Attitudes toward using clinical decision support in community pharmacies to promote antibiotic stewardship.

BACKGROUND: Outpatient antibiotic prescriptions drive antibiotic overuse in humans, and the Centers for Disease Control and Prevention has identified community pharmacies as potential partners in outpatient stewardship efforts. Clinical decision support (CDS) tools can potentially be used at community pharmacies to aid in outpatient stewardship efforts. OBJECTIVES: We sought to determine community pharmacist attitudes toward using a computerized CDS tool to evaluate and manage common complaints and thus promote appropriate antibiotic prescribing. METHODS: We conducted in-depth semistructured interviews of community pharmacists to determine attitudes toward using CDS tools in their practice and identify potential barriers in implementation. Thematic analysis was used to identify common themes and subthemes in the pharmacist responses. RESULTS: We interviewed 21 pharmacists and identified 5 themes and 14 subthemes in our interviews. The pharmacists reported that patients frequently presented with complaints of acute infections and that they (the pharmacists) were universally supportive of a CDS intervention that would allow them to assess such patients and, in turn, guide appropriate antibiotic prescribing. They noted that communication difficulties with prescribing physicians and lack of information sharing currently made it difficult to implement stewardship interventions, and they stated that they were interested in any intervention that could help overcome these barriers. CONCLUSION: Community pharmacies represent an important point of contact for patients and are a potentially valuable setting for outpatient stewardship interventions. Pharmacists were overwhelmingly supportive of using CDS tools to evaluate patients and promote antimicrobial stewardship. These results suggest that it would be feasible to pilot such an intervention in the community pharmacy setting.

Experiences from the Missouri Antimicrobial Stewardship Collaborative: A mixed methods study.

We performed a mixed-methods study to evaluate antimicrobial stewardship program (ASP) uptake and to assess variability of program implementation in Missouri hospitals. Despite increasing uptake of ASPs in Missouri, there is wide variability in both the scope and sophistication of these programs.

Nasosinusal myiasis in elderly patient with mucocutaneous leishmaniosis.

BACKGROUND: Myiasis is a condition in which flies are attracted to infected and/or necrotic tissues and deposit eggs that hatch into larvae. It may bring serious functional and aesthetic sequelae when involves nasal and parasinusal cavities; however, there is a lack of such reports in the literature. METHODS: We present and briefly discuss herein the clinical and surgical management of nasosinusal myiasis in an elderly patient previously affected by mucocutaneous leishmaniosis. RESULTS: Facial computed tomography was used to confirm the nasosinusal involvement. Next, osteotomies were performed, followed by the mechanical removal of larvae, bilateral sinusectomy and pharmacological therapy. CONCLUSION: A complicated case of nasosinusal myiasis was surgically managed, resulting in a good prognosis for the patient.

Intraventricular pneumocephalus associated with nasocephalic necrosis in a puppy: a case report / Pneumoencéfalo intraventricular associado à área de necrose nasoencefálica em filhote canino: relato de caso

Pneumocephalus is defined as the presence of air in any of the intracranial compartments. Its most frequent causes are trauma and cranial surgery. Clinical signs occur as a result of increased intracranial pressure and vary with the location and extent of the lesion. A case involving a seven-month-old female Saint Bernard, who suffered cranial trauma caused by a bite to the face at ten days of age and had presented with seizures and localized pain four months previously is reported. A computed tomography scan of the skull revealed a nasocephalic mass with low contrast enhancement, bone lysis, and hypodensity (-940 Hounsfield units) of the lateral and third ventricles, indicating intraventricular pneumocephalus. During surgery, a fragment of the mass was collected for histopathological examination, which demonstrated the presence of multifocal areas of necrosis. The computed tomography (CT) is a reliable method for the characterization of intracranial lesions and diagnosis of pneumocephalus, whose occurrence must be considered in pathological processes in which there is increased intracranial pressure and in patients undergoing certain surgical procedures and anesthetic specific, and CT is indicated as a monitoring tool for these patients.(AU)

Pneumoencéfalo é definido como a presença de gás em quaisquer dos compartimentos intracranianos e possui como causas mais frequentes o traumatismo e cirurgias cranianas. Os sinais clínicos ocorrem como consequência do aumento de pressão intracraniana e variam conforme o local e a extensão da lesão. Relata-se o caso de uma cadela de sete meses de idade, da raça São Bernardo, que sofreu trauma por mordedura em face, quatro meses antes, apresentando crises convulsivas e sensibilidade dolorosa local desde então. O exame tomográfico do crânio revelou massa nasoencefálica com baixa captação de contraste, lise óssea e hipodensidade (-940HU) dos ventrículos laterais e terceiro ventrículo encefálico, caracterizando pneumoencéfalo intraventricular. Foi realizada intervenção cirúrgica e coleta de fragmento da massa para exame histopatológico, que demonstrou existência de necrose multifocal. O exame de tomografia computadorizada (TC) é um método confiável para a caracterização de lesões intracranianas e diagnóstico de pneumoencéfalo, cuja ocorrência deve ser considerada em processos patológicos nos quais há aumento da pressão intracraniana e em pacientes submetidos a alguns procedimentos cirúrgicos e anestésicos específicos, sendo a TC indicada como ferramenta de monitoramento desses pacientes.(AU)

Intraventricular pneumocephalus associated with nasocephalic necrosis in a puppy: a case report / Pneumoencéfalo intraventricular associado à área de necrose nasoencefálica em filhote canino: relato de caso

Pneumocephalus is defined as the presence of air in any of the intracranial compartments. Its most frequent causes are trauma and cranial surgery. Clinical signs occur as a result of increased intracranial pressure and vary with the location and extent of the lesion. A case involving a seven-month-old female Saint Bernard, who suffered cranial trauma caused by a bite to the face at ten days of age and had presented with seizures and localized pain four months previously is reported. A computed tomography scan of the skull revealed a nasocephalic mass with low contrast enhancement, bone lysis, and hypodensity (-940 Hounsfield units) of the lateral and third ventricles, indicating intraventricular pneumocephalus. During surgery, a fragment of the mass was collected for histopathological examination, which demonstrated the presence of multifocal areas of necrosis. The computed tomography (CT) is a reliable method for the characterization of intracranial lesions and diagnosis of pneumocephalus, whose occurrence must be considered in pathological processes in which there is increased intracranial pressure and in patients undergoing certain surgical procedures and anesthetic specific, and CT is indicated as a monitoring tool for these patients.

Pneumoencéfalo é definido como a presença de gás em quaisquer dos compartimentos intracranianos e possui como causas mais frequentes o traumatismo e cirurgias cranianas. Os sinais clínicos ocorrem como consequência do aumento de pressão intracraniana e variam conforme o local e a extensão da lesão. Relata-se o caso de uma cadela de sete meses de idade, da raça São Bernardo, que sofreu trauma por mordedura em face, quatro meses antes, apresentando crises convulsivas e sensibilidade dolorosa local desde então. O exame tomográfico do crânio revelou massa nasoencefálica com baixa captação de contraste, lise óssea e hipodensidade (-940HU) dos ventrículos laterais e terceiro ventrículo encefálico, caracterizando pneumoencéfalo intraventricular. Foi realizada intervenção cirúrgica e coleta de fragmento da massa para exame histopatológico, que demonstrou existência de necrose multifocal. O exame de tomografia computadorizada (TC) é um método confiável para a caracterização de lesões intracranianas e diagnóstico de pneumoencéfalo, cuja ocorrência deve ser considerada em processos patológicos nos quais há aumento da pressão intracraniana e em pacientes submetidos a alguns procedimentos cirúrgicos e anestésicos específicos, sendo a TC indicada como ferramenta de monitoramento desses pacientes.

Cutaneous squamous cell carcinoma progression is associated with decreased GATA-3 immunohistochemical staining.

BACKGROUND: The GATA family of transcription factors is an essential regulator of cellular proliferation and differentiation. In the skin, GATA-3 is critical for epidermal stratification and maintenance of barrier function. A role for GATA-3 in the development of human cutaneous squamous cell carcinoma (SCC) is not known. Here, we investigated GATA-3 immunohistochemical staining in premalignant and invasive cutaneous SCC from sun-exposed and sun-protected skin. METHODS: GATA-3 immunohistochemistry was performed on actinic keratoses (AK) (n = 19), in situ squamous cell carcinomas with actinic [SCCIS (A)] (n = 9) or bowenoid features [SCCIS (B)] (n = 17), well-, moderately and poorly differentiated SCC (n = 36), Bowenoid papulosis of the perineum (n = 15) and penile SCC (pSCC) (n = 10). RESULTS: We found that GATA-3 immunohistochemical staining is progressively lost in sun-exposed skin as neoplasia progresses from pre-cancerous AK to SCCIS (A), and ultimately, to SCC, which shows near absent GATA-3 staining. This reduction in GATA-3 staining is independent of histological grade in SCC. Only slight down-regulation of GATA-3 was seen in all cases of SCCIS (B) and Bowenoid papulosis, while near absent GATA-3 expression was seen in pSCC. CONCLUSION: We propose that decreased GATA-3 immunohistochemical staining is associated with cutaneous SCC progression on both sun-exposed and sun-protected sites.

Diagnostic utility of SOX11 immunohistochemistry in differentiating cutaneous spread of mantle cell lymphoma from primary cutaneous B-cell lymphomas.

BACKGROUND: Mantle cell lymphoma (MCL) is associated with the worst prognosis among low-grade B-cell lymphomas. While cutaneous involvement by nodal or systemic MCL is uncommon, its differentiation from primary cutaneous B-cell lymphoma (CBCL) or cutaneous involvement by other extra-cutaneous BCL is challenging as neither histomorphology nor immunophenotype can be absolutely specific. We analyzed the diagnostic utility of SOX11 immunohistochemistry in differentiating secondary cutaneous MCL from other low-grade CBCL. METHODS: Immunohistochemical staining with anti-SOX11 antibody was performed on 8 cases of secondary cutaneous MCL, 16 secondary cutaneous CLL, 20 primary cutaneous MZL, 12 cutaneous FCL (6 primary, 6 secondary), 7 primary cutaneous DLBCL, leg type, 5 systemic DLBCL and 3 B-ALL. SOX11 and cyclin D1 staining were compared in secondary cutaneous MCL. RESULTS: Nuclear SOX11 staining was seen in seven of eight cases (88%) of secondary cutaneous MCL, including a case with minimal cyclin D1 expression. All other CBCL lacked detectable nuclear SOX11 expression. The sensitivity and specificity for SOX11 in MCL were 87.5 and 100%, respectively. Both the sensitivity and specificity for combined SOX11 and cyclin D1 immunohistochemistry were 100%. CONCLUSION: SOX11 immunohistochemistry could be a useful adjunct in distinguishing secondary cutaneous MCL from other CBCL.

Expression of helper T cell master regulators in inflammatory dermatoses and primary cutaneous T-cell lymphomas: diagnostic implications.

BACKGROUND: Mycosis fungoides (MF) is a neoplasm of skin-homing CD4(+) helper T (TH) lymphocytes with dysregulation of TH1 and TH2 immunity. Diagnosis of MF is challenging, as there is significant morphologic overlap with other dermatologic entities. OBJECTIVE: We investigated diagnostic utility of TH1- and TH2-specific markers, T-bet, and GATA-3, respectively, in MF and its reactive and neoplastic mimics. METHODS: Immunohistochemical staining for CD3/T-bet and CD3/GATA-3 was performed on inflammatory dermatoses (n = 56), MF (n = 37), Sezary syndrome (SS; n = 8), and cutaneous anaplastic large cell lymphoma (C-ALCL; n = 14). RESULTS: Inflammatory dermatoses showed epidermal T cells predominantly expressing GATA-3, except psoriasis, which exhibited a mixed GATA-3/T-bet staining. In contrast, neoplastic T cells in patch stage MF showed markedly increased T-bet positivity with minimal GATA-3 expression. Plaque stage MF had a mixed T-bet/GATA-3 phenotype, whereas tumor stage MF and SS exhibited diffuse GATA-3 expression. C-ALCL lacked significant staining for both markers. LIMITATIONS: Sample size was relatively small. CONCLUSIONS: A predominance of T-bet(+) T cells in the epidermis support patch stage MF over dermatitis. A predominance of GATA-3(+) T cells in the dermis support CD30(+) MF with large cell transformation over C-ALCL. These stains do not allow distinction between dermatitis and cutaneous infiltrates of SS.

dsRNA-induced gene silencing in Moniliophthora perniciosa, the causal agent of witches' broom disease of cacao.

The genome sequence of the hemibiotrophic fungus Moniliophthora perniciosa revealed genes possibly participating in the RNAi machinery. Therefore, studies were performed in order to investigate the efficiency of gene silencing by dsRNA. We showed that the reporter gfp gene stably introduced into the fungus genome can be silenced by transfection of in vitro synthesized gfpdsRNA. In addition, successful dsRNA-induced silencing of endogenous genes coding for hydrophobins and a peroxiredoxin were also achieved. All genes showed a silencing efficiency ranging from 18% to 98% when compared to controls even 28d after dsRNA treatment, suggesting systemic silencing. Reduction of GFP fluorescence, peroxidase activity levels and survival responses to H(2)O(2) were consistent with the reduction of GFP and peroxidase mRNA levels, respectively. dsRNA transformation of M. perniciosa is shown here to efficiently promote genetic knockdown and can thus be used to assess gene function in this pathogen.

Absence of the macrophage mannose receptor in mice does not increase susceptibility to Pneumocystis carinii infection in vivo.

Host defense against the opportunistic pathogen Pneumocystis carinii requires functional interactions of many cell types. Alveolar macrophages are presumed to be a vital host cell in the clearance of P. carinii, and the mechanisms of this interaction have come under scrutiny. The macrophage mannose receptor is believed to play an important role as a receptor involved in the binding and phagocytosis of P. carinii. Although there is in vitro evidence for this interaction, the in vivo role of this receptor in P. carinii clearance in unclear. Using a mouse model in which the mannose receptor has been deleted, we found that the absence of this receptor is not sufficient to allow infection by P. carinii in otherwise immunocompetent mice. Furthermore, when mice were rendered susceptible to P. carinii by CD4(+) depletion, mannose receptor knockout mice (MR-KO) had pathogen loads equal to those of wild-type mice. However, the MR-KO mice exhibited a greater influx of phagocytes into the alveoli during infection. This was accompanied by increased pulmonary pathology in the MR-KO mice, as well as greater accumulation of glycoproteins in the alveoli (glycoproteins, including harmful hydrolytic enzymes, are normally cleared by the mannose receptor). We also found that the surface expression of the mannose receptor is not downregulated during P. carinii infection in wild-type mice. Our findings suggest that while the macrophage mannose receptor may be important in the recognition of P. carinii, in vivo, this mechanism may be redundant, and the absence of this receptor may be compensated for.

Comparative analyses of the complete genome sequences of Pierce's disease and citrus variegated chlorosis strains of Xylella fastidiosa.

Xylella fastidiosa is a xylem-dwelling, insect-transmitted, gamma-proteobacterium that causes diseases in many plants, including grapevine, citrus, periwinkle, almond, oleander, and coffee. X. fastidiosa has an unusually broad host range, has an extensive geographical distribution throughout the American continent, and induces diverse disease phenotypes. Previous molecular analyses indicated three distinct groups of X. fastidiosa isolates that were expected to be genetically divergent. Here we report the genome sequence of X. fastidiosa (Temecula strain), isolated from a naturally infected grapevine with Pierce's disease (PD) in a wine-grape-growing region of California. Comparative analyses with a previously sequenced X. fastidiosa strain responsible for citrus variegated chlorosis (CVC) revealed that 98% of the PD X. fastidiosa Temecula genes are shared with the CVC X. fastidiosa strain 9a5c genes. Furthermore, the average amino acid identity of the open reading frames in the strains is 95.7%. Genomic differences are limited to phage-associated chromosomal rearrangements and deletions that also account for the strain-specific genes present in each genome. Genomic islands, one in each genome, were identified, and their presence in other X. fastidiosa strains was analyzed. We conclude that these two organisms have identical metabolic functions and are likely to use a common set of genes in plant colonization and pathogenesis, permitting convergence of functional genomic strategies.

Normal host defense during systemic candidiasis in mannose receptor-deficient mice.

Pathogen pattern recognition receptors (PRRs) recognize common structural and molecular motifs present on microbial surfaces and contribute to induction of innate immune responses. The mannose receptor (MR), a carbohydrate-binding receptor expressed on subsets of macrophages, is considered one such PRR. In vitro experiments have implicated the MR in phagocytosis of mannose-bearing microbes, including Candida albicans, and enhancement of antifungal response by macrophages. However, the significance of the MR's contribution to immune response during systemic C. albicans infection has never been directly demonstrated. Using MR-deficient mice in an in vivo infection experiment, we examined the role of the MR in immune response during disseminated candidiasis. MR(-/-) and wild-type control mice were challenged intraperitoneally with C. albicans, and the survival rates, tissue fungal burden, inflammatory cell recruitment, and specific antibody production after infection were evaluated. We found no significant difference in survival between the two mouse strains. MR(-/-) mice had higher average fungal burdens in some of the organs on days 7 and 21 but exhibited competence in inflammatory cell recruitment and antibody production. We also observed in vitro that MR(-/-) peritoneal cavity macrophages were equally capable of C. albicans uptake and that phagocytosis could be blocked with beta-glucan. We conclude that the MR is not required for the normal host defense during disseminated candidiasis or for the phagocytosis of C. albicans and that a beta-glucan receptor may be required for C. albicans phagocytosis.

Disseminated candidiasis and hepatic malarial infection in mannose-binding-lectin-A-deficient mice.

To examine the physiological functions of mannose-binding lectin A (MBL-A), we generated mice that were deficient in MBL-A and examined their susceptibilities to the microbial pathogens Candida albicans and Plasmodium yoelii, an accepted experimental malaria model in mouse. We found no differences in the survival rates and fungal burdens of wild-type and MBL-A(-/-) mice with disseminated C. albicans infection. The two mouse strains were also similar in their abilities to resist hepatic accumulation of P. yoelii parasites. We conclude that MBL-A deficiency does not alter resistance to disseminated candidiasis or initial hepatic invasion by P. yoelii.

Mannose receptor-mediated regulation of serum glycoprotein homeostasis.

Carbohydrates are thought to function as tags that mark circulatory glycoproteins for rapid clearance. To examine the role of the mannose receptor (MR) in glycoprotein clearance, we generated mice genetically deficient in MR. MR-/- mice were defective in clearing proteins bearing accessible mannose and N-acetylglucosamine residues and had elevated levels of eight different lysosomal hydrolases. Proteomic analysis of MR-/- and control mouse sera showed that an additional 4 out of 52 proteins identified were elevated in MR-/- serum. Each of these is up-regulated during inflammation and wound healing. Thus, MR appears to operate as an essential regulator of serum glycoprotein homeostasis.

Intragraft expression of transforming growth factor-beta 1 by a novel quantitative reverse transcription polymerase chain reaction ELISA in long lasting kidney recipients.

BACKGROUND: Chronic allograft nephropathy (CAN) remains a major problem in clinical transplantation. It has been associated with increased transforming growth factor (TGF-beta1). Our goal was to correlate CAN and levels of TGF-beta1 by using a novel competitive quantitative for reverse transcription-polymerase chain reaction-ELISA (RT-PCR-ELISA) assay. METHODS: We studied 12 transplantation patients (posttransplant time: 36.5+/-11.2 months, range (r): 13-52) with stable creatinine and blood pressure and varied proteinuria. A Kidney biopsy was performed in all patients. Six patients with acute tubular necrosis (ATN) immediately after transplantation were used as controls. Histopathological evaluation was based on Banff working classification criteria. We designed an heterologous RNA competitor (IC) for RT-PCR-ELISA, which co-amplified with the same primer as TGF-beta1. Products were viewed on 96-well plates labeled with probes for IC at the desired sequence. RESULTS: Results were expressed as the number of TGF-beta1 copies/microg of total RNA. Six patients showed more than 1000 mg/24 hr proteinuria (2446+/-1421 mg/24 hr, r: 1200-5000) higher CAN Banff scores, and the other six presented <1,000 mg/24 hr (348+/-267 mg/24 hr, r: 114-800). This difference was significant (P=0.01). There were not significant differences in posttransplant time, creatinine, or blood pressure between groups. TGF-beta1 levels by RT-PCR-ELISA were statistically significant (6038+/-5317, r: 1239-12100 versus 177+/-119.7, r: 51-400, P=0.04). The control group showed levels of 228+/-111, r. 140-444, P=0.04) with significant difference only for the higher proteinuria group (P=0.03). CONCLUSIONS: This study showed that those patients with elevated CAN scores and higher proteinuria levels had higher TGF-beta1 intragraft expression.

[School failure in a cohort of adolescents]. / Fracaso escolar en una cohorte de adolescentes.

OBJECTIVE: To evaluate a cohort of adolescents as to whether their personal characteristics and/or determined habits of health and social relations bore any relation to the state of their studies two years later. DESIGN: A prospective study following a cohort of adolescents. PARTICIPANTS AND SETTING: Third-year ESO (aged c. 14) adolescents from the four state secondary schools in Puerto de Sagunto. INTERVENTIONS: Once the cohort (n = 551) was defined, in November 1995 the students themselves filled in a questionnaire on health and relationship habits. Two years afterwards they were located through school registers and classified as good if they were in the appropriate year, repeat if they were repeating a year and disappeared if they had left school. These last two categories were both considered school failures (SF). MEASUREMENTS AND RESULTS: 222 students were classed as SF (40%). 118 of these (21.4%) had left and 104 (18.9%) were repeating a year. There were statistically significant differences in the following characteristics measured at the start of the study: greater SF among boys than girls (46.4%/35.6%): the disappeared had a higher average age than the good students (14.98/14.17), higher average number of siblings (2.73/2.26), and higher average of nights they went out during the week (1.65/0.84). Mean family income was lower in the repeat group (1926087/2475436 pesetas); the money students received weekly was higher in both SF groups (over 900/641 pesetas). Students whose fathers have university degrees made up only 7.4% of SF; and no student whose mother had a university degree was SF. 17.5% of those who said they spent their free time with their family were SF, whereas 53% of those who devoted their free time basically to enjoying themselves were SF. On drug consumption, those who replied they never smoked had 27.2% SF, never consumed alcohol 25.8% SF, never took marihuana 35.3% SF, and never consumed other drugs 39.5% SF. Students who said their relationships with family and teachers was bad had 70% and 62.2% of SF, respectively. 70% of those who felt depressed were SF. CONCLUSIONS: This study confirms that a favourable family atmosphere is important in preventing school failure. It also makes clear that young people's social relationships and health habits are closely associated to their being a standard student or a school failure.