Vortioxetine for the treatment of post-COVID-19 condition: a randomized controlled trial.

Hitherto no therapeutic has received regulatory approval for the treatment of post-COVID-19 condition (PCC). Cognitive deficits, mood symptoms and significant reduction in health-related quality of life (HRQoL) are highly replicated and debilitating aspects of PCC. We sought to determine the impact of vortioxetine on the foregoing symptoms and HRQoL in persons living with PCC. An 8-week randomized, double-blind, placebo-controlled study of adults ≥ 18 years of age residing in Canada and who are experiencing symptoms of World Health Organization (WHO)-defined PCC, with a history of confirmed SARS-CoV-2 infection, was conducted. Recruitment began November 2021 and ended January 2023. Of the 200 participants enrolled (487 invited: 121 ineligible and 59 eligible but declined participation; 307 cleared pre-screening stage), a total of 149 participants were randomized (1:1) to receive either vortioxetine (5-20 mg, n = 75) or placebo (n = 74) daily for 8 weeks of double-blind treatment (i.e. end point). The primary outcome was the change from baseline-to-end point in the Digit Symbol Substitution Test. Secondary outcomes included the effect on depressive symptoms and HRQoL, as measured by changes from baseline-to-end point on the Quick Inventory of Depressive Symptomatology 16-item and WHO Wellbeing Scale 5-item, respectively. A total of 68 (90.7%) participants randomized to vortioxetine and 73 (98.6%) participants randomized to placebo completed all 8 weeks. Between-group analysis did not show a significant difference in the overall change in cognitive function [P = 0.361, 95% confidence interval (CI) (-0.179, 0.492)]. However, in the fully adjusted model, a significant treatment × time interaction was observed in favour of vortioxetine treatment with baseline c-reactive protein (CRP) as a moderator (P = 0.012). In addition, a significant improvement in Digit Symbol Substitution Test scores were observed in vortioxetine versus placebo treated participants in those whose baseline CRP was above the mean (P = 0.045). Moreover, significant improvement was obtained in measures of depressive symptoms [P < 0.001, 95% CI (-4.378, -2.323)] and HRQoL [P < 0.001, 95% CI (2.297, 4.647)] in vortioxetine-treated participants and between the treatment groups [depressive symptoms: P = 0.026, 95% CI (-2.847, -0.185); HRQoL: P = 0.004, 95% CI (0.774, 3.938)]. Although vortioxetine did not improve cognitive function in the unadjusted model, when adjusting for CRP, a significant pro-cognitive effect was observed; antidepressant effects and improvement in HRQoL in this debilitating disorder were also noted.

Factors associated with bacterial sexually transmitted infections among people of South Asian ethnicity in England.

OBJECTIVES: Despite being the largest ethnic minority group in England, South Asians have historically had low levels of utilisation of sexual health services (SHS) and sexually transmitted infection (STI) diagnoses, although recent data suggests this may be changing. This study aimed to investigate factors associated with a bacterial STI diagnosis among South Asians attending SHS in England. METHODS: Using data from the GUMCAD STI Surveillance system, a descriptive analysis of South Asians attending SHS in England in 2019 was carried out. Factors associated with a bacterial STI diagnosis were examined using univariate and multivariable logistic regression models adjusted for age, Asian ethnic subgroup, HIV status, patient's region of residence and Index of Multiple Deprivation quintile. Analyses were stratified by gender and sexual orientation (heterosexual male versus gay, bisexual and other men who have sex with men (GBMSM) versus women of any sexual orientation). Crude and adjusted associations were derived using binary logistic regression. RESULTS: There were 121 842 attendances by South Asians to SHS in England in 2019. Compared with heterosexual South Asian men, GBMSM had a higher odds of being diagnosed with a bacterial STI (adjusted odds ratio (aOR) 2.32, 95% CI 2.19 to 2.44) and South Asian women had a lower odds (aOR 0.83, 95% CI 0.78 to 0.87). For women and heterosexual South Asian men, a diagnosis was associated with younger age, being of any other Asian background other than Bangladeshi, Indian or Pakistani and not being HIV positive. For heterosexual South Asian men, there was an association with increasing socioeconomic deprivation. For GBMSM, a bacterial STI diagnosis was associated with known HIV-positive status and living in London. CONCLUSION: People of South Asian ethnicity in England are heterogeneous with regard to their sexual health needs, which should be explored further through focused research and policy.

Site staff perspectives on communicating trial results to participants: Cost and feasibility results from the Show RESPECT cluster randomised, factorial, mixed-methods trial.

BACKGROUND/AIMS: Sharing trial results with participants is an ethical imperative but often does not happen. Show RESPECT (ISRCTN96189403) tested ways of sharing results with participants in an ovarian cancer trial (ISRCTN10356387). Sharing results via a printed summary improved patient satisfaction. Little is known about staff experience and the costs of communicating results with participants. We report the costs of communication approaches used in Show RESPECT and the views of site staff on these approaches. METHODS: We allocated 43 hospitals (sites) to share results with trial participants through one of eight intervention combinations (2 × 2 × 2 factorial; enhanced versus basic webpage, printed summary versus no printed summary, email list invitation versus no invitation). Questionnaires elicited data from staff involved in sharing results. Open- and closed-ended questions covered resources used to share results and site staff perspectives on the approaches used. Semi-structured interviews were conducted. Interview and free-text data were analysed thematically. The mean additional site costs per participant from each intervention were estimated jointly as main effects by linear regression. RESULTS: We received questionnaires from 68 staff from 41 sites and interviewed 11 site staff. Sites allocated to the printed summary had mean total site costs of sharing results £13.71/patient higher (95% confidence interval (CI): -3.19, 30.60; p = 0.108) than sites allocated no printed summary. Sites allocated to the enhanced webpage had mean total site costs £1.91/patient higher (95% CI: -14, 18.74; p = 0.819) than sites allocated to the basic webpage. Sites allocated to the email list had costs £2.87/patient lower (95% CI: -19.70, 13.95; p = 0.731) than sites allocated to no email list. Most of these costs were staff time for mailing information and handling patients' queries. Most site staff reported no concerns about how they had shared results (88%) and no challenges (76%). Most (83%) found it easy to answer queries from patients about the results and thought the way they were allocated to share results with participants would be an acceptable standard approach (76%), with 79% saying they would follow the same approach for future trials. There were no significant effects of the randomised interventions on these outcomes. Site staff emphasised the importance of preparing patients to receive the results, including giving opt-in/opt-out options, and the need to offer further support, particularly if the results could confuse or distress some patients. CONCLUSIONS: Adding a printed summary to a webpage (which significantly improved participant satisfaction) may increase costs to sites by ~£14/patient, which is modest in relation to the cost of trials. The Show RESPECT communication interventions were feasible to implement. This information could help future trials ensure they have sufficient resources to share results with participants.

Muslim women's views and experiences of family planning in Saudi Arabia: a qualitative study.

BACKGROUND: Islamic beliefs are associated with decreased contraceptive use compared to other religions, and Muslim women's contraceptive needs are often unmet. Research is needed to provide an in-depth understanding of the complex set of barriers to Muslim women's contraceptive use. Therefore, we aimed to explore Muslim women's awareness and experiences with family planning in Saudi Arabia and investigate barriers to contraceptive use and access to family planning. METHODS: A qualitative study using semi-structured interviews with women in a public hospital, in Riyadh, Saudi Arabia, between January and June 2019. Data was analysed using reflexive thematic analysis. RESULTS: Twenty-eight women participated in the study. Women's contraceptive awareness was limited to two methods. Women expressed positive attitudes towards family planning and did not believe it is forbidden in Islam. Barriers to contraception use included lack of knowledge, misconceptions, fear of side effects, family and community and social norms. Many women expressed that they have the right to use contraception, even if their husbands disapprove. Our findings show that healthcare providers rarely offered contraceptive advice, even when requested. Healthcare providers often prescribe oral contraceptives without offering information on other methods available. CONCLUSION: Our findings suggest that education plays a fundamental role in reproductive autonomy. Men's role in family planning should be encouraged through sharing reproductive responsibility and supporting women's contraceptive choices. Efforts should be directed towards improving women's awareness of different methods of contraception.

A peer-led, school-based social network intervention for young people in the UK, promoting sexual health via social media and conversations with friends: intervention development and optimisation of STASH.

BACKGROUND: The quality of school-based sex and relationships education (SRE) is variable in the UK. Digitally-based interventions can usefully supplement teacher-delivered lessons and positively impact sexual health knowledge. Designed to address gaps in core SRE knowledge, STASH (Sexually Transmitted infections And Sexual Health) is a peer-led social network intervention adapted from the successful ASSIST (A Stop Smoking in Schools Trial) model, and based on Diffusion of Innovation theory. This paper describes how the STASH intervention was developed and refined. METHODS: Drawing on the Six Steps in Quality Intervention Development (6SQuID) framework, we tested a provisional programme theory through three iterative stages -: 1) evidence synthesis; 2) intervention co-production; and 3) adaptation - which incorporated evidence review, stakeholder consultation, and website co-development and piloting with young people, sexual health specialists, and educators. Multi-method results were analysed in a matrix of commonalities and differences. RESULTS: Over 21 months, intervention development comprised 20 activities within the three stages. 1) We identified gaps in SRE provision and online resources (e.g. around sexual consent, pleasure, digital literacy), and confirmed critical components including the core ASSIST peer nomination process, the support of schools, and alignment to the national curriculum. We reviewed candidate social media platforms, ruling out all except Facebook on basis of functionality restrictions which precluded their use for our purposes. 2) Drawing on these findings, as well as relevant behaviour change theories and core elements of the ASSIST model, we co-developed new content with young people and other stakeholders, tailored to sexual health and to delivery via closed Facebook groups, as well as face-to-face conversations. 3) A pilot in one school highlighted practical considerations, including around peer nomination, recruitment, awareness raising, and boundaries to message sharing. From this, a revised STASH intervention and programme theory were co-developed with stakeholders. CONCLUSIONS: STASH intervention development required extensive adaptation from the ASSIST model. Although labour intensive, our robust co-development approach ensured that an optimised intervention was taken forward for feasibility testing. Evidencing a rigorous approach to operationalising existing intervention development guidance, this paper also highlights the significance of balancing competing stakeholder concerns, resource availability, and an ever-changing landscape for implementation. TRIAL REGISTRATION: ISRCTN97369178.

Interventions to support contraceptive choice and use: a global systematic map of systematic reviews.

BACKGROUND: To review the highest level of available evidence, a systematic map identified systematic reviews that evaluated the effectiveness of interventions to improve contraception choice and increase contraception use. METHODS: Systematic reviews published since 2000 were identified from searches of nine databases. Data were extracted using a coding tool developed for this systematic map. Methodological quality of included reviews was assessed using AMSTAR 2 criteria. FINDINGS AND CONCLUSION: Fifty systematic reviews reported evaluations of interventions for contraception choice and use addressing three domains (individual, couples, community); Meta-analyses in 11 of the reviews mostly addressed interventions for individuals. We identified 26 reviews covering High Income Countries, 12 reviews covering Low Middle-Income Countries and the rest a mix of both. Most reviews (15) focussed on psychosocial interventions, followed by incentives (6) and m-health interventions (6). The strongest evidence from meta-analyses is for the effectiveness of motivational interviewing, contraceptive counselling, psychosocial interventions, school-based education, and interventions promoting contraceptive access, demand-generation interventions (community and facility based, financial mechanisms and mass media), and mobile phone message interventions. Even in resource constrained settings, community-based interventions can increase contraceptive use. There are gaps in the evidence on interventions for contraception choice and use, and limitations in study designs and lack of representativeness. Most approaches focus on individual women rather than couples or wider socio-cultural influences on contraception and fertility. This review identifies interventions which work to increase contraception choice and use, and these could be implemented in school, healthcare or community settings.

Effectiveness of eHealth Interventions for HIV Prevention and Management in Sub-Saharan Africa: Systematic Review and Meta-analyses.

HIV is still the leading cause of death in Sub-Saharan Africa (SSA), despite medical advances. eHealth interventions are effective for HIV prevention and management, but it is unclear whether this can be generalised to resource-poor settings. This systematic review aimed to establish the effectiveness of eHealth interventions in SSA. Six electronic databases were screened to identify randomised controlled trials (RCTs) published between 2000 and 2020. Meta-analyses were performed, following Cochrane methodology, to assess the impact of eHealth interventions on HIV-related behaviours and biological outcomes. 25 RCTs were included in the review. Meta-analyses show that eHealth interventions significantly improved HIV management behaviours (OR 1.21; 95% CI 1.05-1.40; Z = 2.67; p = 0.008), but not HIV prevention behaviours (OR 1.02; 95% CI 0.78-1.34; Z = 0.17; p = 0.86) or biological outcomes (OR 1.17; 95% CI 0.89-1.54; Z = 1.10; p = 0.27) compared with minimal intervention control groups. It is a hugely important finding that eHealth interventions can improve HIV management behaviours as this is a low-cost way of improving HIV outcomes and reducing the spread of HIV in SSA. PROSPERO registration number: CRD42020186025.

Sexual and reproductive health knowledge, perceptions and experiences of women in Saudi Arabia: a qualitative study.

BACKGROUND: There is no formal sexual and reproductive health (SRH) education currently offered in Saudi Arabia. Lack of knowledge and misconceptions are evident among Saudi women, which can lead to negative sexual and reproductive experiences. The aim of this study is to explore Saudi women's SRH knowledge, perceptions and experiences. METHODS: Qualitative semi-structured interviews with Saudi women were conducted. Interviews took place in a public hospital in Riyadh, Saudi Arabia. Interviews were conducted in Arabic, recorded and transcribed verbatim, to allow for thematic analysis of the data. The following themes were identified: experience with menarche, deep-rooted negative views towards sex, difficulty discussing SRH topics, knowledge of sex and reproduction, generational gap, sources of SRH information and the role of the mother. RESULTS: A total of 28 women, both married and unmarried, aged 20-50 years were interviewed. A profound lack of SRH knowledge was observed among Saudi women which contributed greatly to negative experiences both in childhood and adulthood. Lack of knowledge about menstruation often caused emotional distress for young girls, and menarche was associated with bad memories and negative emotions. Lack of knowledge about sexual intercourse and the deep-rooted negative views towards sex were linked with physical and psychological issues for women. Women rarely received information from their parents or teachers and preferred the internet for their SRH information. CONCLUSION: There is a substantial unmet need for SRH education for women in Saudi Arabia. It is our recommendation that SRH education should be tailored to meet Saudi women's unique needs, while understanding specific socio-cultural barriers to SRH education and discussions. Research and policy efforts should be directed towards regulating and producing evidence-based health information on the internet, particularly Arabic language websites.

Views, attitudes and experiences of South Asian women concerning sexual health services in the UK: a qualitative study.

OBJECTIVE: To explore the views, attitudes, and experiences of South Asian women in the UK regarding sexual health services. METHODS: We performed virtual semi-structured interviews with South Asian women 18 and over living in the UK. We explored participants' experiences of accessing sexual health services, including contraception, smear tests and sexually transmitted infection (STI) tests. We coded interview transcripts and analysed them thematically. RESULTS: From February to April 2021, we conducted 14 interviews with South Asian women between the ages of 18 and 40 living in England and Wales, from February to April 2021. We identified four overarching themes: Access to sexual health services, entry to sexual health services, quality of sexual health services and stigma associated with sexual health services. Important barriers to sexual health services include limited knowledge of local provision, stigma and shame, and concerns about confidentiality. Participants found it difficult to discuss their sexual health (with anyone) and were often being met with judgement and a lack of partnership from clinicians. CONCLUSION: Our results suggest that South Asian women are uncomfortable accessing sexual health services and communicating their sexual health concerns with health care professionals. Service providers should collaborate with community-based organisations to ensure that services are discrete, confidential, and culturally appropriate.

Factors influencing contraception choice and use globally: a synthesis of systematic reviews.

BACKGROUND: Unintended pregnancy has a huge adverse impact on maternal, child and family health and wealth. There is an unmet need for contraception globally, with an estimated 40% of pregnancies unintended worldwide. METHODS: We systematically searched PubMed and specialist databases for systematic reviews addressing contraceptive choice, uptake or use, published in English between 2000 and 2019. Two reviewers independently selected and appraised reports and synthesised quantitative and qualitative review findings. We mapped emergent themes to a social determinants of health framework to develop our understanding of the complexities of contraceptive choice and use. FINDINGS: We found 24 systematic reviews of mostly moderate or high quality. Factors affecting contraception use are remarkably similar among women in very different cultures and settings globally. Use of contraception is influenced by the perceived likelihood and appeal of pregnancy, and relationship status. It is influenced by women's knowledge, beliefs, and perceptions of side effects and health risks. Male partners have a strong influence, as do peers' views and experiences, and families' expectations. Lack of education and poverty is linked with low contraception use, and social and cultural norms influence contraception and expectations of family size and timing. Contraception use also depends upon their availability, the accessibility, confidentiality and costs of health services, and attitudes, behaviour and skills of health practitioners. INTERPRETATION: Contraception has remarkably far-reaching benefits and is highly cost-effective. However, women worldwide lack sufficient knowledge, capability and opportunity to make reproductive choices, and health care systems often fail to provide access and informed choice.

Variant Intestinal-Cell Kinase in Juvenile Myoclonic Epilepsy.

BACKGROUND: In juvenile myoclonic epilepsy, data are limited on the genetic basis of networks promoting convulsions with diffuse polyspikes on electroencephalography (EEG) and the subtle microscopic brain dysplasia called microdysgenesis. METHODS: Using Sanger sequencing, we sequenced the exomes of six members of a large family affected with juvenile myoclonic epilepsy and confirmed cosegregation in all 37 family members. We screened an additional 310 patients with this disorder for variants on DNA melting-curve analysis and targeted real-time DNA sequencing of the gene encoding intestinal-cell kinase ( ICK). We calculated Bayesian logarithm of the odds (LOD) scores for cosegregating variants, odds ratios in case-control associations, and allele frequencies in the Genome Aggregation Database. We performed functional tests of the effects of variants on mitosis, apoptosis, and radial neuroblast migration in vitro and conducted video-EEG studies in mice lacking a copy of Ick. RESULTS: A variant, K305T (c.914A→C), cosegregated with epilepsy or polyspikes on EEG in 12 members of the family affected with juvenile myoclonic epilepsy. We identified 21 pathogenic ICK variants in 22 of 310 additional patients (7%). Four strongly linked variants (K220E, K305T, A615T, and R632X) impaired mitosis, cell-cycle exit, and radial neuroblast migration while promoting apoptosis. Tonic-clonic convulsions and polyspikes on EEG resembling seizures in human juvenile myoclonic epilepsy occurred more often in knockout heterozygous mice than in wild-type mice (P=0.02) during light sleep with isoflurane anesthesia. CONCLUSIONS: Our data provide evidence that heterozygous variants in ICK caused juvenile myoclonic epilepsy in 7% of the patients included in our analysis. Variant ICK affects cell processes that help explain microdysgenesis and polyspike networks observed on EEG in juvenile myoclonic epilepsy. (Funded by the National Institutes of Health and others.).

Peer-to-Peer Sharing of Social Media Messages on Sexual Health in a School-Based Intervention: Opportunities and Challenges Identified in the STASH Feasibility Trial.

BACKGROUND: There is a strong interest in the use of social media to spread positive sexual health messages through social networks of young people. However, research suggests that this potential may be limited by a reluctance to be visibly associated with sexual health content on the web or social media and by the lack of trust in the veracity of peer sources. OBJECTIVE: The aim of this study was to investigate opportunities and challenges of using social media to facilitate peer-to-peer sharing of sexual health messages within the context of STASH (Sexually Transmitted Infections and Sexual Health), a secondary school-based and peer-led sexual health intervention. METHODS: Following training, and as a part of their role, student-nominated peer supporters (aged 14-16 years) invited school friends to trainer-monitored, private Facebook groups. Peer supporters posted curated educational sex and relationship content within these groups. Data came from a feasibility study of the STASH intervention in 6 UK schools. To understand student experiences of the social media component, we used data from 11 semistructured paired and group interviews with peer supporters and their friends (collectively termed students; n=42, aged 14-16 years), a web-based postintervention questionnaire administered to peer supporters (n=88), and baseline and follow-up questionnaires administered to students in the intervention year group (n=680 and n=603, respectively). We carried out a thematic analysis of qualitative data and a descriptive analysis of quantitative data. RESULTS: Message sharing by peer supporters was hindered by variable engagement with Facebook. The trainer-monitored and private Facebook groups were acceptable to student members (peer supporters and their friends) and reassuring to peer supporters but led to engagement that ran parallel to-rather than embedded in-their routine social media use. The offline context of a school-based intervention helped legitimate and augment Facebook posts; however, even where friends were receptive to STASH messages, they did not necessarily engage visibly on social media. Preferences for content design varied; however, humor, color, and text brevity were important. Preferences for social media versus offline message sharing varied. CONCLUSIONS: Invitation-only social media groups formed around peer supporters' existing friendship networks hold potential for diffusing messages in peer-based sexual health interventions. Ideally, interactive opportunities should not be limited to single social media platforms and should run alongside offline conversations. There are tensions between offering young people autonomy to engage flexibly and authentically and the need for adult oversight of activities for information accuracy and safeguarding.

Healthcare provider and service user perspectives on STI risk reduction interventions for young people and MSM in the UK.

OBJECTIVE: Behavioural interventions have been shown to reduce sexual behaviours associated with increased risk of sexually transmitted infections in young people (<25 years) and men who have sex with men (MSM) internationally, but evidence from England is limited. We aimed to explore service provider and user experiences and perspectives on behavioural interventions to reduce sexual behaviour risks, and the use of automated methods to triage individuals to these services. METHODS: We conducted a sequential mixed methods study with sexual health service providers and users in 2015/2016. Qualitative interviews with providers and service users (heterosexual young people and MSM) in London and Brighton allowed us to explore a range of experiences and expectations. A subsequent national web-survey of service providers measured the feasibility of delivery within existing resources and preferences for intervention attributes. RESULTS: We conducted 35 service user (15 heterosexual young people; 20 MSM) and 26 provider interviews and had 100 web-survey responses. We found considerable heterogeneity in prevention services offered. Service users and providers were broadly supportive of tailoring interventions offered, but service users raised concerns about automated, data-driven triage, particularly around equity and fairness of service delivery. Digital technologies, including social media or apps, were appealing to providers, being less resource intensive. However, one-to-one talking interventions remained popular with both service users and providers, being familiar, trustworthy and personal. Key tensions between desirability of interventions and availability of resources to deliver them were acknowledged/recognised by providers and users. CONCLUSION: Overall, behavioural interventions to reduce sexual behaviour risks were viewed favourably by service providers and users, with key considerations including: privacy, personalisation and convenience. However, introducing desirable targeted interventions within heterogeneous sexual health settings will require resources to adapt interventions and research to fully understand the barriers and facilitators to use within routine services.

Factors influencing sexual and reproductive health of Muslim women: a systematic review.

BACKGROUND: In Islamic societies, issues related to sexual and reproductive health (SRH) are rarely discussed and considered sensitive subjects. This review aimed to identify any personal, religious, cultural, or structural barriers to SRH service and education among Muslim women worldwide. METHODS: A search for qualitative and quantitative studies was conducted on seven electronic databases. A narrative synthesis using thematic analysis was conducted. RESULTS: Fifty-nine studies were included from 22 countries: 19 qualitative, 38 quantitative and two mixed methods. Many Muslim women have poor SRH knowledge, and negative attitudes which influence their access to, and use of SRH services. Barriers to contraception use among Muslim women included a lack of basic reproductive knowledge, insufficient knowledge about contraception, misconceptions, and negative attitudes. Women had negative attitudes towards family planning for limiting the number of children but not for child spacing, which reflected religious views towards family planning. Religious and cultural beliefs were barriers to contraception use and access to SRH services and information. Family and the community have a significant impact on women's contraceptive use and access to SRH services. Husband and family opposition played a significant role in contraception access and use. Fear of stigmatization and being labelled as having pre-marital sexual relations among unmarried women acted as the main barrier to accessing contraception and seeking SRH information and services. CONCLUSION: The findings reveal that there are multiple levels of factors that influence Muslim women's SRH. Poor SRH knowledge and practices among Muslim women is complex matter that is affected by personal, community, cultural, religious factors and existing policies and regulations. All these factors overlap and are affected by each other. There is an urgent need for interventions addressing modifiable barriers to SRH education and services to improve knowledge, informed choice and access to services to facilitate better sexual and reproductive wellbeing for Muslim women. It is important to note that while this review aimed to report findings on Muslim women, we acknowledge that significant variations exist within every culture and religion.

The psychosexual impact of testing positive for high-risk cervical human papillomavirus (HPV): A systematic review.

OBJECTIVES: Many countries are implementing human papillomavirus (HPV)-based cervical screening due to the higher sensitivity of the test compared with cytology. As HPV is sexually transmitted, there may be psychosexual consequences of testing positive for the virus. We aimed to review the literature exploring the psychosexual impact of testing positive for high-risk cervical HPV. METHODS: MEDLINE, PsycINFO, CINAHL Plus, Web of Science, and EMBASE were searched with no date limits. We also searched the grey literature, reference lists of included articles and carried out forward citation searching. Eligible studies reported at least one psychosexual outcome among HPV-positive women. Qualitative and quantitative papers were included. We extracted data using a standardised form and carried out a quality assessment for each article. We conducted a narrative synthesis for quantitative studies and a thematic synthesis for qualitative studies. RESULTS: Twenty-five articles were included. Quantitative study designs were diverse making it difficult to determine the impact that an HPV positive result would have in the context of routine screening. The qualitative literature suggested that psychosexual concerns cover a broad range of aspects relating to women's current and past relationships, both interpersonal and sexual. CONCLUSIONS: The psychosexual impact of testing positive for high-risk cervical HPV is unclear. This review highlights the need for further research in the context of HPV-based cervical screening. As primary HPV testing is introduced more widely, it is important to understand women's responses to testing HPV positive in the cancer screening context to minimise any adverse psychosexual impact.

EFHC1 variants in juvenile myoclonic epilepsy: reanalysis according to NHGRI and ACMG guidelines for assigning disease causality.

PURPOSE: EFHC1 variants are the most common mutations in inherited myoclonic and grand mal clonic-tonic-clonic (CTC) convulsions of juvenile myoclonic epilepsy (JME). We reanalyzed 54 EFHC1 variants associated with epilepsy from 17 cohorts based on National Human Genome Research Institute (NHGRI) and American College of Medical Genetics and Genomics (ACMG) guidelines for interpretation of sequence variants. METHODS: We calculated Bayesian LOD scores for variants in coinheritance, unconditional exact tests and odds ratios (OR) in case-control associations, allele frequencies in genome databases, and predictions for conservation/pathogenicity. We reviewed whether variants damage EFHC1 functions, whether efhc1-/- KO mice recapitulate CTC convulsions and "microdysgenesis" neuropathology, and whether supernumerary synaptic and dendritic phenotypes can be rescued in the fly model when EFHC1 is overexpressed. We rated strengths of evidence and applied ACMG combinatorial criteria for classifying variants. RESULTS: Nine variants were classified as "pathogenic," 14 as "likely pathogenic," 9 as "benign," and 2 as "likely benign." Twenty variants of unknown significance had an insufficient number of ancestry-matched controls, but ORs exceeded 5 when compared with racial/ethnic-matched Exome Aggregation Consortium (ExAC) controls. CONCLUSIONS: NHGRI gene-level evidence and variant-level evidence establish EFHC1 as the first non-ion channel microtubule-associated protein whose mutations disturb R-type VDCC and TRPM2 calcium currents in overgrown synapses and dendrites within abnormally migrated dislocated neurons, thus explaining CTC convulsions and "microdysgenesis" neuropathology of JME.Genet Med 19 2, 144-156.

Filtering genetic variants and placing informative priors based on putative biological function.

High-density genetic marker data, especially sequence data, imply an immense multiple testing burden. This can be ameliorated by filtering genetic variants, exploiting or accounting for correlations between variants, jointly testing variants, and by incorporating informative priors. Priors can be based on biological knowledge or predicted variant function, or even be used to integrate gene expression or other omics data. Based on Genetic Analysis Workshop (GAW) 19 data, this article discusses diversity and usefulness of functional variant scores provided, for example, by PolyPhen2, SIFT, or RegulomeDB annotations. Incorporating functional scores into variant filters or weights and adjusting the significance level for correlations between variants yielded significant associations with blood pressure traits in a large family study of Mexican Americans (GAW19 data set). Marker rs218966 in gene PHF14 and rs9836027 in MAP4 significantly associated with hypertension; additionally, rare variants in SNUPN significantly associated with systolic blood pressure. Variant weights strongly influenced the power of kernel methods and burden tests. Apart from variant weights in test statistics, prior weights may also be used when combining test statistics or to informatively weight p values while controlling false discovery rate (FDR). Indeed, power improved when gene expression data for FDR-controlled informative weighting of association test p values of genes was used. Finally, approaches exploiting variant correlations included identity-by-descent mapping and the optimal strategy for joint testing rare and common variants, which was observed to depend on linkage disequilibrium structure.

Testing genetic association with rare and common variants in family data.

With the advance of next-generation sequencing technologies in recent years, rare genetic variant data have now become available for genetic epidemiology studies. For family samples, however, only a few statistical methods for association analysis of rare genetic variants have been developed. Rare variant approaches are of great interest, particularly for family data, because samples enriched for trait-relevant variants can be ascertained and rare variants are putatively enriched through segregation. To facilitate the evaluation of existing and new rare variant testing approaches for analyzing family data, Genetic Analysis Workshop 18 (GAW18) provided genotype and next-generation sequencing data and longitudinal blood pressure traits from extended pedigrees of Mexican American families from the San Antonio Family Study. Our GAW18 group members analyzed real and simulated phenotype data from GAW18 by using generalized linear mixed-effects models or principal components to adjust for familial correlation or by testing binary traits using a correction factor for familial effects. With one exception, approaches dealt with the extended pedigrees in their original state using information based on the kinship matrix or alternative genetic similarity measures. For simulated data our group demonstrated that the family-based kernel machine score test is superior in power to family-based single-marker or burden tests, except in a few specific scenarios. For real data three contributions identified significant associations. They substantially reduced the number of tests before performing the association analysis. We conclude from our real data analyses that further development of strategies for targeted testing or more focused screening of genetic variants is strongly desirable.

The influence of traditional and complementary and alternative medicine on medication adherence in Honduras.

BACKGROUND: Adherence to medication is a worldwide problem and deserves country-specific attention. Honduras, like many other countries, has allopathic providers, traditional medicine (TM), and complementary and alternative medicine (CAM). Understanding a population's health behaviors is essential to satisfactory integration of these systems and successful patient care. STUDY OBJECTIVE: The objective was to identify factors that influence medication adherence in Honduras. DESIGN: The research team administered a cross-sectional, 25-item questionnaire to various neighborhoods based on national demographic statistics in order to obtain a quota sample. Setting • The survey took place in Tegucigalpa, Honduras, Central America. PARTICIPANTS: The research team surveyed 614 Hondurans, aged ≥ 18 y, within the general population of Tegucigalpa, the largest and capital city of Honduras, in neighborhoods representing areas where primarily the lower and middle classes lived. OUTCOME MEASURES: The primary outcome measure was a modified Medication Adherence Report Scale (MARS). Results • The research team collected 610 surveys that had complete answers to questions about adherence (610/614, 99.3%) total complete responses to other items varied. The prevalence of use of TM was 62.8% (381/607). Nearly one-half, 47.3% (287/607), of all the respondents had used herbs or teas for health in the prior year, and 26.1% (159/607) of all respondents had received a sobada (therapeutic rubbing). Respondents with daily private spiritual devotions (OR = 0.610, P = .018) and diabetes (OR = 0.154, P = .004) were less likely to report low adherence. Receiving a sobada and a history of fever were independently associated with low adherence (OR = 1.718, P = .017 and OR = 2.226, P < .001, respectively). CONCLUSIONS: Hondurans use both allopathic and TM. Although private spiritual devotion may help improve adherence to medication, only use of traditional massage therapy, the sobada, was associated with decreased adherence. Effective integration of alternative therapies in Central America will require proper counseling on how to combine multiple therapies to maximize the health benefits.