by skin patch to be replaced every 84 hours. The patients were further treated with a two-week progestogen administration every fortnight. This consisted of transdermal norethisterone acetate (0.25 mg/daily) combined with estradiol in the same patch in the first year, and oral dihydrogesterone (10 mg/daily) in the second year, without wash-out period. Before treatment (T0), and at the 12th (T1) and 24th (T2) month we measured the body mass index, the arterial blood pressure (AP), lipoproteins, coagulation parameters and bone metabolism parameters. The systolic pressure presented mean values (+/-SD) equal to 128.5+/-10.2 mmHg (T0), 131.1+/-7.4 mmHg (T1) and 130.4+/-7.5 mmHg (T2). Diastolic pressure values showed mean value ranging from 85.4+/-8.7 mmHg (T0) to 83.9+/-5.3 (T1) and 83.4+/-5.8 mmHg (T2). The detailed analysis of values of triglycerides, HDL cholesterol, apolipoprotein A1, apolipoprotein B and coagulation parameters at different times of therapy showed no statistically significant changes. With regard to bone metabolism, no statistically significant changes from baseline values were observed in parathormone, alkaline phosphatase, calcitonin, urinary calcium/creatinine ratio, and bone mineral content expressed by the bone density.

Effect of benzene on the swimming activity of Mysidopsis juniae (Crustacea, Mysidacea)

The effects of benzene on the swimming activity of the crustacean Mysidopsis juniae were investigated. The swimming activity of M. juniae was observed after 1.3 and 6 h of exposure to 5, 10 15 and 20 ppm benzene in sea water (35 ñ 1 grade/00 S, 25 ñ 1 grade C). The mysids were observed with a pair of coupled to a camara lucida, and the swimming activity was measured in a Petri dish, corresponding to the distance (cm) covered by the animals in 1 min (N=150 animals). The swimming activity of mysids exposed to 20 ppm benzene decreased significantly after all three periods of exposure to values which were 80-90% smaller than the control value. On the other hand, after 6 h exposure to 5 ppm benzene, the swimming activity of the mysids was significantly higher, increasing by 87% in relation to the control (29.8 ñ 8.9 cm?min). Furthermore, a slight nonsignificant increase in swimming activity was also observed in mysids submitted to 5, 10, 15 and even 20 ppm benzene, as the period of exposure to the pollutant increased from 1 to 6 h. These results indicate that short-term exposure to sublethal benzene concentrations can affect the swimming activity of mysids. in these situations, mysid populations can be seriously damaged since alterations in swimming activity could lead to a reduction in food intake and to a marked increase in their susceptibility to predation by other organisms

Slow reversible inhibition of rabbit muscle aldolase by D-erythrulose 1-phosphate.

Rabbit muscle aldolase was found to be inactivated in a slow, reversible manner by D-erythrulose 1-phosphate. This compound combined rapidly and reversibly with the enzyme to form an initial complex, which then only slowly (ki = 0.28 min-1) converted to a kinetically more stable form. This stable enzyme-ligand form was inactive toward the normal substrate of aldolase, fructose 1,6-bisphosphate. The inactive enzyme-ligand complex, however, could be decomposed (kr = 0.0041 min-1) to yield active enzyme once again by incubation in a solution devoid of D-erythrulose 1-phosphate.

Alteration of the Cloudman melanoma cell cycle by prostaglandins E1 and E2 determined by using a 5-bromo-2'-deoxyuridine method of DNA analysis.

Prostaglandins (PGs) E1 and E2 stimulate tyrosinase activity and suppress the proliferation of Cloudman S91 melanoma cells by altering their progression through the cell cycle. Prostaglandin E1 and PGE2 have prolonged or residual effects on melanoma cells. Cells treated for 5 or 24 hours with 10 micrograms/ml PGE1 or cells treated for 8 or 24 hours with 10 micrograms/ml PGE2 demonstrated decreased proliferation and increased tyrosinase activity for 48 hours after removal of the PGs. The effects of PGs on the cell cycle were investigated by determining total DNA content in cells stained with propidium iodide (PI) and analyzed by a fluorescence activated cell sorter (FACS). Prostaglandin E1 blocked cells in G2 phase after 5 hours of treatment, corresponding to when inhibition of proliferation was first evident. Similarly, after 9 hours of treatment with PGE2, more cells were in late S, early G2 phase and less in G1 than their control counterparts. Also, melanoma cells were pulse-labeled with 5-bromo-2'-deoxyuridine (BrdUrd) prior to or at the end of PG treatment and then stained with a fluoresceinated monoclonal antibody to BrdUrd, and with PI. This allows one to observe how BrdUrd-labeled S-phase cells cycle with time. Both PGE1 and PGE2 inhibit proliferation by blocking cells in G2 phase of the cell cycle. The PG-induced block in G2 may be required by melanoma cells to synthesize mRNA and proteins that are essential for stimulation of tyrosinase activity. Ultrastructurally, only a subpopulation of the cells treated with PGE1 or PGE2 contained more mature melanosomes than control cells.

A sensitive in vitro toad skin bioassay for melanotropic peptides.

1. An in vitro bioassay for melanotropic peptide utilizing reflectance measurements of toad skin (Bufo ictericus ictericus) is described as an alternative to the commonly used Rana pipiens bioassay. 2. The toad skin bioassay is as sensitive to melanotropins and melanin concentrating hormone (MCH) as the frog bioassay. 3. On the basis of parallel dose-response curves obtained with the toad skin assay we found that beta-MSH is slightly less active than alpha-MSH, whereas the synthetic analogue [Nle4-D-Phe7]-alpha-MSH is about 10 times more potent and exhibits prolonged biological activity. 4. MCH, a putative neurohormone, can also be bioassayed in the in vitro toad skin bioassay, since it has alpha-MSH-like activity on amphibian melanocytes. 5. Since neither adreno- nor cholinoceptors are present in the toad melanocytes, the assay provides great specificity and sensitivity for the determination of melanotropin activity in tissue or blood.

alpha-MSH (melanocyte stimulating hormone) and MCH (melanin concentrating hormone) actions in Bufo ictericus ictericus melanophores.

1. The darkening actions of MCH (melanin concentrating hormone), alpha-MSH and the synthetic analog [Nle4, D-Phe7]-alpha-MSH on the toad, Bufo ictericus ictericus, melanophores were studied regarding the role of calcium in the hormone receptor coupling, signal transduction and intracellular pigment translocation. 2. In the absence of external calcium, MCH and both melanotropins still elicit maximal skin darkening. 3. Verapamil, a calcium-channel blocker, completely abolishes the alpha-MSH-induced response and partially inhibits MCH-induced darkening, although the calcium carrier, ionophore A23187, was unable to promote any pigment translocation. 4. Since darkening responses promoted by cyclic nucleotides proceeded normally in the presence of verapamil and extracellular calcium was not necessary for melanotropin dispersing action, it is suggested that the blocking activity obtained with verapamil is probably due to an impairment of the Ca2+-dependent adenylate cyclase activity. 5. Reversal of melanotropin-induced darkening could be obtained with melatonin, in both normal and Ca2+-free Ringer, whereas MCH darkening is reversed by melatonin only in the absence of calcium. 6. The results seem to indicate that calcium is not required for hormone receptor binding and pigment migration, whereas it is specifically needed for signal transduction.