Syndemics of intimate partner violence among women in HIV endemic South Africa: geospatial analysis of nationally representative data

This is the final version. Available from Nature Research via the DOI in this record. Despite some improvement in lowering HIV incidence, HIV-related challenges, such as intimate partner violence (IPV), remain unacceptably high among women in South Africa. For decades, researchers and activists have pointed to the complex and intertwined reality of the substance abuse, violence and AIDS (SAVA) syndemic that endangers women. However, more recent systematic review/meta-analysis evidence points to inconclusive association between IPV and alcohol use. Furthermore, much of the evidence is often non-population-based that focuses on the co-occurrence rather than synergistic SAVA interaction. In this study, using the latest data from the South Africa Demographic and Health Survey (SA-DHS), we identified geographic synergistic clustering of IPV associated with HIV and substance abuse in South Africa as a measure of population-level interactions among these factors. The SA-DHS is a nationally representative sample that includes wide-ranging data on health, social challenges and household geo-locations of 5,874 women who participated in the domestic violence module. First, geographical IPV, harmful alcohol use (as the substance abuse measure available in SA-DHS) and HIV clusters were identified using the Kulldorff spatial scan statistic in SaTScan. Second, synergistic interactions related to recent IPV (i.e. recent physical, sexual, emotional violence during the last 12 months) with harmful alcohol use and HIV challenge were measured using RERI [Relative excess risk due to interaction], AP [attributable proportion] and S [Synergy index]. In our results, we spatially identified geographical physical IPV syndemic interactions in parts of the Eastern Cape/Free State Provinces (RERI = 4.42 [95% CI: 2.34–6.51], AP = 0.56 [95% CI: 0.44–0.68], S = 2.77 [95% CI: 2.01–3.84], but not in other forms of IPV. Although IPV, based on decade old concept of SAVA syndemic, was less common/widespread than expected from the national scale population-based data, we identified population-level physical violence syndemic occurring in South Africa. Our study highlights the need to prioritize public health response targeting vulnerable populations residing in these high-risk areas of syndemic mechanisms linking these synergistic epidemics that women face in South Africa.UK Global Challenge Research Fun

Spatial clustering of codeine use and its association with depression: a geospatial analysis of nationally representative South African data

This is the final version. Available on open access from Elsevier via the DOI in this recordBackground There is an alarming trend in sub-Saharan Africa in the use of codeine-containing pharmaceuticals, but its risk of common comorbidities, such as mental health, remains unquantified at a national-level. We investigated the relationship between codeine use and onset of depression in South Africa at a population-level. Methods We used nationally representative panel data from the South Africa National Income Dynamic Study to investigate the relationship between exposure to codeine use in the community (i.e. residing in a codeine hotspot) and onset of depression. Geographical hotspots of codeine use were identified using Kulldorff spatial scan statistic in SaTScan. We quantified depression onset at Wave 5 (year 2017) between individuals residing inside and outside a codeine hotspot who were depression-free at enrolment (Wave 4: 2015) using generalised estimating equation (GEE) regression models. Results We identified four statistically significant hotspots of codeine use, mostly located at the northern part of the country. Among 13,020 participants who were depression-free at enrolment, residing within a codeine use hotspot was significantly associated with higher subsequent onset of depression (aRR=1.21, 95% CI:1.08-1.44). Limitations Data on diagnosis of depressive disorder were not available. Conclusion South Africa, a resource scarce nation with chronically limited mental health services, is not spared from the global opioid epidemic and its impact on depression. Targeted scale-up access to agonist therapy to effectively treat (opioid) addiction in communities at risk for high exposure to codeine use could reduce the risk of subsequent mental health challenges

Topiramate in the treatment of compulsive sexual behavior: case report

BACKGROUND: Among the multiple mechanisms of action of topiramate, AMPA/kainate antagonism may be particularly interesting for the treatment of disorders characterized by conditioned cognitive and behavioral cue reactivity. CASE PRESENTATION: We report the case of a patient consulting primarily for obesity and cue triggered snacking, who responded well on topiramate at doses up to 50 mg. Coincidentally he reported on an improvement of compulsive nonparaphilic sexual behaviors (consumption of prostitution), which was also strongly triggered by environmental cues. Both addictive behaviors (snacking and consumption of prostitution) reoccurred after discontinuation of topiramate and again responded reintroduction of the drug. CONCLUSION: The present case report of topiramate's effect on comorbid obesity and nonparaphilic addiction could be interpreted as a further indication that topiramate acts on the common pathway underlying conditioned behaviors and seems to be a treatment of behavioral disorders associated with environmental cues

Biallelic mutations in IRF8 impair human NK cell maturation and function

Human NK cell deficiencies are rare yet result in severe and often fatal disease, particularly as a result of viral susceptibility. NK cells develop from hematopoietic stem cells, and few monogenic errors that specifically interrupt NK cell development have been reported. Here we have described biallelic mutations in IRF8, which encodes an interferon regulatory factor, as a cause of familial NK cell deficiency that results in fatal and severe viral disease. Compound heterozygous or homozygous mutations in IRF8 in 3 unrelated families resulted in a paucity of mature CD56dim NK cells and an increase in the frequency of the immature CD56bright NK cells, and this impairment in terminal maturation was also observed in Irf8–/–, but not Irf8+/–, mice. We then determined that impaired maturation was NK cell intrinsic, and gene expression analysis of human NK cell developmental subsets showed that multiple genes were dysregulated by IRF8 mutation. The phenotype was accompanied by deficient NK cell function and was stable over time. Together, these data indicate that human NK cells require IRF8 for development and functional maturation and that dysregulation of this function results in severe human disease, thereby emphasizing a critical role for NK cells in human antiviral defense

Pretreatment malnutrition and quality of life - association with prolonged length of hospital stay among patients with gynecological cancer: a cohort study

Background Length of hospital stay (LOS) is a surrogate marker for patients' well-being during hospital treatment and is associated with health care costs. Identifying pretreatment factors associated with LOS in surgical patients may enable early intervention in order to reduce postoperative LOS. Methods This cohort study enrolled 157 patients with suspected or proven gynecological cancer at a tertiary cancer centre (2004-2006). Before commencing treatment, the scored Patient Generated - Subjective Global Assessment (PG-SGA) measuring nutritional status and the Functional Assessment of Cancer Therapy-General (FACT-G) scale measuring quality of life (QOL) were completed. Clinical and demographic patient characteristics were prospectively obtained. Patients were grouped into those with prolonged LOS if their hospital stay was greater than the median LOS and those with average or below average LOS. Results Patients' mean age was 58 years (SD 14 years). Preoperatively, 81 (52%) patients presented with suspected benign disease/pelvic mass, 23 (15%) with suspected advanced ovarian cancer, 36 (23%) patients with suspected endometrial and 17 (11%) with cervical cancer, respectively. In univariate models prolonged LOS was associated with low serum albumin or hemoglobin, malnutrition (PG-SGA score and PG-SGA group B or C), low pretreatment FACT-G score, and suspected diagnosis of cancer. In multivariable models, PG-SGA group B or C, FACT-G score and suspected diagnosis of advanced ovarian cancer independently predicted LOS. Conclusions Malnutrition, low quality of life scores and being diagnosed with advanced ovarian cancer are the major determinants of prolonged LOS amongst gynecological cancer patients. Interventions addressing malnutrition and poor QOL may decrease LOS in gynecological cancer patients

STORIES Statement: publication standards for healthcare education evidence synthesis

Fully copy of the STORIES statement - a checklist of reporting guidance for health education evidence synthesis Structured approach for Reporting In health education of Evidence Synthesis Background Evidence synthesis techniques in healthcare education have been enhanced through the activities of experts in the field and the Best Evidence Medical Education (BEME) collaborative. Despite this, significant heterogeneity in techniques and reporting of healthcare education systematic review still exist and limit the usefulness of such reports. The aim of this project was to produce the STORIES (STructured apprOach to the Reporting In healthcare education of Evidence Synthesis) statement to offer a guide for reporting evidence synthesis in health education for use by authors and journal editors. Methods A review of existing published evidence synthesis consensus statements was undertaken. A modified Delphi process was used. In stage one, expert participants were asked to state whether common existing items identified were relevant, to suggest relevant texts and specify any items they feel should be included. The results were analysed and a second stage commenced where all synthesised items were presented and participants asked to state whether they should be included or amend as needed. After further analysis, the full statement was sent for final review and comment. Results Nineteen experts participated in the panel from 35 invitations. Thirteen text sources were proposed, six existing items amended and twelve new items synthesised. After stage two, 25 amended consensus items were proposed for inclusion. The final statement contains several items unique to this context, including description of relevant conceptual frameworks or theoretical constructs, description of qualitative methodologies with rationale for their choice and presenting the implications for educators in practice of the results obtained. Conclusions An international expert panel has agreed upon a consensus statement of 25 items for the reporting of evidence synthesis within healthcare education. This unique set of items is focused on context, rather than a specific methodology. This statement can be used for those writing for publication and reviewing such manuscripts to ensure reporting supports and best informs the wider healthcare education community

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

Prolonged Antigen Presentation Is Required for Optimal CD8+ T Cell Responses against Malaria Liver Stage Parasites

Immunization with irradiated sporozoites is currently the most effective vaccination strategy against liver stages of malaria parasites, yet the mechanisms underpinning the success of this approach are unknown. Here we show that the complete development of protective CD8+ T cell responses requires prolonged antigen presentation. Using TCR transgenic cells specific for the malaria circumsporozoite protein, a leading vaccine candidate, we found that sporozoite antigen persists for over 8 weeks after immunization—a remarkable finding since irradiated sporozoites are incapable of replication and do not differentiate beyond early liver stages. Persisting antigen was detected in lymphoid organs and depends on the presence of CD11c+ cells. Prolonged antigen presentation enhanced the magnitude of the CD8+ T cell response in a number of ways. Firstly, reducing the time primed CD8+ T cells were exposed to antigen in vivo severely reduced the final size of the developing memory population. Secondly, fully developed memory cells expanded in previously immunized mice but not when transferred to naïve animals. Finally, persisting antigen was able to prime naïve cells, including recent thymic emigrants, to become functional effector cells capable of eliminating parasites in the liver. Together these data show that the optimal development of protective CD8+ T cell immunity against malaria liver stages is dependent upon the prolonged presentation of sporozoite-derived antigen