Reduction in unplanned hospitalizations associated with a physician focused intervention to reduce potentially inappropriate medication use among older adults: a population-based cohort study.

BACKGROUND: A multimodal general practitioner-focused intervention in the Local Health Authority (LHA) of Parma, Italy, substantially reduced the prevalence of potentially inappropriate medication (PIM) use among older adults. Our objective was to estimate changes in hospitalization rates associated with the Parma LHA quality improvement initiative that reduced PIM use. METHODS: This population-based longitudinal cohort study was conducted among older residents (> 65 years) using the Parma LHA administrative healthcare database. Crude and adjusted unplanned hospitalization rates were estimated in 3 periods (pre-intervention: 2005-2008, intervention: 2009-2010, post-intervention: 2011-2014). Multivariable negative binomial models estimated trends in quarterly hospitalization rates among individuals at risk during each period using a piecewise linear spline for time, adjusted for time-dependent and time-fixed covariates. RESULTS: The pre-intervention, intervention, and post-intervention periods included 117,061, 107,347, and 121,871 older adults and had crude hospitalization rates of 146.2 (95% CI: 142.2-150.3), 146.8 (95% CI: 143.6-150.0), and 140.8 (95% CI: 136.9-144.7) per 1000 persons per year, respectively. The adjusted pre-intervention hospitalization rate was declining by 0.7% per quarter (IRR = 0.993; 95% CI: 0.991-0.995). The hospitalization rate declined more than twice as fast during the intervention period (1.8% per quarter, IRR = 0.982; 95% CI: 0.979-0.985) and was nearly constant post-intervention (IRR: 0.999; 95% CI: 0.997-1.001). Contrasting model predictions for the intervention period (Q1 2009 to Q4 2010), the intervention was associated with 1481 avoided hospitalizations. CONCLUSION: In a large population of older adults, a multimodal general practitioner-focused intervention to decrease PIM use was associated with a decline in the unplanned hospitalization rate. Such interventions to reduce high risk medication use among older adults warrant consideration by health systems seeking to improve health outcomes and reduce high-cost acute care utilization.

Photokeratitis induced by ultraviolet radiation in travelers: A major health problem.

Ultraviolet (UV) irradiation is one of the several environmental hazards that may cause inflammatory reactions in ocular tissues, especially the cornea. One of the important factors that affect how much ultraviolet radiation (UVR) humans are exposed to is travel. Hence, traveling is considered to include a more acute UVR effect, and ophthalmologists frequently evaluate and manage the ocular manifestations of UV irradiation, including UV-induced keratitis. The purpose of this paper is to provide an evidence-based analysis of the clinical effect of UVR in ocular tissues. An extensive review of English literature was performed to gather all available articles from the National Library of Medicine PubMed database of the National Institute of Health, the Ovid MEDLINE database, Scopus, and ScienceDirect that had studied the effect of UVR on the eye and its complications, between January 1970 and June 2014. The results show that UVR at 300 nm causes apoptosis in all three layers of the cornea and induces keratitis. Apoptosis in all layers of the cornea occurs 5 h after exposure. The effect of UVR intensity on the eye can be linked to numerous factors, including solar elevation, time of day, season, hemisphere, clouds and haze, atmospheric scattering, atmospheric ozone, latitude, altitude, longitudinal changes, climate, ground reflection, and geographic directions. The most important factor affecting UVR reaching the earth's surface is solar elevation. Currently, people do not have great concern over eye protection. The methods of protection against UVR include avoiding direct sunlight exposure, using UVR-blocking eyewear (sunglasses or contact lenses), and wearing hats. Hence, by identifying UVR intensity factors, eye protection factors, and public education, especially in travelers, methods for safe traveling can be identified.

Implementation of a critical care outreach service: a qualitative study.

AIM: The aim of this study was to explore hospital staff perceptions of the perceived challenges and outcomes of implementing a critical care outreach service. BACKGROUND: A nurse-led critical care outreach service was designed and implemented to identify and treat acutely ill patients in a large tertiary care hospital in Iran. METHODS: A qualitative analysis of data from two focus groups and seven interviews was carried out using conventional content analyses techniques. A total of 24 hospital staff members participated, including critical care outreach team members, physicians, ward head nurses and ward staff. FINDINGS: Two main categories described the perceived challenges to the implementation of the critical care outreach service: 1) the hospital context, with four subcategories related to staff shortages, the instability of physician positions, the lack of specialized essential services and the absence of a system to establish do-not-resuscitate orders, and 2) staff resistance to different nursing priorities, routines and extra work. In two additional main categories, participants also described positive and negative perceived outcomes. The positive perceived outcomes included three subcategories of alleviating equipment shortages, improving nursing knowledge and patient care and improving patient and healthcare professional satisfaction. DISCUSSION: While critical care outreach has the potential to improve patient perceived outcomes and both patient and provider satisfaction with care, the contextual and clinical realities in hospitals are significant and must be examined during the planning and implementation of future outreach. CONCLUSION AND IMPLICATIONS FOR NURSING AND HEALTH POLICY: A critical care outreach service in the context of an Iranian hospital has the potential to improve ward nurse familiarity with the care of acutely ill patients and the quality of palliative care. However, attention ought to be paid to the hospital's structural and contextual factors. Alleviating nursing shortages, reducing staff resistance and preparing goals of care guidelines that address restrictions on resuscitation could facilitate implementation of critical care outreach services.

Comparative trial of Aloe vera/olive oil combination cream versus phenytoin cream in the treatment of chronic wounds.

OBJECTIVE: Aloe vera is a medicinal plant that has been traditionally used to accelerate wound healing. Olive oil is also a natural product that may contribute to wound healing owing to its antimicrobial and anti-inflammatory effects. The present study aimed to evaluate the effect of an Aloe vera-olive oil (AVO) combination cream on the healing process of chronic wounds. METHOD: In this randomised, double-blind, comparator-controlled, parallel-group trial, patients with chronic wounds were treated with either AVO cream or phenytoin cream as the standard treatment for a period of 30 days. Wound healing was evaluated using Bates-Jensen assessment tool and the severity of pain was assessed using a visual analogue scale (VAS). RESULTS: After initial assessment, 60 patients with chronic wounds (41 with pressure ulcer, 13 with diabetic wounds and 6 with venous ulcers), were recruited and randomised into 2 groups of 30. After 30 days of treatment, significant improvements in the wound size, depth, and edges; necrotic tissue type and amount; exudate type and amount; colour of wound surroundings; and peripheral tissue oedema score were observed in the AVO cream group (p<0.001). The total score of wound healing showed significant improvement with both AVO (p<0.001) and phenytoin (p<0.01) creams, although AVO was more efficacious (p<0.001). Likewise, although both treatments reduced the initial VAS score, the efficacy of AVO was significantly greater (p<0.001). CONCLUSION: AVO cream significantly accelerates biological healing of chronic wounds and helps to reduce pain severity with a higher efficacy compared with phenytoin cream.

Protection of lactoperoxidase activity with sugars during lyophilization and evaluation of its antibacterial properties.

The purpose of the present study was to compare the stabilizing effect of four disaccharides alone or in combination on the lactoperoxidase (LP) derived from bovine milk during lyophilization. Sucrose, lactose, maltose, and trehalose at different concentrations (5-500 mM) were used to compare their protective effects on LP activity. The activity of lyophilized and native LP enzyme was evaluated using the procedure of Schindler with slight modifications. The antibacterial activity of the lyophilized enzyme against Pseudomonas aeroginosa, Escherichia coli, and Staphylococcus aureus was also investigated using the antimicrobial effectiveness test. Trehalose at concentration of 500 mM was the most effective cryoprotectant in protecting the enzyme activity. It preserved LP activity for 40 days, while the native enzyme lost its activity after 6 days. Combinations of disaccharides resulted in an increment in the stability of the enzyme, compared to the native enzyme. Combination of 200 mM trehalose and 200 mM sucrose were found most effective cryoprotectant in freeze-drying of LP. The lyophilized LP decreased the growth rate of Ps.aeroginosa, E.coli, and S.aureus between up to 30.8% in 10(6) cfu/ml and 53.3% in 10(5) cfu/ml. Antimicrobial efficacy of LP was more pronounced when 10(5) cfu/ml was used as compared to 10(6) cfu/ml.

Application of the 2010 revised criteria for the diagnosis of multiple sclerosis to patients with clinically isolated syndromes.

BACKGROUND AND PURPOSE: Recently, the McDonald criteria for the diagnosis of multiple sclerosis (MS) have been revised, with the aims to diagnose earlier and to simplify the use of brain MRI. To validate the 2010 revised criteria they were applied to a cohort of patients with clinically isolated syndromes (CIS). METHODS: In all, 178 CIS patients were followed from onset. Test characteristics were calculated after 1, 3 and 5 years and compared between the 2005 and 2010 revised criteria. The time to diagnosis of the 2005 and 2010 criteria was compared using survival analysis and the log-rank test. Clinical evidence for dissemination in space and time was the gold standard for clinically definite MS (CDMS). RESULTS: During follow-up, 76 patients converted to CDMS (mean time to conversion 23.9 months). At 1 year, the specificity and accuracy of the 2005 criteria were a little higher than those of the 2010 criteria (98.0% and 98.4% vs. 86.3% and 88.5%). However, at 5 years, differences completely disappeared (specificity 85.7% and accuracy 93.3% for both criteria). MS diagnosis could be made significantly faster with the 2010 criteria (P = 0.007). Using the 2010 criteria, in 19% of patients the diagnosis could already be made at baseline. CONCLUSIONS: By applying the 2010 revised criteria a diagnosis of MS can be made earlier, whilst prediction of disease progression is maintained. This validation brings along great advantages, for treatment possibilities as well as patient counselling.

Differential effect of long-term drug selection with doxorubicin and vorinostat on neuroblastoma cells with cancer stem cell characteristics.

Numerous studies have confirmed that cancer stem cells (CSCs) are more resistant to chemotherapy; however, there is a paucity of data exploring the effect of long-term drug treatment on the CSC sub-population. The purpose of this study was to investigate whether long-term doxorubicin treatment could expand the neuroblastoma cells with CSC characteristics and histone acetylation could affect stemness gene expression during the development of drug resistance. Using n-myc amplified SK-N-Be(2)C and non-n-myc amplified SK-N-SH human neuroblastoma cells, our laboratory generated doxorubicin-resistant cell lines in parallel over 1 year; one cell line intermittently treated with the histone deacetylase inhibitor (HDACi) vorinostat and the other without exposure to HDACi. Cells' sensitivity to chemotherapeutic drugs, the ability to form tumorspheres, and capacity for in vitro invasion were examined. Cell-surface markers and side populations (SPs) were analyzed using flow cytometry. Differentially expressed stemness genes were identified through whole genome analysis and confirmed with real-time PCR. Our results indicated that vorinostat increased the sensitivity of only SK-N-Be(2)C-resistant cells to chemotherapy, made cells lose the ability to form tumorspheres, and reduced in vitro invasion and the SP percentage. CD133 was not enriched in doxorubicin-resistant or vorinostat-treated doxorubicin-resistant cells. Nine stemness-linked genes (ABCB1, ABCC4, LMO2, SOX2, ERCC5, S100A10, IGFBP3, TCF3, and VIM) were downregulated in vorinostat-treated doxorubicin-resistant SK-N-Be(2)C cells relative to doxorubicin-resistant cells. A sub-population of cells with CSC characteristics is enriched during prolonged drug selection of n-myc amplified SK-N-Be(2)C neuroblastoma cells. Vorinostat treatment affects the reversal of drug resistance in SK-N-Be(2)C cells and may be associated with downregulation of stemness gene expression. This work may be valuable for clinicians to design treatment protocols specific for different neuroblastoma patients.

Sexual experience blocks the ability of clitoral stimulation to induce a conditioned place preference in the rat.

We have previously established the rewarding value of clitoral stimulation (CLS) through the demonstration that manual, distributed, CLS induces a significant conditioned place preference (CPP) and conditioned partner preference in naïve, hormonally primed and non-hormonally primed rats. The present experiment asks whether previous sexual experience might inhibit the ability of clitoral stimulation to induce a conditioned place preference. Female Long-Evans rats were ovariectomized and treated with 10 µg of estradiol benzoate (EB) 48 h and 500 µg of progesterone (P) 4h prior to receiving either 0, 1, or 5 consecutive copulatory sessions with a sexually vigorous male. Each copulatory session ended when females received at least 1 ejaculation. Females then experienced 10 alternating trials of distributed CLS or no CLS paired with one side of a non-biased CPP box under the same hormone-priming regimen. Females that experienced 5 consecutive copulatory sessions did not develop a significant place preference indicated by both a preference score (the proportion of time spent in the reinforced chamber) and a difference score (time in the non-reinforced chamber minus the time in the reinforced chamber) compared prior to and following the 10 conditioning trials. This suggests that repeated copulatory experience might induce a desensitization of the genitosensory circuit since copulation includes both clitoral, and vaginocervical stimulation from mounts plus intromissions. Alternatively, repeated sexual experience prior to conditioning may generate a UCS pre-exposure effect that cannot be altered when manual clitoral stimulation is paired with a new environment.

Selective glucocorticoid receptor translational isoforms reveal glucocorticoid-induced apoptotic transcriptomes.

Induction of T-cell apoptosis contributes to the anti-inflammatory and antineoplastic benefits of glucocorticoids. The glucocorticoid receptor (GR) translational isoforms have distinct proapoptotic activities in osteosarcoma cells. Here we determined whether GR isoforms selectively induce apoptosis in Jurkat T lymphoblastic leukemia cells. Jurkat cells stably expressing individual GR isoforms were generated and treated with vehicle or dexamethasone (DEX). DEX induced apoptosis in cells expressing the GR-A, -B, or -C, but not the GR-D, isoform. cDNA microarray analyses of cells sensitive (GR-C3) and insensitive (GR-D3) to DEX revealed glucocorticoid-induced proapoptotic transcriptomes. Genes that were regulated by the proapoptotic GR-C3, but not by the GR-D3, isoform likely contributed to glucocorticoid-induced apoptosis. The identified genes include those that are directly involved in apoptosis and those that facilitate cell killing. Chromatin immunoprecipitation assays demonstrated that distinct chromatin modification abilities may underlie the distinct functions of GR isoforms. Interestingly, all GR isoforms, including the GR-D3 isoform, suppressed mitogen-stimulated cytokines. Furthermore, the GR-C isoforms were selectively upregulated in mitogen-activated primary T cells and DEX treatment induced GR-C target genes in activated T cells. Cell-specific expressions and functions of GR isoforms may help to explain the tissue- and individual-selective actions of glucocorticoids and may provide a basis for developing improved glucocorticoids.

Pregnancy in multiple sclerosis: clinical and self-report scales.

Relapse rate is decreased during pregnancy in multiple sclerosis (MS). Risk for postpartum relapse is increased in the first 3 months after delivery. We aimed to study clinical course of MS around pregnancy, using clinical as well as self-report scales, including data on quality of life (QoL), and to identify clinical factors predisposing for postpartum relapse. We performed a prospective, longitudinal study among 35 MS patients and 20 controls. In patients we assessed expanded disability status scale (EDSS), the Guy's neurological disability scale (GNDS) and the multiple sclerosis impact scale 29 (MSIS-29). In patients and controls we assessed the MOS 36 item short form health survey questionnaire (SF36), consisting of eight domains. The previously described surge in relapses after delivery was also obvious in this study (p = 0.005). At group level EDSS and MSIS-29 did not show overt fluctuations over time. The GNDS, however, improved during the third trimester, compared to the first trimester (p = 0.003). A concomitant improvement in the SF36 domains vitality (p < 0.001) and general health (p = 0.001) was found in patients. At the final visit, at least 9 months after delivery, no worsening of EDSS, GNDS, MSIS-29 or SF36 was observed compared with the (for MS, beneficial) third trimester. Duration of disease, relapses in the year preceding pregnancy or relapses during pregnancy were not associated with postpartum relapse. QoL is improved during pregnancy. Although relapse rate was increased directly after delivery, in the mid long term after delivery no adverse effects of pregnancy on MS were found.

The role of family physician in case finding, referral, and insurance coverage in the rural areas.

BACKGROUND: WHO suggest that family physician is the core in the world efforts for quality improvement, cost effectiveness, and equity in the health care systems. This study evaluates the impact of the program on accessibility of the services, case finding, patient referral, feedback process and insurance coverage in the rural health units. METHODS: This study was quasi experimental. It compared the function of four health centers and eight health houses in the last three months of year 2004 with 2008. Data extracted from the available documents in the health units. Descriptive and analytical analysis was performed by using SPSS software. RESULTS: The presence of physicians in health centers were 75 and 100 percent for 2004 and 2008 respectively, this rate for midwives were 50 and 100 percent for the same years respectively. The total referral cases to the hospitals were 2676, the feedback rate was recorded in 36% of the cases. In this case the follow up rate by physicians was 0% in 2004 and 3.17% in 2008. Insurance coverage rate was 27% and 97% for 2004 and 2008 respectively within a meaningful P value range at 95% CI. CONCLUSION: The findings of this study show that the family physician program has the positive impact on function of health units in terms of availability of physicians and midwives and also insurance coverage at health centers in rural area, No impact on patient follow up and case referral rate was detected.

Regulation of pancreatic islet gene expression in mouse islets by pregnancy.

Pancreatic ß cells adapt to pregnancy-induced insulin resistance by unclear mechanisms. This study sought to identify genes involved in ß cell adaptation during pregnancy. To examine changes in global RNA expression during pregnancy, murine islets were isolated at a time point of increased ß cell proliferation (E13.5), and RNA levels were determined by two different assays (global gene expression array and G-protein-coupled receptor (GPCR) array). Follow-up studies confirmed the findings for select genes. Differential expression of 110 genes was identified and follow-up studies confirmed the changes in select genes at both the RNA and protein level. Surfactant protein D (SP-D) mRNA and protein levels exhibited large increases, which were confirmed in murine islets. Cytokine-induced expression of SP-D in islets was also demonstrated, suggesting a possible role as an anti-inflammatory molecule. Complementing these studies, an expression array was performed to define pregnancy-induced changes in expression of GPCRs that are known to impact islet cell function and proliferation. This assay, the results of which were confirmed using real-time reverse transcription-PCR assays, demonstrated that free fatty acid receptor 2 and cholecystokinin receptor A mRNA levels were increased at E13.5. This study has identified multiple novel targets that may be important for the adaptation of islets to pregnancy.

Assessing sources of inconsistencies in genotypes and their effects on genome-wide association studies with HapMap samples.

The discordance in results of independent genome-wide association studies (GWAS) indicates the potential for Type I and Type II errors. We assessed the repeatibility of current Affymetrix technologies that support GWAS. Reasonable reproducibility was observed for both raw intensity and the genotypes/copy number variants. We also assessed consistencies between different SNP arrays and between genotype calling algorithms. We observed that the inconsistency in genotypes was generally small at the specimen level. To further examine whether the differences from genotyping and genotype calling are possible sources of variation in GWAS results, an association analysis was applied to compare the associated SNPs. We observed that the inconsistency in genotypes not only propagated to the association analysis, but was amplified in the associated SNPs. Our studies show that inconsistencies between SNP arrays and between genotype calling algorithms are potential sources for the lack of reproducibility in GWAS results.

Specific PCR Assay for Rapid and Direct Detection of Neisseria meningitidis in Cerebrospinal Fluid Specimens.

BACKGROUND: Neisseria meninigitidis is one of the most frequently encountered microorganisms associated with central nervous system infections. The aim of this study was to evaluate a PCR-based assay for specific and rapid detection of N. meninigitidis in CSF specimens. METHODS: Since April 2002 to July 2006, 130 CSF specimens were collected from patients suspected of having bacterial meningitis. Bacterial isolation and identification was carried out according to the standard bacteriological methods. The PCR was used to amplify a 101bp fragment of capsular transport gene A (ctrA) of N. meningitidis. RESULTS: PCR yielded an amplified product with the expected size of 101 base pair fragment. Sensitivity test proved 500 ng of N. meningitidis DNA as the final detection limit and specificity test revealed no cross-reaction for a wide range of respiratory pathogenic organisms. CONCLUSION: The PCR assay was more sensitive than the bacterial culturing. It might be possible to apply this procedure for rapid diagnosis of meningococci in clinical samples.

Callosal lesion predicts future attacks after clinically isolated syndrome.

BACKGROUND: Current MRI criteria can help predict a second attack after a clinically isolated syndrome (CIS). Given the known association between corpus callosum lesions (CC) and multiple sclerosis (MS), such lesions on MRI could provide additional predictive information. This study assessed whether the presence of CC lesion on MRI could, next to the modified Barkhof criteria, further enhance prediction of conversion from CIS to MS. METHODS: Follow-up study of 158 patients with CIS who underwent MRI after CIS was performed. MRI were scored for the Barkhof criteria and CC lesion. Patients were classified as having MS according to Poser criteria. Cox regression models were used for the time to conversion from CIS to MS. RESULTS: The Barkhof criteria and CC lesion were strongly associated with conversion to MS with hazard ratios (HR), respectively, of 2.6 (95% confidence interval [CI] 1.5-4.3) and 2.7 (95% CI 1.6-4.5). The HRs of CC lesion adjusted for the Barkhof criteria and the Barkhof criteria adjusted for CC lesion were similar (HRs 1.8, not significant). The combined prediction of the Barkhof criteria and CC lesion was 3.3 (95% CI 1.9-5.7). Patients not fulfilling the Barkhof criteria had a fourfold increased risk of MS (HR 3.8, 95% CI 1.5-9.3) when they had a lesion in the CC. CONCLUSIONS: Corpus callosum (CC) lesion and the Barkhof criteria both predicted conversion to multiple sclerosis (MS). When both variables were combined, the association was stronger. The assessment of CC lesion may be a useful additional tool for predicting conversion to MS in patients with clinically isolated syndrome.

The study of prevalence and antimicrobial susceptibility of tracheal bacterial strains isolated from pediatric patients.

The aim of this study was to investigate the prevalence and antimicrobial susceptibility of bacterial strains isolated from tracheal specimens obtained from pediatric patients admitted to a major children hospital in Tehran, in 2007. Tracheal specimens were cultured on the appropriate bacteriological media. Bacterial isolates were identified by standard biochemical and serological tests. Antimicrobial susceptibility testing was performed according to Clinical and Laboratory Standards Institute (CLSI) guidelines. Pseudomonas spp. was identified as the most prevalent bacterial isolate (32%) followed by Staphylococcus aureus (27.6%). Thirty strains (16%) were identified as Klebsiella spp., 18 (9.6%) as Enterobacter spp. and the rest belonged to coagolase negative Staphylococci, Streptococcus viridans, Acinetobacter spp., Escherichia coli and Neisseria spp. All Pseudomonas spp. were resistant to ampicllin, kanamycin and ceftizoxime. Staphylococcus and Klebsiella spp. showed high degree of resistance to 40% of examined antibiotics.

Rapid detection of Borrelia burgdorferi strains by nested polymerase chain reaction.

This study was carried out to evaluate the nested PCR for specific detection of different strains of B. burgdorferi. Five strains of B. burgdorferi including ACA-1, B-31, 2B45, 3B45, 7B49 obtained from different countries were used in this study. The strains of B. hermsii, Escherichia. coli and T. pallidum were also included as control strains. Two pairs of nested PCR primers were used to amplify the gene encoding the Osp-A protein of B. burgdorfer under standard PCR condition. In a two stage procedure, nested PCR yielded a positive reaction for five tested strains of B. burgdorferi. None the strains including B. hermsii, E. coli and T. pallidum showed positive reaction when used as control strains in PCR. In conclusion, nested PCR showed acceptable specificity for rapid detection ofB. burgdorferi.

Visfatin genotype may modify the insulin resistance and lipid profile in type 2 diabetes patients.

AIM: We investigated the role of the -4689G/T promoter variant of the visfatin gene on serum visfatin concentration and biochemical markers in T2DM patient. METHODS: In a cross-sectional study we recruited 93 patients with type 2 diabetes. Laboratory and anthropometric measurements were included FBG, OGTT, HbA1C, lipid Profile, fasting serum visfatin, fasting serum insulin, weight, height, Body Mass Index (BMI) and waist hip ratio (WHR). Genotyping for visfatin gene was performed by using the PCR-RFLP method. RESULTS: Our findings showed significant differences in levels of low density lipoprotein (LDL) cholesterol, total cholesterol, high density lipoprotein (HDL) cholesterol and fasting serum insulin among various types of visfatin genotype (TT, GG, and GT). This study showed a significant correlation between circulating levels of visfatin and weight, BMI, hs-CRP and fasting insulin in TT genotype. But regarding GG genotype only fasting insulin had a significant correlation with circulating visfatin. CONCLUSIONS: Visfatin genotypes may account for insulin resistance and levels of lipid profile that may cause by different visfatin expression between genotypes.