Hepatitis B and C in Switzerland - healthcare provider initiated testing for chronic hepatitis B and C infection

Hepatitis B and hepatitis C are contagious liver diseases caused by the hepatitis B virus (HBV) and the hepatitis C virus (HCV), respectively. In particular, chronic infection with HBV or HCV is a major public health problem throughout Europe. The majority of persons chronically infected (65%-75%) are not aware of their infection status until symptoms of advanced liver disease appear. In addition, the peak in the number of patients suffering from advanced stages of the disease, such as cirrhosis and hepatocellular carcinoma, has not yet been reached. In order to reduce the current and future morbidity and mortality associated with chronic HBV or HCV infection, the timely detection of chronically infected persons, with follow-up and case management, is crucial. However, the current screening strategies in Europe and Switzerland have to be considered as inadequate to detect the majority of chronically infected persons. Hence, we emphasise the importance of an alternative approach: the healthcare provider initiated identification of HBV or HCV infection in defined risk groups. This entails determining whether a person is not only at risk of being chronically infected, but also at risk of becoming infected with HBV or HCV and, if necessary, testing for HBV or HCV infection.

Outpatient Parenteral Antimicrobial Therapy Practices among Adult Infectious Disease Physicians

Objective. To identify current outpatient parenteral antibiotic therapy practice patterns and complications. Methods. We administered an 11-question survey to adult infectious disease physicians participating in the Emerging Infections Network (EIN), a Centers for Disease Control and Prevention-sponsored sentinel event surveillance network in North America. The survey was distributed electronically or via facsimile in November and December 2012. Respondent demographic characteristics were obtained from EIN enrollment data. Results. Overall, 555 (44.6%) of EIN members responded to the survey, with 450 (81%) indicating that they treated 1 or more patients with outpatient parenteral antimicrobial therapy (OPAT) during an average month. Infectious diseases consultation was reported to be required for a patient to be discharged with OPAT by 99 respondents (22%). Inpatient (282 [63%] of 449) and outpatient (232 [52%] of 449) infectious diseases physicians were frequently identified as being responsible for monitoring laboratory results. Only 26% (118 of 448) had dedicated OPAT teams at their clinical site. Few infectious diseases physicians have systems to track errors, adverse events, or "near misses" associated with OPAT (97 [22%] of 449). OPAT-associated complications were perceived to be rare. Among respondents, 80% reported line occlusion or clotting as the most common complication (occurring in 6% of patients or more), followed by nephrotoxicity and rash (each reported by 61%). Weekly laboratory monitoring of patients who received vancomycin was reported by 77% of respondents (343 of 445), whereas 19% of respondents (84 of 445) reported twice weekly laboratory monitoring for these patients. Conclusions. Although use of OPAT is common, there is significant variation in practice patterns. More uniform OPAT practices may enhance patient safety.

Psychosocial aspects on the treatment of HIV-infection

Psychological and social factors have a deep impact on the treatment of HIV-infection, from the readiness to start antiretroviral therapy to treatment adherence over time. Among psychological factors, anxiety may affect HIV-infected persons in all stages of disease, from the disclosure of HIV diagnosis to the decision to start and maintain treatment. This is a lifelong challenge for both patients and doctors. Psychiatric comorbidities (depression, addiction) may enhance negative psychological effects of HIV. Among social factors, stigma and discrimination may occur in families and at work, leading to a loss of social support resulting in isolation and poverty. This may prevent HIV-positive individuals from seeking medical care. These aspects are particularly important in some groups of patients as injecting drug users and migrants. Acknowledgment and consideration of psychosocial factors are therefore essential for the long term success of antiretroviral therapy.

[Collagenase injection in Dupuytren's disease, evaluation of the ultrasound assisted technique].

Since October 2011, the enzymatic lysis of Dupuytren's cord was introduced in Switzerland (Xiapex(®), Auxilium Pharmaceuticals, Pfizer). Here we present our first university experience and underline the major role of ultrasound during the injection. Between December 2011 and February 2013, 52 injections were performed to eliminate 43 Dupuytren's cords in 33 patients. The mean age of the patients was 64.4 ± 8.5 years. Complications were documented for each patient. Before, directly after and after a minimum of 6 months post-injection, the contracture of the treated joint was measured with use of a goniometer. The DASH score was evaluated after a minimum of 6 months and the patients were asked to subjectively evaluate the outcome of the treatment (very good, good, mild, poor) and whether they would reiterate it if necessary. Four skin defects, one lymphangitis, and one CRPS were responsible for a complication rate of 18%. There was no infection and no tendon rupture in the series. The mean MCP joint contracture was respectively 36.8 ± 27.4°, 3.5 ± 7.8° (gain of mobility compared to the preoperative situation 33.3°, P<0.001), and 8.4 ± 13.9° (gain 28.4°, P<0.001) respectively before, just after and at the long-term clinical control. The mean PIP joint contracture was respectively 36.5 ± 29.1°, 5.9 ± 6.7° (gain 30.6°, P<0.001), and 15.1 ± 13.8° (gain 21.4°, P<0.001) respectively before injection, just after and at the long-term clinical control. The DASH score decreased from 24 ± 14 to 7 ± 9 (P<0.001). Eighty-one per cent of the patients were satisfied or very satisfied of the treatment. All but two would reiterate the treatment if necessary. Ultrasound is able to target the injection of collagenase in order to reduce complications. The short-term results of this non-invasive therapy are very promising however comparison with conventional procedures is difficult as the long-term results are lacking.

Fractional Flow Reserve–Guided PCI for Stable Coronary Artery Disease

Background We hypothesized that in patients with stable coronary artery disease and stenosis, percutaneous coronary intervention (PCI) performed on the basis of the fractional flow reserve (FFR) would be superior to medical therapy. Methods In 1220 patients with stable coronary artery disease, we assessed the FFR in all stenoses that were visible on angiography. Patients who had at least one stenosis with an FFR of 0.80 or less were randomly assigned to undergo FFR-guided PCI plus medical therapy or to receive medical therapy alone. Patients in whom all stenoses had an FFR of more than 0.80 received medical therapy alone and were included in a registry. The primary end point was a composite of death from any cause, nonfatal myocardial infarction, or urgent revascularization within 2 years. Results The rate of the primary end point was significantly lower in the PCI group than in the medical-therapy group (8.1% vs. 19.5%; hazard ratio, 0.39; 95% confidence interval [CI], 0.26 to 0.57; P<0.001). This reduction was driven by a lower rate of urgent revascularization in the PCI group (4.0% vs. 16.3%; hazard ratio, 0.23; 95% CI, 0.14 to 0.38; P<0.001), with no significant between-group differences in the rates of death and myocardial infarction. Urgent revascularizations that were triggered by myocardial infarction or ischemic changes on electrocardiography were less frequent in the PCI group (3.4% vs. 7.0%, P=0.01). In a landmark analysis, the rate of death or myocardial infection from 8 days to 2 years was lower in the PCI group than in the medical-therapy group (4.6% vs. 8.0%, P=0.04). Among registry patients, the rate of the primary end point was 9.0% at 2 years. Conclusions In patients with stable coronary artery disease, FFR-guided PCI, as compared with medical therapy alone, improved the outcome. Patients without ischemia had a favorable outcome with medical therapy alone. (Funded by St. Jude Medical; FAME 2 ClinicalTrials.gov number, NCT01132495 .).

Detection and quantification of leptospires in urine of dogs: a maintenance host for the zoonotic disease leptospirosis.

Leptospirosis is a global zoonotic disease. Pathogenic Leptospira species, the causative agent of leptospirosis, colonize the renal tubules of chronically infected maintenance hosts such as dogs, rats and cattle. Maintenance hosts typically remain clinically asymptomatic and shed leptospires into the environment via urine. In contrast, accidental hosts such as humans can suffer severe acute forms of the disease. Infection results from direct contact with infected urine or indirectly, through contaminated water sources. In this study, a quantitative real-time PCR specific for lipL32 was designed to detect the urinary shedding of leptospires from dogs. The sensitivity and specificity of the assay was evaluated using both a panel of pathogenic Leptospira species and clinical microbial isolates, and samples of urine collected from experimentally infected rats and non-infected controls. The lower limit of detection was approximately 3 genome equivalents per reaction. The assay was applied to canine urine samples collected from local dog sanctuaries and the University Veterinary Hospital (UVH) at University College Dublin. Of 525 canine urine samples assayed, 37 were positive, indicating a prevalence of urinary shedding of leptospires of 7.05%. These results highlight the need to provide effective canine vaccination strategies and raise public health awareness.

Influence of IFNL3/4 polymorphisms on the incidence of cytomegalovirus infection after solid-organ transplantation

BACKGROUND  Polymorphisms in the interferon-λ (IFNL) 3/4 region have been associated with reduced hepatitis C virus clearance. We explored the role of such polymorphisms on the incidence of CMV infection in solid-organ transplant (SOT) recipients. METHODS  Caucasian patients participating in the Swiss Transplant Cohort Study in 2008-2011 were included. A novel functional TT/-G polymorphism (rs368234815) in the CpG region upstream of IFNL3 was investigated. RESULTS  A total of 840 SOT recipients at risk for CMV were included, among whom 373 (44%) received antiviral prophylaxis. The 12-months cumulative incidence of CMV replication and disease were 0.44 and 0.08, respectively. Patient homozygous for the minor rs368234815 allele (-G/-G) tended to have a higher cumulative incidence of CMV replication (SHR=1.30 [95%CI 0.97-1.74], P=0.07) compared to other patients (TT/TT or TT/-G). The association was significant among patients followed by a preemptive approach (SHR=1.46 [1.01-2.12], P=0.047), especially in patients receiving an organ from a seropositive donor (D+, SHR=1.92 [95%CI 1.30-2.85], P=0.001), but not among those who received antiviral prophylaxis (SHR=1.13 [95%CI 0.70-1.83], P=0.6). These associations remained significant in multivariate competing risk regression models. CONCLUSIONS  Polymorphisms in the IFNL3/4 region influence susceptibility to CMV replication in SOT recipients, particularly in patients not receiving antiviral prophylaxis.

Reactivated Moraxella osteitis presenting as granulomatous disease.

Granulomatous infections are commonly associated with mycobacteria, brucellosis, actinomycosis, nocardiosis, spirochetes, and fungi. Rarely, granuloma formation is a host response to other bacterial infection. Osteomyelitis and osteitis that reactivate many years after the primary episode is a known phenomenon. A reactivation that presents as a granulomatous disease is rare. We present a case of reactivated osteitis due to Moraxella osloensis with consecutive granuloma formation.

Observed management practices in relation to the risk of infection with paratuberculosis and to the spread of Mycobacterium avium subsp. paratuberculosis in Swiss dairy and beef herds

Abstract BACKGROUND: Many studies have been conducted to define risk factors for the transmission of bovine paratuberculosis, mostly in countries with large herds. Little is known about the epidemiology in infected Swiss herds and risk factors important for transmission in smaller herds. Therefore, the presence of known factors which might favor the spread of paratuberculosis and could be related to the prevalence at animal level of fecal shedding of Mycobacterium avium subsp. paratuberculosis were assessed in 17 infected herds (10 dairy, 7 beef). Additionally, the level of knowledge of herd managers about the disease was assessed. In a case-control study with 4 matched negative control herds per infected herd, the association of potential risk factors with the infection status of the herd was investigated. RESULTS: Exposure of the young stock to feces of older animals was frequently observed in infected and in control herds. The farmers' knowledge about paratuberculosis was very limited, even in infected herds. An overall prevalence at animal level of fecal shedding of Mycobacterium avium subsp. paratuberculosis of 6.1% was found in infected herds, whereby shedders younger than 2 years of age were found in 46.2% of the herds where the young stock was available for testing. Several factors related to contamination of the heifer area with cows' feces and the management of the calving area were found to be significantly associated with the within-herd prevalence. Animal purchase was associated with a positive herd infection status (OR = 7.25, p = 0.004). CONCLUSIONS: Numerous risk factors favoring the spread of Mycobacterium avium subsp. paratuberculosis from adult animals to the young stock were observed in infected Swiss dairy and beef herds, which may be amenable to improvement in order to control the disease. Important factors were contamination of the heifer and the calving area, which were associated with higher within-herd prevalence of fecal shedding. The awareness of farmers of paratuberculosis was very low, even in infected herds. Animal purchase in a herd was significantly associated with the probability of a herd to be infected and is thus the most important factor for the control of the spread of disease between farms.

The role of adipokines in periodontal infection and healing.

Periodontitis is a chronic inflammatory disease of the periodontium, which is caused by pathogenic bacteria in combination with other risk factors. The bacteria induce an immunoinflammatory host response, which can lead to irreversible matrix degradation and bone resorption. Periodontitis can be successfully treated. To achieve regenerative periodontal healing, bioactive molecules, such as enamel matrix derivative (EMD), are applied during periodontal surgery. Recently, it has been shown that obesity is associated with periodontitis and compromised healing after periodontal therapy. The mechanisms underlying these associations are not well understood so far, but adipokines may be a pathomechanistic link. Adipokines are bioactive molecules that are secreted by the adipose tissue, and that regulate insulin sensitivity and energy expenditure, but also inflammatory and healing processes. It has also been demonstrated that visfatin and leptin increase the synthesis of proinflammatory and proteolytic molecules, whereas adiponectin downregulates the production of such mediators in periodontal cells. In addition, visfatin and leptin counteract the beneficial effects of EMD, whereas adiponectin enhances the actions of EMD on periodontal cells. Since visfatin and leptin levels are increased and adiponectin levels are reduced in obesity, these adipokines could be a pathomechanistic link whereby obesity and obesity-related diseases enhance the risk for periodontitis and compromised periodontal healing. Recent studies have also revealed that adipokines, such as visfatin, leptin and adiponectin, are produced in periodontal cells and regulated by periodontopathogenic bacteria. Therefore, adipokines may also represent a mechanism whereby periodontal infections can impact on systemic diseases.

A review on bovine besnoitiosis: a disease with economic impact in herd health management, caused by Besnoitia besnoiti (Franco and Borges, 1916).

Bovine besnoitiosis is caused by the largely unexplored apicomplexan parasite Besnoitia besnoiti. In cows, infection during pregnancy often results in abortion, and chronically infected bulls become infertile. Similar to other apicomplexans B. besnoiti has acquired a largely intracellular lifestyle, but its complete life cycle is still unknown, modes of transmission have not been entirely resolved and the definitive host has not been identified. Outbreaks of bovine besnoitiosis in cattle were described in the 1990s in Portugal and Spain, and later several cases were also detected in France. More cases have been reported recently in hitherto unaffected countries, including Italy, Germany, Switzerland, Hungary and Croatia. To date, there is still no effective pharmaceutical compound available for the treatment of besnoitiosis in cattle, and progress in the identification of novel targets for intervention through pharmacological or immunological means is hampered by the lack of molecular data on the genomic and transcriptomic level. In addition, the lack of an appropriate small animal laboratory model, and wide gaps in our knowledge on the host-parasite interplay during the life cycle of this parasite, renders vaccine and drug development a cost- and labour-intensive undertaking.

Use of early corticosteroid therapy on ICU admission in patients affected by severe pandemic (H1N1)v influenza A infection.

INTRODUCTION Early use of corticosteroids in patients affected by pandemic (H1N1)v influenza A infection, although relatively common, remains controversial. METHODS Prospective, observational, multicenter study from 23 June 2009 through 11 February 2010, reported in the European Society of Intensive Care Medicine (ESICM) H1N1 registry. RESULTS Two hundred twenty patients admitted to an intensive care unit (ICU) with completed outcome data were analyzed. Invasive mechanical ventilation was used in 155 (70.5%). Sixty-seven (30.5%) of the patients died in ICU and 75 (34.1%) whilst in hospital. One hundred twenty-six (57.3%) patients received corticosteroid therapy on admission to ICU. Patients who received corticosteroids were significantly older and were more likely to have coexisting asthma, chronic obstructive pulmonary disease (COPD), and chronic steroid use. These patients receiving corticosteroids had increased likelihood of developing hospital-acquired pneumonia (HAP) [26.2% versus 13.8%, p < 0.05; odds ratio (OR) 2.2, confidence interval (CI) 1.1-4.5]. Patients who received corticosteroids had significantly higher ICU mortality than patients who did not (46.0% versus 18.1%, p < 0.01; OR 3.8, CI 2.1-7.2). Cox regression analysis adjusted for severity and potential confounding factors identified that early use of corticosteroids was not significantly associated with mortality [hazard ratio (HR) 1.3, 95% CI 0.7-2.4, p = 0.4] but was still associated with an increased rate of HAP (OR 2.2, 95% CI 1.0-4.8, p < 0.05). When only patients developing acute respiratory distress syndrome (ARDS) were analyzed, similar results were observed. CONCLUSIONS Early use of corticosteroids in patients affected by pandemic (H1N1)v influenza A infection did not result in better outcomes and was associated with increased risk of superinfections.

Kidney disease in antiretroviral-naïve HIV-positive adults with high CD4 counts: prevalence and predictors of kidney disease at enrolment in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial.

OBJECTIVES HIV infection has been associated with an increased risk of chronic kidney disease (CKD). Little is known about the prevalence of CKD in individuals with high CD4 cell counts prior to initiation of antiretroviral therapy (ART). We sought to address this knowledge gap. METHODS We describe the prevalence of CKD among 4637 ART-naïve adults (mean age 36.8 years) with CD4 cell counts > 500 cells/μL at enrolment in the Strategic Timing of AntiRetroviral Treatment (START) study. CKD was defined by estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m(2) and/or dipstick urine protein ≥ 1+. Logistic regression was used to identify baseline characteristics associated with CKD. RESULTS Among 286 [6.2%; 95% confidence interval (CI) 5.5%, 6.9%] participants with CKD, the majority had isolated proteinuria. A total of 268 participants had urine protein ≥ 1+, including 41 with urine protein ≥ 2+. Only 22 participants (0.5%) had an estimated glomerular filtration rate < 60 mL/min/1.73 m(2) , including four who also had proteinuria. Baseline characteristics independently associated with CKD included diabetes [adjusted odds ratio (aOR) 1.73; 95% CI 1.05, 2.85], hypertension (aOR 1.82; 95% CI 1.38, 2.38), and race/ethnicity (aOR 0.59; 95% CI 0.37, 0.93 for Hispanic vs. white). CONCLUSIONS We observed a low prevalence of CKD associated with traditional CKD risk factors among ART-naïve clinical trial participants with CD4 cell counts > 500 cells/μL.

The impact of smoking on HPV infection and the development of anogenital warts

PURPOSE: The worldwide prevalence of human papillomavirus (HPV) infection is estimated at 9-13 %. Persistent infection can lead to the development of malignant and nonmalignant diseases. Low-risk HPV types are mostly associated with benign lesions such as anogenital warts. In the present systematic review, we examined the impact of smoking on HPV infection and the development of anogenital warts, respectively. METHODS: A systematic literature search was performed using MEDLINE database for peer-reviewed articles published from January 01, 1985 to November 30, 2013. Pooled rates of HPV prevalence were compared using the χ (2) test. RESULTS: In both genders, smoking is associated with higher incidence and prevalence rates for HPV infection, whereas the latter responds to a dose-effect relationship. The overall HPV prevalence for smoking patients was 48.2 versus 37. 5 % for nonsmoking patients (p < 0.001) (odds ratio (OR) = 1.5, 95 % confidence interval (CI) 1.4-1.7). Smoking does also increase persistence rates for high-risk HPV infection, while this correlation is debatable for low-risk HPV. The incidence and recurrence rates of anogenital warts are significantly increased in smokers. CONCLUSIONS: Most current data demonstrate an association between smoking, increased anogenital HPV infection, and development of anogenital warts. These data add to the long list of reasons for making smoking cessation a keystone of patient health.

A common polymorphism in the NCAN gene is associated with hepatocellular carcinoma in alcoholic liver disease

BACKGROUND & AIMS: The genetic background of alcoholic liver diseases and their complications are increasingly recognized. A common polymorphism in the neurocan (NCAN) gene, which is known to be expressed in neuronal tissue, has been identified as a risk factor for non-alcoholic fatty liver disease (NAFLD). We investigated if this polymorphism may also be related to alcoholic liver disease (ALD) and hepatocellular carcinoma (HCC). METHODS: We analysed the distribution of the NCAN rs2228603 genotypes in 356 patients with alcoholic liver cirrhosis, 126 patients with alcoholic HCC, 382 persons with alcohol abuse without liver damage, 362 healthy controls and in 171 patients with hepatitis C virus (HCV) associated HCC. Furthermore, a validation cohort of 229 patients with alcoholic cirrhosis (83 with HCC) was analysed. The genotypes were determined by LightSNiP assays. The expression of NCAN was studied by RT-PCR and immunofluorescence microscopy. RESULTS: The frequency of the NCAN rs2228603 T allele was significantly increased in patients with HCC due to ALD (15.1%) compared to alcoholic cirrhosis without HCC (9.3%), alcoholic controls (7.2%), healthy controls (7.9%), and HCV associated HCC (9.1%). This finding was confirmed in the validation cohort (15.7% vs. 6.8%, OR=2.53; 95%CI: 1.36-4.68; p=0.0025) and by multivariate analysis (OR=1.840; 95%CI: 1.22-2.78; p=0.004 for carriage of the rs2228603 T allele). In addition, we identified and localised NCAN expression in human liver. CONCLUSIONS: NCAN is not only expressed in neuronal tissue, but also in the liver. Its rs2228603 polymorphism is a risk factor for HCC in ALD, but not in HCV infection.