The prevalence of asthma and allergic diseases has increased dramatically during the past few decades not only in industrialized countries. Urban air pollution from motor vehicles has been indicated as one of the major risk factors responsible for this increase.
Although genetic factors are important in the development of asthma and allergic diseases, the rising trend can be explained only in changes occurred in the environment. Despite some differences in the air pollution profile and decreasing trends of some key air pollutants, air quality is an important concern for public health in the cities throughout the world.
Due to climate change, air pollution patterns are changing in several urbanized areas of the world, with a significant effect on respiratory health.
The observational evidence indicates that recent regional changes in climate, particularly temperature increases, have already affected a diverse set of physical and biological systems in many parts of the world. Associations between thunderstorms and asthma morbidity in pollinosis subjects have been also identified in multiple locations around the world.
Allergens patterns are also changing in response to climate change and air pollution can modify the allergenic potential of pollens especially in presence of specific weather conditions.
The underlying mechanisms of all these interactions are not well known yet. The consequences on health vary from decreases in lung function to allergic diseases, new onset of diseases, and exacerbation of chronic respiratory diseases.
Factor clouding the issue is that laboratory evaluations do not reflect what happens during natural exposition, when atmospheric pollution mixtures in polluted cities are inhaled. In addition, it is important to recall that an individual’s response to pollution exposure depends on the source and components of air pollution, as well as meteorological conditions. Indeed, some air pollution-related incidents with asthma aggravation do not depend only on the increased production of air pollution, but rather on atmospheric factors that favour the accumulation of air pollutants at ground level.
Considering these aspects governments worldwide and international organizations such as the World Health Organization and the European Union are facing a growing problem of the respiratory effects induced by gaseous and particulate pollutants arising from motor vehicle emissions.
Airways hyper-responsiveness; Bronchial asthma; Climate change and allergy; Environment and respiratory allergy; Pollen allergy; Respiratory allergy; Urban air pollution
The inguinal hernia is one of the most common diseases in the elderly. Treatment of this type of pathology is exclusively surgical and relies almost always on the use of local anesthesia. While in the past hernia surgery was carried out mainly by general anesthesia, in recent years there has been growing emphasis on the role of local anesthesia.
The aim of our study was to compare intra-and postoperative analgesia obtained by the use of levobupivacaine compared with that of bupivacaine. Bupivacaine is one of the main local anesthetics used in the intervention of inguinal hernioplasty. Levobupivacaine is an enantiomer of racemic bupivacaine with less cardiotoxicity and neurotoxicity. The study was conducted from April 2010 to May 2012. We collected data of forty male patients, aged between 73 and 85 years, who underwent inguinal hernioplasty with local anesthesia for the first time.
Minimal pain is the same in both groups. Mild pain was more frequent in the group who used bupivacaine, moderate pain was slightly more frequent in the group who used levobupivacaine, and the same for intense pain. It is therefore evident how Bupivacaine is slightly less preferred after four and twenty four hours, while the two drugs seem to have the same effect at a distance of twelve and forty-eight hours. Bupivacaine shows a significantly higher number of complications, as already demonstrated by previous studies. The request for an analgesic was slightly higher in patients receiving levobupivacaine.
After considering all these elements, we can conclude that the clinical efficacy of levobupivacaine and racemic bupivacaine are essentially similar, when used under local intervention of inguinal hernioplasty.
Bronchial asthma is recognized as a highly prevalent health problem in the developed and developing world with significant social and economic consequences. Increased asthma severity is not only associated with enhanced recurrent hospitalization and mortality but also with higher social costs. The pathogenetic background of allergic-atopic bronchial asthma is characterized by airway inflammation with infiltration of several cells (mast cells, basophils, eosinophils, monocytes, and T-helper (Th)2 lymphocytes). However, in atopic asthma the trigger factors for acute attacks and chronic worsening of bronchial inflammation are aeroallergens released by pollens, dermatophagoides, and pets, which are able to induce an immune response by interaction with IgE antibodies. Currently anti-inflammatory treatments are effective for most asthma patients, but there are asthmatic subjects whose disease is not completely controlled by inhaled or systemic corticosteroids and who account for a significant portion of the healthcare costs of asthma. A novel therapeutic approach to asthma and other allergic respiratory diseases involves interference in the action of IgE, and this antibody has been viewed as a target for novel immunological drug development in asthma. Omalizumab is a humanized recombinant monoclonal anti-IgE antibody approved for treatment of moderate to severe IgE-mediated (allergic) asthma. This non-anaphylactogenic anti-IgE antibody inhibits IgE functions, blocking free serum IgE and inhibiting their binding to cellular receptors. By reducing serum IgE levels and IgE receptor expression on inflammatory cells in the context of allergic cascade, omalizumab represents a new class of mast cells stabilizing drugs; it is a novel approach to the treatment of atopic asthma. Omalizumab therapy is well tolerated and significantly improves symptoms and disease control, reducing asthma exacerbations and the need to use high dosage of inhaled corticosteroids. Moreover, omalizumab improves quality of life of patients with severe persistent allergic asthma which is inadequately controlled by currently available asthma medications. In conclusion omalizumab may fulfil an important need in patients with moderate to severe asthma.
airway hyper-reactivity; asthma; allergic respiratory diseases; atopic respiratory diseases; anti-IgE therapy; hypersensitivity; monoclonal anti-IgE antibody; omalizumab
study documented that, in patients with chronic obstructive pulmonary
disease (COPD), addition of ipratropium bromide at the clinically
recommended dose (40 µg) does not produce any further
bronchodilation than that achieved with salmeterol 50 µg alone.
However, the dose of ipratropium bromide needed to produce near maximal
bronchodilation is several times higher than the customary dosage. The
full therapeutic potential of combined salmeterol plus an
anticholinergic drug can therefore only be established using doses
higher than those currently recommended in the marketing of these
agents. A study was undertaken to examine the possible acute effects of
higher than conventional doses of an anticholinergic agent on the
single dose salmeterol induced bronchodilation in patients with stable
and partially reversible COPD.
two outpatients received 50 µg salmeterol or placebo. Two hours
after inhalation a dose-response curve to inhaled oxitropium bromide
(100 µg/puff) or placebo was constructed using one puff, one puff,
two puffs, and two puffs—that is, a total cumulative dose of 600 µg
oxitropium bromide. Dose increments were given at 20 minute
intervals with measurements being made 15 minutes after each dose. On
four separate days all patients received one of the following: (1)
50 µg salmeterol + 600 µg oxitropium bromide; (2) 50 µg
salmeterol + placebo; (3) placebo + 600 µg oxitropium bromide; (4)
induced a good bronchodilation (mean increase 0.272 l; 95% CI 0.207 to 0.337) two hours after its inhalation. Oxitropium bromide elicited
an evident dose-dependent increase in forced expiratory volume in one
second (FEV1) and this occurred also after pretreatment
with salmeterol with a further mean maximum increase of 0.152 l (95%
CI of differences 0.124 to 0.180).
shows that acute pretreatment with 50 µg salmeterol does not block
the possibility of inducing more bronchodilation with an
anticholinergic agent when a higher than normal dosage of the
muscarinic antagonist is used.
To investigate and quantify the impact of moderate lead exposure on students' ability to score at the “proficient” level on end-of-grade standardized tests.
We compared the scores of 3757 fourth grade students from Milwaukee, Wisconsin, on the Wisconsin Knowledge and Concepts Exam (WKCE). The sample consisted of children with a blood lead test before age 3 years that was either unquantifiable at the time of testing (<5 μg/dL) or in the range of moderate exposure (10–19 μg/dL).
After controlling for gender, poverty, English language learner status, race/ethnicity, school disciplinary actions, and attendance percentage, results showed a significant negative effect of moderate lead exposure on academic achievement for all 5 subtests of the WKCE. Test score deficits owing to lead exposure were equal to 22% of the interval between student categorization at the “proficient” or “basic” levels in Reading, and 42% of the interval in Mathematics.
Children exposed to amounts of lead before age 3 years that are insufficient to trigger intervention under current policies in many states are nonetheless at a considerable educational disadvantage compared with their unexposed peers 7 to 8 years later. Exposed students are at greater risk of scoring below the proficient level, an outcome with serious negative consequences for both the student and the school.
Lead poisoning; Lead exposure; Childhood; School; Testing; Environmental pollutants; Environmental pollution; Environmental policy
Non-dystrophic Myotonia (NDM) is characterized by myotonia without muscle wasting. A standardized quantitative myotonia assessment (QMA) is important for clinical trials.
Myotonia was assessed in 91 individuals enrolled in a natural history study using a commercially available computerized handgrip myometer and automated software. Average peak force and 90% to 5% relaxation times were compared to historical normal controls studied with identical methods.
30 subjects had chloride channel mutations, 31 sodium channel mutations, 6 DM2, and 24 no identified mutation. Chloride channel mutations were associated with prolonged 1st handgrip relaxation times, and warm up on subsequent handgrips. Sodium channel mutations were associated with prolonged 1st handgrip relaxation times and paradoxical myotonia or warm-up, depending on underlying mutations. DM2 subjects had normal relaxation times but decreased peak force. Sample size estimates are provided for clinical trial planning.
QMA is an automated, non-invasive technique for evaluating myotonia in NDM.
natural history; ion channel mutation; muscle disease; myotonia; non-dystrophic myotonia
Soft tissue sarcomas (STS) represent a diverse group of histologic subtypes with targetable molecular alterations, often treated as a single disease. Sunitinib malate is a multitargeted receptor tyrosine kinase inhibitor active in other solid tumors carrying similar alterations (i.e., imatinib mesylate-refractory gastrointestinal stromal tumors). This single-institution phase II study investigated the safety and efficacy of sunitinib malate in three common STS subtypes. Patients with documented unresectable or metastatic STS (liposarcoma, leiomyosarcoma, and malignant fibrous histiocytoma [MFH]), measurable disease, and 3 or less prior lines of therapy were eligible. Treatment consisted of sunitinib malate, 50 mg daily, for 4 weeks every 6 weeks. Forty-eight patients were enrolled, and 35% were heavily pretreated (≥2 prior lines of chemotherapy). The safety profile resembled previously known sunitinib malate toxicities. Median progression-free and overall survivals for liposarcoma, leiomyosarcoma, and MFH were 3.9 and 18.6, 4.2 and 10.1, and 2.5 and 13.6 months, respectively. The 3-month progression-free rates in the untreated and pretreated (chemotherapy) patients with liposarcoma, leiomyosarcoma, and MFH were 75% and 69.2%, 60%, and 62.5%, and and 25% and 44.4%, respectively. With the caveats that a minority of patients with potentially indolent or low-grade disease could have been included and the small numbers, a 3-month progression-free rate of >40% suggests activity for sunitinib malate at least in liposarcomas and leiomyosarcomas. Thus, we believe that further investigation in these susceptible STS subtypes is warranted.
soft tissue sarcoma; targeted therapy; sunitinib malate; progression-free rate; survival; tyrosine kinase inhibitor
Genome-wide association studies and follow-up meta-analyses in Crohn's disease (CD) and ulcerative colitis (UC) have recently identified 163 disease-associated loci that meet genome-wide significance for these two inflammatory bowel diseases (IBD). These discoveries have already had a tremendous impact on our understanding of the genetic architecture of these diseases and have directed functional studies that have revealed some of the biological functions that are important to IBD (e.g. autophagy). Nonetheless, these loci can only explain a small proportion of disease variance (∼14% in CD and 7.5% in UC), suggesting that not only are additional loci to be found but that the known loci may contain high effect rare risk variants that have gone undetected by GWAS. To test this, we have used a targeted sequencing approach in 200 UC cases and 150 healthy controls (HC), all of French Canadian descent, to study 55 genes in regions associated with UC. We performed follow-up genotyping of 42 rare non-synonymous variants in independent case-control cohorts (totaling 14,435 UC cases and 20,204 HC). Our results confirmed significant association to rare non-synonymous coding variants in both IL23R and CARD9, previously identified from sequencing of CD loci, as well as identified a novel association in RNF186. With the exception of CARD9 (OR = 0.39), the rare non-synonymous variants identified were of moderate effect (OR = 1.49 for RNF186 and OR = 0.79 for IL23R). RNF186 encodes a protein with a RING domain having predicted E3 ubiquitin-protein ligase activity and two transmembrane domains. Importantly, the disease-coding variant is located in the ubiquitin ligase domain. Finally, our results suggest that rare variants in genes identified by genome-wide association in UC are unlikely to contribute significantly to the overall variance for the disease. Rather, these are expected to help focus functional studies of the corresponding disease loci.
Genetic studies of common diseases have seen tremendous progress in the last half-decade primarily due to recent technologies that enable a systematic examination of genetic markers across the entire genome in large numbers of patients and healthy controls. The studies, while identifying genomic regions that influence a person's risk for developing disease, often do not pinpoint the actual gene or gene variants that account for this risk (called a causal gene/variant). A prime example of this can be seen with the 163 genetic risk factors that have recently been associated with the chronic inflammatory bowel diseases known as Crohn's disease and ulcerative colitis. For less than a handful of these 163 is the causative change in the genetic code known. The current study used an approach to directly look at the genetic code for a subset of these and identified a causative change in the genetic code for eight risk factors for ulcerative colitis. This finding is particularly important because it directs biological studies to understand the mechanisms that lead to this chronic life-long inflammatory disease.
The computer-based method allows the computerized planning of a surgical implantology procedure, using computed tomography (CT) of the maxillary bones and prosthesis. This procedure, however, is not error-free, unless the operator has been well trained and strictly follows the protocol. A 70-year-old woman whom was edentulous asked for a lower jaw implant-supported prosthesis. A computer-guided surgery was planned with an immediate loading according to the NobelGuide technique. However, prior to surgery, new dentures were constructed to adjust the vertical dimension. An interim screwed metal-resin prosthesis was delivered just after the surgery; however, after only two weeks, it was removed because of a complication. Finally, a screwed implant bridge was delivered. The computer guided surgery is a useful procedure when based on an accurate 3D CT-based image data and an implant planning software which minimizes errors.
To report the long-term management of a case of premature ovarian insufficiency of unknown origin in a young woman with Crohn’s disease.
Here is reported the case of a 20 years old woman with Cronh’s disease presenting with two years amenorrhea and FSH and LH levels of 255 mIU/ml and 182 mIU/ml respectively, who received 10 months corticosteroid treatment followed by 7 years of estro-progestin treatment.
Corticosteroid treatment was ineffective in restoring patients gonadotropin levels as well as ovarian volume, while estro-progestins promoted a prompt reduction in gonadotrophin levels, which returned in the normal range after two years of treatment, as well as restoration of ovarian function, which occurred after four years of estrogens administration, as demonstrated by normal ovarian volume and ovulatory follicles at ultrasound, and by the re-establishment of regular menses after estroprogestin discontinuation.
Long-term suppression of the endogenous gonadotropins using estroprogestins may be suggested as a treatment able to restore ovarian responsiveness even in patients with premature ovarian insufficiency showing highly elevated gonadotropin levels.
To assess the effects of subcutaneous (sc) interferon (IFN) -1a on cognition over 5 years in mildly disabled patients with relapsing–remitting multiple sclerosis (RRMS).
Patients aged 18–50 years with RRMS (Expanded Disability Status Scale score ≤4.0) who had completed the 3-year COGIMUS study underwent standardized magnetic resonance imaging, neurological examination, and neuropsychological testing at years 4 and 5. Predictors of cognitive impairment at year 5 were identified using multivariate analysis.
Of 331 patients who completed the 3-year COGIMUS study, 265 participated in the 2-year extension study, 201 of whom (75.8%; sc IFN β-1a three times weekly: 44 µg, n = 108; 22 µg, n = 93) completed 5 years' follow-up. The proportion of patients with cognitive impairment in the study population overall remained stable between baseline (18.0%) and year 5 (22.6%). The proportion of patients with cognitive impairment also remained stable in both treatment groups between baseline and year 5, and between year 3 and year 5. However, a significantly higher proportion of men than women had cognitive impairment at year 5 (26.5% vs 14.4%, p = 0.046). Treatment with the 22 versus 44 µg dose was predictive of cognitive impairment at year 5 (hazard ratio 0.68; 95% confidence interval 0.48–0.97).
This study suggests that sc IFN β-1a dose-dependently stabilizes or delays cognitive impairment over a 5-year period in most patients with mild RRMS. Women seem to be more protected against developing cognitive impairment, which may indicate greater response to therapy or the inherently better prognosis associated with female sex in MS.
Several studies suggest that Vitamin A may be involved in the pathogenesis of inflammatory bowel disease (IBD), but the mechanism is still unknown. Cytochrome P450 26 B1 (CYP26B1) is involved in the degradation of retinoic acid and the polymorphism rs2241057 has an elevated catabolic function of retinoic acid, why we hypothesized that the rs2241057 polymorphism may affect the risk of Crohn’s disease (CD) and Ulcerative Colitis (UC). DNA from 1378 IBD patients, divided into 871 patients with CD and 507 with UC, and 1205 healthy controls collected at Örebro University Hospital and Karolinska University Hospital were analyzed for the CYP26B1 rs2241057 polymorphism with TaqMan® SNP Genotyping Assay followed by allelic discrimination analysis. A higher frequency of patients homozygous for the major (T) allele was associated with CD but not UC compared to the frequency found in healthy controls. A significant association between the major allele and non-stricturing, non-penetrating phenotype was evident for CD. However, the observed associations reached borderline significance only, after correcting for multiple testing. We suggest that homozygous carriers of the major (T) allele, relative to homozygous carriers of the minor (C) allele, of the CYP26B1 polymorphism rs2241057 may have an increased risk for the development of CD, which possibly may be due to elevated levels of retinoic acid. Our data may support the role of Vitamin A in the pathophysiology of CD, but the exact mechanisms remain to be elucidated.
Cancer genome sequencing efforts recently identified EPHA3, which encodes the EPHA3 receptor tyrosine kinase, as one of the most frequently mutated genes in lung cancer. Although receptor tyrosine kinase mutations often drive oncogenic conversion and tumorigenesis, the oncogenic potential of the EPHA3 mutations in lung cancer remains unknown.
We used immunoprecipitation, western blotting, and kinase assays to determine the activity and signaling of mutant EPHA3 receptors. A mutation-associated gene signature was generated from one large dataset, mapped to another training dataset with survival information, and tested in a third independent dataset. EPHA3 expression levels were determined by quantitative reverse transcription-polymerase chain reaction in paired normal-tumor clinical specimens and by immunohistochemistry in human lung cancer tissue microarrays. We assessed tumor growth in vivo using A549 and H1299 human lung carcinoma cell xenografts in mice (n = 7–8 mice per group). Tumor cell proliferation was measured by bromodeoxyuridine incorporation and apoptosis by multiple assays. All P values are from two-sided tests.
At least two cancer-associated EPHA3 somatic mutations functioned as dominant inhibitors of the normal (wild type) EPHA3 protein. An EPHA3 mutation–associated gene signature that was associated with poor patient survival was identified. Moreover, EPHA3 gene copy numbers and/or expression levels were decreased in tumors from large cohorts of patients with lung cancer (eg, the gene was deleted in 157 of 371 [42%] primary lung adenocarcinomas). Reexpression of wild-type EPHA3 in human lung cancer lines increased apoptosis by suppression of AKT activation in vitro and inhibited the growth of tumor xenografts (eg, for H1299 cells, mean tumor volume with wild-type EPHA3 = 437.4mm3 vs control = 774.7mm3, P < .001). Tumor-suppressive effects of wild-type EPHA3 could be overridden in trans by dominant negative EPHA3 somatic mutations discovered in patients with lung cancer.
Cancer-associated EPHA3 mutations attenuate the tumor-suppressive effects of normal EPHA3 in lung cancer.
Genetic aberrations in various components of cAMP signalling pathway predispose to endocrine tumors. Growing evidence has shown that mutations in the phosphodiesterases (PDEs) are involved in the predisposition to adrenocortical neoplastic conditions.
Screen for genetic variations in PDE8B among patients with different types of adrenocortical tumors.
Design and Subjects
Case-control study followed by functional analyses. 216 unrelated patients with different types of adrenocortical tumors and 192 healthy control individuals.
Bi-directional Sanger sequencing, in vitro cell line transfection, in silico modelling.
Nine different PDE8B sequence changes, 6 novel and 3 previously reported, were identified in our patients and controls. Two of the variations, seen only in the patient group, showed significant potential to impair protein function, both in vitro and in silico.
PDE8B is another gene in which variations may contribute to predisposition of adrenocortical tumors.
PDE8B variants; adrenal tumors; cAMP signalling pathway
Mutations in mitochondrial DNA (mtDNA) are associated with serious human diseases and inherited from mother's eggs. Here we investigated the feasibility of mtDNA replacement in human oocytes by spindle transfer (ST). Of 106 human oocytes donated for research, 65 were subjected to reciprocal ST and 33 served as controls. Fertilization rate in ST oocytes (73%) was similar to controls (75%). However, a significant portion of ST zygotes (52%) displayed abnormal fertilization as determined by irregular number of pronuclei. Among normally fertilized ST zygotes, blastocyst development (62%) and embryonic stem cell (ESC) isolation (38%) rates were comparable to controls. All ESC lines derived from ST zygotes displayed normal euploid karyotypes and contained exclusively donor mtDNA. The mtDNA can be efficiently replaced in human oocytes. Although some ST oocytes displayed abnormal fertilization, remaining embryos were capable of developing to blastocysts and producing ESCs similar to controls.
Here, we evaluated the hypothesis that CD8+ T cell responses to caspase-cleaved antigens derived from effector T cells undergoing apoptosis, may contribute to multiple sclerosis (MS) immunopathology.
The percentage of autoreactive CD8+ T effector cells specific for various apoptotic T cell-associated self-epitopes (apoptotic epitopes) were detected in the peripheral blood and cerebrospinal fluid (CSF) by both enzyme-linked immunospot and dextramers of class I molecules complexed with relevant apoptotic epitopes. Moreover, the capacity of dextramer+ CD8+ T cells to produce interferon (IFN)-γ and/or interleukin (IL)-17 in response to the relevant apoptotic epitopes was evaluated by the intracellular cytokine staining. Cross-presentation assay of apoptotic T cells by dendritic cells was also evaluated ex vivo.
We found that polyfunctional (IFN-γ and/or IL-17 producing) autoreactive CD8+ T cells specific for apoptotic epitopes were represented in MS patients with frequencies significantly higher than in healthy donors. These autoreactive CD8+ T cells with a strong potential to produce IFN-γ or IL-17 in response to the relevant apoptotic epitopes were significantly accumulated in the CSF from the same patients. In addition, the frequencies of these autoreactive CD8+ T cells correlated with the disease disability. Cross-presentation assay revealed that caspase-cleaved cellular proteins are required to activate apoptotic epitope-specific CD8+ T cells ex vivo.
Taken together, these data indicate that apoptotic epitope-specific CD8+ T cells with strong inflammatory potential are recruited at the level of the inflammatory site, where they may be involved in MS immunopathology through the production of high levels of inflammatory cytokines.
Apoptosis; CD8+ T cells; Multiple sclerosis
In order to assess if ambient air pollution in urban areas could be related to alterations in male/female ratio this study objectives to evaluate changes in ambient particulate matter (PM10) concentrations after implementation of pollution control programmes in São Paulo city and the secondary sex ratio (SRR).
Design and methods
A time series study was conducted. São Paulo’s districts were stratified according to the PM10 concentrations levels and were used as a marker of overall air pollution. The male ratio was chosen to represent the secondary sex ratio (SSR=total male birth/total births). The SSR data from each area was analysed according to the time variation and PM10 concentration areas using descriptive statistics. The strength association between annual average of PM10 concentration and SSR was performed through exponential regression, and it was adopted as a statistical significance level of p<0.05.
The exponential regression showed a negative and significant association between PM10 and SSR. SSR varied from 51.4% to 50.7% in São Paulo in the analysed period (2000–2007). Considering the PM10 average concentration in São Paulo city of 44.72 μg/m3 in the study period, the SSR decline reached almost 4.37%, equivalent to 30 934 less male births.
Ambient levels of PM10 are negatively associated with changes in the SSR. Therefore, we can speculate that higher levels of particulate pollution could be related to increased rates of female births.
air pollution; sex ratio; reproductive health; environmental health; SÃ£o Paulo
To evaluate the accuracy of ultrasonography in the diagnosis of acute calculous cholecystitis in comparison with other imaging modalities.
The authors performed a search of the Medline/ PubMed (National Library of Medicine, Bethesda, Maryland) for original research and review publications examining the accuracy of ultrasonography in the diagnosis of acute calculous cholecystitis. The search design utilized a single or combination of the following terms : (1) acute cholecystitis, (2) ultrasonography, (3) computed tomography, (4) magnetic resonance cholangiopancreatography and (5) cholescintigraphy. This review was restricted to human studies and to English-language literature. Four authors reviewed all the titles and subsequent the abstract of 198 articles that appeared appropriate. Other articles were recognized by reviewing the reference lists of significant papers. Finally, the full text of 31 papers was reviewed.
Sonography is still used as the initial imaging technique for evaluating patients with suspected acute calculous cholecystitis because of its high sensitivity at the detection of GB stones, its real-time character, and its speed and portability. Cholescintigraphy still has the highest sensitivity and specificity in patients who are suspected of having acute cholecystitis. However, due to a combination of reasons including logistic drawbacks, broad imaging capability and clinician referral pattern the use of cholescintigraphy is limited in clinical practice. CT is particularly useful for evaluating the many complications of acute calculous cholecystitis. The lack of widespread availability of MRI and the relatively high cost prohibits its primary use in patients with acute calculous cholecystitis.
US is currently considered the preferred initial imaging technique for patients who are clinically suspected of having acute calculous cholecystitis.
Acute calculous cholecystitis; Ultrasonography; Computed Tomography; Magnetic Resonance Cholangiopancreatography; Cholescintigraphy
Acute vascular emergencies can arise from direct traumatic injury to the vessel or be spontaneous (non-traumatic).
The vascular injuries can also be divided into two categories: arteial injury and venous injury.
Most of them are life-treatening emergencies, sice they may cause an important ipovolemic shock or severe ischemia in their end organ and require prompt diagnosis and treatment.
In the different clinical scenarios, the correct diagnostic approach to vascular injuries isn’t firmly established and advantages of one imaging technique over the other are not obvious.
Ultrasound (US) is an easy accessible, safe and non-invasive diagnostic modality but Computed Tomography (CT) with multiphasic imaging study is an accurate modality to evaluate the abdominal vascular injuries therefore can be considered the primary imaging modality in vascular emergencies.
The aim of this review article is to illustrate the different imaging options for the diagnosis of abdominal vascular emergencies, including traumatic and non traumatic vessel injuries, focusing of US and CT modalities.
Acute diverticulitis (AD) results from inflammation of a colonic diverticulum. It is the most common cause of acute left lower-quadrant pain in adults and represents a common reason for acute hospitalization, as it affects over half of the population over 65 years with a prevalence that increases with age. Although 85% of colonic diverticulitis will recover with a nonoperative treatment, some patients may have complications such as abscesses, fistulas, obstruction, and /or perforation at presentation. For these reasons, different classifications were introduced through times to help clinicians to develop a correct diagnosis and guide the treatment and for the same reasons imaging is used in most cases both to realise a differential diagnosis and to guide the therapeutic management. US and CT are both usefull in diagnosis of diverticolitis, and their sensibility and specificity are similar. However CT scanning is essential for investigating complicated diverticular disease especially where there are diffuse signs and clinical suspicion of secondary peritonitis; instead in most uncomplicated cases the experienced sonographer may quickly confirm a diagnosis guided by the clinical signs. US is to be recommended in premenopausal women, and in young people to reduce dose exposure.
It is uncertain if computerized physician order entry (CPOE) systems are effective at reducing adverse drug event (ADE) rates in community hospitals, where mainly vendor-developed applications are used.
To evaluate the impact of vendor CPOE systems on the frequency of ADEs.
DESIGN AND PATIENTS
Prospective before-and-after study conducted from January 2005 to September 2010 at five Massachusetts community hospitals. Participants were adults admitted during the study period. A total of 2,000 charts were reviewed for orders, medication lists, laboratory reports, admission histories, notes, discharge summaries, and flow sheets.
The primary outcome measure was the rate of preventable ADEs. Rates of potential ADEs and overall ADEs were secondary outcomes.
The rate of preventable ADEs decreased following implementation (10.6/100 vs. 7.0/100 admissions; p = 0.007) with a similar effect observed at each site. However, the associated decrease in preventable ADEs was balanced against an increase in potential ADEs (44.4/100 vs. 57.5/100 admissions; p < 0.001). We observed a reduction of 34.0% for preventable ADEs, but an increase of 29.5% in potential ADEs following implementation. The overall rate of ADEs increased (14.6/100 vs. 18.7/100 admissions; p = 0.03), which was driven by non-preventable events (4.0/100 vs. 11.7/100 admissions; p < 0.001).
Adoption of vendor CPOE systems was associated with a decrease in the preventable ADE rate by a third, although the rates of potential ADEs and overall ADEs increased. Our findings support the use of vendor CPOE systems as a means to reduce drug-related injury and harm. The potential ADE rate could be reduced by making refinements to the vendor applications and their associated decision support.
Electronic supplementary material
The online version of this article (doi:10.1007/s11606-012-1987-7) contains supplementary material, which is available to authorized users.
medication safety; adverse drug events; unintended consequences
Computerized Provider Order Entry (CPOE) can improve patient safety, quality and efficiency, but hospitals face a host of barriers to adopting CPOE, ranging from resistance among physicians to the cost of the systems. In response to the incentives for meaningful use of health information technology and other market forces, hospitals in the United States are increasingly moving toward the adoption of CPOE. The purpose of this study was to characterize the experiences of hospitals that have successfully implemented CPOE.
We used a qualitative approach to observe clinical activities and capture the experiences of physicians, nurses, pharmacists and administrators at five community hospitals in Massachusetts (USA) that adopted CPOE in the past few years. We conducted formal, structured observations of care processes in diverse inpatient settings within each of the hospitals and completed in-depth, semi-structured interviews with clinicians and staff by telephone. After transcribing the audiorecorded interviews, we analyzed the content of the transcripts iteratively, guided by principles of the Immersion and Crystallization analytic approach. Our objective was to identify attitudes, behaviors and experiences that would constitute useful lessons for other hospitals embarking on CPOE implementation.
Analysis of observations and interviews resulted in findings about the CPOE implementation process in five domains: governance, preparation, support, perceptions and consequences. Successful institutions implemented clear organizational decision-making mechanisms that involved clinicians (governance). They anticipated the need for education and training of a wide range of users (preparation). These hospitals deployed ample human resources for live, in-person training and support during implementation. Successful implementation hinged on the ability of clinical leaders to address and manage perceptions and the fear of change. Implementation proceeded smoothly when institutions identified and anticipated the consequences of the change.
The lessons learned in the five domains identified in this study may be useful for other community hospitals embarking on CPOE adoption.
Quality of care; Clinical decision support; Meaningful use; Transformation
Existing computational methods for drug repositioning either rely only on the gene expression response of cell lines after treatment, or on drug-to-disease relationships, merging several information levels. However, the noisy nature of the gene expression and the scarcity of genomic data for many diseases are important limitations to such approaches. Here we focused on a drug-centered approach by predicting the therapeutic class of FDA-approved compounds, not considering data concerning the diseases. We propose a novel computational approach to predict drug repositioning based on state-of-the-art machine-learning algorithms. We have integrated multiple layers of information: i) on the distances of the drugs based on how similar are their chemical structures, ii) on how close are their targets within the protein-protein interaction network, and iii) on how correlated are the gene expression patterns after treatment. Our classifier reaches high accuracy levels (78%), allowing us to re-interpret the top misclassifications as re-classifications, after rigorous statistical evaluation. Efficient drug repurposing has the potential to significantly impact the whole field of drug development. The results presented here can significantly accelerate the translation into the clinics of known compounds for novel therapeutic uses.
Drug repositioning; Connectivity map; CMap; ATC code; Mode of action; Machine learning; SVM; Integrative genomics; SMILES; Anthelmintics; Antineoplastic; Oxamniquine; Niclosamide