Portraying persons who inject drugs recently infected with hepatitis C accessing antiviral treatment : a cluster analysis

Objectives. To empirically determine a categorization of people who inject drug (PWIDs) recently infected with hepatitis C virus (HCV), in order to identify profiles most likely associated with early HCV treatment uptake. Methods.The study population was composed of HIV-negative PWIDs with a documented recent HCV infection. Eligibility criteria included being 18 years old or over, and having injected drugs in the previous 6 months preceding the estimated date of HCV exposure. Participant classification was carried out using a TwoStep cluster analysis. Results. FromSeptember 2007 to December 2011, 76 participants were included in the study. 60 participants were eligible for HCV treatment. Twenty-one participants initiated HCV treatment.The cluster analysis yielded 4 classes: class 1: Lukewarm health seekers dismissing HCV treatment offer; class 2: multisubstance users willing to shake off the hell; class 3: PWIDs unlinked to health service use; class 4: health seeker PWIDs willing to reverse the fate. Conclusion. Profiles generated by our analysis suggest that prior health care utilization, a key element for treatment uptake, differs between older and younger PWIDs. Such profiles could inform the development of targeted strategies to improve health outcomes and reduce HCV infection among PWIDs.

Desenvolvimento de um sistema multidimensional para classificação e gestão de informação em saúde: aplicabilidade à informação clínica

Introdução: A profusão de informação na área médica cria problemas de gestão, sendo necessários métodos sistematizados para armazenamento e recuperação. Quando a informação se insere no contexto do processo clínico, os métodos devem integrar terminologias biomédicas controladas e igualmente devem integrar as características desejáveis dirigidas à estrutura, conteúdo e resultados clínicos. O objectivo deste artigo é testar a aplicabilidade e capacidade de recuperação, de um sistema multidimensional desenvolvido para classificação e gestão de informação em saúde. Métodos: A partir das questões recebidas em seis anos (Serviço de Informação de Medicamentos, Serviços Farmacêuticos, Hospitais da Universidade de Coimbra), seleccionaram-se 300 questões sobre informação clínica, por método aleatório informatizado. Caracterizou-se e avaliou-se a aplicabilidade pela quantidade classificada e pela necessidade de alterações ao sistema que é constituído por várias dimensões independentes e que englobam conceitos por vezes hierarquizados. A recuperação das questões foi testada pesquisando informação numa dimensão ou cruzamento de dimensões. Resultados: Todas as questões foram classificadas: 53% são casos clínicos com incidência nas doenças geniturinárias; doenças metabólicas, nutricionais e endócrinas; neoplasias; infecções e doenças do sistema nervoso. Em 81%, o objecto é o medicamento, sobretudo anti-infecciosos e anti-neoplásicos. As áreas de terapêutica e segurança foram as mais solicitadas, incidindo principalmente sobre os assuntos: utilização, reacções adversas, identificação de medicamentos e tecnologia farmacêutica. Na aplicabilidade, foi necessário adicionar alguns conceitos e modificar alguns grupos hierárquicos que não modificaram a estrutura base, nem colidiram com as características desejáveis. As limitações prenderam-se com os sistemas de classificação externos integrados. A pesquisa na dimensão assunto, do conceito administração de medicamentos, recuperou 19 questões. O cruzamento de duas dimensões: anti-infecciosos (externa) e teratogenicidade (assunto), recuperou três questões. Nos dois exemplos recupera-se informação a partir de qualquer um dos níveis da hierarquia, do mais geral ao mais específico e mesmo a partir de dimensões externas. Conclusões: A utilização do sistema nesta amostra demonstrou aplicabilidade na classificação e arquivo de informação clínica, capacidade de recuperação e flexibilidade, sofrendo alterações sem interferir com as características desejáveis. Esta ferramenta permite a recuperação da evidência que interessa orientada para o doente. Introduction: The large amount of information in the medical area creates management problems, being necessary systematic methods for filing and retrieval. With information on the context of clinical records, methods must integrate controlled biomedical terminologies and desirable characteristics oriented to the structure, content and clinical results. The objective is to test the applicability and capacity for retrieval of a multidimensional system developed for classification and management of health information. Methods: Three hundred questions were randomly selected, by computerized method, from the questions received in six years (Medicine Information Service, Pharmaceutical Department, Coimbra University Hospitals). They were characterized and applicability evaluated by classified amount and need to alter the system, which is composed of various independent dimensions, incorporating concepts sometimes hierarchical. Questions retrieval was tested searching information in a dimension or between dimensions. Results: All questions were classified: 53% are clinical cases with illnesses incidence in the genitourinary system; metabolic, nutritional and endocrine disease; cancer; infections and nervous system. In 81%, the object is a drug, mostly anti-infectious and anti-neoplastic agents. The therapeutic and safety areas had been the most requested, regarding the subjects: use, adverse reactions, drug identification and pharmaceutical technology. As to applicability, it was necessary to add some concepts and modify same hierarchical groups, that didn’t modify the basic structure, nor had collided with the desirable characteristics. The limitations were related with the incorporated external classification systems. The search in the subject dimension of the concept drug administration retrieved 19 questions. The search between two dimensions: antiinfectious (external) and teratogenicity (subject) retrieved three questions. In the two examples, it was possible to retrieve information from any one of the levels of the hierarchy, from the most general to the most specific and even from external dimensions. Conclusions: The use of the system in this sample showed its applicability in clinical information classification and filing, retrieval capacity and flexibility, supporting modifications without interfering with desirable characteristics. This tool allows retrieval of patient-oriented evidence that matters.

Ultra-deep sequencing provides insights into the virology of hepatitis C super-infections in a case of three sequential infections with different genotypes

The current epidemic of Hepatitis C infection in HIV-positive men who have sex with men is associated with increasing use of recreational drugs. Multiple HCV infections have been reported in haemophiliacs and intravenous drug users. Using ultra-deep sequencing analysis, we present the case of an HIV-positive MSM with evidence of three sequential HCV infections, each occurring during the acute phase of the preceding infection, following risk exposures. We observed rapid replacement of the original strain by the incoming genotype at subsequent time points. The impact of HCV super-infection remains unclear and UDS may provide new insights.

Post-surgical wound infections involving Enterobacteriaceae with reduced susceptibility to ß-lactams in two Portuguese hospitals

The post-surgical period is often critical for infection acquisition. The combination of patient injury and environmental exposure through breached skin add risk to pre-existing conditions such as drug or depressed immunity. Several factors such as the period of hospital staying after surgery, base disease, age, immune system condition, hygiene policies, careless prophylactic drug administration and physical conditions of the healthcare centre may contribute to the acquisition of a nosocomial infection. A purulent wound can become complicated whenever antimicrobial therapy becomes compromised. In this pilot study, we analysed Enterobacteriaceae strains, the most significant gram-negative rods that may occur in post-surgical skin and soft tissue infections (SSTI) presenting reduced β-lactam susceptibility and those presenting extended-spectrum β-lactamases (ESBL). There is little information in our country regarding the relationship between β-lactam susceptibility, ESBL and development of resistant strains of microorganisms in SSTI. Our main results indicate Escherichia coli and Klebsiella spp. are among the most frequent enterobacteria (46% and 30% respectively) with ESBL production in 72% of Enterobacteriaceae isolates from SSTI. Moreover, coinfection occurred extensively, mainly with Pseudomonas aeruginosa and Methicillin-resistant Staphylococcus aureus (18% and 13%, respectively). These results suggest future research to explore if and how these associations are involved in the development of antibiotic resistance.

Low-Dose Vascular Photodynamic Therapy Decreases Tumor Interstitial Fluid Pressure, which Promotes Liposomal Doxorubicin Distribution in a Murine Sarcoma Metastasis Model.

INTRODUCTION: Solid tumors are known to have an abnormal vasculature that limits the distribution of chemotherapy. We have recently shown that tumor vessel modulation by low-dose photodynamic therapy (L-PDT) could improve the uptake of macromolecular chemotherapeutic agents such as liposomal doxorubicin (Liporubicin) administered subsequently. However, how this occurs is unknown. Convection, the main mechanism for drug transport between the intravascular and extravascular spaces, is mostly related to interstitial fluid pressure (IFP) and tumor blood flow (TBF). Here, we determined the changes of tumor and surrounding lung IFP and TBF before, during, and after vascular L-PDT. We also evaluated the effect of these changes on the distribution of Liporubicin administered intravenously (IV) in a lung sarcoma metastasis model. MATERIALS AND METHODS: A syngeneic methylcholanthrene-induced sarcoma cell line was implanted subpleurally in the lung of Fischer rats. Tumor/surrounding lung IFP and TBF changes induced by L-PDT were determined using the wick-in-needle technique and laser Doppler flowmetry, respectively. The spatial distribution of Liporubicin in tumor and lung tissues following IV drug administration was then assessed in L-PDT-pretreated animals and controls (no L-PDT) by epifluorescence microscopy. RESULTS: L-PDT significantly decreased tumor but not lung IFP compared to controls (no L-PDT) without affecting TBF. These conditions were associated with a significant improvement in Liporubicin distribution in tumor tissues compared to controls (P < .05). DISCUSSION: L-PDT specifically enhanced convection in blood vessels of tumor but not of normal lung tissue, which was associated with a significant improvement of Liporubicin distribution in tumors compared to controls.

Renal response to the angiotensin II receptor subtype 1 antagonist irbesartan versus enalapril in hypertensive patients.

OBJECTIVE: To compare the acute and sustained renal hemodynamic effects on hypertensive patients of 100 mg irbesartan and 20 mg enalapril each once daily. PATIENTS: Twenty patients (aged 35-70 years) with uncomplicated, mild-to-moderate essential hypertension and normal serum creatinine levels completed this study. STUDY DESIGN: After random allocation to treatment (n=10 per group), administration schedule (morning or evening) was determined by further random allocation, with crossover of schedules after 6 weeks' therapy. Treatment and administration assignments were double-blind. Twenty-four-hour ambulatory blood pressure was monitored before and after 6 and 12 weeks of therapy. Renal hemodynamics were determined on the first day of drug administration and 12 and 24 h after the last dose during chronic treatment. RESULTS: Administration of each antihypertensive agent induced a renal vasodilatation with no significant change in glomerular filtration rate. However, the time course appeared to differ: irbesartan had no significant acute effect 4 h after the first dose, but during chronic administration a renal vasodilatory response was found 12 and 24 h after the dose; enalapril was effective acutely and 12 h after administration, but no residual effect was found 24 h after the dose. Both antihypertensive agents lowered mean ambulatory blood pressure effectively, with no significant difference between treatments or between administration schedules (morning versus evening). CONCLUSIONS: Irbesartan and enalapril have comparable effects on blood pressure and renal hemodynamics in hypertensive patients with normal renal functioning. However, the time profiles of the renal effects appear to differ, which might be important for long-term renoprotective effects.

Adjuvant early breast cancer systemic therapies according to daily used technologies.

Prognosis of early breast cancer patients is significantly improved with the use of adjuvant therapies. Various guidelines have been proposed to select patients who will derive the most benefit from such treatments. However, classifications have limited usefulness in subsets of patients such as those with node negative breast cancer. The 2007 St. Paul de Vence Clinical Practice Recommendations proposed to consider adjuvant therapy in accordance with the 10-year relapse-free survival reduction estimated by Adjuvant! Online. However, many limitations remain regarding the use of Adjuvant! Online. Among them, adverse prognostic and/or predictive factors such as vascular invasion, mitotic activity, progesterone receptor negativity, and HER-2 expression are not incorporated in the routine clinical decision process. Our group has therefore issued guidelines based on the consideration of both Adjuvant! Online calculations and the prognostic and/or predictive effects of these markers. In addition, web-accessible comprehensive tables summarizing these recommendations are provided.

Myoclonies chez une personne très âgée; une cause fréquente et réversible [Myoclonia in an oldest old woman: a frequent and reversible etiology]

A 98-year-old woman was referred to our hospital because of myoclonia. The concentration of calcium and vitamin D in the serum was low. In this context, we concluded of neuromuscular irritability secondary to hypocalcaemia. The symptoms disappeared after a treatment of intravenous calcium. This case shows how important it is to investigate electrolytes in case of neuromuscular irritability symptoms in elderly people.

Impact of international consensus guidelines on antiviral therapy of chronic hepatitis C patients in Switzerland.

To assess the impact of international consensus conference guidelines on the attitude of Swiss specialists when facing the decision to treat chronic hepatitis C patients. Questionnaires focusing on the personal situation and treatment decisions were mailed to 165 patients who were newly diagnosed with hepatitis C virus (HCV) infection and enrolled into the Swiss Hepatitis C Cohort Study during the years 2002-2004. Survey respondents (n = 86, 52.1%) were comparable to non-respondents with respect to severity of liver disease, history of substance abuse and psychiatric co-morbidities. Seventy percent of survey respondents reported having been offered antiviral treatment. Patients deferred from treatment had less advanced liver fibrosis, were more frequently infected with HCV genotypes 1 or 4 and presented more often with a history of depression. There were no differences regarding age, socio-economic background, alcohol abuse, intravenous drug abuse or methadone treatment when compared with patients to whom treatment was proposed. Ninety percent of eligible patients agreed to undergo treatment. Overall, 54.6% of respondents and 78.3% of those considered eligible had actually received antiviral therapy by 2007. Ninety-five percent of patients reported high satisfaction with their own hepatitis C management. Consistent with latest international consensus guidelines, patients enrolled in the Swiss Hepatitis C Cohort with a history of substance abuse were not withheld antiviral treatment. A multidisciplinary approach is warranted to provide antiviral treatment to patients suffering from depression.

Swiss consensus statement: Recommendations for optimising re-treatment with MabThera (rituximab) in rheumatoid arthritis.

Rituximab is an effective treatment of rheumatoid arthritis (RA), which has been approved for the treatment of moderate to severe disease in patients with an inadequate response to anti-TNF therapies. Rituximab differs from other available biological agents for RA by way of its unique mode of action and unrivalled long dosing interval. The efficacy of rituximab subsides progressively over time and re-therapy is generally required to maintain long term disease control. The timing of re-treatment is currently not well established and varies widely in clinical practice. The present document is a concise recommendation regarding re-treatment with rituximab, based on validated outcomes such as the DAS28 and the EULAR response criteria. The recommendation was established through consensus between practitioners familiar with rituximab therapy in RA. Optimisation of the rituximab re-treatment schedule may improve patient outcomes and balance risks and benefits for the individual patient.

Correcting Interdevice Bias of Horizontal White-to-White and Sulcus-to-Sulcus Measures Used for Implantable Collamer Lens Sizing.

PURPOSE: To assess the agreement and repeatability of horizontal white-to-white (WTW) and horizontal sulcus-to-sulcus (STS) diameter measurements and use these data in combination with available literature to correct for interdevice bias in preoperative implantable collamer lens (ICL) size selection. DESIGN: Interinstrument reliability and bias assessment study. METHODS: A total of 107 eyes from 56 patients assessed for ICL implantation at our institution were included in the study. This was a consecutive series of all patients with suitable available data. The agreement and bias between WTW (measured with the Pentacam and BioGraph devices) and STS (measured with the HiScan device) were estimated. RESULTS: The mean spherical equivalent was -8.93 ± 5.69 diopters. The BioGraph measures of WTW were wider than those taken with the Pentacam (bias = 0.26 mm, P < .01), and both horizontal WTW measures were wider than the horizontal STS measures (bias >0.91 mm, P < .01). The repeatability (Sr) of STS measured with the HiScan was 0.39 mm, which was significantly reduced (Sr = 0.15 mm) when the average of 2 measures was used. Agreement between the horizontal WTW measures and horizontal STS estimates when bias was accounted for was г = 0.54 with the Pentacam and г = 0.64 with the BioGraph. CONCLUSIONS: Large interdevice bias was observed for WTW and STS measures. STS measures demonstrated poor repeatability, but the average of repeated measures significantly improved repeatability. In order to conform to the US Food and Drug Administration's accepted guidelines for ICL sizing, clinicians should be aware of and account for the inconsistencies between devices.

Investigation of the role of the nucleus accumbens in amphetamine-induced 50 kHz ultrasonic vocalizations in the rat

There is extensive evidence that the mesolimbic dopamine system underlies the production of 50 kHz ultrasonic vocalizations in rats. In particular, the shell of the nucleus accumbens is associated with generation of frequency modulated 50 kHz calls (a specific type of 50 kHz call which can be subdivided into various subtypes). There is also evidence that amphetamine administered systemically preferentially increases the proportion of trill and step calls compared to other frequency modulated 50 kHz subtypes. The purpose of this study was to investigate the effect of drug administration route and the role of the nucleus accumbens shell in amphetamine-induced 50 kHz call profile in the rat. Three experiments investigated this by using subcutaneous and intra-accumbens microinjections of amphetamine, as well as procaine (a local anesthetic) blockade of the nucleus accumbens. Ultrasonic vocalizations were recorded digitally from 24 rats and were analysed for sonographic structure based on general call parameters. The results of the three experiments were partially supportive of the hypotheses. Systemic amphetamine was found to induce greater bandwidth in 50 kHz calling compared to spontaneous calls in a vehicle condition. Systemic amphetamine was also found to preferentially increase the proportion of trill and step subtypes compared to vehicle. Moreover, there was no difference in the proportions of 50 kHz subtypes resulting from intracerebral or systemic application of amphetamine. There was, however, a significant difference for bandwidth, with systemic amphetamine inducing greater bandwidth over intraaccumbens application. Procaine blockade of the nucleus accumbens shell paired with subcutaneous amphetamine produced no difference in bandwidth of calls compared with those after a vehicle pre-treatment similarly paired. There was no reduction in the proportions of trill and step 50 kHz subtypes as well, with the procaine condition showing significantly greater proportion of step calls. The results of the study support a role for the iii nucleus accumbens shell in the amphetamine-induced changes on 50 kHz call profile. They also indicate there are more regions and pathways involved in generating 50 kHz calls than the projections from the ventral tegmental area to the nucleus accumbens. The implications of this work are that frequency modulated 50 kHz subtypes may be generated by distinct neurophysiological mechanisms and may represent a profitable avenue for investigating different circuits of 50 kHz call categories in the rat.