Summary The burden of visible skin diseases (VSDs) includes not only physical symptoms but also psychosocial consequences such as depression, anxiety, impaired quality of life and low self-esteem. Stigmatisation was shown to play a major role in people with skin diseases The aim of the study was to review the evidence for the components, drivers, and impacts of (self-) stigma, and to organise the data into a series of conceptual models. A targeted literature search was conducted to identify studies on (self-) stigma in relation to VSD. Conceptual models of stigma in VSDs were developed from existing generic conceptual models for VSD and of generic conceptual models of stigma and were refined after discussion with a board of experts, patient advocacy groups, clinicians and researchers. A total of 580 references were identified, of which 56 references were analysed and summarised. Two conceptual models of stigma were identified: one with external stigma and self-stigma dimensions, the other for self-stigma in mental health. These models were adapted to allow a complete description of stigma in VSDs. For this, a distinction was made between ‘discrimination’ and ‘impact’. Finally, five models were developed: Macro-overview; Stigma, Impact and Socio-demographics; Stigma, Impact and Disease Characteristics; Stigma, Impact and Quality of Life; and Stigma, Impact and Coping. Gaps were identified in available quantitative evidence. To our knowledge, this is the first conceptual model of stigma in VSDs. The model will help to standardise evaluation of stigma and to enhance empirical evaluation of anti-stigma interventions in VSDs. Further research should be conducted to develop a more complete model in stigma due to significant gaps in existing evidence, particularly including the stigma in others (external stigma) and also to cover a broader range of VSDs as their impact on particular dimensions of stigma differs.

Coronavirus 2019 (COVID-19) has caused significant disruption to the cell and gene therapy (CGT) industry, which has historically faced substantial complexities in supply of materials, and manufacturing and logistics processes. As decision-makers shifted their priorities to COVID-19-related issues, the challenges in market authorisation, and price and reimbursement of CGTs were amplified. Nevertheless, it is encouraging to see that some CGT developers are adapting their efforts toward the development of promising COVID-19-related therapeutics and vaccines. Manufacturing resilience, digitalisation, telemedicine, value-based pricing, and innovative payment mechanisms will be increasingly harnessed to ensure that market access of CGTs is not severely disrupted.

INTRODUCTION: The COVID-19 pandemic can cause emotional distress, which can in turn lead to the development of mental and physical symptoms. AIM: We examined the association of the COVID-19 outbreak and the mental, physical and sexual health of the female Polish population. METHODS: Data were collected in an online survey distributed on social media from April 22, 2020 through to May 7, 2020. The data collection began one month after the start of lockdown in Poland. MAIN OUTCOME MEASURE: Women were asked to complete the Beck Depression Inventory (BDI) and the Female Sexual Function Index (FSFI) questionnaires. RESULTS: Overall, 1644 women (median age 23 years) took part in the survey. They reported a lower frequency of sexual activity (P < .001) and a lower libido level (P < .001) during the pandemic then before it. 57.5% of the study group (n = 944) strongly agreed or agreed that fear of the health condition of loved ones was a source of stress and depressed mood. The average BDI-II total score was 11 (range 0-51; IQR 5-18), which corresponds to minimal depression. The average FSFI total score was 27.01 ± 7.61 (range 2-36). The FSFI and BDI scores were significantly correlated (P < .001). The FSFI score was significantly correlated with the presence of any comorbid chronic disease, the intensity of the fear of infection and fear of health conditions, perceived loneliness, and the being up to date with media news. The BDI score was significantly correlated with age, the intensity of the fear of infection and fear of health conditions, perceived loneliness, being up to date with media news, and the more frequent use of stimulants. CONCLUSIONS: The COVID-19 lockdown setting was associated with a high occurrence of depressive symptoms and increased risk of sexual dysfunction with decreased libido and lower sexual frequency the most commonly reported issues. Szuster E, Kostrzewska P, Pawlikowska A, et al. Mental and Sexual Health of Polish Women of Reproductive Age During the COVID-19 Pandemic - An Online Survey. Sex Med 2021;XX:XXXXXX.

Aims: This article aimed to examine the cost-effectiveness of rivaroxaban in comparison to warfarin for stroke prevention in Japanese patients with non-valvular atrial fibrillation (NVAF), from a public healthcare payer’s perspective.Materials and methods: Baseline event risks were obtained from the J-ROCKET AF trial and the treatment effect data were taken from a network meta-analysis. The other model inputs were extracted from the literature and official Japanese sources. The outcomes included the number of ischaemic strokes, myocardial infarctions, systemic embolisms and bleedings avoided, life-years, quality-adjusted life-years (QALYs), incremental costs and incremental cost-effectiveness ratio (ICER). The scenario analysis considered treatment effect data from the same network meta-analysis.Results: In comparison with warfarin, rivaroxaban was estimated to avoid 0.284 ischaemic strokes per patient, to increase the number of QALYs by 0.535 per patient and to decrease the total costs by ¥118,892 (€1,011.11) per patient (1 JPY = 0.00850638 EUR; XE.com, 7 October 2019). Consequently, rivaroxaban treatment was found to be dominant compared to warfarin. In the scenario analysis, the ICER of rivaroxaban versus warfarin was ¥2,873,499 (€24,446.42) per QALY.Limitations: The various sources of data used resulted in the heterogeneity of the cost-effectiveness analysis results. Although, rivaroxaban was cost-effective in the majority of cases.Conclusion: Rivaroxaban is cost-effective against warfarin for stroke prevention in Japanese patients with NVAF, giving the payer WTP of 5,000,000 JPY.

BACKGROUND: Regional variations in gastric cancer incidence are not explained by prevalence of Helicobacter pylori, the main cause of the disease, with several areas presenting high H. pylori prevalence but low gastric cancer incidence. The IARC worldwide H. pylori prevalence surveys (ENIGMA) aim at systematically describing age and sex-specific prevalence of H. pylori infection around the world and generating hypotheses to explain regional variations in gastric cancer risk. METHODS: We selected age- and sex-stratified population samples in two areas with different gastric cancer incidence and mortality in Chile: Antofagasta (lower rate) and Valdivia (higher rate). Participants were 1-69 years old and provided interviews and blood for anti-H. pylori antibodies (IgG, VacA, CagA, others) and atrophy biomarkers (pepsinogens). RESULTS: H. pylori seroprevalence (Age-standardized to world population) and antibodies against CagA and VacA were similar in both sites. H. pylori seroprevalence was 20% among children <10 years old, 40% among 10-19 year olds, 60% in the 20-29 year olds and close to or above 80% in those 30+ years. The comparison of the prevalence of known and potential H. pylori cofactors in gastric carcinogenesis between the high and the low risk area showed that consumption of chili products was significantly higher in Valdivia and daily non-green vegetable consumption was more common in Antofagasta. Pepsinogen levels suggestive of gastric atrophy were significantly more common and occurred at earlier ages in Valdivia, the higher risk area. In a multivariate model combining both study sites, age, chili consumption and CagA were the main risk factors for gastric atrophy. CONCLUSIONS: The prevalence of H. pylori infection and its virulence factors was similar in the high and the low risk area, but atrophy was more common and occurred at younger ages in the higher risk area. Dietary factors could partly explain higher rates of atrophy and gastric cancer in Valdivia. IMPACT: The ENIGMA study in Chile contributes to better understanding regional variations in gastric cancer incidence and provides essential information for public health interventions.

ABSTRACTThe results of a clinical trial comparing hydroxychloroquine with or without azithromycin to the standard of care for the treatment of COVID-19 were recently published by Philippe Gautret et al. This study provides outstanding results for the combination of hydroxychloroquine and azithromycin over the standard of care, but the evidence was deemed insufficiently robust to warrant a public health decision to widen the use of hydroxychloroquine for the treatment of COVID-19. We provide a scientific critical review of the Gautret et al. publication, put the results in the context of the current knowledge, provide an evaluation of the validity of the results (from a methodologic perspective), and discuss public health implications. The study has a number of limitations, including small sample size, lack of comparability between patients in active treatment and control arms, lack of blinding, use of interim analyses without controlling for the risk of type 1 error, use of analysis in the per-protocol population instead of the intention-to-treat population, and inconsistencies between the study protocol and article. However, none of these observations is of a nature to reverse the conclusions. The study brings useful knowledge consistent with available evidence and clinical practice from China and South Korea, which could have prompted quicker policy decision-making.

INTRODUCTION: Human papillomavirus (HPV) testing is replacing cytology in primary screening. Its limited specificity demands using a second (triage) test to better identify women at high-risk of cervical disease. Cytology represents the immediate triage but its low sensitivity might hamper HPV testing sensitivity, particularly in low-income and middle-income countries (LMICs), where cytology performance has been suboptimal. The ESTAMPA (EStudio multicéntrico de TAMizaje y triaje de cáncer de cuello uterino con pruebas del virus del PApiloma humano; Spanish acronym) study will: (1) evaluate the performance of different triage techniques to detect cervical precancer and (2) inform on how to implement HPV-based screening programmes in LMIC. METHODS AND ANALYSIS: Women aged 30-64 years are screened with HPV testing and Pap across 12 study centres in Latin America. Screened positives have colposcopy with biopsy and treatment of lesions. Women with no evident disease are recalled 18 months later for another HPV test; those HPV-positive undergo colposcopy with biopsy and treatment as needed. Biological specimens are collected in different visits for triage testing, which is not used for clinical management. The study outcome is histological high-grade squamous intraepithelial or worse lesions (HSIL+) under the lower anogenital squamous terminology. About 50 000 women will be screened and 500 HSIL+ cases detected (at initial and 18 months screening). Performance measures (sensitivity, specificity and predictive values) of triage techniques to detect HSIL+ will be estimated and compared with adjustment by age and study centre. ETHICS AND DISSEMINATION: The study protocol has been approved by the Ethics Committee of the International Agency for Research on Cancer (IARC), of the Pan American Health Organisation (PAHO) and by those in each participating centre. A Data and Safety Monitoring Board (DSMB) has been established to monitor progress of the study, assure participant safety, advice on scientific conduct and analysis and suggest protocol improvements. Study findings will be published in peer-reviewed journals and presented at scientific meetings. TRIAL REGISTRATION NUMBER: NCT01881659.

BACKGROUND: The cost of treating Clostridioides difficile infection (CDI), particularly recurrent disease, is high. In clinical trials, fidaxomicin has been associated with significantly lower recurrence rates and higher sustained cure rates versus vancomycin. The high acquisition cost of fidaxomicin has limited its acceptance into clinical practice. OBJECTIVE: To evaluate the cost-effectiveness of fidaxomicin versus vancomycin in patients with CDI after failure of metronidazole in the Japanese healthcare setting. METHODS: Clinical results from three phase III trials and inputs based on assumptions validated by clinical experts in Japan were used in a semi-Markov model with 1-year time horizon. Incremental cost-effectiveness ratios (ICERs) for fidaxomicin versus vancomycin were expressed as cost per quality-adjusted life year (QALY) and interpreted using willingness-to-pay thresholds of JPY 5,000,000 (primary) and JPY 7,500,000 (secondary) per QALY gained in Japan. Probabilistic sensitivity analyses and scenario analyses were performed. RESULTS: Higher drug acquisition costs for fidaxomicin were partially offset by lower hospitalization costs driven by fewer recurrences, lower costs of complications, and fewer general practitioner visits versus vancomycin. The ICER for fidaxomicin versus vancomycin was estimated at JPY 5,715,183 per QALY gained. Sensitivity analyses showed a 46% probability of fidaxomicin being cost-effective versus vancomycin at a willingness-to-pay threshold of JPY 5,000,000 per QALY gained. At a threshold of JPY 7,500,000, there was a 54% probability of fidaxomicin being cost-effective. CONCLUSIONS: Fidaxomicin treatment in patients with CDI following failure of metronidazole improves health outcomes with partial offset of higher drug acquisition costs versus vancomycin.

BACKGROUND: Mounting pressures on the healthcare system, such as budget constraints and new, costly health technologies reaching the market, have pushed payers and manufacturers to engage in managed entry agreements (MEAs) to address uncertainty and facilitate market access. OBJECTIVES: This study was conducted to illustrate the current landscape of MEAs in Europe and to analyze the main hurdles they face in implementation, providing a policy perspective. METHODS: We conducted a health policy analysis based on a literature review and described the emergence, classification, current use, and implementation obstacles of MEAs in Europe. RESULTS: Throughout Europe, uncertainty and high prices of health technologies have pushed stakeholders towards MEAs. Two main types of MEAs were applied heavily, finance-based agreements (FBAs) and performance-based agreements, including individual performance-based agreements and coverage with evidence development (CED). Service-based agreements have not been as heavily considered so far, yet are increasingly used. Many European countries are turning to CEDs to address uncertainty and facilitate market access while negotiating the pricing and reimbursement rates of products. Despite the interest in CEDs, European countries have moved toward FBAs due to the complexities and burdens associated with PBAs. CONCLUSIONS: Ultimately, in Europe, with the exception of Italy, where MEAs have proven to be inefficient, MEAs are predominantly FBAs dedicated to addressing cost containment from payers’ perspective and external reference pricing from the manufacturers’ perspective. It has been speculated that MEAs will disappear in the medium-term as they are counterproductive for extending patient access and emergence of innovation. To inform value-based decision making and allow early access to innovative medicines, CEDs should be revisited.