Gender, migration and violence among third country nationals accessing the sexual health clinic in Malta.

BACKGROUND: In 2020, the number of displaced people worldwide reached 41.3 million (IOM, 2020). Among them, are many migrants and refugees at risk of sexual and gender-based violence (SGBV). Healthcare providers have a key role to play in identifying migrant victims/survivors of violence. OBJECTIVES: This paper seeks to assess STIs prevalence, sexual health and sexual violence among third country nationals (TCNs) attending the GUC in Malta. METHODS: This is a mixed methods study carried out at the Genitourinary Clinic (GUC), which is the only public sexual health clinic in Malta. Demographic data, sexual history and diagnoses of patients attending the GUC between January 2018 and December 2019 were collected and retrospectively analysed. A SGBV risk assessment was performed through a semi-structured questionnaire. RESULTS: In the 24-month study period, a total of 12 654 patients accessed the GUC in Malta. Demographic data were collected on age, gender, nationality, marital status and sexual orientation. 16.4% (n = 2064) of these were extra-European migrants, predominantly male. 80 different nationalities were recorded, with the 5 most common being Nigerian, Filipino, Libyan, Syrian and Brazilian. The average age was 32.6 years. Over 110 sex workers were visited at the GUC in the study period - 20 were foreign, primarily from China. The presence of a 'massage parlour owner' during consultation, lack of control over passports and other factors were identified as warning signs of trafficking. 5 cases of sexual violence and forced prostitution involving girls from Sub-Saharan Africa and, in 2 cases, boys recently arrived in Malta by boat, were encountered. 6 African women accessing the service exhibited a type of female genital mutilation (FGM). CONCLUSIONS: Migration, sexual health and SGBV overlap in important ways. Further research and training in SGBV and migration in the healthcare setting and awareness-raising about existing services among the migrant population are required.

Sexually transmitted infections' epidemiology and knowledge, attitude and practice survey in a set of migrants attending the sexual health clinic in Malta.

BACKGROUND: The number of international migrants is estimated at 272 million people worldwide. In Europe, migrants face the disproportionate burden of infectious diseases, including hepatitis B and C, HIV and sexually transmitted infections (STIs). High-risk behaviours, sexual abuse, poor living conditions and barriers to accessing health care may affect migrants' sexual health, leading to infections. OBJECTIVES: The study evaluates STIs and HIV prevalence and knowledge, attitude and practice (KAP) in non-European migrants attending the sexual health clinic in Malta. It also seeks to explore situations of human trafficking (HT), sex/gender-based violence (S/GBV) and female genital mutilations (FGM). METHODS: This is a mixed-method study, based on quantitative and qualitative research within a single centre. An anonymous pretested questionnaire was administered to non-European migrants attending the genitourinary clinic (GUC) with the assistance of an ethnocultural agent. Demographics, STI diagnoses and risk behaviours were collected from the GUC database, linked to the questionnaires and analysed. RESULTS: A total of 143 migrants took part in the study, 73% were young male and 16.7% men who have sex with men (MSM). Forty-one different nationalities were recorded, and the top ones were Nigerian (12%), Filipino (7.4%) and Chinese (5.4%). Concerning risk behaviours, 33.8% of respondents had never used a condom and 76.5% had had sex with multiple partners in the 6 months prior to the study. STI prevalence was 73.1%. Of the patients interviewed, six females were Chinese sex workers employed in massage parlours, potentially trafficked to Malta. CONCLUSIONS: The study outcomes support the need of improving awareness about STIs/HIV risk and testing. In migrants at particular risk for HIV, combination prevention strategies should include access to pre-exposure prophylaxis and antiretrovirals independently from migrants' legal status. Finally, STIs/HIV prevention in migrants should be linked with interventions tackling HT and other forms of S/GBV.

Targeted next generation sequencing application in cardiac channelopathies: Analysis of a cohort of autopsy-negative sudden unexplained deaths.

Genetic testing for cardiac channelopathies in sudden unexplained death (SUD) has developed substantially over the last years. The Next Generation Sequencing (NGS) technology provides an unprecedented opportunity to screen for genetic variations underlying arrhythmogenic genes in a short period of time at a low cost. The present study aimed to perform genetic testing with NGS technologies on the Ion Torrent Personal Genome Machine™ (Ion PGM™) sequencer, in targeting a total of 23 genes reported to be associated with inherited cardiac channelopathies in order to identify the possible cause of death in a cohort of post-mortem cases. The molecular analyses focused on 16 cases of SUD, aged less than 35 years old. In all cases, the cause of death could not be determined after a rigorous autopsy associated with histopathological and toxicological analyses according to the guidelines of the Association for European Cardiovascular Pathology. DNA was extracted from fresh frozen tissue. An average of 200 variants was identified per case. However, after the prioritization process using a new scoring program (VaRank) and after the conjunction of clinical data and molecular findings, four "likely pathogenic" variants (including two undescribed variants), were identified in three cases (18.75%) of our cohort in the genes KCNH2, ANK2, SCN5A and RYR2. One case, who died during psychiatric hospitalization after administration of a QT prolonging drug, showed a double "likely pathogenic" variant in Long QT genes (ANK2 and SCN5A) which may have predisposed to drug-induced cardiac arrhythmias. Our study illustrates that the NGS approach based on AmpliSeq™ libraries and Ion Torrent PGM™ sequencing may be an efficient approach, integrated to post-mortem examination. Given the massive amount of information generated by NGS, a rigorous filtration strategy of variants coupled with multidisciplinary collaboration is crucial to determine the potential pathogenic role of identified variants in the cause of death.

Joint WFH-ISTH session: issues in clinical trial design.

Haemophilia therapy is experiencing an unprecedented expansion in the number and novelty of clotting factor concentrates. Every product must be licensed by regulatory authorities, primarily on the basis of its safety and efficacy profiles. The low prevalence of haemophilia, and other inherited bleeding disorders, presents a significant challenge to patient recruitment for preauthorization clinical trials, especially given the low frequency of inhibitory antibodies, the major adverse event related to clotting factor exposure. Other challenges include a lack of harmonization between the major regulatory authorities in certain key areas, the selection of laboratory monitoring methodologies and the difficulty in obtaining high-quality phase IV safety data following authorization. These aspects will be reviewed in this session, which will also highlight the roles played by the World Federation of Hemophilia and International Society on Thrombosis and Haemostasis in the promotion of these discussions.

Relative survival benefit and morbidity with fluids in severe sepsis - a network meta-analysis of alternative therapies.

BACKGROUND: Fluid resuscitation is widely practiced in intensive care units for the treatment of sepsis. A comparison of the evidence base of different fluids may inform therapeutic choice. METHODS: The risks of mortality and morbidity (the need for renal replacement therapies (RRT)) were assessed in patients with severe sepsis. A network meta-analysis compared trials for crystalloids, albumin and hydroxyethyl starch (HES). A literature search of human randomized clinical trials was conducted in databases, the bibliographies of other recent relevant systematic reviews and data reported at recent conferences. Mortality outcomes and RRT data with the longest follow up period were compared. A Bayesian network meta-analysis assessed the risk of mortality and a pair-wise metaanalysis assessed RRT using crystalloids as the reference treatment. RESULTS: 13 studies were identified. A fixed-effects meta-analysis of mortality data in the trials demonstrated an odds-ratio (OR) of 0.90 between crystalloids and albumin, 1.25 between crystalloids and HES and 1.40 between albumin and HES. The probability that albumin is associated with the highest survival was 96.4% followed by crystalloid at 3.6%, with a negligible probability for HES. Sub-group analyses demonstrated the robustness of this result to variations in fluid composition, study source and origin of septic shock. A random-effects pairwise comparison for the risk of RRT provided an OR of 1.52 favoring crystalloid over HES. CONCLUSION: Fluid therapy with albumin was associated with the highest survival benefit. The higher morbidity with HES may affect mortality and requires consideration by prescribers.

Treatment for life for severe haemophilia A- A cost-utility model for prophylaxis vs. on-demand treatment.

Prophylaxis has been established as the treatment of choice in children with haemophilia and its continuation into the adult years has been shown to decrease morbidity throughout life. The cost of factor therapy has made the option questionable in cost-effectiveness studies. The role of prophylaxis in pharmacokinetic dosage and tolerization against inhibitor formation were used to model the cost utility of prophylaxis vs. on-demand (OD) therapy over a lifetime horizon in severe haemophilia A. The model was applied to a single provider national health system exemplified by the United Kingdom's National Health Service and a third party provider in the United States. The incremental cost-effectiveness ratio (ICER) was estimated and compared to threshold values used by payer agencies to guide reimbursement decisions. A cost per quality-adjusted life year (QALY) was also estimated for Sweden. Prophylaxis was dominant over OD treatment in the UK. The model resulted in an ICER - $68 000 - within the range of treatments reimbursed in the USA. In Sweden, a cost/QALY of SEK 1.1 million was also within the range of reimbursed treatments in that country. Dosage- and treatment-induced inhibitor incidence were the most important variables in the model. Subject to continuing clinical evidence of the effectiveness of pharmacokinetic dosage and the role of prophylaxis in decreasing inhibitor incidence, treatment for life with prophylaxis is a cost-effective therapy, using current criteria for the reimbursement of health care technologies in a number of countries.

Health technology assessment and haemophilia.

Although the funding of rare diseases such as haemophilia in developing countries remains a low priority, pressures on the funding of haemophilia treatment are also emerging in developed economies affected by the global economic downturn and the other demands on health care budgets. This is leading advisory bodies and payers alike to explore the tools of Health Technology Assessment (HTAs) in deriving recommendations for reimbursement policies. In particular, the use of cost utility analysis (CUA) in deriving costs per quality adjusted life year (QALY) for different interventions is being used to rank interventions in order of priorities relative to a threshold cost per QALY. In these exercises, rare chronic disorders such as haemophilia emerge as particularly unattractive propositions for reimbursement, as the accepted methodology of deriving a CUA. For e.g. the use of prophylaxis in haemophilia leads to a range of costs/QALY which exceed the willingness to pay thresholds of most payers. In this commentary, we review the principles utilized in a recent systematic review of the use of haemophilia products carried out in Sweden as part of an HTA. We suggest that ranking haemophilia related interventions with the standard interventions of therapeutics and public health in CUA comparisons is inappropriate. Given that haemophilia treatment is a form of blood replacement therapy, we propose that such comparisons should be made with the interventions of mainstream blood transfusion. We suggest that unequivocally effective treatments such as haemophilia therapies should be assessed differently from mainstream interventions, that new methodologies are required for these kinds of diseases and that evidence of a societal willingness to support people with rare disorders needs to be recognized when reimbursement policies are developed.