[Complications of intravesical BCG therapy].

INTRODUCTION: BCG instillations are considered to be the standard of care therapy for superficial urothelial bladder carcinoma. Although serious adverse events are uncommon, the presence of high fever for at least two days in conjunction with systemic and/or local organ manifestations (except for urogenital symptoms), with the exclusion of other causes, suffice for the diagnosis of a disseminated BCG infection. Microbiologic detection of the pathogen is not necessary for diagnosis, as the detection of granuloma is more often successful and sufficient. Therapy for this infection includes oral Isoniazid, Rifampicin and Ethambutol for six months.

Enoxaparin for outpatients with COVID-19: 90-day results from the randomised, open-label, parallel-group, multinational, phase III OVID trial.

INTRODUCTION: The benefits of early thromboprophylaxis in symptomatic COVID-19 outpatients remain unclear. We present the 90-day results from the randomised, open-label, parallel-group, investigator-initiated, multinational OVID phase III trial. METHODS: Outpatients aged 50 years or older with acute symptomatic COVID-19 were randomised to receive enoxaparin 40 mg for 14 days once daily vs. standard of care (no thromboprophylaxis). The primary outcome was the composite of untoward hospitalisation and all-cause death within 30 days from randomisation. Secondary outcomes included arterial and venous major cardiovascular events, as well as the primary outcome within 90 days from randomisation. The study was prematurely terminated based on statistical criteria after the predefined interim analysis of 30-day data, which has been previously published. In the present analysis, we present the final, 90-day data from OVID and we additionally investigate the impact of thromboprophylaxis on the resolution of symptoms. RESULTS: Of the 472 patients included in the intention-to-treat population, 234 were randomised to receive enoxaparin and 238 no thromboprophylaxis. The median age was 57 (Q1-Q3: 53-62) years and 217 (46 %) were women. The 90-day primary outcome occurred in 11 (4.7 %) patients of the enoxaparin arm and in 11 (4.6 %) controls (adjusted relative risk 1.00; 95 % CI: 0.44-2.25): 3 events per group occurred after day 30. The 90-day incidence of cardiovascular events was 0.9 % in the enoxaparin arm vs. 1.7 % in controls (relative risk 0.51; 95 % CI: 0.09-2.75). Individual symptoms improved progressively within 90 days with no difference between groups. At 90 days, 42 (17.9 %) patients in the enoxaparin arm and 40 (16.8 %) controls had persistent respiratory symptoms. CONCLUSIONS: In adult community patients with COVID-19, early thromboprophylaxis with enoxaparin did not improve the course of COVID-19 neither in terms of hospitalisation and death nor considering COVID-19-related symptoms.

Low secondary attack rate after prolonged exposure to sputum smear positive miliary tuberculosis in a neonatal unit.

BACKGROUND: Several neonatal intensive care units (NICU) have reported exposure to sputum smear positive tuberculosis (TB). NICE guidelines give support regarding investigation and treatment intervention, but not for contact definitions. Data regarding the reliability of any interferon gamma release assay (IGRA) in infants as a screening test for TB infection is scarce. We report an investigation and management strategy and evaluated the viability of IGRA (T-Spot) in infants and its concordance to the tuberculin skin test (TST). METHODS: We performed an outbreak investigation of incident TB infection in a NICU after prolonged exposure to sputum smear positive miliary TB by an infant's mother. We defined individual contact definitions and interventions and assessed secondary attack rates. In addition, we evaluated the technical performance of T-Spot in infants and compared the results with the TST at baseline investigation. RESULTS: Overall, 72 of 90 (80%) exposed infants were investigated at baseline, in 51 (56.7%) of 54 (60%) infants, follow-up TST at the age of 6 months was performed. No infant in our cohort showed a positive TST or T-Spot at baseline. All blood samples from infants except one responded to phytohemagglutinin (PHA), which was used as a positive control of the T-Spot, demonstrating that cells are viable and react upon stimulation. 149 of 160 (93.1%) exposed health care workers (HCW) were investigated. 1 HCW was tested positive, having no other reason than this exposure for latent TB infection. 5 of 92 (5.5%) exposed primary contacts were tested positive, all coming from countries with high TB incidences. In total, 1 of 342 exposed contacts was newly diagnosed with latent TB infection. The secondary attack rate in this study including pediatric and adult contacts was 0.29%. CONCLUSION: This investigation highlighted the low transmission rate of sputum smear positive miliary TB in a particularly highly susceptible population as infants. Our expert definitions and interventions proved to be helpful in terms of the feasibility of a thorough outbreak investigation. Furthermore, we demonstrated concordance of T-Spot and TST. Based on our findings, we assume that T-Spot could be considered a reliable investigation tool to rule out TB infection in infants.

Nosocomial COVID-19 Incidence and Secondary Attack Rates among Patients of Tertiary Care Center, Zurich, Switzerland.

Of 1,118 patients with COVID-19 at a university hospital in Switzerland during October 2020-June 2021, we found 83 (7.4%) had probable or definite healthcare-associated COVID-19. After in-hospital exposure, we estimated secondary attack rate at 23.3%. Transmission was associated with longer contact times and with lower cycle threshold values among index patients.

Identifying Contact Risks for SARS-CoV-2 Transmission to Healthcare Workers during Outbreak on COVID-19 Ward.

We assessed the risk for different exposures to SARS-CoV-2 during a COVID-19 outbreak among healthcare workers on a hospital ward in late 2020. We found working with isolated COVID-19 patients did not increase the risk of COVID-19 among workers, but working shifts with presymptomatic healthcare coworkers did.

Multifactorial seroprofiling dissects the contribution of pre-existing human coronaviruses responses to SARS-CoV-2 immunity.

Determination of SARS-CoV-2 antibody responses in the context of pre-existing immunity to circulating human coronavirus (HCoV) is critical for understanding protective immunity. Here we perform a multifactorial analysis of SARS-CoV-2 and HCoV antibody responses in pre-pandemic (N = 825) and SARS-CoV-2-infected donors (N = 389) using a custom-designed multiplex ABCORA assay. ABCORA seroprofiling, when combined with computational modeling, enables accurate definition of SARS-CoV-2 seroconversion and prediction of neutralization activity, and reveals intriguing interrelations with HCoV immunity. Specifically, higher HCoV antibody levels in SARS-CoV-2-negative donors suggest that pre-existing HCoV immunity may provide protection against SARS-CoV-2 acquisition. In those infected, higher HCoV activity is associated with elevated SARS-CoV-2 responses, indicating cross-stimulation. Most importantly, HCoV immunity may impact disease severity, as patients with high HCoV reactivity are less likely to require hospitalization. Collectively, our results suggest that HCoV immunity may promote rapid development of SARS-CoV-2-specific immunity, thereby underscoring the importance of exploring cross-protective responses for comprehensive coronavirus prevention.

Data linkage to evaluate the long-term risk of HIV infection in individuals seeking post-exposure prophylaxis.

Evidence on the long-term risk of HIV infection in individuals taking HIV post-exposure prophylaxis remains limited. In this retrospective data linkage study, we evaluate the occurrence of HIV infection in 975 individuals who sought post-exposure prophylaxis in a tertiary hospital between 2007 and 2013. Using privacy preserving probabilistic linkage, we link these 975 records with two observational databases providing data on HIV events (Zurich Primary HIV Infection study and the Swiss HIV Cohort Study). This enables us to identify 22 HIV infections and to obtain long-term follow-up data, which reveal a median of 4.1 years between consultation for post-exposure prophylaxis and HIV diagnosis. Even though men who have sex with men constitute only 35.8% of those seeking post-exposure prophylaxis, all 22 events occur in this subgroup. These findings should strongly encourage early consideration of pre-exposure prophylaxis in men who have sex with men after a first episode of post-exposure prophylaxis.

Determinants for voluntary participation in staff screening during an methicillin-resistant Staphylococcus aureus (MRSA) outbreak on a neonatal ward.

We investigated healthcare worker (HCW) behavior with regard to a voluntary methicillin-resistant Staphylococcus aureus (MRSA) staff screening during a MRSA outbreak in a neonatal ward. Avoiding MRSA transmission from HCWs to patients was the most important reason for participation. Inconvenient screening time was the most frequently cited reason for nonparticipation.

Systemic and mucosal antibody responses specific to SARS-CoV-2 during mild versus severe COVID-19.

BACKGROUND: Whereas severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibody tests are increasingly being used to estimate the prevalence of SARS-CoV-2 infection, the determinants of these antibody responses remain unclear. OBJECTIVES: Our aim was to evaluate systemic and mucosal antibody responses toward SARS-CoV-2 in mild versus severe coronavirus disease 2019 (COVID-19) cases. METHODS: Using immunoassays specific for SARS-CoV-2 spike proteins, we determined SARS-CoV-2-specific IgA and IgG in sera and mucosal fluids of 2 cohorts, including SARS-CoV-2 PCR-positive patients (n = 64) and PCR-positive and PCR-negtive health care workers (n = 109). RESULTS: SARS-CoV-2-specific serum IgA titers in patients with mild COVID-19 were often transiently positive, whereas serum IgG titers remained negative or became positive 12 to 14 days after symptom onset. Conversely, patients with severe COVID-19 showed a highly significant increase of SARS-CoV-2-specific serum IgA and IgG titers after symptom onset. Very high titers of SARS-CoV-2-specific serum IgA were correlated with severe acute respiratory distress syndrome. Interestingly, some health care workers with negative SARS-CoV-2-specific serum antibody titers showed SARS-CoV-2-specific IgA in mucosal fluids with virus-neutralizing capacity in some cases. SARS-CoV-2-specific IgA titers in nasal fluids were inversely correlated with age. CONCLUSIONS: Systemic antibody production against SARS-CoV-2 develops mainly in patients with severe COVID-19, with very high IgA titers seen in patients with severe acute respiratory distress syndrome, whereas mild disease may be associated with transient production of SARS-CoV-2-specific antibodies but may stimulate mucosal SARS-CoV-2-specific IgA secretion.

Does respiratory co-infection facilitate dispersal of SARS-CoV-2? investigation of a super-spreading event in an open-space office.

BACKGROUND: Super-spreaders are individuals infecting disproportionately large numbers of contacts. They probably play a crucial role in the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We describe a super-spreading event within a team working in an open-space office and investigate factors potentially having facilitated SARS-CoV-2 transmission. METHODS: In this retrospective cohort study, semi-structured telephone interviews with all team members were carried out to identify symptoms, contacts, and adherence to basic hygiene measures. During site visits, we gathered information about workplace and seating arrangements. The secondary attack rate in office and households was calculated. Potential respiratory viral co-infections were assessed by multiplex PCR. SARS-CoV-2 whole-genome sequencing was performed using a tiled-amplicon sequencing approach. RESULTS: Of 13 team members, 11 fell ill with Coronavirus disease 2019 (COVID-19). Due to the sequence of events and full genome sequence data, one person was considered the index case for this outbreak, directly infecting 67 to 83% of the teammates. All team members reported repetitive close contacts among themselves during joint computer work, team meetings and a "Happy Birthday" serenade. Two individuals shared nuts and dates. The arrangement of the office and meeting rooms precluded sufficient adherence to physical distancing. The index case and a further individual were diagnosed with an adenovirus serotype 4 co-infection. CONCLUSION: We identified several environmental and behavioral factors that probably have facilitated the transmission of SARS-CoV-2. The relevance of the adenovirus co-infection remains unclear and merits further investigation.

[CME-Answers: CME: Chronic Generalized Pruritus without Dermatological Cause]. / CME-Antworten: Chronisch generalisierter Pruritus nicht-dermatologischer Ursache.

CME-Answers: CME: Chronic Generalized Pruritus without Dermatological Cause Abstract. Chronic generalized pruritus is a common symptom. Dermatological causes must be distinguished from non-dermatological causes. Non-dermatological chronic pruritus has many causes, such as systemic, infectious, neurological, psychogenic disorders, and drug-related side effects, some of which may be associated with significant morbidity. The possibility of systemic disease should be considered in patients with generalized pruritus and no signs of primary skin lesions. In addition to a careful history and physical examination, selected laboratory examinations can be helpful in making a diagnosis. Pruritus can be the first sign of malignant hematological disease. Pruritus associated with solid tumors is not that rare. This article offers an approach to chronic generalized pruritus of adults without concomitant skin changes with a possible clarification strategy and explanation of the most important differential diagnoses.

[CME: Chronic Generalized Pruritus without Dermatological Cause]. / CME: Chronisch generalisierter Pruritus nicht-dermatologischer Ursache.

CME: Chronic Generalized Pruritus without Dermatological Cause Abstract. Chronic generalized pruritus is a common symptom. Dermatological causes must be distinguished from non-dermatological causes. Non-dermatological chronic pruritus has many causes, such as systemic, infectious, neurological, psychogenic disorders, and drug-related side effects, some of which may be associated with significant morbidity. The possibility of a systemic disease should be considered in patients with generalized pruritus and no signs of primary skin lesions. In addition to a careful history and physical examination, selected laboratory examinations can be helpful in making a diagnosis. Pruritus can be the first sign of a malignant hematological disease. Pruritus associated with solid tumors is not that rare. This article offers an approach to chronic generalized pruritus in adults without concomitant skin changes with a viable clarification strategy and consideration of the most important differential diagnoses.

The Swiss Prison Study (SWIPS): Protocol for Establishing a Public Health Registry of Prisoners in Switzerland.

BACKGROUND: The health aspects, disease frequencies, and specific health interests of prisoners and refugees are poorly understood. Importantly, access to the health care system is limited for this vulnerable population. There has been no systematic investigation to understand the health issues of inmates in Switzerland. Furthermore, little is known on how recent migration flows in Europe may have affected the health conditions of inmates. OBJECTIVE: The Swiss Prison Study (SWIPS) is a large-scale observational study with the aim of establishing a public health registry in northern-central Switzerland. The primary objective is to establish a central database to assess disease prevalence (ie, International Classification of Diseases-10 codes [German modification]) among prisoners. The secondary objectives include the following: (1) to compare the 2015 versus 2020 disease prevalence among inmates against a representative sample from the local resident population, (2) to assess longitudinal changes in disease prevalence from 2015 to 2020 by using cross-sectional medical records from all inmates at the Police Prison Zurich, Switzerland, and (3) to identify unrecognized health problems to prepare successful public health strategies. METHODS: Demographic and health-related data such as age, sex, country of origin, duration of imprisonment, medication (including the drug name, brand, dosage, and release), and medical history (including the International Classification of Diseases-10 codes [German modification] for all diagnoses and external results that are part of the medical history in the prison) have been deposited in a central register over a span of 5 years (January 2015 to August 2020). The final cohort is expected to comprise approximately 50,000 to 60,000 prisoners from the Police Prison Zurich, Switzerland. RESULTS: This study was approved on August 5, 2019 by the ethical committee of the Canton of Zurich with the registration code KEK-ZH No. 2019-01055 and funded in August 2020 by the "Walter and Gertrud Siegenthaler" foundation and the "Theodor and Ida Herzog-Egli" foundation. This study is registered with the International Standard Randomized Controlled Trial Number registry. Data collection started in August 2019 and results are expected to be published in 2021. Findings will be disseminated through scientific papers as well as presentations and public events. CONCLUSIONS: This study will construct a valuable database of information regarding the health of inmates and refugees in Swiss prisons and will act as groundwork for future interventions in this vulnerable population. TRIAL REGISTRATION: ISRCTN registry ISRCTN11714665; http://www.isrctn.com/ISRCTN11714665. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/23973.

Management of hyperglycaemia in persons with non-insulin-dependent type 2 diabetes mellitus who are started on systemic glucocorticoid therapy: a systematic review.

OBJECTIVES: What is the most effective pharmacological intervention for glycaemic control in known type 2 diabetes mellitus (DM) without prior insulin treatment and newly started on systemic glucocorticoid therapy? DESIGN: We conducted a systematic literature review. DATA SOURCES: We searched MEDLINE, Embase and Cochrane Library databases and Google for articles from 2002 to July 2018. ELIGIBILITY CRITERIA: We combined search terms relating to DM (patients, >16 years of age), systemic glucocorticoids, glycaemic control, randomised controlled trials (RCTs) and observational studies. DATA EXTRACTION AND SYNTHESIS: We screened and evaluated articles, extracted data and assessed risk of bias and quality of evidence according to Grading of Recommendations Assessment, Development and Evaluation guidelines. RESULTS: Eight of 2365 articles met full eligibility criteria. Basal-bolus insulin (BBI) strategy for patients under systemic glucocorticoid therapy was comparatively effective but provided insufficient glucose control, depending on time of day. BBI strategy with long-acting insulin and neutral protamin Hagedorn as basal insulin provided similar overall glycaemic control. Addition of various insulin strategies to standard BBI delivered mixed results. Intermediate-acting insulin (IMI) as additional insulin conferred no clear benefits, and glycaemic control with sliding scale insulin was inferior to BBI or IMI. No studies addressed whether anticipatory or compensatory insulin adjustments are better for glycaemic control. CONCLUSION: The lack of suitably designed RCTs and observational studies, heterogeneity of interventions, target glucose levels and glucose monitoring, poor control of DM subgroups and low to moderate quality of evidence render identification of optimal pharmacological interventions for glycaemic control and insulin management difficult. Even findings on the widely recommended BBI regimen as intensive insulin therapy for patients with DM on glucocorticoids are inconclusive. High-quality evidence from studies with well-defined DM phenotypes, settings and treatment approaches is needed to determine optimal pharmacological intervention for glycaemic control. PROSPERO REGISTRATION NUMBER: CRD42015024739.

Antiviral Activity of HIV gp120-Targeting Bispecific T Cell Engager Antibody Constructs.

Today's gold standard in HIV therapy is combined antiretroviral therapy (cART). It requires strict adherence by patients and lifelong medication, which can lower the viral load below detection limits and prevent HIV-associated immunodeficiency but cannot cure patients. The bispecific T cell-engaging (BiTE) antibody technology has demonstrated long-term relapse-free outcomes in patients with relapsed and refractory acute lymphocytic leukemia. Here, we generated BiTE antibody constructs that target the HIV-1 envelope protein gp120 (HIV gp120) using either the scFv B12 or VRC01, the first two extracellular domains (1 + 2) of human CD4 alone or joined to the single chain variable fragment (scFv) of the antibody 17b fused to an anti-human CD3ε scFv. These engineered human BiTE antibody constructs showed engagement of T cells for redirected lysis of HIV gp120-transfected CHO cells. Furthermore, they substantially inhibited HIV-1 replication in peripheral blood mononuclear cells (PBMCs) as well as in macrophages cocultured with autologous CD8+ T cells, the most potent being the human CD4(1 + 2) BiTE [termed CD(1 + 2) h BiTE] antibody construct and the CD4(1 + 2)L17b BiTE antibody construct. The CD4(1 + 2) h BiTE antibody construct promoted HIV infection of human CD4-/CD8+ T cells. In contrast, the neutralizing B12 and the VRC01 BiTE antibody constructs, as well as the CD4(1 + 2)L17b BiTE antibody construct, did not. Thus, BiTE antibody constructs targeting HIV gp120 are very promising for constraining HIV and warrant further development as novel antiviral therapy with curative potential.IMPORTANCE HIV is a chronic infection well controlled with the current cART. However, we lack a cure for HIV, and the HIV pandemic goes on. Here, we showed in vitro and ex vivo that a BiTE antibody construct targeting HIV gp120 resulted in substantially reduced HIV replication. In addition, these BiTE antibody constructs display efficient killing of gp120-expressing cells and inhibited replication in ex vivo HIV-infected PBMCs or macrophages. We believe that BiTE antibody constructs recognizing HIV gp120 could be a very valuable strategy for a cure of HIV in combination with cART and compounds which reverse latency.

The frequent and underrecognised co-occurrence of acute exacerbated COPD and depression warrants screening: a systematic review.

Patients with acute exacerbated chronic obstructive pulmonary disease (AECOPD) and concurrent depression suffer significant psychological stress and decreased quality of life. The aim of this study was to collate data, guidelines and recommendations from publications on the screening and management of depressive mood disorders in patients hospitalised with AECOPD.We systematically searched four databases for publications reporting screening or management of depression in patients hospitalised for AECOPD. The identification of articles was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.Out of 1494 original articles screened, 35 met all inclusion criteria. These report a prevalence of depression in AECOPD ranging between 9.5% and 85.6%. Some studies report high postadmission mortality rates for depressive AECOPD patients, and higher readmission rates in depressive versus nondepressive AECOPD patients. Importantly, none of the 35 publications included suggestions on the screening and management of depression in AECOPD.Depression and AECOPD frequently co-occur, and this worsens outcomes. Yet we did not find recommendations on management, and few interventional studies. Patients hospitalised with AECOPD should be systematically screened for depression and treatment recommendations should be developed for these patients. Randomised studies on how to screen and treat depression in hospitalised AECOPD are necessary.

Prescription of Postexposure Prophylaxis for HIV-1 in the Emergency Room: Correct Transmission Risk Assessment Remains Challenging.

BACKGROUND: Limited data are available about the accuracy of postexposure prophylaxis (PEP) prescription in the emergency rooms. Here, we evaluated PEP prescription decision making with respect to the risk of sexual HIV transmission and the exposed person's fear vis-à-vis HIV. METHODS: Using a risk assessment algorithm, we retrospectively evaluated the adequacy of PEP prescription for all persons presenting at the emergency room of the University Hospital Zurich after consensual sex from 2007 to 2013. We used logistic regression to identify factors that correlate with risk-concordant and risk-discordant decisions. RESULTS: We documented 975 persons with a total of 1051 visits for PEP: 83% were men, 71% were Swiss, and 37% were men who have sex with men. In 74% of visits, the decisions were concordant with the risk evaluation algorithm (22% discordant, 4% unknown). In 61% (644/1051) PEP was prescribed; however, in 12% (76/644) the prescriptions were without indication of HIV transmission risk and were attributed to the exposed person's request. Importantly, in 10% (101/1051) of all visits, there were potential risks but PEP was not prescribed, either because of physician's decision or exposed person's refusal. The presence of the source partner strongly correlated with appropriately withholding PEP (adjusted odds ratio for giving PEP 0.05; 95% confidence interval: 0.03 to 0.08). CONCLUSIONS: We found that 22% of PEP decisions were risk discordant because of exposed person's request, incorrect estimation of the sexual transmission risk by the physician, or exposed person's refusal to accept PEP. Emergency physicians may benefit from specialized risk assessment training and patients from education in HIV transmission risk awareness.

Similar efficacy of broad-range ITS PCR and conventional fungal culture for diagnosing fungal infections in non-immunocompromised patients.

BACKGROUND: Broad-range fungal inter spacer region (ITS) polymerase chain reaction (PCR) has been evaluated for the detection and identification of fungi in clinical specimens from severely immunocompromised patients, but not in non-selected patients. Thus, the aim of this study was to compare the diagnostic performance of ITS PCR with that of fungal culture and to investigate its clinical impact on the diagnosis of fungal infections in non-immunocompromised patients. The corresponding patients' data were retrieved by detailed medical chart reviews. RESULTS: Results from 251 specimens showed a high concordance of 89.6 % for ITS PCR and fungal culture. The analytical sensitivity and specificity of ITS PCR considering culture as gold standard were 87.7 and 90.3 %, respectively, the positive and negative predictive value (PPV and NPV) were 76 and 95.5 %, respectively. Assessing the clinical probability of a fungal infection based on detailed chart reviews, PCR had a clinical sensitivity of 88.9 %, a specificity of 86.3 %, a PPV of 64.0 % and a NPV of 96.6 %. The overall performance of fungal broad-range PCR was similar to that of culture. CONCLUSIONS: Our data show that, in non-selected and non-immunocompromised patients, the performance of ITS PCR is similar to that of culture for detecting fungal infections, not the least because sensitivity of culture in patients under antifungal treatment is surprisingly high. Compared to culture, PCR has the advantage of a rapid time-to-result (approximately two working days), proper identification of rare pathogens, prompt initiation of a species-targeted antifungal treatment, and prospects for automation.