A Mobile Phone–Based Sexual and Reproductive Health Intervention for Female Sex Workers in Kenya: Development and Qualitative Study

Background: Female sex workers (FSWs) have high rates of both unintended pregnancy and HIV, but few health promotion interventions address their contraceptive needs or other sexual and reproductive health and rights (SRHR) concerns. A broader approach integrates contraceptive promotion with HIV and sexually transmitted infection (STI) prevention and management, alcohol awareness, gender-based violence and rights, and health care utilization. The Women\u27s Health Intervention using SMS for Preventing Pregnancy (WHISPER) mobile phone intervention uses a participatory development approach and behavior change theory to address these high-priority concerns of FSWs in Mombasa, Kenya. Objective: This paper aimed to (1) describe the process of development of the WHISPER intervention, its theoretical framework, key content domains and strategies and (2) explore workshop participants\u27 responses to the proposed intervention, particularly with regard to message content, behavior change constructs, and feasibility and acceptability. Methods: The research team worked closely with FSWs in two phases of intervention development. First, we drafted content for three different types of messages based on a review of the literature and behavior change theories. Second, we piloted the intervention by conducting six workshops with 42 FSWs to test and refine message content and 12 interviews to assess the technical performance of the intervention. Workshop data were thematically analyzed using a mixed deductive and inductive approach. Results: The intervention framework specified six SRHR domains that were viewed as highly relevant by FSWs. Reactions to intervention content revealed that social cognitive strategies to improve knowledge, outcome expectations, skills, and self-efficacy resonated well with workshop participants. Participants found the content empowering, and most said they would share the messages with others. The refined intervention was a 12-month SMS program consisting of informational and motivational messages, role model stories portraying behavior change among FSWs, and on-demand contraceptive information. Conclusions: Our results highlight the need for health promotion interventions that incorporate broader components of SRHR, not only HIV prevention. Using a theory-based, participatory approach, we developed a digital health intervention that reflects the complex reality of FSWs\u27 lives and provides a feasible, acceptable approach for addressing SRHR concerns and needs. FSWs may benefit from health promotion interventions that provide relevant, actionable, and engaging content to support behavior change

Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Funder: Funder: Fundación bancaria ‘La Caixa’ Number: LCF/PR/PR16/51110003 Funder: Grifols SA Number: LCF/PR/PR16/51110003 Funder: European Union/EFPIA Innovative Medicines Initiative Joint Number: 115975 Funder: JPco-fuND FP-829-029 Number: 733051061Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Changing geographical patterns and trends in cancer incidence in children and adolescents in Europe, 1991–2010 (Automated Childhood Cancer Information System): a population-based study

Background: A deceleration in the increase in cancer incidence in children and adolescents has been reported in several national and regional studies in Europe. Based on a large database representing 1·3 billion person-years over the period 1991–2010, we provide a consolidated report on cancer incidence trends at ages 0–19 years. Methods: We invited all population-based cancer registries operating in European countries to participate in this population-based registry study. We requested a listing of individual records of cancer cases, including sex, age, date of birth, date of cancer diagnosis, tumour sequence number, primary site, morphology, behaviour, and the most valid basis of diagnosis. We also requested population counts in each calendar year by sex and age for the registration area, from official national sources, and specific information about the covered area and registration practices. An eligible registry could become a contributor if it provided quality data for all complete calendar years in the period 1991–2010. Incidence rates and the average annual percentage change with 95% CIs were reported for all cancers and major diagnostic groups, by region and overall, separately for children (age 0–14 years) and adolescents (age 15–19 years). We examined and quantified the stability of the trends with joinpoint analyses. Findings: For the years 1991–2010, 53 registries in 19 countries contributed a total of 180 335 unique cases. We excluded 15 162 (8·4%) of 180 335 cases due to differing practices of registration, and considered the quality indicators for the 165 173 cases included to be satisfactory. The average annual age-standardised incidence was 137·5 (95% CI 136·7–138·3) per million person-years and incidence increased significantly by 0·54% (0·44–0·65) per year in children (age 0–14 years) with no change in trend. In adolescents, the combined European incidence was 176·2 (174·4–178·0) per million person-years based on all 35 138 eligible cases and increased significantly by 0·96% (0·73–1·19) per year, although recent changes in rates among adolescents suggest a deceleration in this increasing trend. We observed temporal variations in trends by age group, geographical region, and diagnostic group. The combined age-standardised incidence of leukaemia based on 48 458 cases in children was 46·9 (46·5–47·3) per million person-years and increased significantly by 0·66% (0·48–0·84) per year. The average overall incidence of leukaemia in adolescents was 23·6 (22·9–24·3) per million person-years, based on 4702 cases, and the average annual change was 0·93% (0·49–1·37). We also observed increasing incidence of lymphoma in adolescents (average annual change 1·04% [0·65–1·44], malignant CNS tumours in children (average annual change 0·49% [0·20–0·77]), and other tumours in both children (average annual change 0·56 [0·40–0·72]) and adolescents (average annual change 1·17 [0·82–1·53]). Interpretation: Improvements in the diagnosis and registration of cancers over time could partly explain the observed increase in incidence, although some changes in underlying putative risk factors cannot be excluded. Cancer incidence trends in this young population require continued monitoring at an international level. Funding: Federal Ministry of Health of the Federal German Government, the European Union's Seventh Framework Programme, and International Agency for Research on Cancer

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Arthroscopic Deltoid Ligament Repair

Category: Arthroscopy Introduction/Purpose: Background: Recent studies have underscored the importance of open repair of the deltoid ligament for rotational ankle instability in purely ligamentous injuries as well as with ankle fractures. With the advent of successfull arthroscopic lateral ligament techniques the authors have explored the use of similar arthroscopic techniques for deltoid repair. This study aimed to describe a novel arthroscopic technique for deltoid ligament repair and relate the proximity of anatomic structures at risk. Purpose: To evaluate the proximity of anatomic structures for a novel arthroscopic deltoid ligament stabilization technique and to define ideal landmarks and “safe zones” for this repair. Methods: Methods: Five human cadaveric ankle specimens were screened for the study. All specimens underwent arthroscopic deltoid ligament repair with a suture passer and suture anchor technique. Five cadaveric specimens were dissected to determine the proximity of anatomic structures after repair. Several distances were measured, including those of different anatomic structures to the suture knot to determine the “safe zones.” Measurements were obtained and statistical analysis was performed. Results: Results: None of the specimens revealed entrapment of the suture knots to the posterior tibial tendon (PTT) or saphenous nerve. The safe zone between the PTT and saphenous vein was a mean of 20 mm (range, 16-25 mm). On average, a 16 mm (range, 12-20 mm) safe distance was maintained from the suture knot to the PTT. The saphenous vein was in close proximity to the suture knot at a mean distance of 3 mm (range, 0-9 mm). Conclusion: The results indicate that there is a relatively wide safe zone between the PTT and the saphenous vein when performing the arthroscopic deltoid ligament stabilization technique. While none of the critical anatomic structures (except for saphenous vein) were entrapped by the suture knot, it was evident that the variable course of the saphenous vein renders it at risk for entrapment. This study further defines the proximity of adjacent anatomic structures and establishes the anatomic safe zones for the arthroscopic deltoid ankle stabilization procedure. By defining this relatively risk-free zone, surgeons less experienced with arthroscopic ligament repair techniques may approach arthroscopic suture passage with more confidence