To Approve or not to Approve? A Comparative Analysis of State-Company-Indigenous Community Interactions in Mining in Canada and Sweden.

This Special Section explores the interplay between Indigenous peoples, industry, and the state in five proposed and active mining projects in Canada and Sweden. The overall aim is to identify factors shaping the quality of Indigenous community-industry-state interactions in mining and mine development. An ambition underlying the research is to develop knowledge to help manage mining related land-use conflicts in Sweden by drawing on Canadian comparisons and experience. This paper synthesizes the comparative research that has been conducted across jurisdictions in three Canadian provinces and Sweden. It focuses on the interplay between the properties of the governance system, the quality of interaction and governance outcomes. We combine institutional and interactive governance theory and use the concept of governability to assess how and why specific outcomes, such as mutually beneficial interaction, collaboration, or opposition, occurred. The analysis suggests there are measures that can be taken by the Swedish Government to improve the governability of mining related issues, by developing alternative, and more effective, avenues to recognize, and protect, Sámi rights and culture, to broaden the scope and increase the legitimacy and transparency of the EIAs, to raise the quality of interaction and consultation, and to develop tools to actively stimulate and support collaboration and partnerships on equal terms. Generally, we argue that Indigenous community responses to mining must be understood within a larger framework of Indigenous self-determination, in particular the communities' own assessments of their opportunities to achieve their long-term objectives using alternative governing modes and types of interactions.

The cascade of care for patients with chronic hepatitis delta in Southern Stockholm, Sweden for the past 30 years.

BACKGROUND AND AIMS: Previous studies have shown suboptimal screening for hepatitis D virus (HDV) among patients with chronic hepatitis B (CHB). This study presents the cascade of care for HDV infection in a major secondary referral centre in Southern Stockholm, Sweden. METHODS: HBsAg+ve patients attending Karolinska University Hospital (KUH) from 1992 to 2022 were identified. The prevalence of anti-HDV and/or HDV RNA positivity, interferon (IFN) therapy and maintained virological responses (MVR) after HDV treatment were assessed. Also, time to anti-HDV testing was analysed in relation to liver-related outcomes with logistic regression. RESULTS: Among 4095 HBsAg+ve persons, 3703 (90.4%) underwent an anti-HDV screening; within a median of 1.8 months (range 0.0-57.1) after CHB diagnosis. This screening rate increased over time, to 97.9% in the last decade. Overall, 310 (8.4%) were anti-HDV+ve, of which 202 (65.2%) were HDV RNA+ve. Eighty-five (42%) received IFN, and 9 (10.6%) achieved MVR at the last follow-up. The predictive factors for anti-HDV screening were Asian origin, diagnosis after the year 2012, HIV co-infection (negative factor) and HBV DNA level < 2000 IU/mL in univariable analysis, while HIV co-infection was the only remaining factor in multivariable analysis. Delayed anti-HDV test >5 years was independently associated with worsened liver-related outcomes (adjusted odds ratio = 7.6, 95% CI 1.8-31.6). CONCLUSION: Higher frequency of HDV screening than previously published data could be seen among CHB patients at KUH in a low-endemic setting. Receiving a delayed screening test seems to be associated with worse outcomes, stressing the need of a strategy for timely HDV diagnosis.

Why do Mines Fail to Obtain a Social License to Operate?: Insights from the Proposed Kallak Iron Mine (Sweden) and the Prosperity/New Prosperity Gold-Copper Mine (Canada).

Opposition to mines endures even in countries with relatively strong environmental assessment processes and regulations. Why proposed mines fail to obtain a social license to operate is analyzed by developing a framework comprised of three concepts-process legitimacy, distributional outcomes, and values compatibility-drawing from the social license to operate, interactive governance, and environmental justice literatures. The framework is applied to understand opposition from local Indigenous people to two mine projects, one in Sweden and the other in British Columbia, Canada. Evidence from interviews with Sami legal experts and Reindeer Herding Community representatives and an advisor with the Tsilhqot'in National Government, as well as from secondary sources is used to analyze the contestation. Despite the proposed mines being situated in different governance contexts, the reasons for the opposition are markedly similar - environmental assessment processes are illegitimate, distributional outcomes unfair, and values incompatible. The comparative empirical analysis leads to refining the framework as a scaffold with values compatibility as the foundational plank, rather than three independent planks contributing to a social license to operate. The analysis offers insights into company commitments to Indigenous engagement, enhancements to process legitimacy, and evolving and paradigmatic shifts in governance processes, as articulated by Indigenous peoples and international governance mechanisms such as the 2007 United Nations Declaration on the Rights of Indigenous Peoples.

Exploring prospects of deliberation in intractable natural resource management conflicts.

Deliberative processes are increasingly advocated as means to handle intractable natural resource management (NRM) conflicts. Research shows that disputing actors can deliberate and achieve higher degrees of mutual understanding and working agreements under ideal conditions, but the transferability of these findings to real-world intractable NRM conflicts can be questioned. This paper explores the possibilities of designing and realizing deliberation and its expected outcomes in real-world NRM conflicts. We used recommended design principles to set up deliberative processes in two intractable mining conflicts involving indigenous peoples in Northern Sweden and assessed the actors' communication and outcomes using frame analysis. The results show that the recommended design principles are hard, but not impossible, to fully implement in intractable NRM conflicts. Both conflicts proved difficult to deliberate and resolve in the sense of reaching agreements. However, the findings suggest that deliberation, as well as meta-consensus, or structured disagreement, is possible to achieve in settings with favorable conditions, e.g. good and established inter-group relations prior to the conflict. In the absence of these conditions, where relations were hostile and shaped by historical and institutional injustices, deliberation was not achieved. In both cases, polarization among the participants remained, or increased, in spite of the deliberative activities. The study highlights the importance of understanding deliberation as embedded in place specific historical and institutional contexts which shape both process and outcomes in powerful ways. More efforts should focus on alternative, or complementary, ways to handle intractable NRM conflicts, including how contested experiences of history, institutions and Indigenous rights can be addressed.

Persisting Salivary IgG Against SARS-CoV-2 at 9 Months After Mild COVID-19: A Complementary Approach to Population Surveys.

BACKGROUND: Declining humoral immunity in coronavirus disease 2019 (COVID-19) patients and possible reinfection have raised concern. Mucosal immunity, particularly salivary antibodies, may be short lived although long-term studies are lacking. METHODS: Using a multiplex bead-based array platform, we investigated antibodies specific to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins in 256 saliva samples from convalescent patients 1-9 months after symptomatic COVID-19 (n = 74, cohort 1), undiagnosed individuals with self-reported questionnaires (n = 147, cohort 2), and individuals sampled prepandemic (n = 35, cohort 3). RESULTS: Salivary IgG antibody responses in cohort 1 (mainly mild COVID-19) were detectable up to 9 months postrecovery, with high correlations between spike and nucleocapsid specificity. At 9 months, IgG remained in blood and saliva in most patients. Salivary IgA was rarely detected at this time point. In cohort 2, salivary IgG and IgA responses were significantly associated with recent history of COVID-19-like symptoms. Salivary IgG tolerated temperature and detergent pretreatments. CONCLUSIONS: Unlike SARS-CoV-2 salivary IgA that appeared short lived, specific saliva IgG appeared stable even after mild COVID-19, as for blood serology. This noninvasive saliva-based SARS-CoV-2 antibody test with home self-collection may be a complementary alternative to conventional blood serology.

Anti-HCV prevalence and risk factor-based screening for hepatitis C in pregnant women and their partners in Sweden.

BACKGROUND: The hepatitis C virus (HCV) prevalence in Sweden is estimated to be <0.5%, but unclear in pregnant women. The dominating route of transmission is drug use (DU), blood transfusions constituted a risk before 1992. The aim was to examine the anti-HCV prevalence and risk factors for HCV among pregnant women and their partners to evaluate screening strategies. METHODS: Pregnant women and partners in Örebro County and in southern Stockholm were offered HCV-screening when visiting an antenatal clinic in 2013-2016, and completed a questionnaire concerning the country of birth, knowledge of HCV-status and HCV risk factors. RESULTS: In Örebro 2,827 pregnant women and 707 partners, and in Stockholm 1,281 pregnant women and 320 partners participated. Anti-HCV was positive in 34 (0.7%) (25 pregnant women) and the associated risk factors were DU (n = 27), partner with HCV (n = 24) and not born in Sweden (n = 8). HCV RNA was positive in 23 (0.4%), 4 previously unknown and 10 who had been lost to follow-up. The most effective risk factor-based screening model for pregnant women included DU, blood transfusions, born in high prevalence country, partner with HCV, resulting in 538 (13%) pregnant women tested with 96% sensitivity, 87% specificity. CONCLUSIONS: In this study of expecting parents in two Swedish regions, the anti-HCV prevalence was 0.7% and 0.4% were viraemic, of which about 60% were previously unknown or lost to follow-up. Awaiting more studies, including cost-benefit analysis evaluating universal screening, we recommend this improved risk factor-based screening model to identify HCV-infected individuals who need follow-up and therapy.

Management of hepatitis B virus infection, updated Swedish guidelines.

Despite access to effective antiviral drugs and vaccines, hepatitis B virus (HBV) infection remains a major health issue worldwide. HBV is highly infectious and may cause chronic infection, progressive liver damage, hepatocellular cancer (HCC) and death. Early diagnosis, proper management and timing of treatment are crucial. The Swedish Reference group for Antiviral Treatment (RAV) here provides updated evidence-based guidelines for treatment and management of HBV infection which may be applicable also in other countries. Tenofovir alafenamide (TAF) has been introduced as a novel treatment option and new principles regarding indication and duration of treatment and characterization of hepatitis B have been gradually introduced which justifies an update of the previous guidelines from 2007. Updated guidelines on HCC surveillance in HBV-infected patients, treatment and prophylaxis for patients undergoing liver transplantation as well as management of pregnant women and children with HBV infection are also provided.

Prevalence of Viremic hepatitis C, hepatitis B, and HIV infection, and vaccination status among prisoners in Stockholm County.

BACKGROUND: Identification and knowledge of settings with high prevalence of hepatitis C virus (HCV) infection is important when aiming for elimination of HCV. The primary aim of this study was to estimate the prevalence of viremic HCV infection among Swedish prisoners. Secondary aims were to estimate the prevalence of hepatitis B surface antigen (HBsAg), human immunodeficiency virus (HIV), and the proportion who have received hepatitis B virus (HBV) vaccination. METHODS: A cross-sectional study of all incarcerated persons (n = 667) at all prisons (n = 9) in Stockholm County was conducted. All prisoners are routinely offered opt-in screening for HCV antibodies (anti-HCV), HCV RNA, HBsAg, anti-HBs, anti-HBc and HIV Ag/Ab at prison in Sweden. Data on the results of these tests and the number of received HBV vaccine doses were collected from the prison medical records. The parameters of HCV RNA, anti-HCV, and occurrence of testing for HCV were analysed in multiple logistic regression models in relation to age, sex and prison security class. RESULTS: The median age was 35 (IQR 26-44) years, and 93.4% were men. Seventy-one percent (n = 471) had been tested for anti-HCV, 70% (n = 465) for HBsAg and 71% (n = 471) for HIV. The prevalence of anti-HCV, HCV RNA, HBsAg and HIV Ag/Ab was 17.0, 11.5, 1.9, and 0.2%, respectively among tested persons. The proportion of prisoners who had received full HBV vaccination was 40.6% (n = 271) among all study subjects. CONCLUSIONS: The prevalence of viremic HCV infection among Swedish prisoners in Stockholm County was 11.5%, which is high in comparison to the general population. Therefore, when aiming for the WHO goal of HCV elimination, prisons could suit as a platform for identification and treatment of HCV infection. There is a need to increase testing for blood-borne viruses and to improve vaccination coverage against HBV in Swedish prisons.

Prevalence of chronic hepatitis C virus infection among childhood cancer survivors in Stockholm, Sweden.

Background: Childhood cancer survivors treated before 1992, when blood donor screening for hepatitis C virus (HCV) infection was introduced, are at risk of transfusion-transmitted HCV infection. A national HCV screening campaign targeting blood transfusion recipients was launched in Sweden in 2007-2010. The aims of this study were to, among adult childhood cancer survivors in Stockholm County, investigate the prevalence of HCV infection, the natural course of infection, treatment outcome and anti-HCV testing frequency before, during and after the screening campaign and finally to actively screen the untested ones. Material and Methods: This was a combined retrospective register based and prospective screening study of adult childhood cancer survivors (n = 686) treated for malignancy in Stockholm before 1992. In the first part, we investigated the prevalence of HCV infection and previous anti-HCV testing, and in the second part, we actively traced and HCV-screened the remaining untested cohort living in Stockholm. Analysis of previous documented anti-HCV tests in medical records, laboratory records, and the national communicable disease registry was performed. In the second part, 231 presumably untested individuals were contacted by mail and offered an anti-HCV test. The natural course of HCV infection and treatment outcome was analyzed for those found to be chronically infected. Results: In total, 235 patients were tested and 11 were HCV-RNA positive. The overall prevalence of chronic HCV infection among the tested childhood cancer survivors was thus 4.7% (95% CI = 2.6-8.2%), which is almost 10 times higher than the national prevalence of 0.5%. Only 12% of the Stockholm cohort were tested during the screening campaign in 2007-2010, while the test uptake using active tracing screening within this study was 40% (p < .001). Conclusion: With today's effective treatment options, active tracing and HCV screening of childhood cancer survivors are recommended.

Direct acting anti-viral medications for hepatitis C: Clinical trials in patients with advanced chronic kidney disease.

Hepatitis C is a global health concern, with important implications in chronic kidney disease (CKD) due to its increased prevalence in this population. Patients with advanced CKD have until recently been excluded from the pivotal direct acting anti-viral (DAA) trials, which have demonstrated high virological cure numbers. Sofosbuvir-free DAAs dasabuvir, ombitasvir/paritaprevir/ritonavir with or without ribavirin, and elbasvir/grazoprevir are well-tolerated in patients with genotype 1 and 4 CHC with CKD 4 or 5 (including HD), with virologic cure rates of above 90%, in both single-arm and placebo-controlled studies. More recently a pangenotypic approach using glecaprevir and pibrentasvir has also been shown to be highly effective in CKD 4-5. With increasingly successful treatment options with minimal side-effects most hepatitis C virus (HCV)-infected patients with CKD and ESRD can be cured. Outstanding issues to be considered is how to raise the awareness of the availability of safe DAAs and excellent outcomes in CKD, and moreover to define optimal timing of treatment and address the question of HCV eradication in all stages of CKD including the dialysis population.

Prevalence and outcome of post-transfusion hepatitis C acquired at different ages and detected in look-back screening.

OBJECTIVES: The prevalence of hepatitis C virus (HCV) infection in Sweden is estimated to 0.5%. Before 1992, blood transfusion posed a risk of HCV transmission. The primary aim of this study was to estimate anti-HCV prevalence in Stockholm County among individuals receiving blood transfusions 1965-1991. The secondary aim was to study the effect of age at transfusion on the development of liver disease and treatment outcome. MATERIALS AND METHODS: This is a retrospective analysis of individuals found to be anti-HCV tested positive in Stockholm County during a national screening campaign in Sweden 2008-2010. All anti-HCV-positive individuals were also HCV RNA tested. Data on age at transfusion, age at diagnosis, HCV genotype, viral load, fibrosis score, liver histology and antiviral treatment were recorded. RESULTS: Out of 7473, 134 (1.8%) tested individuals were anti-HCV positive and 102 were HCV RNA positive resulting in a prevalence of chronic hepatitis C (CHC) of 1.4%. The rate of advanced liver damage was 18% (10/56). Patients younger than 19 years of age at transfusion were significantly more often started on antiviral treatment compared to adult patients, 65% vs 29% p < .001. No significant correlation was found between treatment outcome and gender or age at transfusion. CONCLUSIONS: In this study, we found an anti-HCV prevalence of 1.8% which is considerably higher than the estimated prevalence in the Swedish general population (0.5%), and patients infected during childhood were more likely to receive antiviral treatment. Additional data on the HCV epidemic in Sweden are needed regarding prevalence and age distribution.

Competing pathways to sustainability? Exploring conflicts over mine establishments in the Swedish mountain region.

Natural resource (NR) exploitation often gives rise to conflict. While most actors intend to manage collectively used places and their NRs sustainably, they may disagree about what this entails. This article accordingly explores the origin of NR conflicts by analysing them in terms of competing pathways to sustainability. By comparing conflicts over mine establishments in three places in northern Sweden, we specifically explore the role of place-based perceptions and experiences. The results indicate that the investigated conflicts go far beyond the question of metals and mines. The differences between pathways supporting mine establishment and those opposing it refer to fundamental ideas about human-nature relationships and sustainable development (SD). The study suggests that place-related parameters affect local interpretations of SD and mobilisation in ways that explain why resistance and conflict exist in some places but not others. A broader understanding of a particular conflict and its specific place-based trajectory may help uncover complex underlying reasons. However, our comparative analysis also demonstrates that mining conflicts in different places share certain characteristics. Consequently, a site-specific focus ought to be combined with attempts to compare, or map, conflicts at a larger scale to improve our understanding of when and how conflicts evolve. By addressing the underlying causes and origins of contestation, this study generates knowledge needed to address NR management conflicts effectively and legitimately.

Higher risk of renal disease in chronic hepatitis C patients: Antiviral therapy survival benefit in patients on hemodialysis.

BACKGROUND & AIMS: Several studies have shown that chronic hepatitis C (CHC) infection has a negative impact on kidney function, as well as survival, in patients with chronic kidney disease (CKD) or on hemodialysis. The aim of this nationwide registry study was to describe renal disease in Swedish patients with CHC. METHODS: In the present study, patients were identified for CHC (B18.2) and CKD (N18) according to the International Classification of Diseases (ICD)-10 in the nationwide Swedish inpatient care day surgery (1997-2013) and non-primary outpatient care (2001-2013) patient registries. Hemodialysis was defined using the procedure code in the non-primary outpatient care. For each patient, up to five non-CHC diagnosed age/sex/place of residency-matched comparators were drawn from the general population at the time of diagnosis. Follow-up started at the date of CHC diagnosis and patients accrued person-time until, whichever came first, death, emigration or December 31st, 2013. RESULTS: Between 2001 and 2013, 42,522 patients received a CHC diagnosis. Of these patients, 2.5% (1,077/45,222) were diagnosed with CKD during 280,123 person-years, compared with 0.7% (1,454/202,694) in the matched general population comparators (1,504,765 person-years), resulting in a standardized incidence ratio (SIR) of 4.0. There was a 3.3-7.0-fold risk of patients with CHC requiring hemodialysis. Overall, 17% of patients with CHC receiving hemodialysis were treated for CHC; 24% in the treated cohort died compared with 56% of the untreated cohort (p <0.0001), with antiviral treatment improving survival with an odds ratio of 3.901 (p = 0.001). CONCLUSIONS: The results from this nationwide registry study showed that patients with CHC are at a higher risk of developing CKD. Furthermore, hepatitis C treatment seemed to improve survival for patients with CHC on hemodialysis compared with untreated patients. LAY SUMMARY: Hepatitis C is an infectious disease that mainly infects the liver, but has also been shown to have negative effects on other organs. This nationwide study demonstrates an increased risk of hepatitis C patients developing reduced kidney function and the need for dialysis. The study also showed improved survival in dialysis patients who received antiviral treatment.

Randomized Trial Evaluating the Impact of Ribavirin Mono-Therapy and Double Dosing on Viral Kinetics, Ribavirin Pharmacokinetics and Anemia in Hepatitis C Virus Genotype 1 Infection.

In this pilot study (RibaC), 58 hepatitis C virus (HCV) genotype 1 infected treatment-naïve patients were randomized to (i) 2 weeks ribavirin double dosing concomitant with pegylated interferon-α (pegIFN-α), (ii) 4 weeks ribavirin mono-therapy prior to adding pegIFN-α, or (iii) standard-of-care (SOC) ribavirin dosing concurrent with pegIFN-α. Four weeks of ribavirin mono-therapy resulted in a mean 0.46 log(10) IU/mL HCV RNA reduction differentially regulated across IL28B genotypes (0.89 vs. 0.21 log(10) IU/mL for CC and CT/TT respectively; P = 0.006), increased likelihood of undetectable HCV RNA week 4 after initiating pegIFN-α and thus shortened treatment duration (P<0.05), and decreased median IP-10 concentration from 550 to 345 pg/mL (P<0.001). Both experimental strategies impacted on ribavirin concentrations, and high levels were achieved after one week of double dosing. However, by day 14, double dosing entailed a greater hemoglobin decline as compared to SOC (2.2 vs. 1.4 g/dL; P = 0.03). Conclusion: Ribavirin down-regulates IP-10, and may have an anti-viral effect differently regulated across IL28B genotypes.

Understanding consistencies and gaps between desired forest futures: An analysis of visions from stakeholder groups in Sweden.

Conflicting perspectives on forests has for a long time challenged forest policy development in Sweden. Disagreements about forest futures create intractable deadlocks when stakeholders talk past each other. The purpose of this study is to move beyond this situation through the application of participatory backcasting. By comparing visions of the future forest among stakeholder groups, we highlight contemporary trajectories and identify changes that were conceived as desirable. We worked with four groups: the Biomass and Bioenergy group, the Conservation group, the Sami Livelihood group and the Recreation and Rural Development group; in total representatives from 40 organizations participated in workshops articulating the groups' visions. Our results show well-known tensions such as intrinsic versus instrumental values but also new ones concerning forests' social values. Identified synergies include prioritization of rural development, new valued-added forest products and diversified forest management. The results may feed directly into forest policy processes facilitating the process and break current deadlocks.

High-Dose Ribavirin Enhances Early Virological Response in Hepatitis C Genotype 1-Infected Patients.

BACKGROUND: The aim of the study was to investigate whether patients with a previous nonresponse to standard of care treatment with ribavirin dosed according to body weight would respond to a high individualized dose of concentration-monitored ribavirin. METHODS: Previous nonresponders to standard of care treatment with peginterferon (peg-IFN) and ribavirin were included. Ribavirin was dosed aiming at a plasma concentration of >15 µmol/L. The initial ribavirin dose was calculated from a formula based on renal function and body weight. Erythropoietin treatment was started 2 weeks before antiviral therapy. RESULTS: Twenty patients (16 men and 4 women) with a mean age of 52 years were included. Sixty percent had advanced fibrosis. Eighty percent of patients achieved an early viral response, and 60% were negative for hepatitis C virus ribonucleic acid (HCV RNA) at treatment week 24. High-dose ribavirin resulted in a significantly increased HCV RNA drop at week 12 (mean: 3.13 versus 2.05 IU/mL; P < 0.001). Nine patients were negative for HCV RNA at the end of treatment, and 1 achieved sustained viral response. The final steady-state daily dose of ribavirin varied from 1400 to 4400 mg. Hemoglobin levels decreased during treatment, mean Hb 163, 134, and 110 g/L at week 0, 4, and 12, respectively. Two patients received blood transfusions. No other severe adverse events were recorded. CONCLUSIONS: An individualized high ribavirin dose resulted in a more pronounced early viral HCV RNA decline than a standard-dose ribavirin scheme. This regime is safe provided that close monitoring of anemia is undertaken and that treatment with erythropoietin is given.

Strategies in health-promoting dialogues--primary healthcare nurses' perspectives--a qualitative study.

AIM AND OBJECTIVES: The aim of this study was to describe dialogic strategies about health and lifestyle used by primary healthcare nurses (PHNs) in the Västerbotten Intervention Programme (VIP) in Sweden. BACKGROUND: The VIP offers all citizens aged 40, 50 and 60 in Västerbotten County an individual health check-up followed by a health-promoting dialogue with a specialist PHN. Inconsistencies in previous reports of the effects of lifestyle counselling and health promotion suggest that it is important to study dialogues about health and lifestyle to understand health-promoting strategies and to highlight aspects important to improving their effects. METHOD: In 2010, we conducted in-depth interviews with ten experienced PHNs working with the VIP at eight healthcare centres in Västerbotten County, Sweden. Qualitative content analysis was used to illuminate the nurses' strategies in health-promoting dialogues. The Regional Ethics Board (Dno 06-126M) approved the study. RESULTS: The PHNs used various strategies in dialogues about health and lifestyle that fell under the five themes 'Guiding patients vs. pressuring them; Adjusting to patients vs. directing the conversation; Inspiring confidence vs. instilling fear; Motivating and supporting patients vs. demanding responsibility; and lastly, Introducing emotionally charged subjects or avoiding them'. CONCLUSIONS: The results of this study may add knowledge about the difficulties and opportunities in health counselling. In the discussion, we suggest professional reflection as a means to increase knowledge and awareness about the self and context in the process of health counselling.

Novel method for studying photolability of topical formulations: a case study of titanium dioxide stabilization of ketoprofen.

Sunlight may decompose active substances and excipients in pharmaceuticals. This may cause formulation problems as well as induce adverse skin reactions. The photodecomposition of topical preparations may occur on the skin surface, but also deeper in the skin after penetration of light into the viable tissues. The aim of the present study was to investigate whether microparticles of titanium dioxide could protect against photodecomposition using ketoprofen as a photolabile model substance. The results showed quality differences between titanium dioxide, where surface-coated particles were superior to pharmaceutical grades in reducing the degradation in vitro. The protective effect was also studied in humans. The skin was treated for 3 h with the gels and then exposed to ultraviolet (UV) light (11.7 J/cm2 UVA and 5.4 mJ/cm2 UVB). Layers of the stratum corneum were then removed by consecutive tape strippings and assayed for content of ketoprofen. The remaining amount was higher in the different stratum corneum compartments after treatment with a gel containing 4% coated titanium dioxide compared with a transparent gel. Thus, surface-coated microparticles of titanium dioxide may well be of clinical benefit in protecting photolabile drug substances against sunlight.

High-dose ribavirin in combination with standard dose peginterferon for treatment of patients with chronic hepatitis C.

Improved treatment regimens for patients with chronic hepatitis C, genotype 1 and high viral load are needed. Increasing the dose of ribavirin has increased the response rate, but experience with doses of more than 1,200 mg/day is limited. The aim of this study was to investigate the safety and tolerance to treatment with a high and individualized dose of ribavirin in combination with peginterferon. Ten patients with chronic hepatitis C, genotype 1 and high viral load were treated with peginterferon alfa-2a and ribavirin for 48 weeks in a prospective trial. The initial ribavirin dose was individualized and calculated from a pharmacokinetic formula based mainly on renal function. Ribavirin plasma concentrations were monitored, and the dose was adjusted to reach the target concentration. Hemoglobin was monitored, and patients were treated with erythropoietin and blood transfusions when indicated. After dose adjustments, the mean dose of ribavirin was 2,540 mg/day (range, 1,600-3,600) at week 24. The main side effect was anemia, which was controlled with erythropoietin. Two patients required blood transfusions. One patient was withdrawn at week 24 because of a lack of viral response, and one patient at week 39 because of side effects, primarily interferon associated. At follow-up (>or=24 weeks posttreatment), nine of ten patients had undetectable HCV RNA and thus were cured by standard definitions. In conclusion, a high dose of ribavirin according to an individualized schedule is feasible but associated with more frequent and serious side effects such as anemia. The viral response merits further evaluation.