Validazione di un nuovo algoritmo per identificare le anomalie cromosomiche utilizzando i flussi sanitari correnti: il Registro delle malformazioni congenite di Milano.

OBJECTIVES: to assess the potential of a new algorithm based on current healthcare databases to identify potential cases of malformation, particularly chromosomal anomalies associated with terminations of pregnancy. DESIGN: retrospective observational study. SETTING AND PARTICIPANTS: Registry of Congenital Anomalies of Milan, live births, still births, and termination of pregnancies for fetal anomalies from 2012 to 2016, detected by using current healthcare data. MAIN OUTCOME MEASURES: prevalence between 2012 and 2016 of congenital malformations recorded by Milan's Registry of Congenital Anomalies, with particular regard to chromosomal anomaly trends. Variation in the percentage of malformations detected from terminations of pregnancy. RESULTS: prevalence of malformations increased from 270 in 2012 to 283 per 10,000 in 2016; specifically, chromosomal abnormalities increased from 35 to 51 per 10,000 births. The algorithm detected a greater proportion of anomalies associated with therapeutic abortion, especially with respect to chromosomal anomalies, with an increase from 57.7% in 2012 to 75.8% in 2016 (test for trend p=0.002). CONCLUSIONS: the proposed algorithm identified a greater number of chromosomal anomalies that caused termination of pregnancy and may be applied to existing Italian registries to evaluate the quality of healthcare services, in particular with regard to the effectiveness of prenatal trisomy screening policies. The algorithm may also be used where no active surveillance systems are present, as well as in epidemiological studies, to assess environmental impact on congenital anomalies.

Association between autoimmune diseases and COVID-19 as assessed in both a test-negative case-control and population case-control design.

BACKGROUND: COVID-19 epidemic has paralleled with the so called infodemic, where countless pieces of information have been disseminated on putative risk factors for COVID-19. Among those, emerged the notion that people suffering from autoimmune diseases (AIDs) have a higher risk of SARS-CoV-2 infection. METHODS: The cohort included all COVID-19 cases residents in the Agency for Health Protection (AHP) of Milan that, from the beginning of the outbreak, developed a web-based platform that traced positive and negative cases as well as related contacts. AIDs subjects were defined ad having one the following autoimmune disease: rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, Sjogren disease, ankylosing spondylitis, myasthenia gravis, Hashimoto's disease, acquired autoimmune hemolytic anemia, and psoriatic arthritis. To investigate whether AID subjects are at increased risk of SARS-CoV-2 infection, and whether they have worse prognosis than AIDs-free subjects once infected, we performed a combined analysis of a test-negative design case-control study, a case-control with test-positive as cases, and one with test-negative as cases (CC-NEG). RESULTS: During the outbreak, the Milan AHP endured, up to April 27th 2020, 20,364 test-positive and 34,697 test-negative subjects. We found no association between AIDs and being positive to COVID-19, but a statistically significant association between AIDs and being negative to COVID-19 in the CC-NEG. If, as likely, test-negative subjects underwent testing because of respiratory infection symptoms, these results imply that autoimmune diseases may be a risk factor for respiratory infections in general (including COVID-19), but they are not a specific risk factor for COVID-19. Furthermore, when infected by SARS-CoV-2, AIDs subjects did not have a worse prognosis compared to non-AIDs subjects. Results highlighted a potential unbalance in the testing campaign, which may be correlated to the characteristics of the tested person, leading specific frail population to be particularly tested. CONCLUSIONS: Lack of availability of sound scientific knowledge inevitably lead unreliable news to spread over the population, preventing people to disentangle them form reliable information. Even if additional studies are needed to replicate and strengthen our results, these findings represent initial evidence to derive recommendations based on actual data for subjects with autoimmune diseases.

Latent composite indicators for evaluating adherence to guidelines in patients with a colorectal cancer diagnosis.

Evidence-based guidelines for the correct management of cancer patients are developed on the idea that timely care can improve health prognoses and quality of life.The aim of this paper is to evaluate the adherence of clinical pathways to clinical guidelines provided at the hospital level, for colorectal cancer care.By using a retrospective observational study, we proposed a method for associating each patient to a healthcare provider and modeling adherence as a latent construct governed by a set of 10 influential indicators. These indicators measure the adherence to specific guidelines for diagnosis, surgical treatment, chemotherapy, and follow-up. The model used was that of the item response theory (IRT). When evaluating providers, the IRT allows for a comparison of indicators in terms of their discriminating ability and difficulty, and in terms of their adherence to guidelines. The IRT results were compared with non-latent methods: numerator-based weight and denominator-based weight.A strong degree of coherence of the indicators in measuring adherence, and a high level of overall agreement between latent and non-latent methods were noted. The IRT approach demonstrated similar providers' evaluations between endoscopy and histological assessment indicators. The greatest discriminating ability among providers could be attributed to all diagnostic exams, while the lowest was associated with follow-up endoscopies. The most difficult indicator to achieve was fecal occult blood test, while follow-up imaging was the easiest.In a decision-making framework, valuable indications can be derived from the use of IRT models rather than weighting methods. Using IRTs, we were able to highlight the principal indicators in terms of strength of discrimination, and to isolate those that merely duplicated information.

Describing the epidemic trends of COVID-19 in the area covered by Agency for Health Protection of the Metropolitan Area of Milan.

OBJECTIVES: to describe the epidemic trends of COVID-19 over time and by area in the territory covered by Milan's Agency for Health Protection (ATS-MI) from February to May 2020. DESIGN: descriptive study of COVID-19 cases. SETTING AND PARTICIPANTS: a new information system was developed to record COVID-19 cases with positive nasopharyngeal swab. Patients resident in the area covered by ATS-MI with symptom onset between February and May 2020 were selected. Different epidemic periods were considered based on the timeline of the various regional and national containment measures. MAIN OUTCOME MEASURES: case fatality ratios, incidence rates, and reproduction number by epidemic period and sub-area of ATS-MI. RESULTS: a total of 27,017 swab-positive COVID-19 cases were included. Mean age was 65 years and males were 45%. Incidence in the ATS-MI area was 776 per 100,000 population. The number of deaths was 4,660, the crude case fatality ratio was 17.3%, higher in males (21.2%) than in females (14.0%). The estimated reproduction number registered its peak (3.0) in the early stages of the epidemic and subsequently decreased. Territorial differences were observed in the epidemic spread, with a higher incidence in the Lodi area. CONCLUSIONS: estimated incidence and case fatality ratios were higher than national estimates for Italy. Each ATS-MI area had different epidemic spread patterns.

Assessment of the Overall Mortality during the COVID-19 Outbreak in the Provinces of Milan and Lodi (Lombardy Region, Northern Italy).

OBJECTIVES: to describe the overall mortality increase in the provinces of Milan and Lodi - area covered by the Agency for Health Protection of Milan - during the COVID-19 epidemic in the first four months of 2020, compare it with the same time period in the years 2016-2019, and evaluate to what extent the mortality can be directly attributed to the outbreak. DESIGN: cohort study. SETTING AND PARTICIPANTS: using a new information system developed during the pandemic, we gathered data on the number of daily deaths in the population residing in the provinces of Milan and Lodi by Local Health Unit (ASST) and age groups. To describe the case fatality of COVID-19, we performed a record linkage with a database specially constructed during the epidemic to identify deaths that occurred in confirmed cases. MAIN OUTCOME MEASURES: mortality and excess mortality were analysed by comparing the number of observed deaths in the first 4 months of 2020 with the average deaths of the years 2016-2019 in the same calendar period and with expected deaths, estimated using a Poisson model. Furthermore, a measure of relative risk was calculated as observed/expected ratio with a 95% confidence interval. RESULTS: the increase in mortality for all causes occurring in the study population in the first 4 months of 2020 was 48.8%, 30.8% for ages between 60 and 69, 43.9% for ages between 70 and 79, and 56.7% for subjects above 80 years of age. Focusing on the epidemic period, from 1 March to 30 April, the excess is quantifiable as more than 2-fold and mainly concerns the population over 60 years of age. The excess mortality was observed in all local health units (ASSTs). The highest increments were in the province of Lodi and the North-East of Milan (ASST Nord). In the ASSTs of Lodi and Melegnano-Martesana the mortality excess was detectable from March 15th, while for the other ASSTs the increase began in the first week of April. CONCLUSIONS: evaluation of overall mortality in the provinces of Milan and Lodi during the first wave of the Covid-19 epidemic showed a significant excess compared to the first 4 months of the years 2016-2019, mainly in the population over 60 years of age. However, this excess cannot be completely attributed directly to COVID-19 itself. This phenomenon was more intense in the Lodi ASST, with daily deaths up to 5 times higher than expected.

Cancer incidence and congenital anomalies evaluation in the contaminated sites of Sesto San Giovanni - the SENTIERI Project.

The Italian Institute for Environmental Protection and Research defines national priority contaminated sites (NPCSs) as land where hazardous substances are likely to pose a risk to human health. SENTIERI was the first national project evaluating the health status of residents in NPCSs. We have extended, for the site of Sesto San Giovanni, the evaluation to cancer incidence and congenital anomalies (CAs). We have found an overall significant negative association between living in the NPCS and overall cancer incidence in all ages and no association in paediatric, adolescent and young adults' population. We have found an excess risk for bladder cancer, leukaemia, lymphoid leukaemia and chronic lymphocytic leukaemia in men and for lung and breast cancer in women. For the paediatric and adolescent population, we have found an excess in embryonic tumours. Total CAs were not different from expected, while we have found excesses regarding ear, face and neck, digestive system and chromosomal defects.

Deciding on cystic fibrosis carrier screening: three citizens' juries and an online survey.

Background: Health technology assessment and ethical issues have to be dealt with in deciding on national carrier screening for cystic fibrosis (CF)-the most frequent severe autosomal recessive disease in Caucasian populations and several stakeholders need to be involved. A citizens' jury is one way to ask citizens to deliberate on controversial topics in the interests of a society. The aims of this project were to gather opinions about CF carrier screening through citizens' jury deliberations and to match them with the findings of a large online consultation survey open to the general population, people with CF and families and health professionals. Methods: Three citizens' juries and an online survey were asked: 'Should the Health Service organize screening of the population with the aim of identifying healthy people who may have children with CF?' The jurors had no medical background and no personal or family CF history. The survey was open to people with CF, families, and healthcare professionals. Results: Jurors and survey respondents were in favour of CF carrier screening, mainly considering the severity of CF, the value of informed reproductive choices and the equality of the screening. All the citizens' juries felt positively about the health service actively offer CF carrier screening to provide women and couples of reproductive age equal access and standardized information on the pros and cons. Conclusion: Considering the favourable attitude towards CF screening, the feasibility of CF screening, in terms of best setting, target age and healthcare professionals providing it, should be tested in a clinical trial.

[Applying a set of indicators to evaluate the primary health care]. / Indicatori come strumento di governo della medicina territoriale.

OBJECTIVES: to develop a system of indicators to monitor the quality of health care, in terms of safety, effectiveness, and appropriateness to allow the integrated promotion of the welfare of the effectiveness and quality. DESIGN: retrospective study. SETTING AND PARTICIPANTS: all general practitioners (GPs) with at least 100 patients in loading at 1.1.2015 were included. The setting chosen is the Primary Care of the Agency for Health Protection of the Province of Milan (Northern Italy). MAIN OUTCOME MEASURES: for each GPs 39 indicators were calculated, including 7 on the mix of patients, 4 on prevention, 5 on ER, 5 on hospital admissions, 8 on outpatient, and 10 on pharmaceutical prescription. The correlations between individual indicators were considered and patterns to classify the GPs were determined by the factor analysis and the multiple correspondence analysis. RESULTS: among the expected correlations, we observed those between institutional colorectal screening and institutional breast cancer screening. Among not-expected correlations, the one between pump-inhibitor drugs and routines blood chemistry in the population between 20 and 50 years identifies a positive association between two practices of unrecognized clinical validity. Classifying the 2,217 GPs on the basis of the maximum factorial score, six main factors were identified. CONCLUSION: using approaches based on multivariate methods, interventions aimed at changing the profile of MMG exerting the government primary health care can be proposed, not only by means of system rules or approaches based on economic incentives, but on complex governance mechanisms.

Transperineal Ultrasound for Perianal Fistulas and Abscesses - A Systematic Review and Meta-Analysis.

Purpose Transperineal ultrasound (TPUS) is a practical tool for assessing perianal inflammatory lesions. We systematically review its accuracy for detecting and classifying perianal fistulae and abscesses. Method The National Library of Medicine and Embase were searched for articles on TPUS for the assessment of idiopathic and Crohn's perianal fistulae and abscesses. Two reviewers independently reviewed eligible studies and rated them for quality using the QUADAS tool. The primary outcome measure was the accuracy of TPUS as measured by its sensitivity and positive predictive value (PPV) in detecting and classifying perianal fistulae, internal openings and perianal abscesses. Results We included 12 studies (565 patients). Overall, the methodological quality of the studies was suboptimal. 3 studies were retrospective and 4 showed significant risks of bias in the application of the reference standard. The sensitivity of TPUS in detecting perianal fistulae on a per-lesion basis was 98 % (95 % CI 96 - 100 %) and the PPV was 95 % (95 % CI 90 - 98 %). The detection of internal openings had a sensitivity of 91 % (95 % CI 84 - 97 %) with a PPV of 87 % (95 % CI 76 - 95 %). The classification of fistulae yielded a sensitivity of 92 % (95 % CI 85 - 97 %) and a PPV of 92 % (95 % CI 83 - 98 %). TPUS had a sensitivity of 86 % (95 % CI 67 - 99 %) and PPV of 90 % (95 % CI 76 - 99 %) in the detection of perianal abscesses. Conclusion The current literature on TPUS illustrates good overall accuracy in the assessment of perianal fistulae and abscesses. However, many studies had methodological flaws suggesting that further research is required.

Long-term efficacy and safety of oxycodone-naloxone prolonged release in geriatric patients with moderate-to-severe chronic noncancer pain: a 52-week open-label extension phase study.

BACKGROUND: Two-thirds of older people suffer from chronic pain and finding valid treatment options is essential. In this 1-yearlong investigation, we evaluated the efficacy and safety of prolonged-release oxycodone-naloxone (OXN-PR) in patients aged ≥70 (mean 81.7) years. METHODS: In this open-label prospective study, patients with moderate-to-severe noncancer chronic pain were prescribed OXN-PR for 1 year. The primary endpoint was the proportion of patients who achieved ≥30% reduction in pain intensity after 52 weeks of treatment, without worsening bowel function. The scheduled visits were at baseline (T0), after 4 weeks (T4), and after 52 weeks (T52). RESULTS: Fifty patients completed the study. The primary endpoint was achieved in 78% of patients at T4 and 96% at T52 (P<0.0001). Pain intensity, measured on a 0-10 numerical rating scale, decreased from 6.0 at T0 to 2.8 at T4 and to 1.7 at T52 (P<0.0001). Mean daily dose of oxycodone increased from 10 to 14.4 mg (T4) and finally to 17.4 mg (T52). Bowel Function Index from 35.1 to 28.7 at T52. No changes were observed in cognitive functions (Mini-Mental State Examination evaluation), while daily functioning improved (Barthel Index from 53.1 to 61.0, P<0.0001). The Screener and Opioid Assessment for Patients with Pain-Revised score at 52 weeks was 2.6 (standard deviation 1.6), indicating a low risk of aberrant medication-related behavior. In general, OXN-PR was well tolerated. CONCLUSION: This study of the long-term treatment of chronic pain in a geriatric population with OXN-PR shows satisfying analgesic effects achieved with a stable low daily dose, coupled with a good safety profile and, in particular, with a reduction of constipation, often present during opioid therapy. Our findings support the indications of the American Geriatrics Society, suggesting the use of opioids to treat pain in older people not responsive to acetaminophen or nonsteroidal anti-inflammatory drugs.

Prevalence of Neuropathic Pain in Cancer Patients: Pooled Estimates From a Systematic Review of Published Literature and Results From a Survey Conducted in 50 Italian Palliative Care Centers.

CONTEXT: Because of the increasing body of literature on neuropathic cancer pain (NCP), an accurate estimate of its prevalence requires recurring updates. OBJECTIVES: To provide this estimate using information from a systematic review and a survey. METHODS: Using MEDLINE, Embase, and a previous review, we searched for studies published up to 2014 reporting data on NCP prevalence in adult cancer populations. Pooled prevalence rates from observational prospective studies were computed. The association between NCP prevalence and possible predictors was investigated for oncology and palliative settings. Prevalence rates were extracted from a questionnaire answered by 137 physicians working in 50 Italian centers of palliative care. Estimates from studies conducted in palliative settings and from the experts were analyzed separately and eventually pooled with an informative Bayesian random-effect model. RESULTS: Twenty-nine observational studies were identified. The overall pooled prevalence was 31.2%, with high heterogeneity; similar figures were observed when oncology and palliative settings were individually considered. A slightly higher prevalence of NCP was detected for hospice/inpatients as compared to outpatients, in both settings. The mean NCP prevalence reported by the survey experts was 44.2%; the pooled Bayesian estimate for the palliative setting corresponded to 43.0% (95% CI: 40.0-46.0). The subgroup with the lowest heterogeneity and where the literature and experts' estimates were closest is hospice/inpatients, with a pooled Bayesian prevalence rate of 34.9% (95% CI: 29.9-41.0). CONCLUSION: The systematic review and the survey suggest that more than one in three patients with cancer pain also experiences NCP.

Efficacy and tolerability of oral oxycodone and oxycodone/naloxone combination in opioid-naïve cancer patients: a propensity analysis.

BACKGROUND: World Health Organization step III opioids are required to relieve moderate-to-severe cancer pain; constipation is one of the most frequent opioid-induced side effects. A fixed combination, prolonged-release oxycodone/naloxone (OXN), was developed with the aim of reducing opioid-related gastrointestinal side effects. The objective of this study was to compare the efficacy and safety of prolonged-release oxycodone (OXY) alone to OXN in opioid-naïve cancer patients with moderate-to-severe pain. METHODS: Propensity analysis was utilized in this observational study, which evaluated the efficacy, safety, and quality of life. RESULTS: Out of the 210 patients recruited, 146 were matched using propensity scores and included in the comparative analysis. In both groups, pain intensity decreased by ≈3 points after 60 days, indicating comparable analgesic efficacy. Responder rates were similar between groups. Analgesia was achieved and maintained with similarly low and stable dosages over time (12.0-20.4 mg/d for OXY and 11.5-22.0 mg/d for OXN). Bowel Function Index (BFI) and laxative use per week improved from baseline at 30 days and 60 days in OXN recipients (-16, P<0.0001 and -3.5, P=0.02, respectively); BFI worsened in the OXY group. The overall incidence of drug-related adverse events was 28.9% in the OXY group and 8.2% in the OXN group (P<0.01); nausea and vomiting were two to five times less frequent with OXN. Quality of life improved to a significantly greater extent in patients receiving OXN compared to OXY (increase in Short Form-36 physical component score of 7.1 points vs 3.2 points, respectively; P<0.001). CONCLUSION: In patients with chronic cancer pain, OXN provided analgesic effectiveness that is similar to OXY, with early and sustained benefits in tolerability. The relationship between responsiveness to OXN and clinical characteristics is currently being investigated.

Quality of cancer pain management: an update of a systematic review of undertreatment of patients with cancer.

PURPOSE: Pain is a frequent symptom in patients with cancer, with substantial impact. Despite the availability of opioids and updated guidelines from reliable leading societies, undertreatment is still frequent. METHODS: We updated a systematic review published in 2008, which showed that according to the Pain Management Index (PMI), 43.4% of patients with cancer were undertreated. This review included observational and experimental studies reporting negative PMI scores for adults with cancer and pain published from 2007 to 2013 and retrieved through MEDLINE, Embase, and Google Scholar. To detect any temporal trend and identify potential determinants of undertreatment, we compared articles published before and after 2007 with univariable, multivariable, and sensitivity analyses. RESULTS: In the new set of 20 articles published from 2007 to 2013, there was a decrease in undertreatment of approximately 25% (from 43.4 to 31.8%). In the whole sample, the proportion of undertreated patients fell from 2007 to 2013, and an association was confirmed between negative PMI score, economic level, and nonspecific setting for cancer pain. Sensitivity analysis confirmed the robustness of results. CONCLUSION: Analysis of 46 articles published from 1994 to 2013 using the PMI to assess the adequacy of analgesic therapy suggests the quality of pharmacologic pain management has improved. However, approximately one third of patients still do not receive pain medication proportional to their pain intensity.

Prevalence of breakthrough cancer pain: a systematic review and a pooled analysis of published literature.

CONTEXT: Despite the large body of literature on breakthrough cancer pain (BTcP), an accurate estimate of BTcP prevalence is still not available. OBJECTIVES: To provide an estimate of BTcP prevalence and investigate the association between different prevalence rates and possible determinants. METHODS: We conducted MEDLINE and EMBASE searches for studies published from 1990 to 2012 reporting data on BTcP prevalence in adult cancer populations. Pooled prevalence rates from observational studies with an acceptable methodological quality were computed. The association between BTcP prevalence and possible predictors was investigated using subgroup analyses and meta-regression. RESULTS: Twenty-seven observational studies were identified. When quality criteria were applied, only 19 studies were included in the pooled analysis. The overall pooled prevalence was 59.2%, with high heterogeneity. The lowest prevalence rates were detected in studies conducted in outpatient clinics (39.9%), and the highest prevalence was reported in studies conducted in hospice (80.5%). The association between BTcP prevalence and other determinants such as publication year, age, gender, metastatic disease prevalence, or baseline pain intensity did not reach statistical significance. CONCLUSION: In the context of a large between-studies heterogeneity, more than one in two patients with cancer pain also experiences BTcP, with some variability according to clinical and organizational variables.

[Comparison of different methods for the definition of indicators to assess the diagnostic and therapeutic paths of colorectal cancer]. / Confronto di differenti metodologie per la definizione di indicatori per monitorare i percorsi diagnostico-terapeutici dei tumori del colon retto.

OBJECTIVES: to assess the accuracy of hospital admissions (through hospital discharge records - SDO) in the estimation of incident cases of colorectal cancer, extracted from the cancer registry (CR) of the Local Health Unit "Milano1" and to investigate whether specific indicators to assess the diagnostic-therapeutic paths of this tumour are influenced by the data source. DESIGN: observational cross-sectional study. SETTING AND PARTICIPANTS: incident cases for the period 2007-2009 of colorectal cancer by CR and application of an algorithm to the SDO to identify the same patients. MAIN OUTCOME MEASURES: sensitivity and positive predictive value of SDO data. Indicators to evaluate the diagnostic and therapeutic paths of patients with colorectal cancer and assessment of the level of concordance indicator in SDO and CR databases. Each indicator was related to the volume of specific interventions for colorectal cancer. RESULTS: SDO database showed 2,246 cases, while from RT 2,335 subjects with the colorectal cancer resulted. The sensitivity of the SDO was 90.2%, with 15% of discordant cases. The group identified exclusively by CR had lower survival. The indicators surgery had the lowest levels of correlation (0.64 to 0.69) but the highest level of appropriateness (90%), while the indicators for diagnosis and follow-up showed greater correlation but lower values. CONCLUSION: for some indicators, using the SDO when the CR is not available is useful, considering the volume of specific interventions for colorectal cancer. For indicators where tumour stage is important, the CR is the best data source available.

An exploratory analysis on the effectiveness of four strong opioids in patients with cancer pain.

OBJECTIVE: This analysis, carried out in the context of a wider observational prospective study, tried to explore whether four World Health Organization/step-III opioids (morphine, oxycodone, fentanyl, and buprenorphine) had different effectiveness when using several different outcomes and endpoints. DESIGN: Cross-sectional and longitudinal design. SETTING: Oncologic, palliative, and pain centers in Italy. PATIENTS: Two hundred fifty-eight cancer patients monitored over a 3-week follow-up program. Intervention. Not applicable. OUTCOME MEASURES: The analgesic efficacy was assessed using effectiveness endpoints, such as pain intensity, pain intensity difference (PID), proportion of nonresponders (NR) and full-responders (FR) subjects, percentage of switches and dose escalation. RESULTS: Mean values of PID led to differences among opioids ranging from 10% to 30%. FR (PID ≥ 30%) were more frequent in buprenorphine-fentanyl-oxycodone groups than in morphine; NR (PID ≤ 0%) were variable. The percentage of switches resulted three times more frequent when using morphine than buprenorphine (24.4% vs 8.6%). An increase of dose ≥ 5% a day was observed in 33.3% of fentanyl patients vs 15% of buprenorphine. As a whole, opioids show some different behaviors on the basis of the considered endpoints. CONCLUSIONS: The observed results, even if the small sample size and the nature itself of the study do not allow a definitive evaluation of the effectiveness of the drugs, underline a degree of variability among opioids and address toward a correct planning of a comparative randomized clinical trial that is now underway in Italy. For this reason, a confirmative effectiveness randomized controlled trial is required.

A new informed consent form model for cancer patients: preliminary results of a prospective study by the Italian Association of Medical Oncology (AIOM).

OBJECTIVES: To document the preliminary validity of a new informed consent form (ICF) model in terms of face/content validity and feasibility, to collect patients' and oncologists' opinions on it, and to explore physicians' and patients' "knowledge", "opinions" about "the information exchanged". METHODS: The working group for informed consent promoted by the Italian Association of Medical Oncology developed a new ICF model which was tested in ten Italian cancer centers. Patients and physicians received questionnaires on the new ICF model. Twenty-six independent oncologists were interviewed to collect their opinions. RESULTS: Seventy eight cancer patients were enrolled: about 90% reported having received information about diagnosis and therapy and 80% about prognosis. About 63% of oncologists had no difficulty in administering the ICF. Oncologists used "correct terms" about diagnosis in 92% of patients with localized disease and in 90% with metastasis and about therapy in respectively 75.7% and 80%. About prognosis, oncologists used "vague" and "no information-no pertinent terms" in 79% of patients with localized disease and 92.5% of patients with metastasis. CONCLUSIONS: The ICF seemed to have sufficient validity and feasibility. PRACTICE IMPLICATION: This ICF model could mean that patients require oncologists to spend more time explaining the diagnosis, prognosis and treatment, increasing patient's opportunities to participate actively in the care process.

Epidemiology and pattern of care of breakthrough cancer pain in a longitudinal sample of cancer patients: results from the Cancer Pain Outcome Research Study Group.

OBJECTIVE: Breakthrough cancer pain (BTcP) is a frequent event in cancer patients, with a prevalence from 19% to 95%. The reasons for such variability are explained by several factors, including different definitions across studies. In the framework of a wider initiative, we have analyzed the epidemiology of BTcP and identified factors associated with the pattern of care. METHODS: This study reports the results from a multicenter, prospective, nonrandomized, longitudinal study carried out in Italy between 2006 and 2007 on patients with cancer and pain. Transient exacerbations of pain were assessed with 3 different questions, and 1 composite variable to operationally define BTcP was then used as main outcome. After univariate analysis, a logistic model was also fitted to identify prognostic and predictive factors. RESULTS: One hundred and ten centers recruited 1801 cases of which 40.3% had BTcP at baseline. Most patients did not receive rescue therapy at the time of study inclusion. Univariate analysis identified several associations with clinical variables. A strong association has been also found with the type of recruiting centers, with oncologic wards reporting a somewhat lower proportion of patients with BTcP (-30%) when compared with palliative centers. Patients with BTcP had a high probability of dying (OR=1.4, 95% CI: 1.1-1.7, P-value 0.006) and to change of the opioid with another for analgesic failure or for side effects (OR=1.4, 95% CI: 1.0-1.9, P-value 0.040) DISCUSSION: These findings confirm the high prevalence of BTcP and substantial undertreatment and identify a few factors associated with prevalence and prognosis.

Effects of transdermal buprenorphine on patients-reported outcomes in cancer patients: results from the Cancer Pain Outcome Research (CPOR) Study Group.

OBJECTIVES: Pain still afflicts most cancer patients, mainly in the metastatic phases, and under-treatment is well documented. Transdermal delivery systems (TDS) containing fentanyl or buprenorphine could potentiality have advantages over oral and parenteral routes, but evidence from comparative trials are scanty. In the framework of a wider initiative, an Outcome Research Study was carried out in Italy in 2006 to evaluate the effects of various analgesic options, particularly buprenorphine TDS. METHODS: This is a multicenter, open-label, prospective, nonrandomized study. Data were collected using a web-based standardized system, with a follow-up up of to 3 months. Pain intensity, the primary outcomes of the study, was measured using 11-point numerical rating scales from the Brief Pain Inventory. RESULTS: One-hundred ten centers recruited 1801 cases, most of which (60%) were receiving a strong opioid at the time of inclusion. Of these, 257 had TDS buprenorphine as first choice. Of the remaining 709 patients who at the time of inclusion were not on a strong opioid, 325 changed to a strong opioid and in 43% it was TDS buprenorphine. During the follow-up, physicians had to increase the dosage to control pain (average increase between 16% and 17%). About 34% of patients had an improvement of at least 2 points in worst pain, 15% had a 20% improvement in pain relief, and 40% in satisfaction. Results were in line with those of patients receiving other World Health Organization-level III opioids. CONCLUSIONS: Despite the limitations owing to the observational design, these findings may be useful to clinicians to judge the value of the drug under evaluation better and to help researchers design further comparative studies.