The incidence of psoriasis in Chile: an analysis of the National Waiting List Repository.

BACKGROUND: Psoriasis is a serious and chronic noncommunicable disease. However, the fundamental measure of disease occurrence, the incidence, has been scarcely reported globally. There are no previous studies of psoriasis incidence in Latin America. AIM: To estimate the incidence rates of psoriasis in Chile during 2016 and 2017 using an administrative database, the Waiting List Repository. METHODS: We examined referrals of psoriasis at onset, made by physicians to dermatologists, evaluated the agreement of diagnosis, and estimated the incidence of the disease considering the eligible population at risk. RESULTS: In most cases, the referrals corresponded to incident cases of psoriasis (73.3%; 95% CI: 66.6-79.2). The national incidence rates of psoriasis were 22.1 (95% CI: 21.1-23.1) and 22.7 (95% CI: 21.8-23.6) per 100 000 person-years in 2016 and 2017, respectively. The most common type of psoriasis was the late-onset type. We observed a high variation in the figures throughout the country, with a range from 0.75 (95% CI: 0.3-1.5) per 100 000 person-years in the Metropolitan region to 164.9 (95% CI: 138.6-195.1) per 100 000 person-years in the Aysen region. CONCLUSION: We describe for the first time the incidence of psoriasis in a Latin American country. Our findings could potentially guide collaborations to improve our global understanding of psoriasis in Latin America.

Proactive inter-disciplinary CME to improve medication management in the elderly population.

BACKGROUND: The absence of collaboration between health professionals is known to influence prescriptions' quality, also disadvantaging elderly frail patients' polytherapies. OBJECTIVES: This study aims to improve the adherence to medications of elderly patients suffering from multiple diseases through interpersonal continuing medical education (CME). The CME was organized for general practitioners (GPs) by hospital pharmacists (HPs) from a Territorial Pharmaceutical Centre of Piedmont, in collaboration with pharmacists from the Drug Science and Technology Department of the University of Turin, to enhance awareness on the management of chronic therapies and de-prescription. METHODS: Pharmacists set face-to-face lessons for GPs between April 2018 and November 2018, while therapies' reconciliation and delivery of the Illustrated Therapy Schedules (ITS) lasted until September 2019. Polytherapies were evaluated by pharmacists and GPs in terms of appropriateness (number of potentially inappropriate prescriptions - PIPs according to 2019 Beers Criteria) and number of drug-drug interactions (DDIs), using a clinical decision support system (CDSS - NavFarma©) to help health professionals dealing with the process of review, reconciliation and individuation of possible adverse reactions. RESULTS: From the CME organization it emerged that the collaboration between health professionals supported by a CDSS could improve the quality of elderly patients polytherapies. Two-hundred fifteen patients were enrolled by GPs; patients included were aged - results reported as average (sd) - 76.4 (6.3), mostly men (54.9%), number of daily medications per patient was 8.1 (2.4); 2.1 (1.8) DDIs per patient were individuated, 12.9% of which were solved thanks to the CME. Average number of PIPs found was 2.5 (1.4) per patient. CONCLUSIONS: The CME represented a proactive approach by HPs to the management of elderly patients' polytherapies. Moreover, clinicians' engagement is a mean to enhance quality, safety, professionalism and communication in health processes.

Risk of hospitalization and death due to infection in people with psoriasis: a population-based cohort study using the Clinical Practice Research Datalink.

BACKGROUND: Psoriasis is associated with risk factors for serious infections, but the independent relationship between psoriasis and serious infection is as yet unclear. OBJECTIVES: To determine whether people with psoriasis have a higher risk of hospitalization due to any infection, respiratory infections, soft-tissue and skin infections, or a higher risk of death due to infection. METHODS: We conducted a cohort study of people (≥ 18 years) with psoriasis using the UK Clinical Practice Research Datalink (CPRD GOLD) linked to Hospital Episode Statistics (HES) and Office for National Statistics (ONS) mortality records between 1 April 2003 and 31 December 2016, and matched with up to six comparators on age, sex and general practice. Hospitalization was ascertained from HES records; death was ascertained from ONS mortality records. Stratified Cox proportional hazard models were estimated, with stepwise adjustment in different models for potential confounders or mediators between psoriasis and serious infection. RESULTS: There were 69 315 people with psoriasis and 338 620 comparators who were followed up for a median (interquartile range) of 4·9 (5·9) and 5·1 (6·3) years, respectively. People with psoriasis had a higher incidence rate of serious infection [20·5 per 1000 person-years, 95% confidence interval (CI) 20·0-21·0, n = 7631] compared with those without psoriasis (16·1 per 1000 person-years, 95% CI 15·9-16·3, n = 30 761). The fully adjusted hazard ratio for the association between psoriasis and serious infection was 1·36 (95% CI 1·31-1·40), with similar results across the other outcomes. CONCLUSIONS: Psoriasis is associated with a small increase in the risk of serious infection. Further research is needed to understand how psoriasis predisposes to a higher risk of infection.

Systematic review examining changes over time and variation in the incidence and prevalence of psoriasis by age and gender.

BACKGROUND: There is a lack of any overview of changes over time and variation in the epidemiology of psoriasis with age and between genders. OBJECTIVES: To perform a systematic review of published population-based studies on variations in psoriasis incidence and prevalence with age and between genders, and to explore trends in psoriasis epidemiology over time. METHODS: Eleven electronic and regional databases were searched from their inception dates to October 2019. No language restrictions were applied. Studies were eligible if they reported on changes in psoriasis incidence and/or prevalence over time and/or by age group and gender. RESULTS: In total 308 papers were critically appraised, from which 90 studies from 22 countries were included. Incidence data confirmed a clear bimodal age pattern in psoriasis onset, with the first and second peaks at around 30-39 and 60-69 years of age, respectively, and evidence suggesting that it presents slightly earlier in women than in men. Prevalence data showed an increasing trend with age until around 60 or 70 years, after which it decreases. Although there was lack of agreement on specific gender differences in psoriasis incidence and prevalence, a slight male predominance was reported in several studies. Studies worldwide suggested a stable or slightly decreasing trend in psoriasis incidence, while an increasing trend in psoriasis prevalence has been consistently reported. One particular challenge faced was the vastly different methodologies used in the included studies, which contributed to some of the heterogeneity of the results. CONCLUSIONS: Studies on changes over time in the occurrence of psoriasis have contributed to a greater appreciation of the increasing burden of the disease. However, further research is required to determine the reasons driving the increase in psoriasis prevalence over time.

Incidence and prevalence of psoriasis in Israel between 2011 and 2017.

BACKGROUND: Psoriasis is a common chronic inflammatory skin disease associated with a heavy burden of morbidity, disability and cost. The occurrence of the disease in Israel has not been previously investigated. OBJECTIVES: To provide standardized estimates of trends in psoriasis incidence, prevalence and mortality among patients in Israel between 2011 and 2017. METHODS: Using electronic health records from Clalit Health Services, the largest nationwide public health provider in Israel, we conducted a population-based study investigating trends in the annual incidence and prevalence of psoriasis between the years 2011 and 2017. We report age- and sex-adjusted rates, using the standard European population as a reference. RESULTS: We identified 71 094 incident psoriasis cases. The mean (SD) age of onset was 42.4 (21.0) years with a bimodal distribution, peaking in the early '30s and early '60s. Late-onset psoriasis, occurring after 40 years of age, accounted for 51.1% of incident cases. The annual psoriasis incidence rate was constant throughout the study period (280/100 000 person-years). Psoriasis prevalence rose from 2.5% in 2011 to 3.8% in 2017. CONCLUSIONS: Psoriasis prevalence is increasing in Israel, although its incidence is stable. Clinicians and policymakers should plan to address the growing demands in the clinical, economic and societal burden of psoriasis.

Psychiatric morbidity and suicidal behaviour in psoriasis: a primary care cohort study.

BACKGROUND: Psychological distress among people with psoriasis may lead to elevated risks of suicide and nonfatal self-harm. OBJECTIVES: To investigate psychiatric comorbidity, psychotropic medication prescribing and risk of suicidality in people with psoriasis. METHODS: A cohort of patients with psoriasis (1998-2014) was delineated using the Clinical Practice Research Datalink, with linkage to Hospital Episode Statistics and Office for National Statistics mortality records. Each patient with psoriasis was matched with up to 20 patients without psoriasis on age, sex and general practice. A stratified Cox regression model was used to estimate the hazard ratios (HRs) for suicide or nonfatal self-harm risks adjusted for socioeconomic status. RESULTS: At baseline, among 56 961 and 876 919 patients with and without psoriasis, higher prevalence for histories of alcohol misuse, bipolar disorder, depression, anxiety disorders, self-harm and psychotropic drug prescription were observed. The deprivation-adjusted HR indicated lower suicide risk in people with psoriasis [HR 0·59, 95% confidence interval (CI) 0·41-0·85]. The risk of suicide varied according to age: it was lower in people with psoriasis diagnosed at ≥ 40 years (HR 0·38, 95% CI 0·21-0·66), whereas there was no difference in risk of suicide in people with psoriasis diagnosed before age 40 years (HR 0·92, 95% CI 0·58-1·46). Conversely, there was a small increased risk for self-harm (HR 1·15, 95% CI 1·04-1·27) associated with psoriasis. CONCLUSIONS: The prevalence of mental illness was raised in people with psoriasis, and this may lead to a greater risk of self-harm. Nevertheless, having psoriasis does not appear to be associated with an increased risk of suicide. Healthcare professionals caring for patients with psoriasis should continue to monitor and tackle effectively the psychological needs of these individuals.

Incidence, prevalence and mortality of patients with psoriasis: a U.K. population-based cohort study.

BACKGROUND: The burden of psoriasis across many world regions is high and there is a recognized need to better understand the epidemiology of this common skin disorder. OBJECTIVES: To examine changes in the prevalence and incidence of psoriasis, and mortality rates over a 15-year period. METHODS: Cohort study involving analysis of longitudinal electronic health records between 1999 and 2013 using the U.K. Clinical Practice Research Datalink (CPRD). RESULTS: The prevalence of psoriasis increased steadily from 2·3% (2297 cases per 100 000) in 1999 to 2·8% (2815 per 100 000) in 2013, which does not appear to be attributable to changes in incidence rates. We observed peaks in age bands characteristic of early-onset (type I) and late-onset (type II) psoriasis, and changes in incidence and prevalence rates with increasing latitude in the U.K. All-cause mortality rates for the general population and for patients with psoriasis have decreased over the last 15 years. However, the risk of all-cause mortality for patients with psoriasis remains elevated compared with people without psoriasis (hazard ratio 1·21; 95% confidence interval 1·13-1·3) and we found no significant change in this relative excess mortality gap over time. CONCLUSIONS: We found an increasing population living longer with psoriasis in the U.K., which has important implications for healthcare service delivery and for resource allocation. Importantly, early mortality in patients with psoriasis remains elevated compared with the general population and we found no evidence of change in this premature mortality gap.

Yada: a novel tool for molecular docking calculations.

Molecular docking is a computational method employed to estimate the binding between a small ligand (the drug candidate) and a protein receptor that has become a standard part of workflow in drug discovery. Generally, when the binding site is known and a molecule is similar to known ligands, the most popular docking methods are rather accurate in the prediction of the geometry. Unfortunately, when the binding site is unknown, the blind docking analysis requires large computational resources and the results are often not accurate. Here we present Yada, a new tool for molecular docking that is capable to distribute efficiently calculations onto general purposes computer grid and that combines biological and structural information of the receptor. Yada is available for Windows and Linux and it is free to download at www.yada.unisa.it .

Measurements and evaluation of the risks due to external radiation exposures and to intake of activated elements for operational staff engaged in the maintenance of medical cyclotrons.

The aim of this paper is to assess the activation phenomena and to evaluate the risk of external exposure and intake doses for the maintenance staff of two medical cyclotrons. Two self-shielded cyclotrons are currently operating in the facility for the routine production of (11)C and (18)F. Four radiochemistry laboratories are linked to the cyclotrons by means of shielded radioisotope delivery lines. Radiopharmaceuticals are prepared both for the PET Diagnostic Department, where four CT-PET scanners are operating with a mean patient workload of 40 d(-1) and for [(18)F]FDG external distribution, to provide radiopharmaceuticals for other institutions. In spite of the fact that air contamination inside the radiochemistry laboratories during the synthesis represents the largest 'slice of the pie' in the evaluation of annual intake dose, potential contamination due to the activated particulate, generated during cyclotron irradiation by micro-corrosion of targets and other components potentially struck by the proton beam and generated neutrons, should be considered. In this regard, the most plausible long-lived (T(1/2) > 30 d) radioisotopes formed are: (97)Tc, (56)Co, (57)Co, (58)Co, (60)Co, (49)V, (55)Fe, (109)Cd, (65)Zn and (22)Na. The results for the operating personnel survey has revealed only low-level contamination for (65)Zn in one test, together with minor (18)F intake, probably due to the environmental dispersion of the radioisotope during the [(18)F]FDG synthesis.

Isolated distal deep vein thrombosis: efficacy and safety of a protocol of treatment. Treatment of Isolated Calf Thrombosis (TICT) Study.

AIM: The optimal treatment of isolated distal deep vein thrombosis (ID-DVT) is still controversial. A complete anticoagulation as soon as the diagnosis is made is recommended by some authors. Alternatively, other authors suggest to perform serial ultrasonography assessments to detect the possible extension of DVT towards proximal veins. Only in this case the treatment should be initiated. Furthermore, the optimal duration of treatment is far from established. The Treatment of Isolated Calf Thrombosis (TICT) study was set up to assess the efficacy and safety of a particular treatment regimen of ID-DVT based on low molecular weight heparins (LMWH). METHODS: The drug treatment consisted of a twice-daily subcutaneous administration of a full dose of weight-adjusted LMWH for one week, followed by a half dose of LMWH administered once-daily for another three weeks. At the end of the four-week period of treatment, a colour-coded Doppler ultrasonography (CCDU) assessment was scheduled and after three months a follow-up visit was performed. If a patient was unable to attend the visit, he was contacted by a phone-call to assess if any adverse events occurred. The study enrolled 192 outpatients with ID-DVT confirmed by CCDU. Twenty-one out of 192 patients (10.9%) were excluded for violation of protocol. Thus 171 (39.9% men, mean age of 60.45 years ) were eligible and were included in the study. Sixty-one patients (36.6%) presented an unprovoked ID-DVT. RESULTS: Events during the period of treatment (4 weeks). Ten out of 171 patients (5.8%) had complications: five patients showed an extension proximal to the knee (2.9%) all with an unprovoked ID-DVT; two showed an extension of thrombus within the distal veins. Three patients (1.7%) suffered from minor bleeding; there was no major bleeding. Further events during three months of observation occurred. Five patients had thrombus recurrences: four patients showed a proximal DVT (3 with a previous unprovoked ID-DVT, 1 with a previous ID-DVT secondary to a traumatic leg fracture, with persistent difficulty of deambulation); one, with a previous secondary thrombosis, showed a ID-DVT. CONCLUSIONS: In our study only 2.9% of patients with ID-DVT showed a progression of thrombosis to proximal deep veins; the majority of thrombus progression, during the treatment period, was observed in patients with unprovoked ID-DVT. Our results support the usefulness of a prolonged treatment in unprovoked ID-DVT.

Decommissioning procedures for an 11 MeV self-shielded medical cyclotron after 16 years of working time.

The present article describes the decommissioning of a compact, self-shielded, 11 MeV medical cyclotron. A Monte Carlo simulation of the possible nuclear reactions was performed in order to plan the decommissioning activities. In the course of the cyclotron dismantling, cyclotron components, shields, and floor concrete samples were measured. Residual activities were analyzed with a Ge(Li) detector and compared with simulation data. Doses to staff involved in the decommissioning procedure were monitored by individual TL dosimeters. The simulations identified five radioactive nuclides in shields and floor concrete: 55Fe and 45Ca (beta emitters, total specific activity: 2.29 x 10(4) Bq kg) and 152Eu, 154Eu, 60Co (gamma emitters, total specific activity: 1.62 x 10(3) Bq kg-1). Gamma-ray spectrometry confirmed the presence of gamma emitters, corresponding to a total specific activity of 3.40 x 10(2) Bq kg-1. The presence of the radioisotope 124Sb in the lead contained in the shield structure, corresponding to a simulated specific activity of 9.38 x 10(3) Bq kg-1, was experimentally confirmed. The measured dose from external exposure of the involved staff was <20 muSv, in accordance with the expected range of values between 10 and 20 muSv. The measured dose from intake was negligible. Finally, the decommissioning of the 11 MeV cyclotron does not represent a risk for the involved staff, but due to the presence of long-lived radioisotopes, the cyclotron components are to be treated as low level radioactive waste and stored in an authorized storage area.

Reversal of multidrug-resistance using Valspodar (PSC 833) and doxorubicin in osteosarcoma.

High-grade osteosarcoma is an extremely aggressive neoplasm, where over 80% of patients present with life-threatening micrometastases at diagnosis. Systemic control of the disease is therefore critical for the treatment of these patients and neoadjuvant chemotherapy using various drugs, including doxorubicin (DXR), which has been demonstrated to be the most effective regimen. Multidrug resistance (MDR) to some anticancer agents, including DXR, mediated by the MDR1 gene product P-glycoprotein (Pgp), has been shown to be a major cause of chemotherapy failure in osteosarcoma. We analyzed the effect of a cyclosporine A derivate Valspodar (PSC 833) on MDR human osteosarcoma cells. We also evaluated Pgp expression in sporadic appendicular canine osteosarcoma. Moreover, dogs were treated with combined administration of DXR and PSC 833. Several blood samples were collected for the determination of DXR and PSC 833 levels. PSC 833 induced a complete reversal of the resistant phenotype at concentrations compatible with the clinical use. Pgp was present in 12/18 (66.6%) of the cases. At the time of DXR administration, adequate blood concentrations of PSC 833, to provide a complete MDR reversal, were obtained without clinical or laboratory findings of toxicity. Combination therapy with DXR and PSC 833 allowed a 30% decrease in DXR dose infusion with equivalent therapeutic exposure. The high incidence of Pgp expression in osteosarcoma confers to the study a rationale for an effective regimen based on down-modulation of MDR.

Peri-intubation cardiovascular response during low dose remifentanil or sufentanil administration in association with propofol TCI. A double blind comparison.

AIM: The aim of this study was to compare the effects on cardiovascular modifications induced by tracheal intubation when low dose infusion of remifentanil or sufentanil are used in association with propofol target controlled infusion. METHODS: Sixty normotensive, ASA I-II-III, Mallampati Score <3 undergoing general anaesthesia for major elective abdominal surgery, received i.m. midazolam (0.05 mg/kg) and atropine (0.01 mg/kg) 30 min before induction. They were randomly divided in a double-blind fashion into two groups receiving for induction respectively target controlled infusion of propofol (site-effect 3.0 microg/ml) and sufentanil (0.01 microg/kg/min) or remifentanil (0.1 microg/kg/ min) infusion. Rocuronium (0.6 mg/kg) was administered. Following intubation, the lungs were mechanically ventilated with an oxygen/air mixture. RESULTS: Bispectral index score and haemodynamic variables were recorded at baseline, after induction, during intubation and 1-3-5 min after the trachea was intubated. No differences in systolic and diastolic arterial pressure were observed in the sufentanil group, while the remifentanil group showed transient systolic and diastolic variations after intubating manoeuvers. The heart rate and bispectral index score were not affected in either group. CONCLUSION: In healthy normotensive patients the use of a small dose of either remifentanil or sufentanil after standard midazolam premedication, proved to be an effective strategy to blunt the cardiovascular response to intubation.

Small doses of remifentanil and alfetanil in continuous total intravenous anesthesia in major abdominal surgery. A double blind comparison.

AIM: The purpose of this study was to test the safety and efficacy of small doses of remifentanil and alfentanil in a continuous total intravenous anesthesia technique for patients undergoing major abdominal surgery. METHODS: Sixty patients were enrolled in the study, and received in a double blind fashion either remifentanil (0.1 microg/kg/min) or alfentanil (alfentanil 0.75 microg/kg/min) in association with propofol (12 mg/kg/h at induction; 6-9 mg/kg/h for maintenance) and cisatracurium. Hemodynamic data, hypnosis monitoring data (Bispectral Index Score), ventilatory parameters and settings, drug utilisation were monitored during stress moments and during all the intraoperative period. Patients were evaluated also in the first 6 postoperative hours. RESULTS: Mean amount of propofol for induction (BIS<60) was lower in the remifentanil group than in the alfentanil group. Significantly fewer patients receiving remifentanil responded to intubation in comparison with patients receiving alfentanil in terms of non invasive blood pressure (>30 mmHg) and heart rate variations. Significantly more patients receiving alfentanil had 1 or more responses to surgery. Incidence of hypotension was significantly higher in patients receiving remifentanil. There were no differences between the 2 groups in the times for spontaneous respiration, adequate respiration, adequate responsivness (OAA/s=5) and discharge from the recovery room. Time to extubation resulted slightly shorter (p<0.05) in patients who received remifentanil. CONCLUSIONS: The use of remifentanil and alfentanil in association with propofol, in a continuous infusion total intravenous anesthesia technique, demonstrated to be safe and reliable strategies.

[Multidimensional functional evaluation of social and health care needs of an elderly population in Rome]. / Valutazione del bisogno assistenziale socio-sanitario di una popolazione anziana a Roma.

The aim of this study is to analyse the condition of the elderly of Rome through a multidimensional instrument to determine their assistance needs. To this purpose a sample composed by 693 over 65 subjects was selected (430 women and 263 men). The Geriatric Functional Rating Scale of Grauer was administered to them. The questionnaire is divided into 7 sections (physical health, mental health, functional skills, support to the collectivity, type of housing, social relationships and economic situation); they enable to evaluate the dependency level of each subject. On the base of each area score a total score is obtained which divides the elderly into three categories according to their assistance need. The whole information collected in the single areas led to a definition of non self-sufficiency for 4.9% of the interviewed people and of partial self-sufficiency for 5.3%, the rest of the sample turned out composed by subjects able to live in an autonomous way. This sample of elderly (about 10%) is that on which it is possible to intervene with social and/or health home care plans in order to limit institutionalization.

Genioglossal length and EMG responses to static upper airway pressures during hypercapnia in goats.

Mechanoreflexes that activate genioglossus electromyogram (EMGgg) in response to negative upper airway pressure (UAP) may help defend airway patency in obstructive sleep apnea. Hypercapnia may affect mechanoreflexes by increasing EMGgg response to actively reduce genioglossus length (Lgg, measured by sonomicrometry). We hypothesized that during normocapnia, Lgg would be reduced at positive, and increased at negative UAP but hypercapnia would increase EMGgg responses to negative pressures and cause Lgg reductions. At 0, 3.5 and 7% inhaled CO2 (balance O2), Lgg and EMGgg were measured during static negative and positive UAP applied to the isolated upper airway in four unanesthetized goats. At 3.5 and 7% CO2 EMGgg was significantly increased and Lgg decreased with negative pressure while EMGgg was also greater at 7 than 0% CO2 (P<0.05). Non-significant pressure related Lgg changes were observed during normocapnia. These results suggest that hypercapnia may stimulate greater mechanoreflex EMGgg activation and consequent Lgg reduction in response to negative UAP application.