First-line avelumab for patients with PD-L1-positive metastatic or locally advanced urothelial cancer who are unfit for cisplatin.

BACKGROUND: Cisplatin-based chemotherapy is the most recommended treatment for metastatic urothelial cancer (mUC). However, about 50% of patients are considered to be cisplatin ineligible. Anti-programmed cell death protein 1/programmed death-ligand 1 (PD-L1) therapies have, nevertheless, increased the options available to clinicians and are especially valuable for treating these patients. This study therefore tested the activity and safety of avelumab as first-line therapy for mUC. PATIENTS AND METHODS: Patients with mUC who were ineligible for cisplatin-based chemotherapy were screened centrally for PD-L1 expression and only those with a tumour proportion score ≥ 5% were enrolled in the trial. The primary endpoint was 1-year overall survival (OS), and the secondary endpoints were median OS, median progression-free survival, overall response rate, duration of the response, safety and tolerability. All the survival rates were estimated with the Kaplan-Meier product-limit methodology and compared across groups using the log-rank test. RESULTS: A total of 198 patients were screened, with 71 (35.9%) whose PD-L1 expression was ≥5% enrolled in the study. The median age was 75 years, bladder cancer was the primary tumour in 73.2% of cases and 25.3% had liver metastases. The main reasons for the cisplatin ineligibility were a low rate of creatinine clearance (<60 ml/min), present in 70.4% of patients, and an Eastern Cooperative Oncology Group performance status of 2, which affected 31%. The median OS was 10.0 months (95% confidence interval 5.5-14.5 months) and 43% of patients were alive at 1 year. A complete response was achieved in 8.5% of cases, and 15.5% had a partial response. Adverse any-grade and high-grade events occurred in 49.3% and 8.5% of patients, respectively. A grade 3 infusion reaction was the only high-grade treatment-related adverse event. No treatment-related deaths were reported. CONCLUSIONS: This ARIES trial confirmed the activity and safety of avelumab for treating mUC, adding a new therapy option to the armamentarium of checkpoint inhibitors already approved for platinum-ineligible, locally advanced/mUC.

Immune-inflammatory biomarkers as prognostic factors for immunotherapy in pretreated advanced urinary tract cancer patients: an analysis of the Italian SAUL cohort.

BACKGROUND: Reliable and affordable prognostic and predictive biomarkers for urothelial carcinoma treated with immunotherapy may allow patients' outcome stratification and drive therapeutic options. The SAUL trial investigated the safety and efficacy of atezolizumab in a real-world setting on 1004 patients with locally advanced or metastatic urothelial carcinoma who progressed to one to three prior systemic therapies. PATIENTS AND METHODS: Using the SAUL Italian cohort of 267 patients, we investigated the prognostic role of neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) and the best performing one of these in combination with programmed death-ligand 1 (PD-L1) with or without lactate dehydrogenase (LDH). Previously reported cut-offs (NLR >3 and NLR >5; SII >1375) in addition to study-defined ones derived from receiver operating characteristic (ROC) analysis were used. RESULTS: The cut-off values for NLR and SII by the ROC analysis were 3.65 (sensitivity 60.4; specificity 63.0) and 884 (sensitivity 64.4; specificity 67.5), respectively. The median overall survival (OS) was 14.7 months for NLR <3.65 [95% confidence interval (CI) 9.9-not reached (NR)] versus 6.0 months for NLR ≥3.65 (95% CI 3.9-9.4); 14.7 months for SII <884 (95% CI 10.6-NR) versus 6.0 months for SII ≥884 (95% CI 3.7-8.6). The combination of SII, PD-L1, and LDH stratified OS better than SII plus PD-L1 through better identification of patients with intermediate prognosis (77% versus 48%, respectively). Multivariate analyses confirmed significant correlations with OS and progression-free survival for both the SII + PD-L1 + LDH and SII + PD-L1 combinations. CONCLUSION: The combination of immune-inflammatory biomarkers based on SII, PD-L1, with or without LDH is a potentially useful and easy-to-assess prognostic tool deserving validation to identify patients who may benefit from immunotherapy alone or alternative therapies.

Optimization of resources by drug management: A multicentred web-administered study on the use of ipilimumab in Italy.

OBJECTIVE: In a scenario of new expensive cancer therapies entering the market, strategies of optimisation and cost containment are crucial in oncology care. Better management of drug waste and centralization of drug preparation can be effective strategies to achieve these goals. The aim of this work is to describe the economic management of a high cost anticancer drug (ipilimumab) in some Italian reference centres. METHODS: This was an observational, multicentred study in which economical and clinical data of 21 cancer centres (418 patients) were collected during the enrollment period from February 2013 to August 2014. The follow-up period ended in July 2015. RESULTS: Participants purchased 10.7% more vials of ipilimumab than necessary for compounding. The results were variable among centres, and only five centres had a deviation lower than 5% between the drug purchased and the drug prescribed. Hospitals applying the drug day reached a statistically significant residual of drug effectively used compared to the amount prescribed (P = 0.018). Consequently, the price for treating a model patient was significantly lower in those hospitals (median spare of 7456 euro per patient). CONCLUSIONS: This study demonstrated that the careful management of drug waste and the application of drug-day, through a proper selection of vial and the ability to use the leftover drug, can generate economic savings. However, tailoring the drug stock to clinical need is still an open issue which deserves further analysis.

Circulating cell-free AR and CYP17A1 copy number variations may associate with outcome of metastatic castration-resistant prostate cancer patients treated with abiraterone.

BACKGROUND: This study aimed to investigate copy number variations (CNVs) of CYP17A1 and androgen receptor (AR) genes in serum cell-free DNA collected before starting abiraterone in 53 consecutive patients with castration-resistant prostate cancer (CRPC). METHODS: Serum DNA was isolated and CNVs were analysed for AR and CYP17A1 genes using Taqman copy number assays. The association between CNVs and progression-free/overall survival (PFS/OS) was evaluated by the Kaplan-Meier method and log-rank test. RESULTS: Median PFS of patients with AR gene gain was 2.8 vs 9.5 months of non-gained cases (P < 0.0001). Patients with CYP17A1 gene gain had a median PFS of 2.8 months vs 9.2 months in the non-gained patients (P = 0.0014). A lower OS was reported in both cases (AR: P < 0.0001; CYP17A1: P = 0.0085). Multivariate analysis revealed that PSA decline ⩾ 50%, AR and CYP17A1 CNVs were associated with shorter PFS (P < 0.0001, P = 0.0004 and P = 0.0450, respectively), while performance status, PSA decline ⩾ 50%, AR CNV and DNA concentration were associated with OS (P = 0.0021, P = 0.0014, P = 0.0026 and P = 0.0129, respectively). CONCLUSIONS: CNVs of AR and CYP17A1 genes would appear to be associated with outcome of CRPC patients treated with abiraterone.

Sex differences in activated corticotropin-releasing factor neurons within stress-related neurocircuitry and hypothalamic-pituitary-adrenocortical axis hormones following restraint in rats.

Women may be more vulnerable to certain stress-related psychiatric illnesses than men due to differences in hypothalamic-pituitary-adrenocortical (HPA) axis function. To investigate potential sex differences in forebrain regions associated with HPA axis activation in rats, these experiments utilized acute exposure to a psychological stressor. Male and female rats in various stages of the estrous cycle were exposed to 30min of restraint, producing a robust HPA axis hormonal response in all animals, the magnitude of which was significantly higher in female rats. Although both male and female animals displayed equivalent c-fos expression in many brain regions known to be involved in the detection of threatening stimuli, three regions had significantly higher expression in females: the paraventricular nucleus of the hypothalamus (PVN), the anteroventral division of the bed nucleus of the stria terminalis (BSTav), and the medial preoptic area (MPOA). Dual fluorescence in situ hybridization analysis of neurons containing c-fos and corticotropin-releasing factor (CRF) mRNA in these regions revealed significantly more c-fos and CRF single-labeled neurons, as well as significantly more double-labeled neurons in females. Surprisingly, there was no effect of the estrous cycle on any measure analyzed, and an additional experiment revealed no demonstrable effect of estradiol replacement following ovariectomy on HPA axis hormone induction following stress. Taken together, these data suggest sex differences in HPA axis activation in response to perceived threat may be influenced by specific populations of CRF neurons in key stress-related brain regions, the BSTav, MPOA, and PVN, which may be independent of circulating sex steroids.

Natural history of bone metastasis in colorectal cancer: final results of a large Italian bone metastases study.

BACKGROUND: Data are limited regarding bone metastases from colorectal cancer (CRC). The objective of this study was to survey the natural history of bone metastasis in CRC. PATIENTS AND METHODS: This retrospective, multicenter, observational study of 264 patients with CRC involving bone examined cancer treatments, bone metastases characteristics, skeletal-related event (SRE) type and frequency, zoledronic acid therapy, and disease outcomes. RESULTS: Most patients with bone metastases had pathologic T3/4 disease at CRC diagnosis. The spine was the most common site involved (65%), followed by hip/pelvis (34%), long bones (26%), and other sites (17%). Median time from CRC diagnosis to bone metastases was 11.00 months; median time to first SRE thereafter was 2.00 months. Radiation and pathologic fractures affected 45% and 10% of patients, respectively; 32% of patients had no reported SREs. Patients survived for a median of 7.00 months after bone metastases diagnosis; SREs did not significantly affect survival. Subgroup analyses revealed that zoledronic acid significantly prolonged median time to first SRE (2.00 months versus 1.00 month, respectively, P=0.009) and produced a trend toward improved overall survival versus no zoledronic acid. CONCLUSION: This study illustrates the burden of bone metastases from CRC and supports the use of zoledronic acid in this setting.

Evidence for a lack of phasic inhibitory properties of habituated stressors on HPA axis responses in rats.

This experiment tested the hypothesis that habituation to repeated stressor exposures is produced by phasic inhibitory influence on the neural circuitry that normally drives the paraventricular nucleus of the hypothalamus and subsequently the adrenocortical hormone response to psychological stress. Such a process would be expected to lower the acute response to a novel stressor when experienced concurrently with a habituated stressor. Rats were exposed to restraint or no stress conditions for 14 consecutive days. On the 15th day, the rats were exposed to the control condition (no stress), acute restraint, loud noise, or restraint and loud noise concurrently. Blood was taken and assayed for ACTH and corticosterone and brains were collected to examine c-fos messenger RNA expression in several brain areas. As predicted, the rats that received the same (homotypic) stressor repeatedly and again on the test day displayed low levels of ACTH and corticosterone, similar to the control conditions (i.e., showed habituation). All rats that received a single novel stressor on the test day, regardless of prior stress history, exhibited high levels of ACTH and corticosterone. The rats that received two novel stressors also displayed high levels of ACTH and corticosterone, but little evidence of additivity was observed. Importantly, when a novel stressor was concurrently given with a habituated stressor on the test day, no reduction of HPA axis response was observed when compared to previously habituated rats given only the novel stressor on the test day. In general, c-fos mRNA induction in several stress responsive brain areas followed the same patterns as the ACTH and corticosterone data. These data suggest that habituation of the adrenocortical hormone response to psychological stressors is not mediated by phasic inhibition of the effector system.

Cannabinoid receptor type 1 antagonism significantly modulates basal and loud noise induced neural and hypothalamic-pituitary-adrenal axis responses in male Sprague-Dawley rats.

Altered regulation of the hypothalamic-pituitary-adrenal (HPA) axis is associated with stress-induced changes in cognitive, emotional, and physical health. Recent evidence indicates that the endogenous cannabinoid (eCB) system may modulate HPA-axis function both directly and more centrally, via regulation of limbic brain systems that control HPA-axis activity. The current study examines the contribution of cannabinoid type 1 (CB1) receptor modulation throughout the neuraxis on control and stress-induced HPA-axis activity. Adult male Sprague-Dawley rats were given intraperitoneal injections of either CB1 receptor antagonist (AM251, 2 mg/kg) or vehicle 30 min prior to a session of loud white noise stress (95 dBA for 30 min) or placement in a familiar sound-proof chamber. Immediately following stress and control treatments, rats were killed, the brains and pituitary glands were excised for subsequent immediate early gene (c-fos mRNA) measurement, and trunk blood was collected for subsequent determination of corticosterone (CORT) and adrenocorticotropic (ACTH) hormone levels. AM251 treatment resulted in a potentiated plasma ACTH response to loud noise stress. AM251 treatment also increased stress-induced plasma CORT levels, but that increase may be due to an increase in basal plasma CORT levels, as was evident in control rats. AM251 treatment produced three distinctive c-fos mRNA response patterns across the various brain regions examined. In cortical (prelimbic, infralimbic, somatosensory, and auditory) and some subcortical structures (basolateral amygdala and paraventricular nucleus of the hypothalamus), AM251 treatment produced a substantial increase in c-fos mRNA that was comparable with the elevated c-fos mRNA levels present in those brain regions of both vehicle and AM251-treated stressed rats. In some other subcortical structures (bed nucleus of the stria terminalis and medial preoptic area) and the anterior pituitary, AM251 treatment produced a c-fos mRNA response pattern that was similar to the response pattern of ACTH hormone levels, that is, no effect on no noise control levels, but an augmentation of stress-induced levels. Conversely, in the medial geniculate and ventral posterior thalamus, AM251 treatment inhibited stress-induced c-fos mRNA induction. These data indicate that disruption of eCB signaling through CB1 receptors results in potentiated neural and endocrine responses to loud noise stress, but also substantial increases in activity in various brain regions and the adrenal gland.

Hypothalamic pituitary adrenal axis responses to low-intensity stressors are reduced after voluntary wheel running in rats.

Regular physical exercise is beneficial for both physical and mental health. By contrast, stress is associated with deleterious effects on health and there is growing evidence that regular physical exercise counteracts some of the effects of stress. However, most previous studies have suggested that prior exercise does not alter the acute hypothalamic pituitary adrenal (HPA) axis responses to stress. The present series of studies provides evidence that in rats, 6 weeks (but not 1 or 3 weeks) of voluntary wheel running reduces the HPA axis responses to lower-intensity stressors such as an i.p. saline injection, exposure to a novel environment or exposure to moderate intensity noise, but not to more intense stressors such as predator odour exposure or restraint. Daily exercise does not appear to be necessary for the reduction in HPA axis responses, with intermittent access (24 h out of each 72-h period) to a running wheel for 6 weeks, resulting in similar decrements in adrenocorticotrophic hormone and corticosterone release in response to 85 dBA noise exposure. Data from in situ hybridisation for c-fos mRNA are consistent with the hypothesis that voluntary exercise results in a decrease in HPA axis responsiveness to a low-intensity stressor at a central level, with no changes in primary sensory processing. Together, these data suggest that 6 weeks of daily or intermittent exercise constrains the HPA axis response to mild, but not more intense stressors, and that this regulation may be mediated at a central level beyond the primary sensory input.

Cataract development in a young patient with lathosterolosis: a clinicopathologic case report.

PURPOSE: To report a unique case of cataract in a young patient with lathosterolosis, a singular defect of cholesterol biosynthesis, and to report the clinical results and histopathologic findings after cataract surgery. METHODS: A 7-year-old patient with lathosterolosis, a rare defect of cholesterol biosynthesis, presented with a complex phenotype, including severe mental retardation, liver disease, multiple congenital anomalies, and bilateral posterior subcapsular cataracts. After a severe metabolic decompensation, a worsening in the lens opacity of the left eye occurred. The authors thus performed cataract surgery and made a histopathologic analysis of aspirated lenticular samples. The following examinations were performed at 1 day, 1 week, 3 months, 6 months, 12 months, and 24 months: refraction, biomicroscopy, and fundus evaluation. Visual acuity was not assessable due to lack of patient collaboration. The postoperative follow-up period was 24 months. RESULTS: Histopathologic findings on lenticular fragments revealed the presence of fibers disposed in a honeycomb, samples with homogeneous eosinophilic lens fibers, and other fragments characterized by bulgy elements referable to cortical fibers with degenerative characteristics. After surgery, biomicroscopic evaluation revealed no significant inflammation and good intraocular lens centration at the various control visits. No intraoperative or postoperative complications occurred. No posterior capsule opacification occurred 2 years after surgery. CONCLUSIONS: Lathosterolosis may lead to dysmetabolic cataract development; this unique case of cataract in such a patient has been successfully managed with surgery. Clinical results were excellent, and no complications occurred either intra- or postoperatively.

Acute and chronic effects of ferret odor exposure in Sprague-Dawley rats.

This manuscript describes several behavioral and functional studies evaluating the capacity of ferret odors to elicit a number of acute and long-term responses in male Sprague-Dawley rats. Acute presentation elicits multiple responses, suggesting that ferret odor, likely from skin gland secretions, provides an anxiogenic-like stimulus in this strain of rats. Compared to cat odor, however, ferret odor did not produce rapid fear conditioning, a result perhaps attributable to methodological factors. Inactivation of the olfactory system and medial nucleus of the amygdala, combined with induction of the immediate-early gene c-fos, suggest the necessity of the accessory olfactory system in mediating the effects of ferret odor. Repeated exposures to ferret odor produce variable habituation of neuroendocrine and behavioral responses, perhaps indicative of the lack of control over the exact individual origin or concentration of ferret odor. Ferret odor induces rapid and long-term body weight regulation, thymic involution, adrenal hyperplasia and facilitation of the neuroendocrine response to additional challenges. It is argued that the use of such odors is exquisitely suited to investigate the brain regions coordinating anxiety-like responses and the long-term changes elicited by such stimuli.

Serological association of beta and gamma human papillomaviruses with squamous cell carcinoma of the skin.

BACKGROUND: Cutaneous human papillomaviruses (HPVs) may play a role in the development of squamous cell carcinomas (SCC) of the skin. Objectives Available serological studies on HPV and skin SCC have analysed only few HPV types from the phylogenetic genus beta. The potential association of cutaneous HPV types from the genera alpha, gamma, mu and nu with skin SCC has not been thoroughly analysed so far. METHODS: Using multiplex serology, a method that allows analysing sera for antibodies to up to 100 different antigens simultaneously, we re-analysed an SCC case-control study in immunocompetent individuals (43 cases, 77 controls) for antibodies to L1 capsid proteins of 29 cutaneous and two mucosal HPV types from five different genera. RESULTS: Significantly increased SCC risks were observed for the beta HPV types 15, 17 and 38, as well as for the gamma HPV type 50, with type-specific odds ratios (ORs) ranging from 2.6 to 3.4. Significant associations were also found in cases of seropositivity for any type of the beta 2 species (OR 3.3, 95% confidence interval [CI] 1.2-8.7) and for any type of the gamma genus (OR 3.1, 95% CI 1.1-8.6). With regression models that included all HPV types and forward stepwise selection, two gamma HPV types (HPV 95, OR 25, 95% CI 1.2-509; HPV 50, OR 3.6, 95% CI 1.4-9.4) were each significantly associated with skin SCC. CONCLUSIONS: Our study confirms a possible role of cutaneous HPV in the development of skin SCC. Future studies should include skin HPV types from more than only the beta genus, especially gamma types.

Visual recovery after scleral buckling for macula-off retinal detachments: an optical coherence tomography study.

PURPOSE: To assess the postoperative macular reattachment through OCT3 in eyes treated with episcleral surgery due to macula-off rhegmatogenous retinal detachment, as well as to verify if there is a statistically relevant relation between the persistence of a subfoveal detachment and poor postoperative functional recovery. METHODS: Twelve eyes of 12 patients who underwent episcleral surgery due to macula-off rhegmatogenous retinal detachment were enrolled and examined in a prospective study. Exclusion criteria were the following: traumatic retinal detachments, detachment relapses, macular holes, amblyopia, and grade B proliferative vitreoretinopathy or higher. The time period from the onset of subjective symptoms of retinal detachment to retinal surgery ranged from 3 to 7 days. All patients were evaluated in the preoperative and the postoperative period (after 1, 3, and 6 months) through measurement of visual acuity by ETDRS charts, fundus photographs, and macular tomography with OCT3. The postoperative tomography outcomes and the visual acuity were statistically examined using the Mann-Whitney U-test. RESULTS: One month after surgery, despite the macular reattachment assessable ophthalmoscopically and through fundus photographs, the OCT examination showed macular subretinal fluid persistence in 66.6% of cases. After 3 and 6 months, the persistence of such foveal detachment was respectively observed in 41.6% and in 33.3% of cases. Moreover, the macular subretinal fluid persistence in the postoperative period showed a statistically significant relation with poor functional recovery. CONCLUSIONS: Delayed or incomplete visual recovery after episcleral surgery for macula-off retinal detachment may be related to macular subretinal fluid persistence, assessable with tomography and not visible ophthalmoscopically.

Controllable versus uncontrollable stressors bi-directionally modulate conditioned but not innate fear.

Fear conditioning and fear extinction play key roles in the development and treatment of anxiety-related disorders, yet there is little information concerning experiential variables that modulate these processes. Here we examined the impact of exposure to a stressor in a different environment on subsequent fear conditioning and extinction, and whether the degree of behavioral control that the subject has over the stressor is of importance. Rats received a session of either escapable (controllable) tail shock (ES), yoked inescapable (uncontrollable) tail shock (IS), or control treatment (home cage, HC) 7 days before fear conditioning in which a tone and foot shock were paired. Conditioning was measured 24 h later. In a second experiment rats received ES, IS or HC 24 h after contextual fear conditioning. Extinction then occurred every day beginning 7 days later until a criterion was reached. Spontaneous recovery of fear was assessed 14 days after extinction. IS potentiated fear conditioning when given before fear conditioning, and potentiated fear responding during extinction when given after conditioning. Importantly, ES potently interfered with later fear conditioning, decreased fear responding during fear extinction, and prevented spontaneous recovery of fear. Additionally, we examined if the activation of the ventral medial prefrontal cortex (mPFCv) by ES is critical for the protective effects of ES on later fear conditioning. Inactivation of the mPFCv with muscimol at the time of the initial experience with control prevented ES-induced reductions in later contextual and auditory fear conditioning. Finally, we explored if the protective effects of ES extended to an unconditioned fear stimulus, ferret odor. Unlike conditioned fear, prior ES increased the fear response to ferret odor to the same degree as did IS.

Non-associative defensive responses of rats to ferret odor.

Predators and their odors offer an ethologically valid model to study learning processes. The present series of experiments assessed the ability of ferret odor to serve as an unconditioned stimulus and examined behavioral and endocrine changes in male Sprague-Dawley rats with single or repeated exposures in a defensive withdrawal paradigm or in their home cages. Rats exposed to ferret odor avoided the ferret odor stimulus more, exhibited greater risk assessment and displayed higher adrenocorticotropin hormone (ACTH) and corticosterone release compared with control odor exposed rats and these measures did not significantly habituate over repeated exposures. Ferret odor exposure did not show associative conditioning effects during extinction trials. However, rats that were pre-exposed to ferret odor only once, as compared to control and repeatedly exposed rats, displayed a sensitized ACTH and corticosterone response to an additional ferret odor exposure in small cages. These experiments suggest that ferret odor is a highly potent unconditioned stimulus that has long lasting effects on behavior and endocrine responses, and further suggests the independence of habituation and sensitization processes.

Ferret odor as a processive stress model in rats: neurochemical, behavioral, and endocrine evidence.

Predator odors have been shown to elicit stress responses in rats. The present studies assessed the use of domestic ferret odor as a processive stress model. Plasma corticosterone and adrenocorticotropin hormone levels were higher after 30 min of exposure to ferret odor (fur/skin) but not control odors, ferret feces, urine, or anal gland secretions. Behavioral differences were also found between ferret and the control odors as tested in a defensive withdrawal paradigm. In addition, c-fos messenger RNA expression in several brain areas previously associated with processive stress was significantly higher in ferret odor-exposed rat brains than in control odor-exposed brains. These results suggest that ferret odor produces a reliable unconditioned stress response and may be useful as a processive stress model.

The epidemiology of atopic dermatitis in Italian schoolchildren.

BACKGROUND: Atopic dermatitis (AD) is common in children in industrialized countries. Only one large population study on its prevalence has been conducted in Italy, based on self-report questionnaire. The present study was designed to estimate the prevalence of AD in schoolchildren in Italy by dermatologists' assessment and by UK Working Party criteria, and to investigate associated symptoms and factors. METHODS: Cross-sectional survey on a random sample of 9-year-old schoolchildren from seven Italian cities. Children were examined by experienced dermatologists. Parents and teachers answered standardized questionnaires. RESULTS: Of the 1369 children examined, 88 had a diagnosis of AD, with an estimated point prevalence of 5.8% (95% CI 4.5-7.1) in the reference population. The reported lifetime prevalence was 15.2 (95% CI 12.2-18.2) for AD, 11.9% (95% CI 9.0-14.8) for asthma, and 17.6% (95% CI 14.6-20.7) for rhino-conjunctivitis. The strongest associated factor was the presence of AD in at least one parent. No association of AD with maternal smoking during pregnancy, birth weight, maternal age at the time of the child birth and breast-feeding was observed. The environmental characteristics of the house and the school did not correlate with the prevalence of AD. Episodes of lower respiratory tract infections were associated with asthma, and to a lower extent also with AD and rhinitis. CONCLUSIONS: The prevalence of doctor-diagnosed AD in Italian schoolchildren is comparable to those reported for other developed countries. Family history of atopy was the single most important associated factor, while the complex interplay of environmental factors remains to be elucidated.

What proportion of dermatological patients receive evidence-based treatment?

OBJECTIVE: To determine the proportion of dermatological patients who are offered evidence-based therapy in the routine dermatological practice. METHODS: For every patient seen for the first time at one of our tertiary hospital setting clinics between April and May 1999, the primary diagnosis and the primary intervention were recorded. For each primary diagnosis-primary intervention combination, evidence was searched for in electronic databases from January 1966 to December 1999. The proportion of patients who were offered evidence-based interventions was calculated as the main outcome measure. RESULTS: With a study sample of 136 patients, 61 different diagnosis-treatment couples were generated and 94 queries on electronic databases were performed (to account for "primary interventions" including more than 1 drug or treatment modality). Eighty-seven (64%) of 136 patients received evidence-based interventions. Evidence from randomized controlled trials was found for 69 patients (50.7% of the sample). Controlled studies lacking randomization or double blinding or including fewer than 20 patients per treatment group dealt with treatments offered to 14 patients (10.3%). The treatments offered to 4 patients (2.9%) were judged to have self-evident validity (ie, trials unanimously judged unnecessary). Symptomatic and supportive measures accounted for most interventions lacking substantial evidence (36% of the patients), but we had to include in this class other important treatment regimens, mainly for rare conditions. CONCLUSIONS: Most of the study patients received evidence-based care. However, published trials should be carefully appraised, and relevance of clinical end points should be evaluated together with methodological issues. More accessible, clinically oriented, evidence-based information sources are needed.