Modeling geographic vaccination strategies for COVID-19 in Norway.

Vaccination was a key intervention in controlling the COVID-19 pandemic globally. In early 2021, Norway faced significant regional variations in COVID-19 incidence and prevalence, with large differences in population density, necessitating efficient vaccine allocation to reduce infections and severe outcomes. This study explored alternative vaccination strategies to minimize health outcomes (infections, hospitalizations, ICU admissions, deaths) by varying regions prioritized, extra doses prioritized, and implementation start time. Using two models (individual-based and meta-population), we simulated COVID-19 transmission during the primary vaccination period in Norway, covering the first 7 months of 2021. We investigated alternative strategies to allocate more vaccine doses to regions with a higher force of infection. We also examined the robustness of our results and highlighted potential structural differences between the two models. Our findings suggest that early vaccine prioritization could reduce COVID-19 related health outcomes by 8% to 20% compared to a baseline strategy without geographic prioritization. For minimizing infections, hospitalizations, or ICU admissions, the best strategy was to initially allocate all available vaccine doses to fewer high-risk municipalities, comprising approximately one-fourth of the population. For minimizing deaths, a moderate level of geographic prioritization, with approximately one-third of the population receiving doubled doses, gave the best outcomes by balancing the trade-off between vaccinating younger people in high-risk areas and older people in low-risk areas. The actual strategy implemented in Norway was a two-step moderate level aimed at maintaining the balance and ensuring ethical considerations and public trust. However, it did not offer significant advantages over the baseline strategy without geographic prioritization. Earlier implementation of geographic prioritization could have more effectively addressed the main wave of infections, substantially reducing the national burden of the pandemic.

Unexpected vaginal bleeding and COVID-19 vaccination in nonmenstruating women.

The association between coronavirus disease 2019 (COVID-19) vaccination and vaginal bleeding among nonmenstruating women is not well studied. The Norwegian Institute of Public Health followed several cohorts throughout the pandemic and early performed a systematic data collection of self-reported unexpected vaginal bleeding in nonmenstruating women. Among 7725 postmenopausal women, 7148 perimenopausal women, and 7052 premenopausal women, 3.3, 14.1, and 13.1% experienced unexpected vaginal bleeding during a period of 8 to 9 months, respectively. In postmenopausal women, the risk of unexpected vaginal bleeding (i.e., postmenopausal bleeding) in the 4 weeks after COVID-19 vaccination was increased two- to threefold, compared to a prevaccination period. The corresponding risk of unexpected vaginal bleeding after vaccination was increased three- to fivefold in both nonmenstruating peri- and premenopausal women. In the premenopausal women, Spikevax was associated with at 32% increased risk as compared to Comirnaty. Our results must be confirmed in future studies.

Heavy bleeding and other menstrual disturbances in young women after COVID-19 vaccination.

BACKGROUND: Many signals of menstrual disturbances as possible side effects of vaccination against COVID-19 have been reported. Our objective was to compare the risk of menstrual disturbances before and after vaccination among women aged 18-30 years in Oslo, Norway. METHODS: We used electronic questionnaires to collect reports of menstrual disturbances from 3972 women aged 18-30 years, participating in the population-based Norwegian Young Adult Cohort. We examined the occurrence of menstrual disturbances (heavier bleeding than usual, prolonged bleeding, shorter interval between menstruations, longer interval between menstruations, spot bleedings, stronger pain during menstruation, period pain without bleeding) before and after the first and second dose of COVID-19 vaccine. Relative risks (RR) according to vaccination were estimated using a self-controlled case-series design. We performed additional analyses stratified by vaccine brand, contraception/hormone use, and presence of gynecological condition(s). RESULTS: The prevalence of any menstrual disturbance was 36.7 % in the last menstrual cycle prior the first vaccine dose. The RR for heavier bleeding than usual was 1.90 (95 % CI: 1.69-2.13) after the first vaccine dose and 1.84 (95 % CI 1.66-2.03) after the second dose. Increased risks of prolonged bleeding, shorter interval between menstruations, and stronger pain during menstruation were also observed after both doses. The RRs did not differ with vaccine brand, contraception/hormone use, or presence of gynecological condition(s) for any of the menstrual disturbances. CONCLUSION: Menstrual disturbances were common regardless of vaccination. We found increased risk of menstrual disturbances after vaccination, particularly for heavier bleeding than usual, prolonged bleeding, shorter interval between menstruations, and stronger period pain. In the future, menstrual characteristics should be included in vaccine trials.

Effectiveness of mRNA Booster Vaccination Against Mild, Moderate, and Severe COVID-19 Caused by the Omicron Variant in a Large, Population-Based, Norwegian Cohort.

BACKGROUND: Understanding how booster vaccination can prevent moderate and severe illness without hospitalization is crucial to evaluate the full advantage of mRNA boosters. METHODS: We followed 85 801 participants (aged 31-81 years) in 2 large population-based cohorts during the Omicron BA.1/2 wave. Information on home testing, PCR testing, and symptoms of coronavirus disease 2019 (COVID-19) was extracted from biweekly questionnaires covering the period 12 January 2022 to 7 April 2022. Vaccination status and data on previous SARS-CoV-2 infection were obtained from national registries. Cox regression was used to estimate the effectiveness of booster vaccination compared to receipt of 2-dose primary series >130 days previously. RESULTS: The effectiveness of booster vaccination increased with increasing severity of COVID-19 and decreased with time since booster vaccination. The effectiveness against severe COVID-19 was reduced from 80.9% shortly after booster vaccination to 63.4% in the period >90 days after vaccination. There was hardly any effect against mild COVID-19. The effectiveness tended to be lower among subjects aged ≥60 years than those aged <50 years. CONCLUSIONS: This is the first population-based study to evaluate booster effectiveness against self-reported mild, moderate, and severe COVID-19. Our findings contribute valuable information on duration of protection and thus timing of additional booster vaccinations.

Age and product dependent vaccine effectiveness against SARS-CoV-2 infection and hospitalisation among adults in Norway: a national cohort study, July-November 2021.

BACKGROUND: COVID-19 vaccines have been crucial in the pandemic response and understanding changes in vaccines effectiveness is essential to guide vaccine policies. Although the Delta variant is no longer dominant, understanding vaccine effectiveness properties will provide essential knowledge to comprehend the development of the pandemic and estimate potential changes over time. METHODS: In this population-based cohort study, we estimated the vaccine effectiveness of Comirnaty (Pfizer/BioNTech; BNT162b2), Spikevax (Moderna; mRNA-1273), Vaxzevria (AstraZeneca; ChAdOx nCoV-19; AZD1222), or a combination against SARS-CoV-2 infections, hospitalisations, intensive care admissions, and death using Cox proportional hazard models, across different vaccine product regimens and age groups, between 15 July and 31 November 2021 (Delta variant period). Vaccine status is included as a time-varying covariate and all models were adjusted for age, sex, comorbidities, county of residence, country of birth, and living conditions. Data from the entire adult Norwegian population were collated from the National Preparedness Register for COVID-19 (Beredt C19). RESULTS: The overall adjusted vaccine effectiveness against infection decreased from 81.3% (confidence interval (CI): 80.7 to 81.9) in the first 2 to 9 weeks after receiving a second dose to 8.6% (CI: 4.0 to 13.1) after more than 33 weeks, compared to 98.6% (CI: 97.5 to 99.2) and 66.6% (CI: 57.9 to 73.6) against hospitalisation respectively. After the third dose (booster), the effectiveness was 75.9% (CI: 73.4 to 78.1) against infection and 95.0% (CI: 92.6 to 96.6) against hospitalisation. Spikevax or a combination of mRNA products provided the highest protection, but the vaccine effectiveness decreased with time since vaccination for all vaccine regimens. CONCLUSIONS: Even though the vaccine effectiveness against infection waned over time, all vaccine regimens remained effective against hospitalisation after the second vaccine dose. For all vaccine regimens, a booster facilitated recovery of effectiveness. The results from this support the use of heterologous schedules, increasing flexibility in vaccination policy.

Cost-utility analysis of the universal pneumococcal vaccination programme for older adults in Norway.

The aim of this study was to establish whether the universal pneumococcal vaccination for older adults in Norway is likely to be cost-effective from the perspective of the health care provider. A decision tree model developed by the Public Health Agency of Sweden was adapted to the Norwegian setting. Two cohorts, consisting of 65-year-olds and 75-year-olds grouped into vaccinated and unvaccinated, were followed over a 5-year time horizon. In the base case, the 23-valent polysaccharide vaccine (PPV23) was used while the 13-valent pneumococcal conjugate vaccine (PCV13) was included in scenario analyses only. The costs and health benefits (measured in quality adjusted life years (QALY) gained) were compared in the two cohorts between the vaccinated and unvaccinated groups. The impact of indirect effects of the vaccine, such as herd immunity and serotype replacement, were not investigated. The relative importance of change in price was assessed by performing one-way sensitivity analyses. Under base-case assumptions, the programme for the 75-year-old cohort is expected to be dominant (cost-effective) from the health care perspective at the current maximal pharmacy retail price and at 75% vaccination coverage. In comparison, for the 65-year-old cohort the cost per QALY gained is approximately NOK 601,784 (EUR 61,281) under the base-case assumptions. A reduction in the cost of the vaccine to one quarter of its current level also brings the cost per QALY gained within the acceptable ranges in a Norwegian context for both the 65- and 75-year-old cohorts. There is no exact cost-effectiveness threshold in Norway. However, introducing a vaccination programme against pneumococcal disease for 65-year-olds in Norway is likely to fall within the acceptable range while for the 75-year-old cohort the universal programme appears to be dominant (cost-effective).

Effects of Physicians' Information Giving on Patient Outcomes: a Systematic Review.

BACKGROUND: Providing diagnostic and treatment information to patients is a core clinical skill, but evidence for the effectiveness of different information-giving strategies is inconsistent. This systematic review aimed to investigate the reported effects of empirically tested communication strategies for providing information on patient-related outcomes: information recall and (health-related) behaviors. METHODS: The databases MEDLINE, Embase, PsycINFO (Ovid), Cochrane Central Register of Controlled Trials, and relevant bibliographies were systematically searched from the inception to April 24, 2020, without restrictions, for articles testing information-giving strategies for physicians (PROSPERO ID: CRD42019115791). Pairs of independent reviewers identified randomized controlled studies with a low risk of selection bias as from the Cochrane risk of bias 2 tool. Main outcomes were grouped into patient information recall and behavioral outcomes (e.g., alcohol consumption, weight loss, participation in screening). Due to high heterogeneity in the data on effects of interventions, these outcomes were descriptively reported, together with studies', interventions', and information-giving strategies' characteristics. PRISMA guidelines were followed. RESULTS: Seventeen of 9423 articles were included. Eight studies, reporting 10 interventions, assessed patient information recall: mostly conducted in experimental settings and testing a single information-giving strategy. Four of the ten interventions reported significant increase in recall. Nine studies assessed behavioral outcomes, mostly in real-life clinical settings and testing multiple information-giving strategies simultaneously. The heterogeneity in this group of studies was high. Eight of the nine interventions reported a significant positive effect on objectively and subjectively measured patients' behavioral outcomes. DISCUSSION: Using specific framing strategies for achieving specific communication goals when providing information to patients appears to have positive effects on information recall and patient health-related behaviors. The heterogeneity observed in this group of studies testifies the need for a more consistent methodological and conceptual agenda when testing medical information-giving strategies. TRIAL REGISTRATION: PROSPERO registration number: CRD42019115791.

Influenza risk groups in Norway by education and employment status.

AIMS: This study aimed to estimate the size of the risk group for severe influenza and to describe the social patterning of the influenza risk group in Norway, defined as everyone ⩾65 years of age and individuals of any age with certain chronic conditions (medical risk group). METHODS: Study data came from a nationally representative survey among 10,923 individuals aged 16-79 years. The medical risk group was defined as individuals reporting one or more relevant chronic conditions. The associations between educational attainment, employment status, age and risk of belonging to the medical risk group were studied with logistic regression. RESULTS: Nearly a fifth (19.0%) of respondents reported at least one chronic condition, while 29.4% belonged to the influenza risk group due to either age or chronic conditions. Being older, having a low educational level (comparing compulsory education to higher education, odds ratio (OR)=1.4, 95% confidence interval (CI) 1.2-1.8 among women, and OR=1.3, 95% CI 1.1-1.7 among men) and a weaker connection to working life (comparing disability pension to working full-time, OR=6.8, 95% CI 5.3-8.7 among women, and OR=6.5, 95% CI 4.9-8.5 among men) was associated with a higher risk of belonging to the medical risk group for severe influenza. CONCLUSIONS: This study indicates that the prevalence of medical risk factors for severe influenza is disproportionally distributed across the socio-economic spectrum in Norway. These results should influence both public funding decisions regarding influenza vaccination and communication strategies towards the public and health professionals.

Safety of Influenza A H1N1pdm09 Vaccines: An Overview of Systematic Reviews.

Background: In 2009, a new influenza A H1N1 virus emerged causing a global pandemic. A range of monovalent influenza A H1N1pdm09 vaccines with or without adjuvants were developed. After the mass vaccination campaigns safety concerns related to H1N1pdm09 vaccines were reported. More than a decade later, reported AEFIs are still under scrutiny. We performed a systematic review aiming to synthesize the evidence on the safety of the H1N1pdm09 vaccines on reported outcomes from existing systematic reviews. Methods: Four electronic databases, PubMed, EMBASE, Epistimonikos and the Cochrane Database of Systematic Reviews were searched for articles on H1N1pdm09 vaccination published from 2009 to January 2021. Systematic reviews assessing short- or long-term adverse events after H1N1pdm09 vaccination were considered for inclusion. Data was extracted from all selected reviews. Outcomes were grouped and results from each included review were presented narratively and in tables. Results: 16 systematic reviews met the inclusion criteria. Reported outcomes were short-term events (3 reviews), fetal/pregnancy outcomes (8 reviews), Guillain-Barré syndrome (GBS) (4 reviews), narcolepsy (2 reviews) demyelinating diseases (1 review based on one study only) and inflammatory bowel disease (IBD) (1 review). Short-term serious adverse events were rare, 3 cases amongst 16725 subjects in 18 randomized controlled trials (0.018%). No deaths were reported. The risks of local events were generally higher for adjuvanted vaccines as compared to unadjuvanted vaccines. Maternal H1N1pdm09 vaccination in any trimester was not associated with an increase in preterm birth, small for gestational age, congenital malformations or fetal death. For GBS, results were conflicting. The main systematic review on narcolepsy found a 5-14-fold increased risk in children, and a 2-7- fold increased risk in adults after vaccination with Pandemrix. The attributable risk of narcolepsy one year after vaccination was 1 case per 18 400 vaccine doses in children/adolescents, and 1 case per 181 000 vaccine doses in adults. Conclusion: Adjuvanted vaccines had more local but not serious adverse events compared to unadjuvanted vaccines. Vaccination with Pandemrix was strongly associated with narcolepsy, particularly in children. No increased risks of pregnancy outcomes were seen after pandemic vaccination. The findings on GBS were inconclusive.

Tested communication strategies for providing information to patients in medical consultations: A scoping review and quality assessment of the literature.

OBJECTIVES: To systematize the scientific knowledge of empirically tested strategies for verbally providing medical information in patient-physician consultations. METHODS: A scoping review searching for terms related to physician, information, oral communication, and controlled study. Four pairs of reviewers screened articles. For each selected study, we assessed the quality and summarized aspects on participants, study, intervention, and outcomes. Information provision strategies were inductively classified by types and main categories. RESULTS: After screening 9422 articles, 39 were included. The methodological quality was moderate. We identified four differently used categories of strategies for providing information: cognitive aid (n = 13), persuasive (n = 8), relationship- (n = 3), and objectivity-oriented strategies (n = 4); plus, one "mixed" category (n = 11). Strategies were rarely theoretically derived. CONCLUSIONS: Current research of tested strategies for verbally providing medical information is marked by great heterogeneity in methods and outcomes, and lack of theory-driven approaches. The list of strategies could be used to analyse real life communication. PRACTICE IMPLICATIONS: Findings may aid the harmonization of future efforts to develop empirically-based information provision strategies to be used in clinical and teaching settings.

Pain in persons with chronic venous leg ulcers: A systematic review and meta-analysis.

Pain is a serious problem for patients with leg ulcers. Research mainly focuses on dressing-related pain; however, chronic background pain may be just as devastating. Our main objective was to describe the prevalence and characteristics of wound-related background pain in persons with chronic venous leg ulcers. We performed a systematic review to synthesise data from quantitative studies. Studies were eligible if they reported original baseline- or cross-sectional data on background pain in chronic venous leg ulcers. The initial search identified 2454 publications. We included 36 descriptive and effect studies. The pooled prevalence of wound-related background pain (from 10 studies) was 80% (95% CI 65-92%). The mean pain intensity score (from 27 studies) was 4 (0-10 numeric rating scale) (95% CI 3.4-4.5). Other pain characteristics could not be synthesised. We identified few sufficiently high-quality studies on prevalence and intensity of wound-related background pain in patients with chronic venous leg ulcers. Four of five persons experience mild to moderate pain. Because of poor quality of pain assessment and report, we believe that the available research does not provide a sufficiently nuanced understanding of background pain in this patient group.

The experience of lived space in persons with dementia: a systematic meta-synthesis.

BACKGROUND: Identifying how persons with dementia experience lived space is important for enabling supportive living environments and creating communities that compensate for the fading capabilities of these persons. Several single studies have explored this topic; however, few studies have attempted to explicitly review and synthesize this research literature. The aim of this systematic meta-synthesis was therefore to interpret and synthesize knowledge regarding persons with dementia's experience of space. METHODS: A systematic, computerized search of AgeLine, CINAHL Complete, Embase, Medline and PsycINFO was conducted using a search strategy that combined MeSH terms and text words for different types of dementia with different descriptions of experience. Studies with 1) a sample of persons with dementia, 2) qualitative interviews as a research method and 3) a description of experiences of lived space were included. The search resulted in 1386 articles, of which 136 were identified as eligible and were read and assessed using the CASP criteria. The analysis was inspired by qualitative content analyses. RESULTS: This interpretative qualitative meta-synthesis included 45 articles encompassing interviews with 672 persons with dementia. The analysis showed that living in one's own home and living in long-term care established different settings and posed diverse challenges for the experience of lived space in persons with dementia. The material revealed four main categories that described the experience of lived space: (1) belonging; (2) meaningfulness; (3) safety and security; and (4) autonomy. It showed how persons with dementia experienced a reduction in their lived space due to the progression of dementia. A comprehensive understanding of the categories led to the latent theme: "Living with dementia is like living in a space where the walls keep closing in". CONCLUSION: This meta-synthesis reveals a process whereby lived space gradually becomes smaller for persons with dementia. This underscores the importance of being aware of the experiences of persons with dementia and the spatial dimensions of their life-world. To sustain person-centred care and support the preservation of continuity and identity, one must acknowledge not only the physical and social environment but also space as an existential experience for persons with dementia.

Antibiotic therapy in neonates and impact on gut microbiota and antibiotic resistance development: a systematic review.

Objectives: To systematically review the impact of antibiotic therapy in the neonatal period on changes in the gut microbiota and/or antibiotic resistance development. Methods: Data sources were PubMed, Embase, Medline and the Cochrane Database, supplemented by manual searches of reference lists. Randomized controlled trials (RCTs) and observational studies were included if they provided data on different categories of antibiotic treatment (yes versus no, long versus short duration and/or broad- versus narrow-spectrum regimens) and subsequent changes in the gut microbiota and/or antibiotic resistance development. We evaluated risk of bias using the Cochrane Handbook, adapted to include observational studies. When appropriate, we used the vote-counting method to perform semi-quantitative meta-analyses. We applied the Grades of Recommendation, Assessment, Development and Evaluation approach to rate the quality of evidence (QoE). Study protocol registration: PROSPERO CRD42015026743. Results: We included 48 studies, comprising 3 RCTs and 45 observational studies. Prolonged antibiotic treatment was associated with reduced gut microbial diversity in all three studies investigating this outcome (very low QoE). Antibiotic treatment was associated with reduced colonization rates of protective commensal anaerobic bacteria in four of five studies (very low QoE). However, all three categories of antibiotic treatment were associated with an increased risk of antibiotic resistance development, in particular MDR in Gram-negative bacteria, and we graded the QoE for these outcomes as moderate. Conclusions: We are moderately confident that antibiotic treatment leads to antibiotic resistance development in neonates and it may also induce potentially disease-promoting gut microbiota alterations. Our findings emphasize the need to reduce unnecessary antibiotic treatment in neonates.

Antibiotic exposure in neonates and early adverse outcomes: a systematic review and meta-analysis.

Objectives: To systematically review and meta-analyse the relationship between antibiotic exposure in neonates and the following early adverse outcomes: necrotizing enterocolitis (NEC), invasive fungal infections (IFIs) and/or death. Methods: Data sources were PubMed, Embase, Medline and the Cochrane Database (to December 2016), supplemented by manual searches of reference lists. Randomized controlled trials (RCTs) and observational studies were included if they provided data on different categories of antibiotic exposures (yes versus no, long versus short duration, and/or broad- versus narrow-spectrum regimens) and the risk of developing NEC, IFI and/or death in the neonatal period. Two reviewers extracted data and evaluated the risk of bias using the Cochrane Handbook, adapted to include observational studies. When appropriate, meta-analyses were conducted using the random-effect model. Results: We identified 9 RCTs and 38 observational studies. The quality of the majority of studies was poor to moderate. There was a significant association between prolonged antibiotic exposure and an increased risk of NEC in five observational studies (5003 participants) and/or risk of death in five observational studies (13 534 participants). Eleven of 15 studies with data on broad- versus narrow-spectrum regimens reported an increased risk of IFI after broad-spectrum antibiotic exposure, in particular with third-generation cephalosporins and carbapenems. Meta-analysis was limited by few and old RCTs, insufficient sample sizes and diversity of antibiotic exposure and outcomes reported. Conclusions: Prolonged antibiotic exposure in uninfected preterm infants is associated with an increased risk of NEC and/or death, and broad-spectrum antibiotic exposure is associated with an increased risk of IFI.

The Experience of Relations in Persons with Dementia: A Systematic Meta-Synthesis.

BACKGROUND: Dementia influences a person's experience of social relationships, as described in several studies. In this systematic meta-synthesis of qualitative studies, we aim to interpret and synthesize the experiences of persons with dementias and their relations with others. SUMMARY: Living with dementia changes life, leading to new social roles and different social statuses. Persons with dementia experience being disconnected and dependent on others, feeling like being a burden, and being a person who is treated in paternalistic ways. Family, friends and others with dementia might play significant roles in their ability to maintain a meaningful life. Key Messages: Three categories emerged from the data, change in life, change in relations, and maintenance of meaningful aspects in life; these categories are intertwined and essential in sustaining a lifeline for persons with dementia. The comprehensive meaning of the material is understood as the expression: Living a meaningful life in relational changes.

HPV catch-up vaccination of young women: a systematic review and meta-analysis.

BACKGROUND: While prophylactic human papilloma virus (HPV) vaccination is considered effective in young girls, it is unclear whether a catch-up vaccination of older girls would be beneficial. We, therefore, aimed to examine the potential health impact of a HPV catch-up vaccination of girls who were too old at the time of vaccine introduction, hence aged 16 and older. METHODS: We systematically searched the literature for randomized clinical trials (RCTs) that examined the effect of HPV vaccines on overall mortality, cancer mortality and incidence, high-grade cervical intraepithelial neoplasia grade 2 and higher (CIN2+), vulvar intraepithelial neoplasia (VIN) and vaginal intraepithelial neoplasia (VaIN) grade 2 and higher lesions (VIN2+ and VaIN2+, respectively) genital warts (condyloma). We considered all lesions and those associated with HPV type(s) included in the vaccines. RCTs reporting on serious adverse events were also eligible. Selected publications were assessed for potential risk of bias, and we ascertained the overall quality of the evidence for each outcome using Grading of Recommendations Assessment, Development and Evaluation (GRADE). Meta-analyses were performed, assuming both random and fixed effects, to estimate risk ratios (RR) and corresponding 95% confidence intervals (CI), using intention-to-treat and per-protocol populations. RESULTS: We included 46 publications reporting on 13 RCTs. Most of the RCTs had a maximum follow-up period of four years. We identified no RCT reporting on the effect of HPV catch vaccination on overall and cancer related mortality, and on cervical cancer incidence. We found a borderline protective effect of a HPV catch-up vaccination on all CIN2+, with a pooled RR of 0.80 (95% CI: 0.62-1.02) for a follow-up period of 4 years. A HPV catch-up vaccination was associated with a reduction in VIN2+ and VaIN2+ lesions, and condyloma. No difference in risk of serious adverse events was seen in vaccinated participants versus unvaccinated women (pooled RR of 0.99 (0.91-1.08)). CONCLUSIONS: This systematic review indicates that a HPV catch-up vaccination could be beneficial, however the long-term effect of such a vaccination, and its effect on cervical cancer incidence and mortality is still unclear.

Psychosocial interventions as part of breast cancer rehabilitation programs? Results from a systematic review.

OBJECTIVE: This systematic review aimed to determine the effectiveness of psychoeducation, cognitive behavioural therapy (CBT) and social support interventions used in the rehabilitation of breast cancer (BC) patients. METHODS: We conducted a systematic literature search to identify randomised controlled trials of female BC patients who underwent different psychosocial interventions during or after primary cancer treatment. The methodological quality of all studies was independently assessed by two reviewers. Studies with low quality, less than 20 participants in each group, patients with metastatic cancer, data not presented separately for BC and studies that included other cancer types were excluded. RESULTS: Among 9617 identified studies, only 18 RCTs published between 1999 and 2008, including 3272 patients were finally included in this systematic evaluation. Outcome measures were categorised into quality of life (QoL), fatigue, mood, health behaviour and social function. Six trials examined psychoeducation had inconsistent results, both during and after the primary treatment. Seven trials examined the effect of CBT, four of which given after primary treatment (range 6-12 weeks) demonstrated improvements in QoL; the other three CBT studies given during primary treatment (range 9-20 weeks) had inconsistencies. Five studies addressed social support and showed no conclusive impacts of this intervention. CONCLUSIONS: Limited documentation exists on the efficacy of psychosocial rehabilitation interventions among BC patients. However, we found that patients might have QoL benefits from CBT given after primary BC treatment. More documentation is needed regarding the effects of CBT during primary treatment and the effects of psychoeducation and social support.

Bile acids reduce SR-BI expression in hepatocytes by a pathway involving FXR/RXR, SHP, and LRH-1.

Hepatic SR-BI mediates uptake of circulating cholesterol into liver hepatocytes where a part of the cholesterol is metabolised to bile acids. In the hepatocytes, bile acids reduce their own synthesis by a negative feedback loop to prevent toxic high levels of bile acids. Bile acid-activated FXR/RXR represses expression of CYP7A1, the rate-limiting enzyme during bile acid synthesis, by inducing the expression of SHP, which inhibits LXR/RXR and LRH-1-transactivation of CYP7A1. The present paper presents data indicating that CDCA suppresses SR-BI expression by the same pathway. As previously reported, LRH-1 induces SR-BI promoter activity. Here we show that CDCA or over-expression of SHP inhibit this transactivation. No FXR-response element was identified in the bile acid-responsive region of the SR-BI promoter (-1200bp/-937bp). However, a binding site for LRH-1 was characterised and shown to specifically bind LRH-1. The present study shows that also the SR-BI-mediated supply of cholesterol, the substrate for bile acid synthesis, is feedback regulated by bile acids.