Global Health in Preconception, Pregnancy and Postpartum Alliance: development of an international consumer and community involvement framework.

BACKGROUND: The goal of the Global Health in Preconception, Pregnancy and Postpartum (HiPPP) Alliance, comprising consumers and leading international multidisciplinary academics and clinicians, is to generate research and translation priorities and build international collaboration around healthy lifestyle and obesity prevention among women across the reproductive years. In doing so, we actively seek to involve consumers in research, implementation and translation initiatives. There are limited frameworks specifically designed to involve women across the key obesity prevention windows before (preconception), during and after pregnancy (postpartum). The aim of this paper is to outline our strategy for the development of the HiPPP Consumer and Community (CCI) Framework, with consumers as central to co-designed, co-implemented and co-disseminated research and translation. METHOD: The development of the framework involved three phases: In Phase 1, 21 Global HiPPP Alliance members participated in a CCI workshop to propose and discuss values and approaches for framework development; Phase 2 comprised a search of peer-reviewed and grey literature for existing CCI frameworks and resources; and Phase 3 entailed collaboration with consumers (i.e., members of the public with lived experience of weight/lifestyle issues in preconception, pregnancy and postpartum) and international CCI experts to workshop and refine the HiPPP CCI Framework (guided by Phases 1 and 2). RESULTS: The HiPPP CCI Framework's values and approaches identified in Phases 1-2 and further refined in Phase 3 were summarized under the following five key principles: 1. Inclusive, 2. Flexible, 3. Transparent, 4. Equitable, and 5. Adaptable. The HiPPP Framework describes values and approaches for involving consumers in research initiatives from design to translation that focus on improving healthy lifestyles and preventing obesity specifically before, during and after pregnancy; importantly it takes into consideration common barriers to partnering in obesity research during perinatal life stages, such as limited availability associated with family caregiving responsibilities. CONCLUSION: The HiPPP CCI Framework aims to describe approaches for implementing meaningful CCI initiatives with women in preconception, pregnancy and postpartum periods. Evaluation of the framework is now needed to understand how effective it is in facilitating meaningful involvement for consumers, researchers and clinicians, and its impact on research to improve healthy lifestyle outcomes.

Health in Preconception, Pregnancy and Postpartum Global Alliance: International Network Pregnancy Priorities for the Prevention of Maternal Obesity and Related Pregnancy and Long-Term Complications.

In this article, we describe the process of establishing agreed international pregnancy research priorities to address the global issues of unhealthy lifestyles and rising maternal obesity. We focus specifically on the prevention of maternal obesity to improve related clinical pregnancy and long-term complications. A team of multidisciplinary, international experts in preconception and pregnancy health, including consumers, were invited to form the Health in Preconception, Pregnancy and Postpartum (HiPPP) Global Alliance. As an initial activity, a priority setting process was completed to generate pregnancy research priorities in this field. Research, practice and policy gaps were identified and enhanced through expert and consumer consultation, followed by a modified Delphi process and Nominal Group Technique, including an international workshop. Research priorities identified included optimising: (1) healthy diet and nutrition; (2) gestational weight management; (3) screening for and managing pregnancy complications and pre-existing conditions; (4) physical activity; (5) mental health; and (6) postpartum (including intrapartum) care. Given extensive past research in many of these areas, research priorities here recognised the need to advance pregnancy research towards pragmatic implementation research. This work has set the agenda for large-scale, collaborative, multidisciplinary, implementation research to address the major public health and clinical issue of maternal obesity prevention.

Health in Preconception, Pregnancy and Postpartum Global Alliance: International Network Preconception Research Priorities for the Prevention of Maternal Obesity and Related Pregnancy and Long-Term Complications.

The preconception period is a key public health and clinical opportunity for obesity prevention. This paper describes the development of international preconception priorities to guide research and translation activities for maternal obesity prevention and improve clinical pregnancy outcomes. Stakeholders of international standing in preconception and pregnancy health formed the multidisciplinary Health in Preconception, Pregnancy, and Postpartum (HiPPP) Global Alliance. The Alliance undertook a priority setting process including three rounds of priority ranking and facilitated group discussion using Modified Delphi and Nominal Group Techniques to determine key research areas. Initial priority areas were based on a systematic review of international and national clinical practice guidelines, World Health Organization recommendations on preconception and pregnancy care, and consumer and expert input from HiPPP members. Five preconception research priorities and four overarching principles were identified. The priorities were: healthy diet and nutrition; weight management; physical activity; planned pregnancy; and physical, mental and psychosocial health. The principles were: operating in the context of broader preconception/antenatal priorities; social determinants; family health; and cultural considerations. These priorities provide a road map to progress research and translation activities in preconception health with future efforts required to advance evidence-translation and implementation to impact clinical outcomes.

Treatment of vaginal agenesis in Mayer-Rokitansky-Küster-Hauser syndrome in Denmark: a nationwide comparative study of anatomical outcome and complications.

OBJECTIVE: To compare the long-term anatomical outcome and complications in treatments of vaginal agenesis in Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. DESIGN: A historical comparative follow-up study using medical chart reviews. SETTING: Public hospitals. PATIENT(S): A nationwide cohort of patients diagnosed with MRKH syndrome (n = 168). INTERVENTION(S): McIndoe vaginoplasty (n = 54), self-dilation (n = 60), coital dilation (n = 20), Baldwin vaginoplasty (n = 4), Williams vaginoplasty (n = 3), Davydov vaginoplasty (n = 2), or no treatment (n = 29). MAIN OUTCOME MEASURES(S): Mean vaginal depth at follow-up, anatomical treatment success rates at levels of ≥6 cm, ≥7 cm, and ≥8 cm, complications, and resurgery. RESULT(S): Mean vaginal depths were 7.4 cm (95% confidence interval [CI] 6.8-8.1 cm), 7.3 cm (95% CI 6.7-7.9 cm), and 8.7 cm (95% CI 7.9-9.5 cm) at follow-up in patients treated by McIndoe vaginoplasty, self-dilation, and coital dilation, respectively. Overall complication rates in the three groups were 35/54 (65%), 21/52 (35%), and 1/20 (5%), respectively. Eighteen (33%) of the patients who underwent McIndoe vaginoplasty needed resurgery. CONCLUSION(S): Our findings support the current recommendations of dilation therapy as the first-line treatment of vaginal agenesis and emphasize the relevance of coital dilation in patients able to regularly engage in coital activity. However, further studies of functional outcome and patient satisfaction are needed.

[Herpes simplex encephalitis].

Herpes simplex encephalitis (HSE) is a rare disease, although it is the most common form of sporadic encephalitis worldwide. Recently, studies have provided important new insight into the genetic and immunological basis of HSE. However, even in the presence of antiviral treatment, mortality and morbidity remain relatively high. Therefore, precise and early diagnosis together with basic and clinical studies to gain better insight into the pathogenesis of HSE is a prerequisite for the development of improved prophylaxis and treatment of this severe disease.

Incidence and mortality of herpes simplex encephalitis in Denmark: A nationwide registry-based cohort study.

OBJECTIVES: We aimed to investigate the incidence and mortality of herpes simplex encephalitis (HSE) in a nationwide cohort. METHODS: From the Danish National Patient Registry, we identified all adults hospitalised with a first-time diagnosis of HSE in Denmark during 2004-2014. The HSE diagnoses were verified using medical records and microbiological data. Patients were followed for mortality through the Danish Civil Registry System. We estimated age-standardised incidence rates of HSE and 30-day, 60-day, and 1-year cumulative mortality. Furthermore, we assessed whether calendar year, age, gender, level of comorbidity, virus type, and department type was associated with HSE mortality. RESULTS: We identified a total of 230 cases of HSE. Median age was 60.7 years (interquartile range: 49.3-71.6). The overall incidence rate was 4.64 cases per million population per year (95% confidence interval: 4.06-5.28). The cumulative mortality within 30 days, 60 days, and 1 year of the HSE admission was 8.3%, 11.3%, and 18.6%, respectively. Advanced age and presence of comorbidity were associated with increased 60-day and 1-year mortality. CONCLUSIONS: This nationwide study of verified HSE found a higher incidence than reported in previous nationwide studies. Presence of comorbidity was identified as a novel adverse prognostic factor. Mortality rates following HSE remain high.

Validity of the coding for herpes simplex encephalitis in the Danish National Patient Registry.

BACKGROUND: Large health care databases are a valuable source of infectious disease epidemiology if diagnoses are valid. The aim of this study was to investigate the accuracy of the recorded diagnosis coding of herpes simplex encephalitis (HSE) in the Danish National Patient Registry (DNPR). METHODS: The DNPR was used to identify all hospitalized patients, aged ≥15 years, with a first-time diagnosis of HSE according to the International Classification of Diseases, tenth revision (ICD-10), from 2004 to 2014. To validate the coding of HSE, we collected data from the Danish Microbiology Database, from departments of clinical microbiology, and from patient medical records. Cases were classified as confirmed, probable, or no evidence of HSE. We estimated the positive predictive value (PPV) of the HSE diagnosis coding stratified by diagnosis type, study period, and department type. Furthermore, we estimated the proportion of HSE cases coded with nonspecific ICD-10 codes of viral encephalitis and also the sensitivity of the HSE diagnosis coding. RESULTS: We were able to validate 398 (94.3%) of the 422 HSE diagnoses identified via the DNPR. Hereof, 202 (50.8%) were classified as confirmed cases and 29 (7.3%) as probable cases providing an overall PPV of 58.0% (95% confidence interval [CI]: 53.0-62.9). For "Encephalitis due to herpes simplex virus" (ICD-10 code B00.4), the PPV was 56.6% (95% CI: 51.1-62.0). Similarly, the PPV for "Meningoencephalitis due to herpes simplex virus" (ICD-10 code B00.4A) was 56.8% (95% CI: 39.5-72.9). "Herpes viral encephalitis" (ICD-10 code G05.1E) had a PPV of 75.9% (95% CI: 56.5-89.7), thereby representing the highest PPV. The estimated sensitivity was 95.5%. CONCLUSION: The PPVs of the ICD-10 diagnosis coding for adult HSE in the DNPR were relatively low. Hence, the DNPR should be used with caution when studying patients with encephalitis caused by herpes simplex virus.

Alternative pre-mRNA splicing leads to potential biomarkers in diffuse large B-cell lymphoma - a systematic review.

INTRODUCTION: The study of potential biomarkers in haematological malignancies has gained momentum in past decades. We compiled a systematic review to outline potential biomarkers based on alternative pre-mRNA splicing that were suggested to be clinically useful for the diagnosis, prognosis and response to therapeutics in diffuse large B-cell lymphoma (DLBCL). METHODS: A comprehensive search of the literature in PubMed, Embase and Scopus was performed and supplemented with screening of reference lists. Only articles concerning potential biomarkers originating from reports on alternative pre-mRNA splicing were included. The contributions of these studies will help develop personalised medicine. Therefore, the clinical utility of the potential biomarkers was evaluated. RESULTS: A total of 16 studies were included of which eight described seven different potential diagnostic biomarkers. Eight studies reported two potential prognostic biomarkers for CD44, its spliced mRNA variants and the resulting proteins that were the most frequently reported. Furthermore, two studies reported two proteins originating from alternative pre-mRNA splicing as potentially predictive biomarkers. CONCLUSIONS: Alternative pre-mRNA splicing is a promising potential diagnostic, prognostic and predictive biomarker for the identification of pathogenic impacts in DLBCL. The use of these potential biomarkers in the clinical management of DLBCL awaits prospective clinical validation supporting its potential to contribute to the shift towards more personalised medicine.

High miR-34a expression improves response to doxorubicin in diffuse large B-cell lymphoma.

The standard treatment for patients with diffuse large B-cell lymphoma (DLBCL) is the immunochemotherapy-based R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone). Resistance to treatment, intrinsic or acquired, is observed in approximately 40% of patients with DLBCL, who thus require novel interventions to survive. To identify biomarkers for cytotoxic response assessment, microRNAs (miRNAs) associated with doxorubicin sensitivity were determined by combining global miRNA expression profiling with systematic dose-response screens in 15 human DLBCL cell lines. One candidate, miR-34a, was tested in functional in vitro studies and in vivo in a retrospective clinical cohort. High expression of miR-34a was observed in cell lines sensitive to doxorubicin, and upregulation of miR-34a is documented here to increase doxorubicin sensitivity in in vitro lentiviral transduction assays. High expression of miR-34a had a prognostic impact using overall survival as outcome. With risk stratification of DLBCL samples based on resistance gene signatures (REGS), doxorubicin-responsive samples had statistically significant upregulated miR-34a expression. Classification of the DLBCL samples into subset-specific B cell-associated gene signatures (BAGS) revealed differentiation-specific expression of miR-34a. Our data further support FOXP1 as a target of miR-34a, suggesting that downregulation of FOXP1 may sensitize DLBCL cells to doxorubicin. We conclude that miRNAs, in particular miR-34a, may have clinical utility in DLBCL patients as both predictive and prognostic biomarkers.

Anxiety, depression, and attachment before and after the first-trimester screening for Down syndrome: comparing couples who undergo ART with those who conceive spontaneously.

OBJECTIVES: This study's aim was to describe the emotional status of parents to be before and after the first-trimester combined prenatal screening test. METHODS: One hundred three couples participated, of which 52 had undergone an in vitro fertilization/intracytoplasmic sperm injection treatment [assisted reproductive technology (ART)] and 51 had conceived spontaneously. Participants completed the state scale of the State-trait Anxiety Inventory, the Edinburgh Depression Scale, and the Maternal and Paternal Antenatal Attachment Questionnaire before the first-trimester combined prenatal screening test at around 12 weeks of gestational age (T1) and just after receiving the results at approximately 14 weeks of gestational age (T2). RESULTS: We observed a significant decrease in anxiety and depression symptoms and a significant increase in attachment from T1 to T2. Results showed no differences between groups at either time point, which suggests that ART parents are more similar to than different from parents conceiving spontaneously. Furthermore, given the importance of anxiety during pregnancy, a subsample of women with clinical anxiety was identified. They had significantly higher rates of clinical depression and lower attachment. CONCLUSIONS: These results indicate that, regardless of whether conception was through ART or spontaneous, clinical anxiety in women over the prenatal testing period is associated with more vulnerability during pregnancy (i.e. clinical depression and less attachment to fetus).

MicroRNAs as novel biomarkers in diffuse large B-cell lymphoma--a systematic review.

INTRODUCTION: MicroRNAs (miRNAs) are short non-coding RNAs that have the ability to regulate gene expression at the post-transcriptional level. MiRNAs are deregulated in many cancer types, and several miRNAs have been suggested as novel diagnostic and prognostic biomarkers in diffuse large B-cell lymphoma (DLBCL). The objective of this study was to systematically collect and evaluate current knowledge of miRNAs functioning as diagnostic and prognostic biomarkers within DLBCL. METHODS: This review was conducted according to the Preferred Reporting for Systematic Reviews and Meta-analyses guidelines. A systematic search of literature in PubMed and Embase was made and supplemented by screening of reference lists. Only original peer-reviewed studies written in English were included and screened based on miRNA expression, molecular subtypes of DLBCL and patient outcome. RESULTS: Out of 277 candidate records, a total of 20 studies qualified for inclusion in this review. In all, 11 studies reported a total of 48 miRNAs with expression patterns associated with specific molecular DLBCL subtypes, and 14 studies reported a total of 30 miRNAs associated with patient outcome. However, only few miRNAs showed significant results in more than one study. CONCLUSION: MiRNAs qualify as potential diagnostic and prognostic biomarkers in DLBCL. However, more clinical validation including prospective and cross-centre studies are required before specific miRNAs can be integrated into the daily practice as biomarkers in DLBCL, which would contribute to an era of more personalised medicine.

Quality of attachment, perinatal risk, and mother-infant interaction in a high-risk premature sample.

Thirty-three families, each with a premature infant born less than 33 gestational weeks, were observed in a longitudinal exploratory study. Infants were recruited in a neonatal intensive care unit, and follow-up visits took place at 4 months and 12 months of corrected age. The severity of the perinatal problems was evaluated using the Perinatal Risk Inventory (PERI; A.P. Scheiner & M.E. Sexton, 1991). At 4 months, mother-infant play interaction was observed and coded according to the CARE-index (P.M. Crittenden, 2003); at 12 months, the Strange Situation Procedure (SSP; M.D.S. Ainsworth, M.C. Blehar, E. Waters, & S. Wall, 1978) was administered. Results indicate a strong correlation between the severity of perinatal problems and the quality of attachment at 12 months. Based on the PERI, infants with high medical risks more frequently tended to be insecurely attached. There also was a significant correlation between insecure attachment and dyadic play interaction at 4 months (i.e., maternal controlling behavior and infant compulsive compliance). Moreover, specific dyadic interactive patterns could be identified as protective or as risk factors regarding the quality of attachment. Considering that attachment may have long-term influence on child development, these results underline the need for particular attention to risk factors regarding attachment among premature infants.