Real-world hepatitis C prevalence and treatment uptake at opioid agonist therapy clinics in Ontario, Canada.

Widespread screening for hepatitis C virus (HCV) is necessary for Canada to meet its HCV elimination goals by 2030. People who currently or previously injected drugs are at high risk for HCV. Opioid agonist therapy (OAT, such as methadone and buprenorphine) has been shown to help stabilize the lives of people who are opioid-dependent. The distribution of OAT in North America typically requires daily, weekly, or monthly clinic visits and presents an opportunity for engagement, screening and treatment for those at high-risk of HCV. In this study, HCV screening was conducted by staff at OAT clinics in Ontario from 2016 to 2020 and those with chronic infections were treated on-site with direct-acting antivirals. Point-of-care or dried blood spot (DBS) testing was used for antibodies, DBS or serum for HCV RNA and serum for HCV RNA at SVR12 (sustained virological response). Clinics screened 1954 people (mean age 40 years ±12, 63% male). Forty-five percent were antibody positive, of whom 64% were HCV RNA+. Eighty percent of those RNA+ set an appointment in which 99% attended. Ninety-six percent started treatment with 87% completing treatment. Sixty-eight percent of people who completed treatment submitted a sample for SVR12 testing of which 97% achieved a virological cure. Results suggest that HCV screening and treatment at OAT clinics is feasible, effective and warrants expansion. Data suggest strong treatment adherence due to high rates of SVR12 comparable with other OAT-based HCV treatment programs. The lack of SVR12 sampling could be addressed by either on-site phlebotomy or incentivizing SVR12 sampling.

Cold indoor temperatures and their association with health and well-being: a systematic literature review.

OBJECTIVE: The study aimed to identify, appraise and update evidence on the association between cold temperatures (i.e. <18°C) within homes (i.e. dwellings) and health and well-being outcomes. STUDY DESIGN: This study was a systematic review. METHODS: Seven databases (MEDLINE, Embase, Cochrane Database of Systematic Reviews, CINAHL, APA PsycInfo, Applied Social Sciences Index and Abstracts, Coronavirus Research Database) were searched for studies published between 2014 and 2022, which explored the association between cold indoor temperatures and health and well-being outcomes. Studies were limited to those conducted in temperate and colder climates due to the increased risk of morbidity and mortality during winter in those climatic zones. Studies were independently quality assessed using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. RESULTS: Of 1209 studies, 20 were included for review. Study outcomes included cardiovascular (blood pressure, electrocardiogram abnormalities, blood platelet count), respiratory (chronic obstructive pulmonary disease symptoms, respiratory viral infection), sleep, physical performance and general health. Seventeen studies found exposure to cold indoor temperatures was associated with negative effects on health outcomes studied. Older individuals and those with chronic health problems were found to be more vulnerable to negative health outcomes. CONCLUSION: Evidence suggests that indoor temperatures <18°C are associated with negative health effects. However, the evidence is insufficient to allow clear conclusions regarding outcomes from specific temperature thresholds for different population groups. Significant gaps in the current evidence base are identified, including research on the impacts of cold indoor temperatures on mental health and well-being, studies involving young children, and the long-term health effects of cold indoor temperatures.

[Feasibility of MMPI-2-RF in patients with borderline intellectual functioning]. / Toepasbaarheid van de MMPI-2-RF bij patiënten met zwakbegaafdheid.

BACKGROUND: There are few psychometrically sound diagnostic instruments available to assess personality characteristics and psychopathology in patients with borderline intellectual functioning (BIF). It is important to assess personality characteristics and psychopathology in this target group because of their high risk on psychopathology. AIM: To determine whether the Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF) is feasible in patients with BIF (Verbal Comprehension Index = 70-85) and psychopathology. METHOD: We examined scores on validity scales of the MMPI-2-RF of patients with BIF and compared these scores to those of a matched group of individuals with average intellectual functioning without psychopathology. RESULTS: Scores on the validity scales indicated that patients with BIF can report in a consistent and valid way about their complaints and personality characteristics. Compared to the comparison group they reported equally consistent and showed significantly more psychopathology. CONCLUSION: The MMPI-2-RF is feasible in the assessment of personality characteristics and psychopathology in patients with BIF..

Features of durable response and treatment efficacy for capecitabine monotherapy in advanced breast cancer: real-world evidence from a large single-centre cohort.

PURPOSE: In metastatic breast cancer (MBC) population treated with capecitabine monotherapy, we investigated clinical-pathological features as possible biomarkers for the oncological outcome. METHODS: Retrospective study of consecutive MBC patients treated at University Hospitals Leuven starting capecitabine between 1999 and 2017. The primary endpoint was the durable response (DR), defined as non-progressive disease for > 52 weeks. Other main endpoints were objective response rate (ORR), time to progression (TTP) and overall survival (OS). RESULTS: We included 506 patients; mean age at primary breast cancer diagnosis was 51.2 years; 18.2% had de novo MBC; 98.8% were pre-treated with taxanes and/or anthracycline. DR was reached in 11.6%. Patients with DR, as compared to those without DR, were more likely oestrogen receptor (ER) positive (91.5% vs. 76.8%, p = 0.010) at first diagnosis, had a lower incidence of lymph node (LN) involvement (35.6% vs. 49.9%, p = 0.039) before starting capecitabine, were more likely to present with metastases limited to ≤ 2 involved sites (54.2% vs. 38.5%, p = 0.020) and time from metastasis to start of capecitabine was longer (mean 3.5 vs. 2.7 years, p = 0.020). ORR was 22%. Median TTP and OS were 28 and 58 weeks, respectively. In multivariate analysis (only performed for TTP), ER positivity (hazard ratio (HR) = 0.529, p < 0.0001), HER2 negativity (HR = 0.582, p = 0.024), absence of LN (HR = 0.751, p = 0.008) and liver involvement (HR = 0.746, p = 0.013), older age at capecitabine start (HR = 0.925, p < 0.0001) and younger age at diagnosis of MBC (HR = 0.935, p = 0.001) were significant features of longer TTP. CONCLUSION: Our data display relevant clinical-pathological features associated with DR and TTP in patients receiving capecitabine monotherapy for MBC.

Periprocedural Safety and Feasibility of the New LVIS EVO Device for Stent-Assisted Coiling of Intracranial Aneurysms: An Observational Multicenter Study.

BACKGROUND AND PURPOSE: Stent-assisted treatment techniques can be an effective treatment option for intracranial aneurysms. The aim of this study was to evaluate the periprocedural feasibility and safety of the new LVIS EVO stent for the treatment of intracranial aneurysms. MATERIALS AND METHODS: Patients with intracranial aneurysms treated with the LVIS EVO in 11 European neurovascular centers were retrospectively reviewed. Patient and aneurysm characteristics, procedural parameters, immediate grade of occlusion, and technical and clinical complications were assessed. RESULTS: Fifty-seven patients with 59 aneurysms were treated with the LVIS EVO device; 57.6% of the aneurysms were incidental; 15.3% were acutely ruptured; 15.3% were recanalized or residual aneurysms; and 11.9% were treated for symptoms other than acute hemorrhage. The most frequent aneurysm locations were the middle cerebral artery (25.4%) and the anterior communicating artery (22.0%). The rate of immediate successful deployment was 93.2%. In 6.8% (n = 4) of cases, additional in-stent angioplasty was needed. The immediate complete occlusion rate was 54.2%, while there was a residual aneurysm in 35.6% and a residual neck in 10.2%. Periprocedural technical complications occurred in 7/59 treatments (11.9%; the most frequent technical complication [n = 3] was thrombus formation), which all resolved completely without clinical sequelae. Postprocedural neurologic complications occurred after 4/59 treatments (6.8%; 2 transient ischemic attacks, 1 minor stroke, 1 major stroke), of which only 1 persistent complication was directly related to the procedure (minor stroke in the vascular territory distal to the stent). CONCLUSIONS: The LVIS EVO stent is a safe, feasible device for the treatment of intracranial aneurysms.

The FRED for Cerebral Aneurysms of the Posterior Circulation: A Subgroup Analysis of the EuFRED Registry.

BACKGROUND AND PURPOSE: Flow diversion for the posterior circulation remains a promising treatment option for selected posterior circulation aneurysms. The Flow-Redirection Intraluminal Device (FRED) system has not been previously assessed in a large cohort of patients with posterior circulation aneurysms. The purpose of the present study was to assess safety and efficacy of FRED in this location. MATERIALS AND METHODS: Consecutive patients with posterior circulation aneurysms treated at 8 centers participating in the European FRED study (EuFRED) between April 2012 and January 2019 were retrospectively reviewed. Complication and radiographic and functional outcomes were evaluated. RESULTS: Eighty-four patients (median age, 54 years) with 84 posterior circulation aneurysms were treated with the FRED. A total of 25 aneurysms (29.8%) had previously ruptured, even though most aneurysms were diagnosed incidentally (45.2%). The intradural vertebral artery was the most common location (50%), and saccular, the most common morphology (40.5%). The median size was 7 mm. There were 8 (9.5%) symptomatic thromboembolic and no hemorrhagic complications. Thromboembolic complications occurred mostly (90.9%) in nonsaccular aneurysms. On last follow-up at a median of 24 months, 78.2% of aneurysms were completely occluded. Functional outcome at a median of 27 months was favorable in 94% of patients. All mortalities occurred in patients with acute subarachnoid hemorrhage and its sequelae. CONCLUSIONS: The largest cohort of posterior circulation aneurysms treated with the FRED to date demonstrated favorable safety and efficacy profiles of the device for this indication. Treatment in the setting of acute subarachnoid hemorrhage was strongly related to mortality, regardless of whether procedural complications occurred.

Integrated impedance bridge for absolute capacitance measurements at cryogenic temperatures and finite magnetic fields.

We developed an impedance bridge that operates at cryogenic temperatures (down to 60 mK) and in perpendicular magnetic fields up to at least 12 T. This is achieved by mounting a GaAs HEMT amplifier perpendicular to a printed circuit board containing the device under test and thereby parallel to the magnetic field. The measured amplitude and phase of the output signal allows for the separation of the total impedance into an absolute capacitance and a resistance. Through a detailed noise characterization, we find that the best resolution is obtained when operating the HEMT amplifier at the highest gain. We obtained a resolution in the absolute capacitance of 6.4 aF/Hz at 77 K on a comb-drive actuator while maintaining a small excitation amplitude of 15 kBT/e. We show the magnetic field functionality of our impedance bridge by measuring the quantum Hall plateaus of a top-gated hBN/graphene/hBN heterostructure at 60 mK with a probe signal of 12.8 kBT/e.

New-generation positional therapy in patients with positional central sleep apnea.

PURPOSE: To evaluate the effect of a sleep position trainer (SPT) in patients with positional central sleep apnea (PCSA). METHODS: A multicentre cohort study was conducted. Patients with symptomatic PCSA were included. Effectiveness, compliance and quality of life were assessed at 1- and 6-month follow-up. RESULTS: Sixteen patients were included. Median AHI dropped from 23.4/h [12.9-31.2] to 11.5/h [7.2-24.5] (p = 0.044) after 1-month SPT therapy and in patients who continued treatment, median AHI further decreased after 6 months to 9.7/h [3.4-27.6] (p = 0.075). Median percentage of supine sleep decreased significantly from 37.6 [17.2-51.8] to 6.7 [0.7-22.8] (p < 0.001), after 1 month, and to 6.8 [0.7-22.1] (p = 0.001), after 6 months. Mean compliance over 1 and 6 months was 78.6 ± 35.3 and 66.0 ± 33.3%, respectively. Epworth Sleepiness Scale at baseline was 9.5 [3.3-11.8] and did not significantly decrease after 1 month (11.0 [3.0-13.0]) and 6 months (4.0 [3.0-10.5]) follow-up. Functional Outcomes of Sleep Questionnaire remained stable within the first month. However, after 6 months, there was a significant improvement compared to baseline values, 15.9 [11.9-18.4] vs. 17.8 [14.3-19.2]; p = 0.030. CONCLUSION: This is the first study on effects of positional therapy with a new-generation smart device in patients with PCSA after 1 and 6 months of follow-up. Results of this study show that the SPT is effective in reducing AHI and central AI, feasible in PCSA, and is associated with symptomatic improvement. While the working mechanism behind this effect remains speculative, the effect is positive and considerable.

[Perioperative cardiovasular morbidity and mortality in noncardiac surgical interventions : Measures for optimal anesthesiological care]. / Perioperative kardiovaskuläre Morbidität und Letalität bei nichtherzchirurgischen Eingriffen : Maßnahmen der optimalen anästhesiologischen Betreuung.

Because of new surgical techniques, advanced monitoring modalities and improvements in perioperative care, perioperative mortality and morbidity have been significantly reduced in the last decades; however, patients still suffer from high perioperative mortality and morbidity, especially those with pre-existing cardiovascular diseases. Not only perioperative myocardial infarction but also myocardial injury after non-cardiac surgery, which presents without clinical symptoms, is associated with an adverse outcome. Patients at risk require particular interdisciplinary attention throughout the perioperative phase. The premedication visit is of particular importance. In addition to a thorough patient medical history and physical assessment, the perioperative handling of the patient's pre-existing medication and possible necessity for further preoperative tests should be verified. If necessary and where possible, optimization of the patient's state of health can be planned together with other disciplines. It is the anesthesiologist's responsibility to optimally guide and support patients with pre-existing cardiovascular diseases through the entire surgical procedure. This review summarizes perioperative interventions that have an influence on patient mortality and morbidity and evaluates the underlying evidence. This covers the perioperative handling of cardioprotective medication, choice of the anesthetic regimen, blood pressure management and transfusion regimens. Furthermore, this review highlights recent findings, e.g. perioperative reloading with statins and short-term preoperative initiation of beta blockers. The pros and cons of thoracic epidural anesthesia in patients with an elevated cardiovascular risk are discussed. Not only intraoperative hypotension should be of concern to anesthesiologists but also postoperative hypotension can have a deleterious impact on the outcome. This is relevant in the time period when a significant proportion of patients have already left the monitoring ward. The recently published recommendations by the World Health Organization concerning perioperative hyperoxia might not be beneficial for patients with an elevated cardiovascular risk. Finally, the treatment options for perioperative cardiovascular events are explained and an algorithm for handling of patients with perioperative myocardial injury without clinical ischemic symptoms is suggested (myocardial injury after non-cardiac surgery).

The degradation and performance of electrospun supramolecular vascular scaffolds examined upon in vitro enzymatic exposure.

To maintain functionality during in situ vascular regeneration, the rate of implant degradation should be closely balanced by neo-tissue formation. It is unknown, however, how the implant's functionality is affected by the degradation of the polymers it is composed of. We therefore examined the macro- and microscopic features as well as the mechanical performance of vascular scaffolds upon in vitro enzymatic degradation. Three candidate biomaterials with supramolecularly interacting bis-urea (BU) hard blocks ('slow-degrading' polycarbonate-BU (PC-BU), 'intermediate-degrading' polycarbonate-ester-BU (PC(e)-BU), and 'fast-degrading' polycaprolactone-ester-BU (PCL-BU)) were synthesized and electrospun into microporous scaffolds. These materials possess a sequence-controlled macromolecular structure, so their susceptibility to degradation is tunable by controlling the nature of the polymer backbone. The scaffolds were incubated in lipase and monitored for changes in physical, chemical, and mechanical properties. Remarkably, comparing PC-BU to PC(e)-BU, we observed that small changes in macromolecular structure led to significant differences in degradation kinetics. All three scaffold types degraded via surface erosion, which was accompanied by fiber swelling for PC-BU scaffolds, and some bulk degradation and a collapsing network for PCL-BU scaffolds. For the PC-BU and PC(e)-BU scaffolds this resulted in retention of mechanical properties, whereas for the PCL-BU scaffolds this resulted in stiffening. Our in vitro study demonstrates that vascular scaffolds, electrospun from sequence-controlled supramolecular materials with varying ester contents, not only display different susceptibilities to degradation, but also degrade via different mechanisms. STATEMENT OF SIGNIFICANCE: One of the key elements to successfully engineer vascular tissues in situ, is to balance the rate of implant degradation and neo-tissue formation. Due to their tunable properties, supramolecular polymers can be customized into attractive biomaterials for vascular tissue engineering. Here, we have exploited this tunability and prepared a set of polymers with different susceptibility to degradation. The polymers, which were electrospun into microporous scaffolds, displayed not only different susceptibilities to degradation, but also obeyed different degradation mechanisms. This study illustrates how the class of supramolecular polymers continues to represent a promising group of materials for tissue engineering approaches.

Comparison of brachytherapy and external beam radiotherapy boost in breast-conserving therapy: Patient-reported outcome measures and aesthetic outcome.

OBJECTIVE: This study aimed to estimate the probability of an unfavourable aesthetic outcome (AO) 2 years after breast-conserving therapy (BCT) and evaluate the possible influence of brachytherapy (BT) and external beam radiotherapy (EBRT) boost on patient-reported outcomes (PROs) and AO. PATIENTS AND METHODS: Patients treated with BCT starting April 2015 were prospectively included. Selection of the boost technique followed an in-house flowchart based on the depth of the tumour bed. An electron boost was performed for a superficial clinical target volume (maximum 28 mm under the epidermis), a BT boost was proposed in all other cases. Patients were followed-up for 2 years. AO was scored by the BCCT.core software and the patient. Further PROs were measured with the EORTC QLQ-C30, QOL-BR23 and the BIBCQ questionnaires. RESULTS: The analysis included 175 patients, 80 received a BT boost and 95 an EBRT boost. BT patients were significantly older; had a higher breast cup and band size, body mass index and surgical specimen weight of the wide excision; more seroma at baseline and less positive surgical section margins than patients in the EBRT group, and more patients drank alcohol. Cancer- and breast cancer-specific quality of life (QOL) and body image did not differ between the boost techniques over time. Although mean scores for breast symptoms and sexual enjoyment did differ significantly over time (p = 0.05 and < 0.01, respectively), the effect was due to differences before boost administration. Measured with BCCT.core, AO was unfavourable in 28% of patients 2 years after treatment (31% scored by the patient) and results were similar in the BT and EBRT groups. CONCLUSION: Using the presented flowchart (See Verhoeven et al. [16]), AO and PROs on QOL or body image up to 2 years after BCT are not influenced by the boost technique.

Visualization of zinc pyrithione particles deposited on the scalp from a shampoo by tape-strip sampling and scanning electron microscopy/energy dispersive X-ray spectroscopy measurement.

OBJECTIVE: Zinc pyrithione (ZnPT) is widely used as an anti-fungal active in commercial anti-dandruff (AD) shampoos. The AD efficacy of ZnPT is highly dependent on the deposition of ZnPT particles onto the scalp during the process of shampoo application and rinse-off. Since ZnPT materials with different particle sizes and morphologies have different deposition behaviours, the measurement of the actual ZnPT deposition is critical to understand the AD performance delivered by different ZnPT shampoos. The aim of this study is to develop a robust and reliable method for visualizing the particle size and morphology of ZnPT deposited on the scalp from AD shampoos. METHODS: Hair was washed with a commercially available AD shampoo containing ZnPT and zinc carbonate (ZnCO3 ). Tape strips were applied to collect the deposited particles from the scalp after AD shampoo application and rinse-off. The scalp tape strip samples were subjected to scanning electron microscopy/energy dispersive X-ray spectroscopy (SEM/EDX) measurement. The morphology of the ZnPT particles was visualized by SEM imaging and identification of ZnPT particles was confirmed by EDX analysis. RESULTS: For the commercial shampoo studied it was observed that two zinc-containing particulates with different morphologies and composition remained on the scalp after shampoo application and rinse-off. As indicated by the EDX spectra, the ZnPT particles deposited onto the scalp surface had polygonal crystal structures. ZnCO3 was also deposited onto the scalp surface. This material was mainly present as aggregated particulates. CONCLUSION: An ex vivo method that combines tape strip sampling and SEM/EDX has been developed for measuring and visualizing the particle size, morphology and composition of ZnPT deposited on the scalp from AD shampoos. This ex vivo measurement method provides higher imaging resolution and more chemical specificity than reflectance confocal microscopy (RCM). To the best of our knowledge, this is the first time that ZnPT particles were distinguishable from other zinc particles on the scalp. Moreover, the new method allows the microstructures of both ZnPT and other zinc particles on the scalp to be imaged.

European Multicenter Study for the Evaluation of a Dual-Layer Flow-Diverting Stent for Treatment of Wide-Neck Intracranial Aneurysms: The European Flow-Redirection Intraluminal Device Study.

BACKGROUND AND PURPOSE: Endoluminal reconstruction with flow-diverting stents represents a widely accepted technique for the treatment of complex intracranial aneurysms. This European registry study analyzed the initial experience of 15 neurovascular centers with the Flow-Redirection Intraluminal Device (FRED) system. MATERIALS AND METHODS: Consecutive patients with intracranial aneurysms treated with the FRED between February 2012 and March 2015 were retrospectively reviewed. Complications and adverse events, transient and permanent morbidity, mortality, and occlusion rates were evaluated. RESULTS: During the defined study period, 579 aneurysms in 531 patients (median age, 54 years; range, 13-86 years) were treated with the FRED. Seven percent of patients were treated in the acute phase (≤3 days) of aneurysm rupture. The median aneurysm size was 7.6 mm (range, 1-36.6 mm), and the median neck size 4.5 mm (range, 1-30 mm). Angiographic follow-up of >3 months was available for 516 (89.1%) aneurysms. There was progressive occlusion witnessed with time, with complete occlusion in 18 (20%) aneurysms followed for up to 90 ± 14 days, 141 (82.5%) for 180 ± 20 days, 116 (91.3%) for 1 year ± 24 days, and 122 (95.3%) aneurysms followed for >1 year. Transient and permanent morbidity occurred in 3.2% and 0.8% of procedures, respectively. The overall mortality rate was 1.5%. CONCLUSIONS: This retrospective study in real-world patients demonstrated the safety and efficacy of the FRED for the treatment of intracranial aneurysms. In most cases, treatment with a single FRED resulted in complete angiographic occlusion at 1 year.

Profiling of volatile organic compounds produced by clinical Aspergillus isolates using gas chromatography-mass spectrometry.

Volatile organic compounds (VOCs) in exhaled breath may identify the presence of invasive pulmonary aspergillosis. We aimed to detect VOC profiles emitted by in vitro cultured, clinical Aspergillus isolates using gas chromatography-mass spectrometry (GC-MS). Three clinical Aspergillus isolates and a reference strain were cultured while conidiation was prevented. Headspace samples were analyzed using a standardized method. Breath samples of patients from which the cultures were obtained were checked for the presence of the VOCs found in vitro. Each Aspergillus isolate produced a distinct VOC profile. These profiles could not be confirmed in exhaled breath in vivo.

A rare missense variant in RCL1 segregates with depression in extended families.

Depression is the most prevalent psychiatric disorder with a complex and elusive etiology that is moderately heritable. Identification of genes would greatly facilitate the elucidation of the biological mechanisms underlying depression, however, its complex etiology has proved to be a major bottleneck in the identification of its genetic risk factors, especially in genome-wide association-like studies. In this study, we exploit the properties of a genetic isolate and its family-based structure to explore whether relatively rare exonic variants influence the burden of depressive symptoms in families. Using a multistep approach involving linkage and haplotype analyses followed by exome sequencing in the Erasmus Rucphen Family (ERF) study, we identified a rare (minor allele frequency (MAF)=1%) missense c.1114C>T mutation (rs115482041) in the RCL1 gene segregating with depression across multiple generations. Rs115482041 showed significant association with depressive symptoms (N=2393, ßT-allele=2.33, P-value=1 × 10-4) and explained 2.9% of the estimated genetic variance of depressive symptoms (22%) in ERF. Despite being twice as rare (MAF<0.5%), c.1114C>T showed similar effect and significant association with depressive symptoms in samples from the independent population-based Rotterdam study (N=1604, ßT-allele=3.60, P-value=3 × 10-2). A comparison of RCL1 expression in human and mouse brain revealed a striking co-localization of RCL1 with the layer 1 interlaminar subclass of astrocytes found exclusively in higher-order primates. Our findings identify RCL1 as a novel candidate gene for depression and offer insights into mechanisms through which RCL1 may be relevant for depression.

HBeAg levels at week 24 predict response to 8 years of tenofovir in HBeAg-positive chronic hepatitis B patients.

BACKGROUND: Hepatitis B e antigen (HBeAg) seroconversion is a treatment endpoint for HBeAg-positive CHB, and a necessary precursor to HBsAg loss. Biomarkers that predict serological outcomes would be useful. AIM: To evaluate the utility of measuring HBeAg levels for predicting HBeAg seroconversion and HBsAg loss under long-term tenofovir (TDF) therapy. METHODS: A total of 266 patients were enrolled into a phase III study of TDF vs adefovir (ADV) for 48 weeks in HBeAg-positive patients, followed by open-label TDF up to 384 weeks. Serum HBeAg levels were measured for subjects with samples available at both baseline and week 24 of treatment (n = 200). Analysis compared subjects who achieved HBeAg seroconversion by week 384 vs no HBeAg seroconversion. RESULTS: HBeAg seroconversion rate was 52% by week 384. Time to HBeAg seroconversion was 80 weeks (IQR: 36-162). HBeAg decline at week 24 was associated with HBeAg seroconversion (1.63 vs 0.90 log10 PEIU/mL, P = .002). The optimal threshold for identifying HBeAg seroconversion was HBeAg decline ≥2.2 log10 PEIU/mL at week 24, with HBeAg seroconversion achieved by 76% of patients, compared to 44% if HBeAg decline <2.2 log10 (P < .0001). HBeAg decline ≥2.2 log10 PEIU/mL at week 24 was associated with HBsAg loss in genotype A or D patients (38% vs 15%, P = .03). Precore/basal core promotor variants were associated with lower baseline HBeAg levels, but not HBeAg seroconversion. CONCLUSION: Decline in HBeAg levels by week 24 was associated with HBeAg seroconversion and HBsAg loss in HBeAg-positive chronic hepatitis B patients treated with long-term TDF.

HBsAg loss after peginterferon-nucleotide combination treatment in chronic hepatitis B patients: 5 years of follow-up.

Combining peginterferon-alfa-2a (pegIFN) with a nucleotide analogue can result in higher rates of HBsAg loss than either therapy given alone. Here, we investigated the durability of the response to combination therapy in chronic hepatitis B (CHB) patients after 5 years of follow-up. In the initial study, 92 CHB patients (44 HBeAg-positive, 48 HBeAg-negative) with HBV DNA >100 000 c/mL (~20 000 IU/mL) and active hepatitis were treated for 48 weeks with pegIFN 180 µg/week and 10 mg adefovir dipivoxil daily. For the long-term follow-up (LTFU) study, patients were followed up for 5 years after the end of treatment. At year 5, 70 (32 HBeAg-positive, 38 HBeAg-negative) patients remained in the study. At year 5, 19% (6/32) of HBeAg-positive patients and 16% (6/38) of HBeAg-negative patients lost HBsAg, and no HBsAg seroreversion was observed. The 5-year cumulative Kaplan-Meier estimate for HBsAg loss was 17.2% for HBeAg-positive patients and 19.3% for HBeAg-negative patients. Fourteen of sixteen patients who lost HBsAg at any time point during follow-up developed anti-HBs antibodies (>10 IU/L). At year 5, in total 63% (20/32) of HBeAg-positive and 71% (27/38) of HBeAg-negative patients were retreated with nucleos(t)ide analogues during follow-up. The cumulative Kaplan-Meier estimate for retreatment was 60% of patients at year 5. At year 5 of follow-up, 18% of CHB patients treated with pegIFN/nucleotide analogue combination therapy had durable HBsAg loss and 88% of these had developed anti-HBs antibodies.

State of Practice: Endovascular Treatment of Acute Aneurysmal SAH in Germany.

BACKGROUND AND PURPOSE: Acute aneurysmal SAH is a severe disease that requires prompt treatment. Endovascular coiling and neurosurgical clipping are established treatment options. Our intention was to determine the state of current practice in acute aneurysmal SAH treatment in Germany, with emphasis on logistic and temporal aspects. MATERIALS AND METHODS: We interviewed 74 German university and nonuniversity hospitals with an anonymous questionnaire comprising 15 questions concerning the practice of treatment and diagnostics of acute aneurysmal SAH at their respective institutions. The response rate was 74% among all institutions (55/74); among university hospitals, 77%; and among nonuniversity hospitals, 72%. RESULTS: The majority of all aneurysms were treated endovascularly (66% of acute aneurysmal SAH, 66% of unruptured aneurysms). Treatment on weekends was provided by 100% of endovascular and 96% of neurosurgical facilities. Average patients with acute aneurysmal SAH were not treated during the night (98%). Seventy percent of endovascular and 78% of neurosurgical treatments were not started later than 8:00 pm. Fifty-three percent of hospitals would not start a same-day diagnostic angiography in acute aneurysmal SAH if treatment was scheduled for the following day. Eighty-two percent of all centers performed DSA after clipping to evaluate the treatment results. CONCLUSIONS: Our survey gives a detailed summary of the current practice of endovascular treatment and related topics in acute aneurysmal SAH in Germany and also reveals considerable changes in practice in comparison with older data.

Prediction of long-term clinical outcome in a diverse chronic hepatitis B population: Role of the PAGE-B score.

An abundance of noninvasive scores have been associated with fibrosis and hepatocellular carcinoma (HCC) development. We aimed to compare the prognostic ability of these scores in relation to liver histology in chronic hepatitis B (CHB) patients. Liver biopsies from treatment-naïve CHB patients at one tertiary care centre were scored by a single hepato-pathologist. Laboratory values at liver biopsy were used to calculate the PAGE-B, REACH-B, GAG-HCC, CU-HCC and FIB-4 scores. Any clinical event was defined as HCC development, liver failure, transplantation and mortality. HCC and mortality data were obtained from national database registries. Of 557 patients, 40 developed a clinical event within a median follow-up of 10.1 (IQR 5.7-15.9) years. The PAGE-B score predicted any clinical event (C-statistic.86, 95% CI: 0.80-0.92), HCC development (C-statistic .91) and reduced transplant-free survival (C-statistic .83) with good accuracy, also when stratified by ethnicity, antiviral therapy after biopsy or advanced fibrosis. The C-statistics (95% CI) of the REACH-B, GAG-HCC, CU-HCC and FIB-4 scores for any event were .70 (0.59-0.81), .82 (0.75-0.89), .73 (0.63-0.84) and.79 (0.69-0.89), respectively. The PAGE-B event risk assessment improved modestly when combined with the Ishak fibrosis stage (C-statistic .87, 95% CI: 0.82-0.93). The PAGE-B score showed the best performance in assessing the likelihood of developing a clinical event among a diverse CHB population over 15 years of follow-up. Additional liver histological characteristics did not appear to provide a clinically significant improvement.