Factors associated with mortality in transplant patients with invasive aspergillosis.

BACKGROUND: Invasive aspergillosis (IA) is an important cause of morbidity and mortality in hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) recipients. The purpose of this study was to evaluate factors associated with mortality in transplant patients with IA. METHODS: Transplant patients from 23 US centers were enrolled from March 2001 to October 2005 as part of the Transplant Associated Infection Surveillance Network. IA cases were identified prospectively in this cohort through March 2006, and data were collected. Factors associated with 12-week all-cause mortality were determined by logistic regression analysis and Cox proportional hazards regression. RESULTS: Six-hundred forty-two cases of proven or probable IA were evaluated, of which 317 (49.4%) died by the study endpoint. All-cause mortality was greater in HSCT patients (239 [57.5%] of 415) than in SOT patients (78 [34.4%] of 227; P<.001). Independent poor prognostic factors in HSCT patients were neutropenia, renal insufficiency, hepatic insufficiency, early-onset IA, proven IA, and methylprednisolone use. In contrast, white race was associated with decreased risk of death. Among SOT patients, hepatic insufficiency, malnutrition, and central nervous system disease were poor prognostic indicators, whereas prednisone use was associated with decreased risk of death. Among HSCT or SOT patients who received antifungal therapy, use of an amphotericin B preparation as part of initial therapy was associated with increased risk of death. CONCLUSIONS: There are multiple variables associated with survival in transplant patients with IA. Understanding these prognostic factors may assist in the development of treatment algorithms and clinical trials.

Bayesian inference of the number of factors in gene-expression analysis: application to human virus challenge studies.

BACKGROUND: Nonparametric Bayesian techniques have been developed recently to extend the sophistication of factor models, allowing one to infer the number of appropriate factors from the observed data. We consider such techniques for sparse factor analysis, with application to gene-expression data from three virus challenge studies. Particular attention is placed on employing the Beta Process (BP), the Indian Buffet Process (IBP), and related sparseness-promoting techniques to infer a proper number of factors. The posterior density function on the model parameters is computed using Gibbs sampling and variational Bayesian (VB) analysis. RESULTS: Time-evolving gene-expression data are considered for respiratory syncytial virus (RSV), Rhino virus, and influenza, using blood samples from healthy human subjects. These data were acquired in three challenge studies, each executed after receiving institutional review board (IRB) approval from Duke University. Comparisons are made between several alternative means of per-forming nonparametric factor analysis on these data, with comparisons as well to sparse-PCA and Penalized Matrix Decomposition (PMD), closely related non-Bayesian approaches. CONCLUSIONS: Applying the Beta Process to the factor scores, or to the singular values of a pseudo-SVD construction, the proposed algorithms infer the number of factors in gene-expression data. For real data the "true" number of factors is unknown; in our simulations we consider a range of noise variances, and the proposed Bayesian models inferred the number of factors accurately relative to other methods in the literature, such as sparse-PCA and PMD. We have also identified a "pan-viral" factor of importance for each of the three viruses considered in this study. We have identified a set of genes associated with this pan-viral factor, of interest for early detection of such viruses based upon the host response, as quantified via gene-expression data.

Factors influencing malaria control policy-making in Kenya, Uganda and Tanzania.

BACKGROUND: Policy decisions for malaria control are often difficult to make as decision-makers have to carefully consider an array of options and respond to the needs of a large number of stakeholders. This study assessed the factors and specific objectives that influence malaria control policy decisions, as a crucial first step towards developing an inclusive malaria decision analysis support tool (MDAST). METHODS: Country-specific stakeholder engagement activities using structured questionnaires were carried out in Kenya, Uganda and Tanzania. The survey respondents were drawn from a non-random purposeful sample of stakeholders, targeting individuals in ministries and non-governmental organizations whose policy decisions and actions are likely to have an impact on the status of malaria. Summary statistics across the three countries are presented in aggregate. RESULTS: Important findings aggregated across countries included a belief that donor preferences and agendas were exerting too much influence on malaria policies in the countries. Respondents on average also thought that some relevant objectives such as engaging members of parliament by the agency responsible for malaria control in a particular country were not being given enough consideration in malaria decision-making. Factors found to influence decisions regarding specific malaria control strategies included donor agendas, costs, effectiveness of interventions, health and environmental impacts, compliance and/acceptance, financial sustainability, and vector resistance to insecticides. CONCLUSION: Malaria control decision-makers in Kenya, Uganda and Tanzania take into account health and environmental impacts as well as cost implications of different intervention strategies. Further engagement of government legislators and other policy makers is needed in order to increase funding from domestic sources, reduce donor dependence, sustain interventions and consolidate current gains in malaria.

Mid-term results and factors affecting outcome of a metal-backed unicompartmental knee design: a case series.

BACKGROUND: Controversies exist regarding the indications for unicompartmental knee arthroplasty. The objective of this study is to report the mid-term results and examine predictors of failure in a metal-backed unicompartmental knee arthroplasty design. METHODS: At a mean follow-up of 60 months, 80 medial unicompartmental knee arthroplasties (68 patients) were evaluated. Implant survivorship was analyzed using Kaplan-Meier method. The Knee Society objective and functional scores and radiographic characteristics were compared before surgery and at final follow-up. A Cox proportional hazard model was used to examine the association of patient's age, gender, obesity (body mass index > 30 kg/m2), diagnosis, Knee Society scores and patella arthrosis with failure. RESULTS: There were 9 failures during the follow up. The mean Knee Society objective and functional scores were respectively 49 and 48 points preoperatively and 95 and 92 points postoperatively. The survival rate was 92% at 5 years and 84% at 10 years. The mean age was younger in the failure group than the non-failure group (p < 0.01). However, none of the factors assessed was independently associated with failure based on the results from the Cox proportional hazard model. CONCLUSION: Gender, pre-operative diagnosis, preoperative objective and functional scores and patellar osteophytes were not independent predictors of failure of unicompartmental knee implants, although high body mass index trended toward significance. The findings suggest that the standard criteria for UKA may be expanded without compromising the outcomes, although caution may be warranted in patients with very high body mass index pending additional data to confirm our results. LEVEL OF EVIDENCE: IV.

HPV16 antibodies as risk factors for oropharyngeal cancer and their association with tumor HPV and smoking status.

BACKGROUND: Antibodies (Abs) to the HPV16 proteome increase risk for HPV-associated OPC (HPVOPC). The goal of this study was to investigate the association of a panel of HPV16 Abs with risk for OPC as well as the association of these Abs with tumor HPV and smoking status among patients with OPC. METHODS: IgG Abs to the HPV16 antigens E1, E2, E4, E5, E6, E7, L1, L2 were quantified using a programmable ELISA assay. Sera were obtained from 258 OPC patients at diagnosis and 250 healthy controls. HPV16 tumor status was measured by PCR for 137 cases. Multivariable logistic regression was used to calculate odds ratios for the association of HPV16 Abs with risk for OPC. RESULTS: HPV16 E1, E2, E4, E5, E6, E7 and L1-specific IgG levels were elevated in OPC patients compared to healthy controls (p<0.05). After multivariable adjustment, Ab positivity for NE2, CE2, E6, and/or E7 was associated with OPC risk (OR [95% CI], 249.1 [99.3-624.9]). Among patients with OPC, Ab positivity for these antigens was associated with tumor HPV status, especially among never or light smokers (OR [95% CI], 6.5 [2.1-20.1] and OR [95% CI], 17.5 [4.0-77.2], respectively). CONCLUSIONS: Antibodies to HPV16 proteins are associated with increased risk for HPVOPC. Among patients with OPC, HPV16 Abs are associated with tumor HPV status, in particular among HPV positive patients with no or little smoking history.

Understanding Antenatal Genetics Services in Sri Lanka: Current Landscape of Screening and Diagnostic Services and Contextual Factors Influencing Their Availability and Uptake

Background: Too little information is available on Sri Lanka’s current capacity to provide community genetic services—antenatal genetic services in particular—to understand whether building that capacity could further improve and reduce disparity in maternal and child health. This qualitative research project seeks to gather information on congenital disorders, routine antenatal care, and the current state of antenatal screening testing services within that routine antenatal to assess the feasibility of and the need for scaling up antenatal genetics services in Sri Lanka. Methods: Nineteen key informant (KI) interviews were conducted with stakeholders in antenatal care and genetic services. Seven focus group discussions were held with a total of 56 Public Health Midwives (PHMs), the health workers responsible for antenatal care at the field level. Transcripts for all interviews and FGDs were analyzed for key themes, and themes were categorized to address the specific aims of the project. Results: Antenatal genetic services play a minor role in antenatal care, with screening and diagnostic procedures available in the private sector and paid for out-of-pocket. KIs and PHMs expect that demand for antenatal genetic services will increase as patients’ purchasing power and knowledge grow but note that prohibitive abortion laws limit the ability of patients to act on test results. Genetic services compete for limited financial and human resources in the free public health system, and inadequate information on the prevalence of congenital disorders limits the ability to understand whether funding for services related to those disorders should be increased. A number of alternatives to scaling up antenatal genetic services within the free health system might be better suited to the Sri Lankan structural and social context. Conclusions: Scaling up antenatal genetic services within the public health system is not feasible in the current financial, legal, and human resource context. Yet current availability and utilization patterns contribute to regional and economic disparities, suggesting that stasis will not bring continued improvements in maternal and child health. More information on the burden of congenital disorders is necessary to fully understand if and how antenatal genetic service availability should be increased in Sri Lanka, but even before that information is gathered, examination of policies for patient referral, termination of pregnancy, and government support for individuals with genetic disease are steps that might bring extend improvements and reduce disparity in maternal and child health.

Factors Impacting Grandparent and Grand Child Communication Across Sex- Related Topics in Kenya

Background: Although many studies have investigated sexual communication between parents and children in Kenya, none have focused singularly on grandparent and grandchild communication when grandparents are primary caregivers. Further, few studies have asked about specific topics related to sex, instead asking generally about “sex related topics” or focusing on HIV/AIDS. This research aims to investigate communication on ten specific sex- related topics between grandparents who are primary caregivers and their grandchildren. The primary research aim was to identify facilitators and barriers to grandparent-grandchild communication associated with frequency of communication. A secondary exploratory question was whether frequency of communication and youth satisfaction with communication were associated with youth’s desire for more communication in the future. Methods: The study was conducted in urban and peri-urban central Kenya. A convenience sample of 193 grandparents and 166 twelve to fifteen year old grandchildren were identified by community health workers. A cross sectional survey assessed nine potential barriers or facilitators to communication (e.g., frequency of communication, perceived grandparent knowledge, grandparent sense of responsibility to communication on a given topic) on ten specified sex- related topics (e.g., peer pressure on sex topics, romantic relationships, condoms). Bivariate and multivariable analyses identified significant associations between communication variables and the outcomes of interest. Results: Bivariate regression showed that higher grandchild age, grandchild gender, higher perceived grandparent knowledge, higher perceived grandparent comfort, higher grandparent-reported sense of responsibility, higher grandparent-reported belief that child should be aware of a given topic before initiating in sex, and higher youth’s own comfort during communication, were significantly associated with higher levels of communication frequency. In the multivariable model, higher grandchild age, gender, higher comfort during communication, and higher perceived grandparent knowledge remained significantly associated with higher levels communication frequency. For the secondary research question, higher communication frequency and higher levels of youth satisfaction were both significantly associated with higher levels of youth desire for more communication in bivariate regression, and higher levels of youth’s satisfaction with communication remained significantly associated with higher levels of youth’s desire for more in the adjusted analysis. Conclusions: This study found that several potential barriers and facilitators of communication are associated with both frequency of and youth’s desire for more communication. The association between grandchild age, gender and perceived grandparent knowledge and frequency of communication is similar to findings from other studies that have examined sex-related communication between parent primary caregivers and children. This finding has important implications for understanding grandparent and grandchild communication, and communication on specific topics in a population from Kenya. The positive association between youth satisfaction of and desire for more communication has important education policy and intervention implications, suggesting that if youth are satisfied with the communication with their caregivers, they may want to learn more.

A Qualitative Study of Contextual Factors’ Impact on the Adaptation of a Caregiver-mediated Early Autism Intervention in South Africa

Background: Autism Spectrum Disorder (ASD) is a major global health challenge as the majority of individuals with ASD live in low- and middle-income countries (LMICs) and receive little to no services or support from health or social care systems. Despite this global crisis, the development and validation of ASD interventions has almost exclusively occurred in high-income countries, leaving many unanswered questions regarding what contextual factors would need to be considered to ensure the effectiveness of interventions in LMICs. This study sought to conduct explorative research on the contextual adaptation of a caregiver-mediated early ASD intervention for use in a low-resource setting in South Africa.

Methods: Participants included 22 caregivers of children with autism, including mothers (n=16), fathers (n=4), and grandmothers (n=2). Four focus groups discussions were conducted in Cape Town, South Africa with caregivers and lasted between 1.5-3.5 hours in length. Data was recorded, translated, and transcribed by research personnel. Data was then coded for emerging themes and analyzed using the NVivo qualitative data analysis software package.

Results: Nine contextual factors were reported to be important for the adaptation process including culture, language, location of treatment, cost of treatment, type of service provider, familial needs, length of treatment, support, and parenting practices. One contextual factor, evidence-based treatment, was reported to be both important and not important for adaptation by caregivers. The contextual factor of stigma was identified as an emerging theme and a specifically relevant challenge when developing an ASD intervention for use in a South African context.

Conclusions: Eleven contextual factors were discussed in detail by caregivers and examples were given regarding the challenges, sources, and preferences related to the contextual adaptation of a parent-mediated early ASD intervention in South Africa. Caregivers reported a preference for an affordable, in-home, individualized early ASD intervention, where they have an active voice in shaping treatment goals. Distrust of community-based nurses and health workers to deliver an early ASD intervention and challenges associated with ASD-based stigma were two unanticipated findings from this data set. Implications for practice and further research are discussed.

Post-cesarean Section Peritonitis at a Referral Hospital in Rwanda: Factors Associated with Maternal Morbidity and Mortality

Background: Post-cesarean section peritonitis is the leading cause of maternal morbidity and mortality at the main referral hospital in Rwanda. Published data on the management of post-cesarean section peritonitis is limited. This study examined predictors of maternal morbidity and mortality for post-cesarean peritonitis.

Methods: We performed a prospective observational cohort study at the University Teaching Hospital Kigali (CHUK) from January 1 until December 31 2015, followed by a retrospective chart review of all subjects with post-cesarean section peritonitis admitted to CHUK from January 1 until December 31, 2014. All patients admitted with the diagnosis of post-cesarean section peritonitis undergoing exploratory laparotomy at CHUK were enrolled. Patients were followed to either discharge or death. Study variables included baseline demographic/clinical characteristics, admission physical exam, intraoperative findings, and management. Data were analyzed using STATA version 14.

Results: Of the 167 patients enrolled, 81 survived without requiring hysterectomy (49%), 49 survived requiring hysterectomy (29%), and 36 died (22%). In the multivariate analysis, severe sepsis was the most significant predictor of mortality (RR=4.0 [2.2-7.7]) and uterine necrosis was the most significant predictor of hysterectomy (RR=6.3 [1.6-25.2]). There were high rates of antimicrobial resistance (AMR) among the bacterial isolates cultured from intra-abdominal pus, with 52% of bacteria resistant to third-generation cephalosporins.

Conclusions: Post-cesarean section peritonitis carries a high mortality rate in Rwanda. It is also associated with a high rate of hysterectomy. Understanding the disease process and identifying factors associated with outcomes can help guide management during admission.

Role of patient factors, preferences, and distrust in health care and access to liver transplantation and organ donation.

Despite major improvements in access to liver transplantation (LT), disparities remain. Little is known about how distrust in medical care, patient preferences, and the origins shaping those preferences contribute to differences surrounding access. We performed a single-center, cross-sectional survey of adults with end-stage liver disease and compared responses between LT listed and nonlisted patients as well as by race. Questionnaires were administered to 109 patients (72 nonlisted; 37 listed) to assess demographics, health care system distrust (HCSD), religiosity, and factors influencing LT and organ donation (OD). We found that neither HCSD nor religiosity explained differences in access to LT in our population. Listed patients attained higher education levels and were more likely to be insured privately. This was also the case for white versus black patients. All patients reported wanting LT if recommended. However, nonlisted patients were significantly less likely to have discussed LT with their physician or to be referred to a transplant center. They were also much less likely to understand the process of LT. Fewer blacks were referred (44.4% versus 69.7%; P = 0.03) or went to the transplant center if referred (44.4% versus 71.1%; P = 0.02). Fewer black patients felt that minorities had as equal access to LT as whites (29.6% versus 57.3%; P < 0.001). For OD, there were more significant differences in preferences by race than listing status. More whites indicated OD status on their driver's license, and more blacks were likely to become an organ donor if approached by someone of the same cultural or ethnic background (P < 0.01). In conclusion, our analysis demonstrates persistent barriers to LT and OD. With improved patient and provider education and communication, many of these disparities could be successfully overcome. Liver Transplantation 22 895-905 2016 AASLD.