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.

[A comparative study on personality characteristics in individuals with borderline intellectual functioning]. / Een vergelijkend onderzoek naar persoonlijkheidskenmerken bij zwakbegaafdheid.

BACKGROUND: Few studies have been conducted on personality traits and psychopathology in females and males with borderline intellectual functioning. AIM: Examining gender differences in psychopathology and behavioral characteristics in patients with borderline intellectual functioning, and patients with average intellectual functioning. METHOD: The MMPI-2-RF was administered to 116 patients with borderline intellectual functioning and psychopathology. Average raw scores on the Restructured Clinical Scales (RC-scales) of female and male patients with borderline intellectual functioning were compared to those of a matched group from the general population, and a matched group with patients with mental disorders and average intelligence. The average raw scores on the RC-scales were compared between males and females with borderline intellectual functioning and between females and males across the various groups. RESULTS: Female patients with borderline intellectual functioning reported more symptoms on RC-scales related to internalizing emotional problems than male patients with borderline intellectual functioning. They reported significantly more complaints on RC-scales related to externalizing problems and thought disorders compared to average intelligent females with mental disorders. Several significant differences between female and male patients with borderline intellectual functioning were greater than within the other groups. We found no significant differences in behavioral characteristics and symptoms between male patients with borderline intellectual functioning and average intelligent males with mental disorders. CONCLUSION: This study underscores the importance of gender sensitivity in the multi-method assessment and treatment of psychopathology in patients with borderline intellectual functioning. Female patients with borderline intellectual functioning constitute the most vulnerable group in terms of nature and severity of psychopathology.

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..

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.

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.

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).

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.

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.

Inducing Hepatitis C Virus Resistance After Pig Liver Transplantation-A Proof of Concept of Liver Graft Modification Using Warm Ex Vivo Perfusion.

Normothermic ex vivo liver perfusion (NEVLP) offers the potential to optimize graft function prior to liver transplantation (LT). Hepatitis C virus (HCV) is dependent on the presence of miRNA(microRNA)-122. Miravirsen, a locked-nucleic acid oligonucleotide, sequesters miR-122 and inhibits HCV replication. The aim of this study was to assess the efficacy of delivering miravirsen during NEVLP to inhibit miR-122 function in a pig LT model. Pig livers were treated with miravirsen during NEVLP or cold storage (CS). Miravirsen absorption, miR-122 sequestration, and miR-122 target gene derepression were determined before and after LT. The effect of miravirsen treatment on HCV infection of hepatoma cells was also assessed. NEVLP improved miravirsen uptake versus CS. Significant miR-122 sequestration and miR-122 target gene derepression were seen with NEVLP but not with CS. In vitro data confirmed miravirsen suppression of HCV replication after established infection and prevented HCV infection with pretreatment of cells, analogous to the pretreatment of grafts in the transplant setting. In conclusion, miravirsen delivery during NEVLP is a potential strategy to prevent HCV reinfection after LT. This is the first large-animal study to provide "proof of concept" for using NEVLP to modify and optimize liver grafts for transplantation.

NK cells in self-limited HCV infection exhibit a more extensively differentiated, but not memory-like, repertoire.

Natural killer (NK) cells have long been thought of as a purely innate immune cell population, but increasing reports have described developmental and functional qualities of NK cells that are commonly associated with cells of the adaptive immune system. Of these features, the ability of NK cells to acquire functional qualities associated with immunological memory and continuous differentiation resulting in the formation of specific NK cell repertoires has recently been highlighted in viral infection settings. By making use of a unique cohort of monitored, at-risk intravenous drug users in this study, we were able to dissect the phenotypic and functional parameters associated with NK cell differentiation and NK cell memory in patients 3 years after acute HCV infection and either the subsequent self-clearance or progression to chronicity. We observed increased expression of cytolytic mediators and markers CD56bright and NKp46+ of NK cells in patients with chronic, but not self-limited HCV infection. Patients with a self-limited infection expressed higher levels of differentiation-associated markers CD57 and KIRs, and lower levels of NKG2A. A more extensively differentiated NK cell phenotype is associated with self-clearance in HCV patients, while the NK cells of chronic patients exhibited more naïve and effector NK cell phenotypic and functional characteristics. The identification of these distinct NK cell repertoires may shed light on the role NK cells play in determining the outcome of acute HCV infections, and the underlying immunological defects that lead to chronicity.

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.

Determination of hepatitis B phenotype using biochemical and serological markers.

The aim of this study was to assess the validity of categorization of chronic hepatitis B viral infection into stages or phases based upon measures of disease activity and viral load, assuming these phenotypes will be useful for prognostication and determining the need for antiviral therapy. We assessed the phenotype of hepatitis B of 1,390 adult participants enrolled in the Hepatitis B Research Network Cohort Study, using a computer algorithm. Only 4% were immune tolerant, while 35% had chronic hepatitis B (18% e antigen positive and 17% e antigen negative) while 23% were inactive carriers. Strikingly, 38% of participants did not fit clearly into any one of these groups and were considered indeterminant. The largest subset of indeterminants had elevated serum aminotransferases with low levels of HBV DNA (less than 10,000 iu/mL). Subsequent determination of hepatitis B phenotype on the next available laboratory tests showed that 64% remained indeterminant. These findings call into question the validity of conventional staging of hepatitis B, in large part because of the substantial proportion of patients who do not fit readily into one of the usual stages or phases. Further studies are needed of the indeterminant category of chronic hepatitis B viral infection, including assessments of whether patients in this group are perhaps in transition to another phase or if they are a distinct phenotype with a need to assess liver disease severity and need for antiviral therapy. (ClinicalTrials.gov identifier NCT01263587).

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.

Prevalence and risk factors for viral blipping in chronic hepatitis B patients treated with nucleos (t) ide analogues.

The clinical relevance of viral blipping during nucleos (t) ide analogue (NA) treatment is unclear in chronic hepatitis B (CHB). We investigated the prevalence, risk factors and clinical outcomes for those with viral blipping during NA treatment. A retrospective cohort study investigated consecutively treated CHB patients from May 2008 to February 2015 on the NAs such as entecavir (ETV), tenofovir (TDF) and lamivudine (LAM). Included patients were previously treatment naive. Viral blipping was defined as serum HBV DNA >20 IU/mL on one occasion, and not >200 IU/mL, with subsequent measurement returning to undetectable levels, that is <20 IU/mL. A total of 242 treatment-compliant CHB patients were included with 44 (18.2%) experiencing viral blipping. In multivariable Cox regression, Asian race (HR=7.40, 95% CI 1.01-54.29, P<.049), LAM therapy (vs ETV/TDF, HR=2.53, 95% CI 1.29-4.95, P<.007), higher creatinine (per SD, HR=1.47, 95% CI 1.21-1.79, P<.001), HBeAg positivity (HR=2.68, 95% CI 1.39-5.03, P<.003) and longer time to achieve undetectable HBV DNA (per month, HR=1.05, 95% CI 1.02-1.08, P=.001) were associated with an increased risk of viral blipping. Viral blipping did not show any significant association with viral breakthrough, HBsAg loss, ALT flares or disease progression. Viral blipping is a frequent event during NA therapy; however, it did not lead to any clinically significant outcomes. Thus, it may not require more frequent blood work and patient visits in clinical practice.

HLA-C and KIR combined genotype as new response marker for HBeAg-positive chronic hepatitis B patients treated with interferon-based combination therapy.

Current treatment for chronic hepatitis B infection (CHB) consists of interferon-based therapy. However, for unknown reasons, a large proportion of patients with CHB do not respond to this treatment. Hence, there is a pressing need to establish response markers to select patients who will benefit from therapy and to spare potential nonresponders from unnecessary side effects of antiviral therapy. Here, we assessed whether HLA-C and KIR genotypes were associated with treatment outcome for CHB. Twelve SNPs in or near the HLA-C gene were genotyped in 86 CHB patients (41 HBeAg positive; 45 HBeAg negative) treated with peginterferon alfa-2a + adefovir. Genotyping of killer immunoglobin-like receptors (KIRs) was performed by SSP-PCR. One SNP in HLA-C (rs2308557) was significantly associated with combined response in HBeAg-positive CHB patients (P = 0.003). This SNP is linked to the HLA-C group C1 or C2 classification, which controls KIR binding. The combination of KIR2DL1 with its ligand HLA-C2 was observed significantly more often in HBeAg-positive patients with a combined response (13/14) than in nonresponders (11/27, P = 0.001). Patients with the KIR2DL1/C2 genotype had significantly higher baseline ALT levels (136 vs 50 U/L, P = 0.002) than patients without this combination. Furthermore, KIR2DL1-C2 predicted response independent of HBV genotype and ALT at baseline. HLA-C and KIR genotype is strongly associated with response in HBeAg-positive CHB patients treated with interferon-based therapy. In combination with other known response markers, HLA-C/KIR genotype could enable the selection of patients more likely to respond to interferon-based therapy.

Peginterferon add-on results in more HBsAg decline compared to monotherapy in HBeAg-positive chronic hepatitis B patients.

It is unknown whether peginterferon (PEG-IFN) add-on to entecavir (ETV) leads to more HBsAg decline compared to PEG-IFN monotherapy or combination therapy, and whether ETV therapy may prevent HBsAg increase after PEG-IFN cessation. We performed a post hoc analysis of 396 HBeAg-positive patients treated for 72 weeks with ETV + 24 weeks PEG-IFN add-on from week 24 to 48 (add-on, n = 85), 72 weeks with ETV monotherapy (n = 90), 52 weeks with PEG-IFN monotherapy (n = 111) and 52 weeks PEG-IFN + lamivudine (combination, n = 110) within 2 randomized trials. HBsAg decline was assessed at the end of PEG-IFN (EOP) and 6 months after PEG-IFN (EOF) discontinuation. Differences in baseline characteristics were accounted for using inversed probability of treatment weights. At EOP, a HBsAg reduction of ≥1log10 IU/mL was more frequently achieved for patients in the add-on or combination therapy arms (both 36%), compared to PEG-IFN mono (20%) or ETV (8%) (add-on vs PEG-IFN mono P = 0.050). At EOF, the HBsAg reduction ≥1log10 IU/mL was only sustained in patients treated with ETV consolidation (add-on vs combination and PEG-IFN mono: 40% vs 23% and 18%, P = 0.029 and P = 0.003, respectively). For add-on, combination, PEG-IFN mono and ETV, the mean HBsAg-level change at EOF was -0.84, -0.81, -0.68 and -0.33 log10 IU/mL, respectively (P > 0.05 for PEG-IFN arms). HBeAg loss at EOF was 36%, 31%, 33% and 20%, respectively (P > 0.05). PEG-IFN add-on for 24 weeks results in more on-treatment HBsAg decline than does 52 weeks of PEG-IFN monotherapy. ETV therapy may maintain the HBsAg reduction achieved with PEG-IFN.

Fatigue in persons with subacute spinal cord injury who are dependent on a manual wheelchair.

STUDY DESIGN: Cross-sectional. OBJECTIVES: To determine the prevalence and severity of fatigue in persons with subacute spinal cord injury (SCI), assess whether demographic and lesion characteristics are related to fatigue and determine the relationship with physical fitness and physical behavior. SETTING: Measurements were performed 2 months before discharge from inpatient rehabilitation. METHODS: Thirty-six persons with subacute SCI, dependent on a manual wheelchair, mean age 43±15 and 83% men, completed the Fatigue Severity Scale (FSS). FSS scores >4 indicated fatigue. We recorded age and lesion characteristics, measured body mass index, measured peak power output and peak oxygen uptake during a maximal handcycling test and determined physical behavior using an accelerometer-based activity monitor. T-tests were used to test for differences in fatigue between subgroups based on age and lesion characteristics, and regression analyses to assess the relationship with physical fitness and physical behavior. RESULTS: Mean FSS was 3.3±1.3. Fatigue, including severe fatigue, was prevalent in 31% (95% confidence interval: 16-46) of participants compared with 18% in the general population. Furthermore, mean fatigue was significantly higher in persons with incomplete compared with complete lesions (t=2.22, P=0.03). Mean scores between other subgroups did not differ significantly. Of the physical fitness and physical behavior measures, only peak oxygen uptake tended to be related to more fatigue (B=-1.47, P=0.05). CONCLUSION: Fatigue was prevalent and is of concern in persons with subacute SCI. Those with incomplete lesions seem to be at higher risk. Because fatigue is known to persist among persons with SCI, interventions to reduce fatigue seem necessary.

Loss of intrahepatic HBsAg expression predicts sustained response to peginterferon and is reflected by pronounced serum HBsAg decline.

There is a lack of knowledge regarding the effect of peginterferon (PEG-IFN) on the expression of intrahepatic hepatitis B core and surface antigen (HBcAg and HBsAg) in chronic hepatitis B (CHB) and its relation with response to therapy. Fifty-two HBeAg-positive and 67 HBeAg-negative CHB patients with paired liver biopsies taken at baseline and after 1 year of PEG-IFN therapy were studied. After PEG-IFN therapy, HBeAg-negative patients showed a significant reduction in both intrahepatic HBcAg (P = 0.04) and HBsAg expression (P < 0.001). In contrast, a reduction in intrahepatic HBcAg expression was not observed in HBeAg-positive patients, while a trend in reduction of intrahepatic HBsAg staining was found (P = 0.09). Post-treatment, 7 (13%) HBeAg-positive and 9 (14%) HBeAg-negative patients had no expression of intrahepatic HBsAg. Patients without any intrahepatic HBsAg expression post-treatment were more likely to achieve a combined response (HBeAg loss with hepatitis B virus (HBV) DNA <2000 IU/mL for HBeAg -positive and HBV DNA <2000 IU/mL and normal alanine aminotransferase for HBeAg-negative CHB): 71% vs 5% for HBeAg-positive (P < 0.001) and 60% vs 16% for HBeAg-negative patients (P = 0.004), respectively. Moreover, a more profound decline of serum HBsAg was observed in patients with absence of intrahepatic HBsAg staining (3.1 vs 0.4 log IU/mL, P < 0.001 and 1.7 vs 0.4 log IU/mL, P = 0.005 for HBeAg-positive and HBeAg-negative CHB, respectively). In conclusion, PEG-IFN reduces expression of intrahepatic HBsAg. Loss of HBsAg as assessed by immunohistochemistry from the liver predicts a sustained response and is reflected in a pronounced serum HBsAg decline.