People with Multiple Tattoos and/or Piercings Are Not at Increased Risk for HBV or HCV in The Netherlands

BACKGROUND: Although published results are inconsistent, it has been suggested that tattooing and piercing are risk factors for HBV and HCV infections. To examine whether tattooing and piercing do indeed increase the risk of infection, we conducted a study among people with multiple tattoos and/or piercings in The Netherlands who acquired their tattoos and piercings in The Netherlands and/or abroad. METHODS: Tattoo artists, piercers, and people with multiple tattoos and/or piercings were recruited at tattoo conventions, shops (N = 182), and a biannual survey at our STI-outpatient clinic (N = 252) in Amsterdam. Participants were interviewed and tested for anti-HBc and anti-HCV. Determinants of HBV and HCV infections were analysed using logistic regression analysis. RESULTS: The median number of tattoos and piercings was 5 (IQR 2-10) and 2 (IQR 2-4), respectively. Almost 40% acquired their tattoo of piercing abroad. In total, 18/434 (4.2%, 95%CI: 2.64%-6.46%) participants were anti-HBc positive and 1 was anti-HCV positive (0.2%, 95%CI: 0.01%-1.29%). Being anti-HBc positive was independently associated with older age (OR 1.68, 95%CI: 1.03-2.75 per 10 years older) and being born in an HBV-endemic country (OR 7.39, 95%CI: 2.77-19.7). Tattoo- and/or piercing-related variables, like having a tattoo or piercing in an HBV endemic country, surface percentage tattooed, number of tattoos and piercings etc., were not associated with either HBV or HCV. CONCLUSIONS: We found no evidence for an increased HBV/HCV seroprevalence among persons with multiple tattoos and/or piercings, which might be due to the introduction of hygiene guidelines for tattoo and piercing shops in combination with the low observed prevalence of HBV/HCV in the general population. Tattoos and/or piercings, therefore, should not be considered risk factors for HBV/HCV in the Dutch population. These findings imply the importance of implementation of hygiene guidelines in other countries

DosEmi study protocol: a phase IV, multicentre, open-label, crossover study to evaluate non-inferiority of pharmacokinetic-guided reduced dosing compared with conventional dosing of emicizumab in people with haemophilia A

INTRODUCTION: Emicizumab effectively prevents bleeding in people with haemophilia A (PwHA), but is a burden for national healthcare budgets and consequently may limit access. According to the drug label, dosing of emicizumab is based on body weight with fixed intervals of 7, 14 or 28 days, which leads to mean plasma concentrations of 55 µg/mL (SD 15 µg/mL). However, a moderate variability of concentrations and a minimal effective concentration of 30 µg/mL have been suggested in studies. Therefore, a dose of emicizumab that targets a trough concentration of 30 µg/mL is hypothesised to be equally effective as conventional dosing in the prevention of bleeding. METHODS AND ANALYSIS: We designed a phase IV, multicentre, open-label, crossover study to evaluate non-inferiority of bleed control of ≥6 months on conventional dosing in comparison to ≥6 months on dose intervention. This dose intervention consists of reducing the dose of emicizumab to target a trough concentrations of 30 µg/mL using individual pharmacokinetic (PK) parameters. Ninety-five PwHA aged >1 years who received conventional dosing of emicizumab for ≥12 months with good bleeding control during the last 6 months will be recruited from all Dutch haemophilia treatment centres. The study is powered to detect a clinically relevant decrease (risk difference) of 15% in the proportion of patients without treated bleeds during follow-up. Secondary endpoints are spontaneous joint or muscle bleeds, and annualised treated bleeding rates (using negative binomial regression). Cost-effectivity between conventional dosing and individualised PK-guided dosing of emicizumab will be compared. ETHICS AND DISSEMINATION: The DosEmi study was approved by the Medical Ethics Review Committee NedMec of the University Medical Center of Utrecht, The Netherlands. Study results will be communicated through publications in international scientific journals and presentations at (inter)national conferences. TRIAL REGISTRATION NUMBER: EUCTR2021-004039-10-NL at https://trialsearch.who.int. PROTOCOL VERSION: V.4.1 on 28 October 2022 (DosEmi protocol_V4.1; NL81112.041.22)

DosEmi study protocol: a phase IV, multicentre, open-label, crossover study to evaluate non-inferiority of pharmacokinetic-guided reduced dosing compared with conventional dosing of emicizumab in people with haemophilia A

INTRODUCTION: Emicizumab effectively prevents bleeding in people with haemophilia A (PwHA), but is a burden for national healthcare budgets and consequently may limit access. According to the drug label, dosing of emicizumab is based on body weight with fixed intervals of 7, 14 or 28 days, which leads to mean plasma concentrations of 55 µg/mL (SD 15 µg/mL). However, a moderate variability of concentrations and a minimal effective concentration of 30 µg/mL have been suggested in studies. Therefore, a dose of emicizumab that targets a trough concentration of 30 µg/mL is hypothesised to be equally effective as conventional dosing in the prevention of bleeding. METHODS AND ANALYSIS: We designed a phase IV, multicentre, open-label, crossover study to evaluate non-inferiority of bleed control of ≥6 months on conventional dosing in comparison to ≥6 months on dose intervention. This dose intervention consists of reducing the dose of emicizumab to target a trough concentrations of 30 µg/mL using individual pharmacokinetic (PK) parameters. Ninety-five PwHA aged >1 years who received conventional dosing of emicizumab for ≥12 months with good bleeding control during the last 6 months will be recruited from all Dutch haemophilia treatment centres. The study is powered to detect a clinically relevant decrease (risk difference) of 15% in the proportion of patients without treated bleeds during follow-up. Secondary endpoints are spontaneous joint or muscle bleeds, and annualised treated bleeding rates (using negative binomial regression). Cost-effectivity between conventional dosing and individualised PK-guided dosing of emicizumab will be compared. ETHICS AND DISSEMINATION: The DosEmi study was approved by the Medical Ethics Review Committee NedMec of the University Medical Center of Utrecht, The Netherlands. Study results will be communicated through publications in international scientific journals and presentations at (inter)national conferences. TRIAL REGISTRATION NUMBER: EUCTR2021-004039-10-NL at https://trialsearch.who.int. PROTOCOL VERSION: V.4.1 on 28 October 2022 (DosEmi protocol_V4.1; NL81112.041.22)

Quantification of emicizumab by mass spectrometry in plasma of people with hemophilia A: A method validation study

Background: Emicizumab is a new treatment option for people with hemophilia A. Emicizumab was approved with a body-weight-based dosage regimen, without laboratory monitoring requirements. Guidelines, however, recommend measuring emicizumab concentrations when the presence of antidrug antibodies is suspected. Furthermore, drug monitoring can be useful in clinical decision making, in adherence checking, and for research purposes. Therefore, we developed a liquid chromatography–tandem mass spectrometry (LC-MS/MS) method for quantifying emicizumab. We performed a validation study on this LC-MS/MS method quantifying emicizumab in the plasma of people with hemophilia A. Methods: Sample preparation for LC-MS/MS analysis included ammonium sulfate protein precipitation and trypsin digestion. A signature peptide of emicizumab and a matching stable isotope-labeled internal standard were used to quantify emicizumab by LC-MS/MS analysis. Validation was performed in accordance with the “Guideline on Bioanalytical Method Validation” of the European Medicines Agency (EMA). The LC-MS/MS method was cross validated against a modified and calibrated (r2 Diagnostics) one-stage clotting assay (OSA). Conclusions: The LC-MS/MS method demonstrated linearity over a wide range of emicizumab concentrations, far exceeding the concentrations observed in people with hemophilia A. Precision and accuracy were excellent, and all other validation parameters were also within the acceptance EMA criteria. Cross validation showed that the LC-MS/MS method and the OSA-based method can be used interchangeably for drug monitoring of emicizumab without the application of a correction factor

Reasons for compliance or noncompliance with advice to test for hepatitis C via an internet-mediated blood screening service: a qualitative study

<p>Abstract</p> <p>Background</p> <p>Hepatitis C virus (HCV) is mainly transmitted by exposure to infected blood, and can lead to liver cirrhosis and liver cancer. Since the onset of HCV and the development of liver cirrhosis usually are asymptomatic, many HCV-infected individuals are still undiagnosed. To identify individuals infected with HCV in the general population, a low threshold, internet-mediated blood testing service was set up. We performed a qualitative study examining reasons for compliance and noncompliance with advice to test for HCV via the online blood testing service.</p> <p>Methods</p> <p>Semistructured telephone interviews were conducted with 33 website visitors who had been advised to test for HCV (18 testers, 15 non-testers). Transcribed interviews were analyzed qualitatively and interpreted using psychosocial theories of health behavior.</p> <p>Results</p> <p>Reasons for testing pertaining to the online service were: the testing procedure is autonomous, personalized test advice is provided online, reminder emails are sent, and there is an online planning tool. Reasons for testing not specific to the online service were: knowing one's status can prevent liver disease and further transmission of HCV, HCV is curable, testing can provide reassurance, physical complaints are present, and there is liver disease in one's social environment. Service-related reasons for not testing pertained to inconvenient testing facilities, a lack of commitment due to the low threshold character of the service, computer/printing problems, and incorrectly interpreting an online planning tool. The reasons for not testing that are not specific to the online service were: the belief that personal risk is low, the absence of symptoms, low perceived urgency for testing and treatment, fear of the consequences of a positive test result, avoiding threatening information, and a discouraging social environment.</p> <p>Conclusions</p> <p>Features specific to the online service played a significant role in motivation to test for HCV above and beyond the more conventional perceived health benefits of HCV testing. However, some online specific features were considered problematic and need to be adapted. Methods and strategies for dealing with these impeding factors and for improving compliance with testing via the online service are outlined.</p

Hepatitis C virus infections among HIV-infected men who have sex with men: an expanding epidemic

Background: Since 2000 outbreaks of sexually transmitted hepatitis C Virus (HCV) infections have been reported among HIV-infected men who have sex with men (MSM). We studied the prevalence and determinants of HCV-infection among MSM attending a large sexually transmitted infection (STI) clinic in the Netherlands. Methods: In 2007-2008, 3125 attendees of the STI clinic Amsterdam, including 689 MSM, participated in an anonymous biannual crosssectional survey. Participants were interviewed and screened for HIV and HCV antibodies. Additionally, all anti-HCV positive and HIV-infected individuals were tested for HCV RNA. Using phylogenetic analysis, HCV strains of the STI clinic attendees were compared with those isolated from MSM with acute HCV in 2000-2007. Determinants of HCV-infection were analysed using logistic regression. Results: Two of 532 (0.4%) HIV-negative MSM and 28 of 157 (17.8%) HIV-positive MSM were infected with HCV. Over the study period, HCV prevalence among HIV-infected MSM increased (14.6%-20.9%). Seven of 28 (25.0%) HIV/HCV coinfected MSM had acute HCV infection. Only five of 28 (17.90%) HIV/HCV coinfected MSM ever injected drugs (IDU). HIV-infection, IDU, fisting and gamma hydroxy butyrate (GHB)-use were significantly associated with HCV-infection. Phylogenetic analyses revealed a high degree of MSM-specific clustering. Conclusion: We found a high and increasing HCV prevalence in HIV-infected MSM. Though not statistically significant, this trend, and the relatively large proportion of acute infections suggest ongoing transmission of HCV in HIV-positive MSM. Regardless of IDU, rough sexual techniques and use of recreational drugs were associated with HCV-infection; phylogenetic analysis supported sexual transmission. Targeted prevention, like raising awareness and routine testing, is needed to stop the further spread among HIV-infected MSM, and to prevent possible spillover to HIV-negative MSM. (C) 2009 Wolters Kluwer Health | Lippincott Williams & Wilkin

Outcomes of hepatitis C screening programs targeted at risk groups hidden in the general population: a systematic review

Background: Effective screening programs are urgently needed to provide undiagnosed hepatitis C virus (HCV)-infected individuals with therapy. This systematic review of characteristics and outcomes of screening programs for HCV focuses on strategies to identify HCV risk groups hidden in the general population. Methods: We conducted a comprehensive search of MEDLINE and EMBASE databases for articles published between 1991-2010, including studies that screened the general population using either a newly developed (nonintegrated) screening program or one integrated in existing health care facilities. Look-back studies, prevalence studies, and programs targeting high-risk groups in care (e.g., current drug users) were excluded. Results: After reviewing 7052 studies, we identified 67 screening programs: 24 nonintegrated; 41 programs integrated in a variety of health care facilities (e.g., general practitioner); and 2 programs with both integrated and nonintegrated strategies. Together, these programs identified approximately 25,700 HCV-infected individuals. In general, higher HCV prevalence was found in programs in countries with intermediate to high HCV prevalence, in psychiatric clinics, and in programs that used a prescreening selection based on HCV risk factors. Only 6 programs used a comparison group for evaluation purposes, and 1 program used theory about effective promotion for screening. Comparison of the programs and their effectiveness was hampered by lack of reported data on program characteristics, clinical follow-up, and type of diagnostic test. Conclusions: A prescreening selection based on risk factors can increase the efficiency of screening in low-prevalence populations, and we need programs with comparison groups to evaluate effectiveness. Also, program characteristics such as type of diagnostic test, screening uptake, and clinical outcomes should be reported systematicall

Is adding HCV screening to the antenatal national screening program in Amsterdam, the Netherlands, cost-effective?

INTRODUCTION: Hepatitis C virus (HCV) infection can lead to severe liver disease. Pregnant women are already routinely screened for several infectious diseases, but not yet for HCV infection. Here we examine whether adding HCV screening to routine screening is cost-effective. METHODS: To estimate the cost-effectiveness of implementing HCV screening of all pregnant women and HCV screening of first-generation non-Western pregnant women as compared to no screening, we developed a Markov model. For the parameters of the model, we used prevalence data from pregnant women retrospectively tested for HCV in Amsterdam, the Netherlands, and from literature sources. In addition, we estimated the effect of possible treatment improvement in the future. RESULTS: The incremental costs per woman screened was €41 and 0.0008 life-years were gained. The incremental cost-effectiveness ratio (ICER) was €52,473 which is above the cost-effectiveness threshold of €50,000. For screening first-generation non-Western migrants, the ICER was €47,113. Best-case analysis for both scenarios showed ICERs of respectively €19,505 and €17,533. We estimated that if costs per treatment were to decline to €3,750 (a reduction in price of €31,000), screening all pregnant women would be cost-effective. CONCLUSIONS: Currently, adding HCV screening to the already existing screening program for pregnant women is not cost-effective for women in general. However, adding HCV screening for first-generation non-Western women shows a modest cost-effective outcome. Yet, best case analysis shows potentials for an ICER below €20,000 per life-year gained. Treatment options will improve further in the coming years, enhancing cost-effectiveness even more

DosEmi study protocol: a phase IV, multicentre, open-label, crossover study to evaluate non-inferiority of pharmacokinetic-guided reduced dosing compared with conventional dosing of emicizumab in people with haemophilia A

Introduction Emicizumab effectively prevents bleeding in people with haemophilia A (PwHA), but is a burden for national healthcare budgets and consequently may limit access. According to the drug label, dosing of emicizumab is based on body weight with fixed intervals of 7, 14 or 28 days, which leads to mean plasma concentrations of 55 µg/mL (SD 15 µg/mL). However, a moderate variability of concentrations and a minimal effective concentration of 30 µg/mL have been suggested in studies. Therefore, a dose of emicizumab that targets a trough concentration of 30 µg/mL is hypothesised to be equally effective as conventional dosing in the prevention of bleeding.Methods and analysis We designed a phase IV, multicentre, open-label, crossover study to evaluate non-inferiority of bleed control of ≥6 months on conventional dosing in comparison to ≥6 months on dose intervention. This dose intervention consists of reducing the dose of emicizumab to target a trough concentrations of 30 µg/mL using individual pharmacokinetic (PK) parameters. Ninety-five PwHA aged &gt;1 years who received conventional dosing of emicizumab for ≥12 months with good bleeding control during the last 6 months will be recruited from all Dutch haemophilia treatment centres. The study is powered to detect a clinically relevant decrease (risk difference) of 15% in the proportion of patients without treated bleeds during follow-up. Secondary endpoints are spontaneous joint or muscle bleeds, and annualised treated bleeding rates (using negative binomial regression). Cost-effectivity between conventional dosing and individualised PK-guided dosing of emicizumab will be compared.Ethics and dissemination The DosEmi study was approved by the Medical Ethics Review Committee NedMec of the University Medical Center of Utrecht, The Netherlands. Study results will be communicated through publications in international scientific journals and presentations at (inter)national conferences.Trial registration number EUCTR2021-004039-10-NL at https://trialsearch.who.int.Protocol version V.4.1 on 28 October 2022 (DosEmi protocol_V4.1; NL81112.041.22)

Quantification of emicizumab by mass spectrometry in plasma of people with hemophilia A: A method validation study

Background: Emicizumab is a new treatment option for people with hemophilia A. Emicizumab was approved with a body-weight-based dosage regimen, without laboratory monitoring requirements. Guidelines, however, recommend measuring emicizumab concentrations when the presence of antidrug antibodies is suspected. Furthermore, drug monitoring can be useful in clinical decision making, in adherence checking, and for research purposes. Therefore, we developed a liquid chromatography–tandem mass spectrometry (LC-MS/MS) method for quantifying emicizumab. We performed a validation study on this LC-MS/MS method quantifying emicizumab in the plasma of people with hemophilia A. Methods: Sample preparation for LC-MS/MS analysis included ammonium sulfate protein precipitation and trypsin digestion. A signature peptide of emicizumab and a matching stable isotope-labeled internal standard were used to quantify emicizumab by LC-MS/MS analysis. Validation was performed in accordance with the “Guideline on Bioanalytical Method Validation” of the European Medicines Agency (EMA). The LC-MS/MS method was cross validated against a modified and calibrated (r2 Diagnostics) one-stage clotting assay (OSA). Conclusions: The LC-MS/MS method demonstrated linearity over a wide range of emicizumab concentrations, far exceeding the concentrations observed in people with hemophilia A. Precision and accuracy were excellent, and all other validation parameters were also within the acceptance EMA criteria. Cross validation showed that the LC-MS/MS method and the OSA-based method can be used interchangeably for drug monitoring of emicizumab without the application of a correction factor