Flavia Carle

Elderly Patients with Advanced Non-Small Cell Lung Cancer

Objectives: The incidence of non-small cell lung cancer (NSCLC) is increasing among the elderly. We studied the toxicity and efficacy of a weekly schedule of gemcitabine and cisplatin in elderly patients with advanced NSCLC. Methods: Patients aged 70 years or above with advanced NSCLC were treated in a phase II prospective trial with gemcitabine 1,000 mg/m2 and cisplatin 35 mg/m2 on days 1, 8 and 15 every 28 days. Results: Forty-eight patients with a median age of 74 years (range 70–78) participated in the study. We observed 14 cases with partial response, 14 with stable disease and 16 with progressive disease, whilst 4 patients were not evaluable. By intention-to-treat analysis, partial response rate was 31.8% whilst progressive disease was 33.3%. Median survival was 9 months; 1-year survival probability was 34.4% and median time to progression was 4 months. Grade III–IV leukopenia was observed in 5/48 patients (10.4%), 20/48 patients (41.7%) had grade III–IV thrombocytopenia and 7/48 patients (14.6%) had grade III–IV anemia. One patient experienced grade III emesis and 2 patients had grade III–IV fatigue. Conclusions: At this dose and schedule the combination of gemcitabine and cisplatin appears to be an active and well-tolerated regimen for elderly patients with advanced NSCLC.

Assessing quality of life in patients with cancer: a comparison of a visual-analogue and a categorical model.

A simple instrument for self-assessment of quality of life (QL) in patients with cancer was elaborated using a linear analogue scale (LAS). The instrument was based on five questions, exploring different functional areas; the same questions were also addressed in a parallel format, where problems were seen from an opposite point of view (positive/negative). The LAS was given to 222 patients, for a total of 372 tests collected. Internal consistency was satisfactory (Cronbachs alpha = 0.75); QL score was significantly correlated to parameters of disease. Concordance between scales, as judged by comparison of parallel formats, was statistically significant but poor. A questionnaire was then elaborated with similar items, based on a categorical scale. A direct comparison between LAS and our questionnaire was made on a group of 41 patients. Internal consistency was poor for the LAS (alpha = 0.58) and good for the questionnaire (alpha = 0.93); Spearmans rank correlation coefficients were disappointing for the LAS and good for the questionnaire; the questionnaire was judged reliable in 82.9% of cases, the LAS in 29.3% only; the questionnaire score, and not the LAS score, was significantly correlated with PS and disease status. In conclusion, many patients appeared unable to correctly interpret the visual-analogue scale; the categorical scale was more immediate and correctly understood by the large majority of patients; the correlation between score and important parameters of QL was maintained, and internal consistency was excellent, indicating a satisfactory reliability of this instrument.

Aldosterone synthase alleles and cardiovascular phenotype in young adults

The C(−344)T promoter polymorphism of the human aldosterone synthase (CYP11B2) gene has been associated with hypertension and cardiac hypertrophy, but there were contrasting data. We analysed the genotype/phenotype associations between this polymorphism and cardiovascular variables in a young adult population, where interactions among genes, gene–environment, and acquired ageing-related organ damage are reduced. Anthropometric measurements, blood pressure, heart rate, left ventricular variables (by echocardiography), and carotid artery wall intimal–media thickness (by high-resolution sonography and digitalized morphometry) were taken in 420 white Caucasian students (mean age 23.5 years, s.d. 2.5 years). CYP11B2 alleles were detected by genomic polymerase chain reaction followed by digestion. Taking into account the three possible models of inheritance, we found no differences in the considered variables, except for an independent effect of the C(−344) allele on SBP in males (TT 125.6 (1.6), TC 128.4 (1.2) and CC 130.5 (2.2), mmHg, media (ES), P=0.03), and on interventricular septum thickness in diastole in females (CC 6.98 (0.12) vs TT 6.87 (0.09) and TC 6.87 (0.07), mmHg, P<0.01), in the codominant model. In conclusion, the CYP11B2 C(−344)T polymorphism appears to have a slight role in the cardiovascular phenotype of young healthy adults, even if these genotype/phenotype relationships might change with ageing.

Cardiovascular phenotype of young adults and angiotensinogen alleles.

Objectives and Design Angiotensinogen (AGT) gene variants influence angiotensinogen plasma levels in children and young adults. The angiotensinogen promoter (-6)A variant facilitates gene transcription in human tissues and it has been associated with high blood pressure in older adults. A young adult population can be used as a model to study genotype/phenotype associations between AGT (-6) variants and cardiovascular variables. Methods and Results Anthropometric measurements, blood pressure and heart rate were taken in 422 white Caucasian students (mean age 23.5 years, SD 2.5 years). Family history for hypertension, physical activity and smoking history were evaluated. Left ventricular variables were measured by echocardiography. Carotid artery wall intimal-media thickness (IMT) was measured by high resolution sonography and digitalized morphometry. The AGT G(-6)A alleles were evaluated by mutagenically separated polymerase chain reaction controlled by direct sequencing. No significant associations were found between angiotensinogen genotype and blood pressure, cardiac variables [except for deceleration time in females which increased with the number of (-6)A alleles] and IMT. Allele frequencies were similar between the first and third tertile of blood pressure and left ventricular mass, and were also similar between negative or positive family history for hypertension (the last group having significantly higher systolic blood pressure in males, P = 0.04 and diastolic blood pressure in females, P < 0.01). Moreover, no relevant interaction on the cardiovascular variables was found between AGT genotype and body mass index. Conclusions The angiotensinogen G(-6)A variants do not affect cardiovascular parameters in young adults, but an effect of this polymorphism on cardiovascular phenotype (and hypertension) in older adults cannot be excluded. Additional factors, associated with ageing, should be present to unleash the supposed unfavourable potential of the (-6)A angiotensinogen variant.

What do Italians at high risk of stroke know about ischaemic stroke? A survey among a group of subjects undergoing neuro-sonographic examination

The objective was to assess the knowledge about ischaemic stroke among selected groups of persons at high risk for stroke. Outpatients referred to 3 hospital ultrasound departments in the Marche Region (Italy) were asked to answer a questionnaire. Data were collected on: (1) demographic characteristics; (2) risk profile determined using Coppola et al.’s scoring system; (3) knowledge about symptoms, risk factors, part of the body injured and best referral option for stroke. Of the 352 respondents, around 52% were unable to report even one warning symptom of stroke, while 58.4% of participants at increased risk did not know any risk factors. Only 64.5% identified the brain as the part of the body injured by stroke. Only 59.4% considered the Emergency Department as the best referral option in the event of stroke. This study confirms poor knowledge about stroke in our study population, particularly in subjects with increased stroke risk.

Perforator flaps in late-stage pressure sore treatment: outcome analysis of 11-year-long experience with 143 patients.

BackgroundIn the last decade, perforator flaps have been introduced for the treatment of pressure ulcers as alternative to the more popular myocutaneous local flaps. We reviewed our single-team 11-year experience in order to define whether real advantages could be achieved. MethodsWe analyzed 143 patients undergoing perforator flap surgery for a single late-stage pressure sore. All patients underwent the same protocol treatment. Data regarding associated pathologies, demographics, complications, healing, and hospitalization times were collected. ResultsNinety-three percent of 143 patients were white Caucasian, and 61% were men, with median age of 51 years. Of 143 stage 4 ulcers, 46.2% were ischial, 42.7% sacral, and 11.2% trochanteric. The most common diagnosis was traumatic paraplegia/tetraplegia (74.9%); no significant difference was found in diagnosis distribution and in ulcer location between recurrent and nonrecurrent patients. We performed 44 S-GAP, 78 I-GAP, 3 PFAP-am, and 18 PFAP-1 flaps. At 2 years’ follow-up, the overall recurrence was 22.4% and new ulcer occurrence was 4.2%. Mean hospital stay was 16 days. The overall complication percentage was 22.4%, mostly due to suture-line dehiscence (14%) and distal flap necrosis (6.3%). PFAP flaps had a significant higher risk of developing recurrence than I-GAP flaps. The recurrence risk was significantly higher for subjects suffering from coronary artery disease. ConclusionsLate-stage pressure sore treatment with local perforator flaps can achieve reliable long-term outcomes in terms of recurrences and complications. When compared to previously published data, perforator flaps surgery decreased postoperative hospital stay (by an average of nearly 1 week), reoperations (5.6%), and occurrences.

Identification of Clinical Prognostic Factors in Patients with Unknown Primary Tumors Treated with a Platinum-Based Combination

Objective: The aim of this study was to evaluate patient and tumor characteristics in 102 patients with unknown primary tumors (UPT) prospectively treated with a combination of carboplatin, doxorubicin, and etoposide, to identify clinical variables predictive of response and survival. Patients and Methods: The association between clinical characteristics and outcome was evaluated by univariate and multivariate analysis: χ2 test and logistic regression analysis were used to study variables predictive of response, and survival analysis, comparison of survival curves and Cox multiple regression analysis to study variables predictive of survival. Results: We obtained 26.5% objective responses (95% confidence interval: 18.2–36.1%) and a median survival of 9 months (95% confidence interval: 7–11 months). Several variables were associated with response to treatment and survival at univariate analysis. At multivariate analysis the number of tumor sites, bone/visceral involvement and epithelial tumor markers were significantly predictive of response; presence of pain, serum alkaline phosphatase, carboplatin AUC and response to treatment were significantly associated with survival. Conclusions: The identification of variables that can predict prognosis and response to treatment in patients with UPT may be useful to offer aggressive treatment to sensitive subsets of patients and provide therapeutic alternatives to those with a low probability of benefiting from standard treatment. In our patients the use of carboplatin AUC higher than 6 and response to treatment were the most important factors associated with prognosis, together with presence of pain and serum alkaline phosphatase. However, larger series and identification of new disease markers are necessary to better define predictive and prognostic variables in UPT patients.

Age-Period-Cohort Analysis of 1990–2003 Incidence Time Trends of Childhood Diabetes in Italy

OBJECTIVE To investigate age-period-cohort effects on the temporal trend of type 1 diabetes in children age 0–14 years in Italian registries. RESEARCH DESIGN AND METHODS This report is based on 5,180 incident cases in the period 1990–2003 from the Registry for Type 1 Diabetes Mellitus in Italy (RIDI). Multilevel (random intercept) Poisson regression models were used to model the effects of sex, age, calendar time, and birth cohorts on temporal trends, taking into account the registry-level variance component. RESULTS The incidence rate was 12.26 per 100,000 person-years and significantly higher in boys (13.13 [95% CI 12.66–13.62]) than in girls (11.35 [10.90–11.82]). Large geographical variations in incidence within Italy were evident; incidence was highest in Sardinia, intermediate in Central-Southern Italy, and high in Northern Italy, particularly in the Trento Province, where the incidence rate was 18.67 per 100,000 person-years. An increasing temporal trend was evident (2.94% per year [95% CI 2.22–3.67]). With respect to the calendar period 1990–1992, the incidence rates increased linearly by 15, 27, 35, and 40% in the following time periods (P for trend < 0.001). With respect to the 1987–1993 birth cohort, the incidence rate ratio increased approximately linearly from 0.63 (95% CI 0.54–0.73) in the 1975–1981 cohort to 1.38 (1.06–1.80) in the 1999–2003 cohort. The best model, however, included sex, age, and a linear time trend (drift). CONCLUSIONS Large geographical variations and an increasing temporal trend in diabetes incidence are evident among type 1 diabetic children in Italy. Age-period-cohort analysis shows that the variation over time has a linear component that cannot be ascribed to either the calendar period or the birth cohort.

The role of socio-economic and clinical factors on HbA1c in children and adolescents with type 1 diabetes: an Italian multicentre survey.

To identify the role of the familys socio‐economic and clinical characteristics on metabolic control in children and adolescents with type 1 diabetes.

RIDI Study Group. Age-period-cohort analysis of 1990-2003 incidence time trends of childhood diabetes in Italy: the RIDI study

OBJECTIVE To investigate age-period-cohort effects on the temporal trend of type 1 diabetes in children age 0–14 years in Italian registries. RESEARCH DESIGN AND METHODS This report is based on 5,180 incident cases in the period 1990–2003 from the Registry for Type 1 Diabetes Mellitus in Italy (RIDI). Multilevel (random intercept) Poisson regression models were used to model the effects of sex, age, calendar time, and birth cohorts on temporal trends, taking into account the registry-level variance component. RESULTS The incidence rate was 12.26 per 100,000 person-years and significantly higher in boys (13.13 [95% CI 12.66–13.62]) than in girls (11.35 [10.90–11.82]). Large geographical variations in incidence within Italy were evident; incidence was highest in Sardinia, intermediate in Central-Southern Italy, and high in Northern Italy, particularly in the Trento Province, where the incidence rate was 18.67 per 100,000 person-years. An increasing temporal trend was evident (2.94% per year [95% CI 2.22–3.67]). With respect to the calendar period 1990–1992, the incidence rates increased linearly by 15, 27, 35, and 40% in the following time periods (P for trend < 0.001). With respect to the 1987–1993 birth cohort, the incidence rate ratio increased approximately linearly from 0.63 (95% CI 0.54–0.73) in the 1975–1981 cohort to 1.38 (1.06–1.80) in the 1999–2003 cohort. The best model, however, included sex, age, and a linear time trend (drift). CONCLUSIONS Large geographical variations and an increasing temporal trend in diabetes incidence are evident among type 1 diabetic children in Italy. Age-period-cohort analysis shows that the variation over time has a linear component that cannot be ascribed to either the calendar period or the birth cohort.