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Background and purpose: A comprehensive individual toxicity risk profile is needed to improve radiation treatment optimisation, minimising toxicity burden, in head and neck cancer (HNC) patients. We aimed to develop and externally validate NTCP models for various toxicities at multiple time points.Materials and methods: Using logistic regression, we determined the relationship between normal tissue irradiation and the risk of 22 toxicities at ten time points during and after treatment in 750 HNC patients. The toxicities involved swallowing, salivary, mucosal, speech, pain and general complaints. Studied pre-dictors included patient, tumour and treatment characteristics and dose parameters of 28 organs. The resulting NTCP models were externally validated in 395 HNC patients.Results: The NTCP models involved 14 organs that were associated with at least one toxicity. The oral cavity was the predominant organ, associated with 12 toxicities. Other important organs included the parotid and submandibular glands, buccal mucosa and swallowing muscles. In addition, baseline toxicity, treatment modality, and tumour site were common predictors of toxicity. The median discrimination performance (AUC) of the models was 0.71 (interquartile range: 0.68-0.75) at internal validation and 0.67 (interquartile range: 0.62-0.71) at external validation.Conclusion: We established a comprehensive individual toxicity risk profile that provides essential insight into how radiation exposure of various organs translates into multiple acute and late toxicities. This comprehensive understanding of radiation-induced toxicities enables a new radiation treatment optimisation concept that balances multiple toxicity risks simultaneously and minimises the overall tox-icity burden for an individual HNC patient who needs to undergo radiation treatment. (C) 2021 The Author(s). Published by Elsevier B.V.

To improve our ability to extrapolate preclinical toxicity to humans, there is a need to understand and quantify the concordance of adverse events (AEs) between animal models and clinical studies. In the present work, we discovered 3011 statistically significant associations between preclinical and clinical AEs caused by drugs reported in the PharmaPendium database of which 2952 were new associations between toxicities encoded by different Medical Dictionary for Regulatory Activities terms across species. To find plausible and testable candidate off-target drug activities for the derived associations, we investigated the genetic overlap between the genes linked to both a preclinical and a clinical AE and the protein targets found to interact with one or more drugs causing both AEs. We discuss three associations from the analysis in more detail for which novel candidate off-target drug activities could be identified, namely, the association of preclinical mutagenicity readouts with clinical teratospermia and ovarian failure, the association of preclinical reflexes abnormal with clinical poor-quality sleep, and the association of preclinical psychomotor hyperactivity with clinical drug withdrawal syndrome. Our analysis successfully identified a total of 77% of known safety targets currently tested in in vitro screening panels plus an additional 431 genes which were proposed for investigation as future safety targets for different clinical toxicities. This work provides new translational toxicity relationships beyond AE term-matching, the results of which can be used for risk profiling of future new chemical entities for clinical studies and for the development of future in vitro safety panels.

Background Giant cell arteritis (GCA) is a disease that relapses often, and some patients run a refractory course. Although prompt recognition of resistant GCA is a major issue, there is no well-recognized, baseline risk factor for poor response to glucocorticoid (GC) treatment. Methods We included all patients consecutively diagnosed with GCA and homogeneously treated since 1976 in a single department and regularly followed-up for at least 18 months. Using a set of customized criteria defining response to GCs, we separated patients into highly responsive, usually responsive, dependent on GCs, and resistant to GCs. We determined which of the baseline variables were associated with GC-resistance and conducted factor analyses of mixed data and decision tree analyses. We also determined whether being GC-resistant was associated with poorer tolerance to GCs and higher death rates. Results In all, 455 patients were followed for 93.4 ± 67.6 (standard deviation) months; 41 (9%) and 21 (4.6%) patients developed GC-dependent and GC-resistant disease, respectively. Factor analyses suggested an association between clinical pattern and degree of responsiveness to GCs; The decision tree analyses, built on an age at GCA onset 〈 66 years and body weight 〉 71 kg, delineated a high risk profile (44% of the patients who featured both characteristics were GC-resistant vs. less than 3% who featured neither, p Conclusion Extra-cranial, large-vessel GCA may be associated with prolonged GC requirements. A simple combination of age and body weight defined a subgroup of patients at high risk for developing GC resistance. Our findings need confirmation in prospective controlled studies.

Arthrofibrosis is an abnormal histopathologic response, is debilitating for patients, and poses a substantial unsolved clinical challenge. This study characterizes molecular biomarkers and regulatory pathways associated with arthrofibrosis by comparing fibrotic and non-fibrotic human knee tissue. The fibrotic group encompasses 4 patients undergoing a revision total knee arthroplasty (TKA) for arthrofibrosis (RTKA-A) while the non-fibrotic group includes 4 patients undergoing primary TKA for osteoarthritis (PTKA) and 4 patients undergoing revision TKA for non-arthrofibrotic and non-infectious etiologies (RTKA-NA). RNA-sequencing of posterior capsule specimens revealed differences in gene expression between each patient group by hierarchical clustering, principal component analysis, and correlation analyses. Multiple differentially expressed genes (DEGs) were defined in RTKA-A versus PTKA patients (i.e., 2059 up-regulated and 1795 down-regulated genes) and RTKA-A versus RTKA-NA patients (i.e., 3255 up-regulated and 3683 down-regulated genes). Our findings define molecular and pathological markers of arthrofibrosis, as well as novel potential targets for risk profiling, early diagnosis and pharmacological treatment of patients.

Penile prosthesis implantation is the gold standard of surgical therapy for patients with medication-refractory erectile dysfunction. However, this umbrella definition includes significant heterogeneity and associated risk profiles that should be candidly discussed and addressed perioperatively. Factors associated with operative success and patient satisfaction are often surgery specific; however, risk profiling via patient selection, preoperative optimization, proper device selection, and intraoperative consideration are highly correlated. Some examples of common risk profiles include comorbidity(ies) such as cardiovascular disease, diabetes mellitus, prior abdominal surgery, Peyronie's disease, and psychological risk factors. Similarly, integration of surgeon- and patient-amenable characteristics is key to decreasing risk of infection, complication, and need for revision. Finally, patient risk profiling provides a unique context for proper device selection and evidence-based intraoperative considerations.

Zika virus is transitioning to become a long-term public health challenge, and countries should remain informed of the risk for emergence. We developed a stochastic epidemiologic model to profile risk for Zika virus emergence, including trimester-specific fetal risk across time, in all 3,208 counties in the United States, including Puerto Rico. Validation against known transmission in North America demonstrated accuracy to predict epidemic dynamics and absolute case counts across scales (R2 = 0.98). We found that, although sporadic single transmission events could occur in most US counties, outbreaks will likely be restricted to the Gulf Coast region and to late spring through autumn. Seasonal fluctuations in birth rates will confer natural population-level protection against early-trimester infections. Overall, outbreak control will be more effective and efficient than prevention, and vaccination will be most effective at >70% coverage. Our county-level risk profiles should serve as a critical resource for resource allocation.

Background: Echocardiography might enhance cardiovascular (CV) risk stratification beyond tools grading the risk for atherosclerotic CV diseases (ASCVD). We therefore studied the complementarity between the ASCVD risk score recommended by American cardiology societies and echocardiographic profiling in predicting adverse CV outcome in the community. Methods: 984 community-dwelling individuals between 40 and 79 years old (51.3% women) underwent CV risk profiling and echocardiography. We estimated their 10-year ASCVD risk from baseline risk factors using the Pooled Cohort Equations. Participants were categorized as at low (amp;lt;2.5%), borderline (2.5-amp;lt;7.5%) or intermediate-to-high (amp;gt;= 7.5%) ASCVD risk. Main outcome was the incidence of CV events collected on average 7.5 years later. Results: The probability for cardiac remodeling and/or dysfunction as assessed by echocardiography rose progressively with increasing 10-year ASCVD risk. During follow-up, 116 participants experienced at least one CV endpoint (15.8 events per 1000 person-years). With increasing 10-year ASCVD risk, the CV event rate increased stronger in participants with amp;gt;= 1 LV abnormality at baseline. Indeed, in individuals with an intermediate-to-high ASCVD risk and amp;gt;= 1 LV abnormality at baseline, the risk was significantly higher than the average population risk for a first CV event (HR: 3.00, P amp;lt; 0.001). Adding the presence of amp;gt;= 1 LV abnormality to a ASCVD risk score-based model yielded significant improvement in C-statistics (P = 0.024), integrated discrimination (P=0.0085) and net reclassification (P amp;lt; 0.001) for adverse CV events. Conclusions: Echocardiographic profiling enhanced CV risk stratification in individuals at intermediate-to-high ASCVD risk. Echocardiographic screening might supplement traditional ASCVD risk grading for CV disease prediction. (C) 2019 Elsevier B.V. All rights reserved. Funding Agencies|Fonds voor Wetenschappelijk Onderzoek Vlaanderen, Brussels, BelgiumFWO [11Z0916N, G0C5319N]

We envisage the development of new Brain Health Services to achieve primary and secondary dementia prevention. These services will complement existing memory clinics by targeting cognitively unimpaired individuals, where the focus is on risk profiling and personalized risk reduction interventions rather than diagnosing and treating late-stage disease. In this article, we review key potentially modifiable risk factors and genetic risk factors and discuss assessment of risk factors as well as additional fluid and imaging biomarkers that may enhance risk profiling. We then outline multidomain measures and risk profiling and provide practical guidelines for Brain Health Services, with consideration of outstanding uncertainties and challenges. Users of Brain Health Services should undergo risk profiling tailored to their age, level of risk, and availability of local resources. Initial risk assessment should incorporate a multidomain risk profiling measure. For users aged 39–64, we recommend the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) Dementia Risk Score, whereas for users aged 65 and older, we recommend the Brief Dementia Screening Indicator (BDSI) and the Australian National University Alzheimer’s Disease Risk Index (ANU-ADRI). The initial assessment should also include potentially modifiable risk factors including sociodemographic, lifestyle, and health factors. If resources allow, apolipoprotein E ɛ4 status testing and structural magnetic resonance imaging should be conducted. If this initial assessment indicates a low dementia risk, then low intensity interventions can be implemented. If the user has a high dementia risk, additional investigations should be considered if local resources allow. Common variant polygenic risk of late-onset AD can be tested in middle-aged or older adults. Rare variants should only be investigated in users with a family history of early-onset dementia in a first degree relative. Advanced imaging with 18-fluorodeoxyglucose positron emission tomography (FDG-PET) or amyloid PET may be informative in high risk users to clarify the nature and burden of their underlying pathologies. Cerebrospinal fluid biomarkers are not recommended for this setting, and blood-based biomarkers need further validation before clinical use. As new technologies become available, advances in artificial intelligence are likely to improve our ability to combine diverse data to further enhance risk profiling. Ultimately, Brain Health Services have the potential to reduce the future burden of dementia through risk profiling, risk communication, personalized risk reduction, and cognitive enhancement interventions.

Introduction: Elite youth soccer players suffer increasing numbers of injuries owing to constantly increasing physical demands. Deficits in neuromuscular performance may increase the risk of injury. Injury risk factors need to be identified and practical cut-off scores defined. Therefore, the purpose of the study was to assess neuromuscular performance parameters within a laboratory-based injury risk screening, to investigate their association with the risk of non-contact lower extremity injuries in elite youth soccer players, and to provide practice-relevant cut-off scores.Methods: Sixty-two elite youth soccer players (age: 17.2 ± 1.1 years) performed unilateral postural control exercises in different conditions, isokinetic tests of concentric and eccentric knee extension and knee flexion (60°/s), isometric tests of hip adduction and abduction, and isometric tests of trunk flexion, extension, lateral flexion and transversal rotation during the preseason period. Non-contact lower extremities injuries were documented throughout 10 months. Risk profiling was assessed using a multivariate approach utilizing a Decision Tree model [Classification and Regression Tree (CART) method].Results: Twenty-five non-contact injuries were registered. The Decision Tree model selected the COP sway, the peak torque for knee flexion concentric, the functional knee ratio and the path of the platform in that hierarchical order as important neuromuscular performance parameters to discriminate between injured and non-injured players. The classification showed a sensitivity of 0.73 and a specificity of 0.91. The relative risk was calculated at 4.2, meaning that the risk of suffering an injury is four times greater for a player, who has been classified as injured by the Decision Tree model.Conclusion: Measuring static postural control, postural control under unstable condition and the strength of the thigh seem to enable a good indication of injury risk in elite youth soccer players. However, this finding has to be taken with caution due to a small number of injury cases. Nonetheless, these preliminary results may have practical implications for future directions in injury risk screening and in planning and developing customized training programs to counteract intrinsic injury risk factors in elite youth soccer players.

Introduction It is a fundamental good clinical practice in our medicolegal rights era to obtain standard, adequate, and transparent informed consent before any planned intervention. Currently, there are neither national approved vascular intervention-specific consents nor explicit guidelines for it. We aim to achieve a standardisation of perioperative risk profiling of infrainguinal bypass surgical consents and produce a model one. Method A retrospective analysis of 45 infrainguinal bypass consents (audit/reaudit) between (2013-2019) retrieved to evaluate quality and completeness against GMC 2008 guidance: "Consent: patients and doctors making decisions together". Data included basic consent requirements according to guidelines and specific risks of infrainguinal bypass. It was registered with the Trust Clinical Audit Department. Results (100%) of audit and reaudit consents documented the intended benefits of surgery. Inclusion into the National Vascular Registry (NVR) was achieved (0%) in audit vs (80%) in reaudit forms. Of the 19 documented postoperative complications, reaudit significant improvement observed in % of documenting 16 items with 9 complications recorded above 50%. The maximum number of audit documented risks was 15 (79%), the median 8 (42%), and the least was 3 (16%) compared to maximum 16 (84%), the median 10 (53%) and the least was 4 (21%) when reaudited, respectively. Conclusions Deficiencies in performing and adequately completing surgical consents still occur. Introducing a national pre-printed vascular intervention-specific consent is vital for accomplishing and maintaining a good clinical practice. It should include all complications with relative % risk to minimise errors, provide good quality consent, and promote clinical practice at a national level.

Introduction It is a fundamental good clinical practice in our medicolegal rights era to obtain standard, adequate, and transparent informed consent before any planned intervention. Currently, there are neither national approved vascular intervention-specific consents nor explicit guidelines for it. We aim to achieve a standardisation of perioperative risk profiling of carotid endarterectomy consents and produce a model one. Method A retrospective analysis of 65 carotid endarterectomy consents (audit/reaudit) between (2016-2019) retrieved to evaluate quality and completeness against GMC 2008 guidance: "Consent: patients and doctors making decisions together". Data included basic consent requirements according to guidelines and specific risks of carotid endarterectomy. It was registered with the Trust Clinical Audit Department. Results (90%) audit vs (87%) reaudit consents documented the intended benefits of surgery. Inclusion into the National Vascular Registry (NVR) was achieved (0%) in audit vs (60%) in reaudit forms. Of the 14 documented postoperative complications, reaudit significant improvement observed in % of documenting 12 items with 6 complications recorded above 50%. The maximum number of audit documented risks was 11 (79%), the median 6 (43%), and the least was 3 (21%) compared to maximum 13 (93%), the median 7 (50%) and the least was 5 (36%) when reaudited, respectively. Conclusions Deficiencies in performing and adequately completing surgical consents still occur. Introducing a national pre-printed vascular intervention-specific consent is vital for accomplishing and maintaining a good clinical practice. It should include all complications with relative % risk to minimise errors, provide good quality consent, and promote clinical practice at a national level.

Introduction Early identification of patients (pts) with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) at high risk for treatment failure may allow for interventions to improve outcomes; however, known prognostic factors are inadequate. Circulating tumor DNA (ctDNA) has demonstrated the ability to identify previously untreated DLBCL pts at high risk of relapse (Kurtz et al. 2018). We assessed the potential for ctDNA to identify pts with R/R DLBCL receiving bendamustine and rituximab (BR) +/- polatuzumab (pola) at higher risk for disease progression. Methods GO29365 (NCT02257567) is a Phase Ib/II study comparing pola+BR versus BR in pts with transplant-ineligible R/R DLBCL and enrolled 80 pts (n=40 per randomized arm). The primary efficacy objective was independent review committee (IRC)-assessed complete response (CR) rate at primary response assessment (PRA, 6-8 weeks after Cycle 6, Day 1 or last dose of study drug). ctDNA was measured in available cohort samples using a customized DLBCL panel on a modified ctDNA CAPP-Seq workflow developed based on the prototype assay reported in Kurtz et al. 2018, with improvement of sensitivity and specificity. ctDNA was reported as mean mutant molecules per mL (MMPM). Plasma depleted whole blood from baseline was used as a source of germline DNA to filter non-tumor-specific variants. A total of 43 samples were available at baseline; eight pts without a paired germline were excluded from efficacy and correlative analyses. Of the 35 samples (n=21 Pola+BR; n=14 BR) with available germline data, paired samples were available for 25 pts at PRA. Detectable ctDNA (+/-) was determined using empirical p-values ( Results Intent-to-treat and biomarker evaluable populations were similar in demographics and efficacy, but there was a higher proportion of pola+BR versus BR pts assayed (60% vs 40%). Analyses are reported for the pooled arms, but results were consistent across both arms. ctDNA was detected in all available baseline (n=43) samples (95% CI: 92-100). Baseline ctDNA levels were correlated with known prognostic factors including International Prognostic Index (IPI), lactate dehydrogenase (LDH), Ann Arbor stage and number of prior therapies (Figure 1A). Higher ctDNA levels at baseline were negatively prognostic; when stratifying pts by median ctDNA levels the hazard ratio (HR) for PFS was 0.16 (95% CI: 0.07-0.41; Figure 1B); OS HR 0.23 (95% CI: 0.10-0.52). Similar results were observed for other quartile stratifications. This significant trend was maintained when adjusted in multivariate analysis for treatment, IPI >3, and LDH > upper limit of normal with an adjusted HR for PFS of 0.24 (95% CI: 0.07-0.81) and for OS an adjusted HR of 0.30 (95% CI: 0.09-0.97). Similar to the first-line setting (Kurtz et al. 2018), on-treatment log fold-changes in ctDNA trended with PRA response (Figure 1C); pts with a CR had a significantly greater average decrease in MMPM across timepoints than non-CR pts (Wilcoxon p-value Conclusions Baseline ctDNA levels were correlated with standard clinical risk factors, and were shown to have independent prognostic value for response, PFS and OS in R/R DLBCL pts treated with BR +/- pola. The degree of ctDNA change upon treatment was also correlated with response, but association with PFS needs further investigation with a larger sample size. This provides early evidence that ctDNA can be used to improve identification of R/R DLBCL pts at high risk for disease progression/relapse. Figure Disclosures Herrera: AstraZeneca: Research Funding; Karyopharm: Consultancy; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Immune Design: Research Funding; Seattle Genetics: Consultancy, Research Funding; Gilead Sciences: Consultancy, Research Funding; Pharmacyclics: Research Funding; Merck: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Other: Travel, Accomodations, Expenses, Research Funding. Tracy:F. Hoffmann-La Roche: Current Employment, Current equity holder in publicly-traded company; Genentech, Inc.: Current Employment. Croft:Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months. Opat:Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZenca: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Beigene: Research Funding; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; CSL: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Mundipharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Epizyme: Research Funding; F. Hoffman-La Roche Ltd: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel accomodations, Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Ray:F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company; Genentech, Inc.: Current Employment. Musick:F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company; Roche/Genentech, Inc.: Current Employment. Paulson:F. Hoffmann-La Roche Ltd.: Current Employment, Current equity holder in publicly-traded company. Sehn:Chugai: Consultancy, Honoraria; Servier: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Teva: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Research Funding; MorphoSys: Consultancy, Honoraria; Merck: Consultancy, Honoraria; Lundbeck: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Kite: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Acerta: Consultancy, Honoraria; Genentech, Inc.: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria; Apobiologix: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Verastem Oncology: Consultancy, Honoraria; TG therapeutics: Consultancy, Honoraria. Jiang:F. Hoffmann-La Roche: Current equity holder in publicly-traded company; Genentech, Inc.: Current Employment.

Purpose This study investigated the implementation of a risk profiling process for physiotherapy clients with a compensable musculoskeletal problem. Implementation targeted personal (clinician) and external (organisational) factors to facilitate behavioural change with regard to the use of formal, questionnaire-based risk profiling. Methods A theoretical construct was developed for formal questionnaire-based screening to be implemented across 12 private, metropolitan physiotherapy clinics. To target personal (clinician) factors, a multimodal educational procedure was developed focused on use of the ten-item Orebro Musculoskeletal Pain Screening Questionnaire (OMPSQ-10). To target external (organisational) factors, an administrative process was enacted to ensure routine completion of the OMPSQ-10 by compensable clients. Global practice behaviour with regard to the use of formal risk profiling was complete pre- and post-implementation. Results Pre-implementation physiotherapists understood the potential usefulness of formal risk profiling, but the large majority did not routinely have clients complete these types of questionnaires. Post-implementation there was a significant positive shift in behaviour to more frequent use the OMPSQ-10 for new compensable clients. Conclusions The results provide initial support for the use of a framework to develop an implementation strategy to increase physiotherapist adherence to the use of guideline recommended risk profiling questionnaires in clinical practice.

We evaluated the outcomes and adverse events after fetoscopic laser surgery (FLS) for twin–twin transfusion syndrome (TTTS) using the Solomon technique in comparison to the selective technique. A retrospective analysis of a single-center consecutive cohort of FLS-treated TTTS using the selective (January 2010 to July 2014) and Solomon (August 2014 to December 2017) techniques was performed. Among 395 cases, 227 underwent selective coagulation and 168 underwent the Solomon technique. The incidence rates of recurrent TTTS (Solomon vs. selective: 0% vs. .9%, p = .510) and twin anemia–polycythemia sequence (.6% vs. .4%, p = .670) were very low in both groups. The incidence rates of placental abruption (Solomon vs. selective: 10.7% vs. 3.5%, p = .007) and preterm premature rupture of the membranes (pPROM) with subsequent delivery before 32 weeks (20.2% vs. 7.1%, p < .001) were higher in the Solomon group. The median birth recipient weight was significantly smaller in the Solomon group (1790 g vs. 1933 g, p = .049). The rate of survival of at least one twin was significantly higher in the Solomon group (98.2% vs. 93.8%, p = .046). The Solomon technique and total laser energy were significant risk factors for pPROM (odds ratio: 2.64, 1.07, 95% CI [1.32, 5.28], [1.01, 1.13], p = .006, p = .014, respectively). These findings suggest that the Solomon technique led to superior survival outcomes but increased risks of placental abruption, pPROM and fetal growth impairment. Total laser energy was associated with the occurrence of pPROM. Close attention to adverse events is required for perinatal management after FLS to treat TTTS using the Solomon technique.

Commercial shipping is the primary pathway of introduction for aquatic nonindigenous species, mainly through the mechanisms of ballast water and biofouling. In response to this threat, regulatory programs have been established across the globe to regulate and monitor commercial merchant and passenger vessels to assess compliance with local requirements to reduce the likelihood of NIS introductions. Resource limitations often determine the inspection efforts applied by these regulatory agencies to reduce NIS introductions. We present a simple and adaptable model that prioritizes vessel arrivals for inspection using proxies for potential propagule pressure, namely a ships’ wetted surface area as a proxy for the likelihood of biofouling-mediated potential propagule pressure and ballast water discharge volume as a proxy for ballast water-mediated potential propagule pressure. We used a California-specific dataset of vessels that arrived at California ports between 2015 and 2018 to test the proposed model and demonstrate how a finite set of inspection resources can be applied to target vessels with the greatest potential propagule pressure. The proposed tool is adaptable by jurisdiction, scalable to different segments of the vessel population, adjustable based on the vector of interest, and versatile because it allows combined or separate analyses of the PPP components. The approach can be adopted in any jurisdiction across the globe, especially jurisdictions without access to, or authority to collect, risk profiling data or direct measurements for all incoming vessel arrivals.

Introduction: We investigated relationships among genetic determinants of Alzheimer's disease (AD), amyloid/tau/neurodegenaration (ATN) biomarkers, and risk of dementia.Methods: We studied cognitively normal individuals with subjective cognitive decline (SCD) from the Amsterdam Dementia Cohort and SCIENCe project. We examined associations between genetic variants and ATN biomarkers, and evaluated their predictive value for incident dementia. A polygenic risk score (PRS) was calculated based on 39 genetic variants. The APOE gene was not included in the PRS and was analyzed separately.Results: The PRS and APOE ε4 were associated with amyloid-positive ATN profiles, and APOE ε4 additionally with isolated increased tau (A-T+N-). A high PRS and APOE ε4 separately predicted AD dementia. Combined, a high PRS increased while a low PRS attenuated the risk associated with ε4 carriers.Discussion: Genetic variants beyond APOE are clinically relevant and contribute to the pathophysiology of AD. In the future, a PRS might be used in individualized risk profiling.

The study by Sehrawat et al. made an important observation that extracellular vesicles (EVs) and sphingolipid cargoes can distinguish alcoholic hepatitis from decompensated cirrhosis. The authors suggest that an EV value of 1.56 × 1011 /mL will help in differentiating alcoholic hepatitis and also predict 90-day survival, permitting risk profiling and thus having important clinical implications.(1).

Objectives To delineate laboratory-confirmed bloodstream infection (LCBI), analyze risk factors for its occurrence and predictors for its short-term mortality in systemic lupus erythematosus (SLE) patients. Methods A single center, retrospective, case-controlled study was performed in 159 SLE patients (2013–2019) to identify risk factors of LCBI by comparing patients with LCBI (n = 39) to those without infection (n = 120). The predictors associated with 30-day mortality in LCBI patients were also analyzed. Results Altogether 40 bacteria strains were isolated in 39 LCBI patients with a predominance of the gram-negative bacilli (24 strains, 60.0%). Escherichia coli and Staphylococcus aureus were the leading Gram-negative and Gram-positive microorganisms, respectively. Occurrence of LCBI was independently predicted by: SLE disease duration >4 years, SLEDAI score >4 points, glucocorticoids dose >7.5 mg/d and the previous or concomitant occurrence of autoimmune hemolytic anemia (AIHA) or thrombotic microangiopathy (TMA). Based on the identified risk factors, we developed a matrix model for the risk of future LCBI. The 30-day mortality (39 cases) was 23.1% and healthcare-associated LCBI was a predictor for 30-day mortality in SLE patients compared with community-acquired LCBI. Conclusion Longer duration, higher disease activity and glucocorticoids dose, and occurrence of AIHA or TMA were risk factors of LCBI in SLE and its poor short-term prognosis may attribute to healthcare-associated LCBI.

Assessing the baseline knowledge status and expectations of the target population of any health promotion and secondary prevention program is essential to the success of such intervention. To obtain this information about the Hong Kong population a priori to implementing these preventive strategies for oral cancer in addition to determining the willingness of potential screening participants to take risk-profiling assessments, a cross-sectional survey was conducted between November 2019 and March 2020. A total of 964 residents between the ages 18 and 86 years were invited to participate in this study across the three geographical areas in Hong Kong. Most participants self-reported being aware of oral cancer (86.3%), although the proportion of those with substantial knowledge on salient risk factors and early identifiable signs were very low (2.9%). Age and level of education were the only demographic characteristics associated with the knowledge status. The proportion of participants willing to attend community screening and partake in risk profiling assessment was high (83.9% and 80.9% respectively). Willingness to attend community screening was directly associated with respondents’ self-reported oral cancer awareness status (OR: 1.9, 95% CI: 1.22–2.96). Also, we observed that those participants who were willing to attend screening are more inclined to take risk prediction assessments that those not willing to attend. These findings have showcased the need to intensify health promotion via personal skills development to encourage early disease presentation and will assist in the planning of these programs accordingly in the Hong Kong population.

Staphylococcus aureus bacteremia (SaB) causes significant disease in humans, carrying mortality rates of ~25%. The ability to rapidly predict SaB patient responses and guide personalized treatment regimens could reduce mortality. Here, we present a resource of SaB prognostic biomarkers. Integrating proteomic and metabolomic techniques enabled the identification of >10,000 features from >200 serum samples collected upon clinical presentation. We interrogated the complexity of serum using multiple computational strategies, which provided a comprehensive view of the early host response to infection. Our biomarkers exceed the predictive capabilities of those previously reported, particularly when used in combination. Lastly, we validated the biological contribution of mortality-associated pathways using a murine model of SaB. Our findings represent a starting point for the development of a prognostic test for identifying high-risk patients at a time early enough to trigger intensive monitoring and interventions.

To effectively manage patients of different vulnerabilities to falls and pressure injury entails understanding the risk drivers and predicting risk profiles in real-time, thus, we determined the core drivers of patients’ proneness to these risks while developing a machine learning strategy for their real-time prediction in acute care hospital. By implementing a multivariate logistic analysis, the risk drivers and injury risk probabilities were obtained while establishing a comparative machine learning technique for patients’ risk-profiling. We observed Multi sclerosis & motor neuron disease (MSN) and Fall during current admission (FDA) as pronounced risk drivers, and Extra Tree Classifier (ETC) and Random Forest (RF) as the best algorithms with prediction accuracy of 90.6% - 99.8%. With a cost saving of 2.3% - 38.89%, our framework will provide an efficient technique for cost-effective management of inpatients susceptible to falls and pressure injury risks on admission.

Contains fulltext : 229568.pdf (Publisher’s version ) (Open Access) INTRODUCTION: Cervical cancer affects half a million women worldwide annually. Given the association between high-risk human papillomavirus (hrHPV) infection and carcinogenesis, hrHPV DNA testing became an essential diagnostic tool. However, hrHPV alone does not cause the disease, and, most importantly, many cervical lesions regress to normal in a year because of the host immune system. Hence, the low specificity of hrHPV DNA tests and their inability to predict the outcome of infections have triggered a further search for biomarkers. AREAS COVERED: We evaluated the latest viral and cellular biomarkers validated for clinical use as primary screening or triage for cervical cancer and assessed their promise for prevention as well as potential use in the future. The literature search focused on effective biomarkers for different stages of the disease, aiming to determine their significance in predicting the outcome of hrHPV infections. EXPERT OPINION: Biomarkers such as p16/Ki-67, hrHPV genotyping, hrHPV transcriptional status, and methylation patterns have demonstrated promising results. Their eventual implementation in the screening programs may support the prompt diagnosis of hrHPV infection and its progression to cancer. These biomarkers will help in making clinical management decisions on time, thus, saving the lives of hrHPV-infected women, particularly in developing countries.

SummaryTo combat the epidemic increase in Type-2-Diabetes (T2D), risk factors need to be identified. Diet, lifestyle and the gut microbiome are among the most important factors affecting metabolic health. We demonstrate in 1,976 subjects of a prospective population cohort that specific gut microbiota members show diurnal oscillations in their relative abundance and we identified 13 taxa with disrupted rhythmicity in T2D. Prediction models based on this signature classified T2D with an area under the curve of 73%. BMI as microbiota-independent risk marker further improved diagnostic classification of T2D. The validity of this arrhythmic risk signature to predict T2D was confirmed in 699 KORA subjects five years after initial sampling. Shotgun metagenomic analysis linked 26 pathways associated with xenobiotic, amino acid, fatty acid, and taurine metabolism to the diurnal oscillation of gut bacteria. In summary, we determined a cohort-specific risk pattern of arrhythmic taxa which significantly contributes to the classification and prediction of T2D, highlighting the importance of circadian rhythmicity of the microbiome in targeting metabolic human diseases.

This is a commentary on the manuscript by Mpody C, Arends J, Aldrink J, et al., titled "Prognostic Profiling of Children with Serious Post-Operative Complications: A Novel Probability Model for Failure to Rescue".

Background: Prediction of patient outcomes following allogeneic hematopoietic stem cell transplantation (HSCT) remains a tenacious problem. An important limitation of current prediction models is the heterogeneity in outcome even among similar cases. We introduce a novel approach to individualizing estimates of leukemia-free survival (LFS) in acute leukemia patients undergoing haploidentical (haplo) HSCT. Methods: Data were obtained from the registry of the European Society for Blood and Marrow Transplantation for all cases of haplo HSCT for acute leukemia performed between 2011 and 2017. Patients receiving ex-vivo T-cell depleted grafts were excluded. Acute myeloid leukemia patients were classified by clinical disease ontogeny (de novo vs. secondary), cytogenetics, and FLT3-ITD/NPM1mut status; acute lymphoblastic leukemia patients by disease status and the presence of the Philadelphia chromosome. Common patient and transplantation parameters including recipient age, Karnofsky performance status (KPS), time from diagnosis to transplantation, conditioning and graft-versus-host disease (GvHD) prophylaxis were included. Data were split into training and geographic validation sets. Results: A total of 2,001 patients was included in the training set and another 270 in the validation cohort. In the training set, the median age was 50 years; 68% of patients were in complete remission, and 69% had a KPS ≥ 90; 87% received post-transplant cyclophosphamide and 13% antithymocyte globulin for GvHD prophylaxis. To provide the clinician insight on outcomes of similar patients, we developed a descriptive tool to visually explore outcomes of cases with comparable features. We next generated 50 random survival forest models for the prediction of 1-year LFS. In contrast to single point-estimates, the ensemble of 50 models generates a prediction interval accounting for predictive uncertainty. There was heterogeneity of variable importance between models, with either disease status or KPS leading in all models (Figure A). The model was well calibrated (Figure B); the median c-statistic was 0.64 on the validation set. An online interface presents the individual outcomes of the fifteen patients most similar to the index case, the prediction interval, and a visualization of all 50 survival forest predictions. Predictions for a sample patient are shown in Figure (C). Conclusions: We present the first system for individualized prediction of leukemia-free survival following T-cell replete haplo transplantation. A key, novel component of the model, distinguishing it from standard risk scores, is that it provides a measure of predictive certainty. This is essential for judging the robustness of prediction. Our approach is applicable to other clinical settings and can be used for designing risk-guided interventions and for informing patients and clinicians. Figure Disclosures Labopin: Jazz Pharmaceuticals: Honoraria. Blaise:Jazz Pharmaceuticals: Honoraria. Sica:F. Hoffmann-La Roche Ltd: Other: All authors received support for third-party writing assistance, furnished by Scott Battle, PhD, provided by F. Hoffmann-La Roche, Basel, Switzerland., Research Funding. Mohty:Stemline: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; Jazz Pharmaceuticals: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Sanofi: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; GSK: Consultancy, Honoraria, Research Funding, Speakers Bureau.

Diarrhoeal diseases remain a major public health problem, causing more than half a million child deaths every year, particularly in low- and middle-income countries (LMICs). Despite existing knowledge on the aetiologies and causes of diarrhoeal diseases, relatively little is known about its spatial patterns in LMICs, including Senegal. In the present study, data from a cross-sectional survey carried out in 2016 were analysed to describe the spatial pattern of diarrhoeal prevalence in children under the age of 5 years in the secondary city of Mbour in the south-western part of Senegal. Bayesian conditional autoregressive (CAR) models with spatially varying coefficients were employed to determine the effect of sociodemographic, economic and climate parameters on diarrhoeal prevalence. We observed substantial spatial heterogeneities in diarrhoea prevalence. Risk maps, stratified by age group, showed that diarrhoeal prevalence was higher in children aged 25-59 months compared to their younger counterparts with the highest risk observed in the north and south peripheral neighbourhoods, especially in Grand Mbour, Médine, Liberté and Zone Sonatel. The posterior relative risk estimate obtained from the Bayesian CAR model indicated that a unit increase in the proportion of people with untreated stored drinking water was associated with a 29% higher risk of diarrhoea. A unit increase in rainfall was also associated with an increase in diarrhoea risk. Our findings suggest that public health officials should integrate disease mapping and cluster analyses and consider the varying effects of sociodemographic factors in developing and implementing areaspecific interventions for reducing diarrhoea.

An emerging objective in the IBD community is to gear the findings from genome-wide association studies towards achieving precision medicine. The main goal of this new model of disease management is to adapt clinical practice to the needs of each patient. This includes, among others, obtaining more detailed characterizations of disease presentation at diagnosis, better prediction of disease prognosis that permits to anticipate and adapt management to variations in symptomatology, and tailoring treatment to individual needs. In this chapter, we will introduce the methodology for estimation of disease risk using genetic data from individuals and discuss the potential and main challenges for using genomic risk profiling as a predictive tool that can pave the way for adoption of precision medicine-based approaches in the clinical management of IBD.

AIM Centenarians represent a biological model of successful aging because they escaped/postponed most invalidating age-related diseases, such as cardiovascular diseases. The aim of the present study was to clarify whether a favorable cardiovascular risk profile increases the survival chances in long-lived people. METHODS A total of 355 community-dwelling nonagenarians and centenarians living in Southern Italy were recruited in the study. Patients were classified as at low and high cardiovascular risk on the basis of serum cholesterol, diabetes, hypertension and smoking status. The relationship between cardiovascular risk factors and 10-year mortality was investigated by Cox regression analysis. Splines-based hazard ratio curves were also estimated for total cholesterol, low-density lipoprotein cholesterol, and systolic and diastolic blood pressure. RESULTS Low levels of selected cardiovascular risk factors usually associated with lower mortality in adults do not increase survival chances among oldest-old individuals. In particular, after adjusting for age, sex, and cognitive, functional and nutritional status, serum cholesterol >200 mg/dL increased the survival chances during the follow-up period (hazard ratio 0.742, 95% CI 0.572-0.963). CONCLUSIONS The present results showed that in nonagenarians and centenarians, the clinical and prognostic meaning associated with traditional cardiovascular risk factors is very different from younger populations. Consequently, considering the increase of this population segment, further studies are required to confirm these results and to translate them into clinical practice/primary care. Geriatr Gerontol Int 2019; 19: 165-170.

Summary Accurate prediction of long-term outcomes remains a challenge in the care of cancer patients. Due to the difficulty of serial tumor sampling, previous prediction tools have focused on pretreatment factors. However, emerging non-invasive diagnostics have increased opportunities for serial tumor assessments. We describe the Continuous Individualized Risk Index (CIRI), a method to dynamically determine outcome probabilities for individual patients utilizing risk predictors acquired over time. Similar to “win probability” models in other fields, CIRI provides a real-time probability by integrating risk assessments throughout a patient’s course. Applying CIRI to patients with diffuse large B cell lymphoma, we demonstrate improved outcome prediction compared to conventional risk models. We demonstrate CIRI’s broader utility in analogous models of chronic lymphocytic leukemia and breast adenocarcinoma and perform a proof-of-concept analysis demonstrating how CIRI could be used to develop predictive biomarkers for therapy selection. We envision that dynamic risk assessment will facilitate personalized medicine and enable innovative therapeutic paradigms.

Actinic keratoses (AKs) represent in-situ squamous cell carcinomas that potentially invade subepidermal structures and may metastasize. Until now, it is unpredictable to determine which AK lesions show this aggressive behavior. As AKs usually occur in large sun exposed areas, field-directed treatments have become the standard treatment regimen. Among these, conventional photodynamic therapy (cPDT) with 5-aminolaevulinic acid (ALA) or methyl-aminolevulinate (MAL) using red light is particularly effective in the treatment of AKs, but acceptance of the therapy is impaired by severe pain during treatment. Daylight PDT (dPDT) has demonstrated to be an equally effective alternative treatment option which is less painful. Recent attempts to determine the risk of AKs that demonstrate particular aggressive biological behavior by implementation of clinical and histological characteristics of AKs have not lead to conclusive results. Therefore, a look at the molecular biology of AKs could serve as a useful tool to develop a risk profiling for separation of those patients that are of particular risk to develop invasive tumor and, by this, to facilitate a more effective and adapted treatment option.

Introduction The purpose of this study is to determine if the risk of receiving a blood transfusion during hip fracture hospitalization can be predicted by a validated risk profiling score (Score for Trauma Triage in Geriatric and Middle Aged (STTGMA)). Materials and Methods A consecutive series of 1449 patients 55 years and older admitted for a hip fracture at one academic medical center were identified from a trauma database. The STTGMA risk score was calculated for each patient. Patients were stratified into risk groups based on their STTGMA score quantile: minimal risk (0–50%), low risk (50–80%), moderate risk (80–95%), and high risk (95–100%). Incidence and volume of blood transfusions were compared between risk groups. Results There were 562 (38.8%) patients who received a transfusion during their admission. 58.3% of patients in the high risk group received a transfusion during admission compared to 31.2% of minimal risk group patients, 42.6% of low risk group patients, and 50.0% of moderate risk group patients ( p < 0.001). STTGMA was predictive of first transfusion incidence in both the preoperative and postoperative periods. There was no difference in mean total transfusion volume between the four risk groups. Conclusion The STTGMA model is capable of risk stratifying hip fracture patients more likely to receive blood transfusions during hospitalization. Surgeons can use this tool to anticipate transfusion requirements.

It has been assumed that the greater the number of flying hours, the better the pilot is at solving problems. The studies suggest, however, that this issue is more complex. What is important is not only a pilot’s experience but also their personality traits such as temperament, aggression, and risk-taking tendencies, which all influence how the pilot reacts under stress. After examining 112 pilots of passenger planes, we found that individuals characterized by a high need for stimulation seek situations, consciously or not, of excessive or unnecessary risk to achieve the right level of stimulation. In terms of their psychological characteristics, the study also revealed that some pilots are less predisposed to be airline pilots.

Background and aims: Subclinical atherosclerosis assessed by sonographic intima-media-thickness measurement of the carotid artery (cIMT) is considered to be an early precursor of cardiovascular disease already in childhood. Structural analysis of the carotid intimal layer (carotid intima-media-roughness, cIMR) improves cardiovascular risk profiling for the adult patient and has been shown to be increased also in paediatric patients with elevated cardiovascular risk. To date, normal values for the paediatric age are lacking. Thus, we present normative data for a paediatric age group. Methods: 602 healthy German school children (age 8-18 y) were studied, and cIMT and cIMR calculated;reference values were given for three age groups (group 1: 8-10.99 years;group 2: 11-13.99 years;group 3: 14-17.99 years). Results: cIMT values were: 0.48 +/- 0.03 mm for girls and boys in age group 1, 0.49 +/- 0.03 mm for girls and boys in age group 2;and 0.45 +/- 0.03 mm for girls and 0.49 +/- 0.03 mm for boys in age group 3;cIMR was 0.04 +/- 0.01 mm for both sexes in age group 1 and 3;while in age group 2, both sexes showed a cIMR of 0.03 +/- 0.01 mm. Physical fitness was significantly negatively correlated with cIMR (r = -0.212, p < 0.0001) and a strong predictor for cIMR increase. Conclusions: The normative data of cIMR for a paediatric age group presented here allow for the identification of patients at elevated cardiovascular risk. By including cIMR as surface analysis of the arterial wall, the individual risk stratification may be improved compared to thickness-analysis of the Intima-Media-Layer (cIMT) also at a paediatric age. (C) 2016 Published by ELSEVIER.

Background Addressing all modifiable risk factors in a composite manner, instead of treating individual risk factors is the current approach in the management of cardiovascular diseases. In patients, attending chronic disease clinic in Urban Health Centre (UHC) functioning under a tertiary care teaching hospital, this study aims to assess 10-year cardiovascular risk using ‘WHO/ISH Cardiovascular Risk Prediction Charts’ and ‘Framingham General Cardiovascular Risk Profile using lipid levels’ and compare the level of agreement between the results obtained. Methodology A retrospective record review was carried out in urban chronic disease clinic during the months of May and June 2013. Records of 280 patients attending the Urban Health Centre were screened using a structured proforma and 180 of them were included subject to selection criteria. The analysis was carried out using IBM SPSS v 21. 10-year cardiovascular risk was calculated using the joint WHO/ISH charts and the General Framingham Cardiovascular Risk Profile charts. Level of agreement between the risk scores was compared using kappa statistics. Institution ethics committee approval was obtained before starting the project. Results 81.7% of the patients were women with a median age of 58 years. Less than half of the patients (45%) had hypertension and another 37.2% had both diabetes and hypertension. 71.6% of the patients had a Conclusion Framingham Risk Profile was found to identify more patients as belonging to the higher risk category as compared to WHO/ISH charts.

Despite modern therapeutics and treatment strategies, a subset of rheumatoid arthritis (RA) patients remains insufficiently responsive to multiple therapies. Here, we identify predictors of such refractory RA ("reRA").Patients from a longitudinal academic clinical database with reRA (defined as failing to reach the treatment target of at least low disease activity with ≥3 DMARD courses, including ≥1 biological, over a total of ≥18 months) were compared to patients who did respond within the first two treatments (treatment amenable RA, "taRA"). We performed logistic regression analysis to identify risk factors for refractory disease, and several sensitivity analyses concerning different potential definitions for reRA to confirm the robustness of the results; key findings were also validated in an independent community cohort.We enrolled 412 patients, of whom 70 were reRA and 102 taRA; 240 patients fulfilled neither definition. ReRA patients were more frequently female (92.9 vs. 70.6%, p 0.001), younger (44.37 vs. 51.14 years, p = 0.002), and had higher CDAI levels at first presentation (26.06 vs. 15.39, p 0.001). Treatment delay was significantly longer for reRA than for taRA (3.17 vs. 1.45 years, p = 0.001). In multivariable analyses, treatment delay, female gender and higher disease activity remained as independent predictors of refractory disease. Based on the identified predictors, we developed a matrix model for risk of future reRA.Our data identified delay to initial treatment, female gender and higher disease activity as important predictors of a later refractory course of RA. Delay of treatment initiation is the single most important modifiable risk factor of refractory disease.

Purpose of Review Hypertension affects more than 30% of the world’s adult population and thiazide (and thiazide-like) diuretics are amongst the most widely used, effective, and least costly treatments available, with all-cause mortality benefits equivalent to angiotensin-converting enzyme inhibitors or calcium channel antagonists. A minority of patients develop thiazide-induced hyponatremia (TIH) and this is largely unpredictable at the point of thiazide prescription. In some cases, TIH can cause debilitating symptoms and require hospital admission. Although TIH affects only a minority of patients exposed to thiazides, the high prevalence of hypertension leads to TIH being the most common cause of drug-induced hyponatremia requiring hospital admission in the UK. This review examines current clinical and scientific understanding of TIH. Consideration is given to demographic associations, limitations of current electrolyte monitoring regimens, clinical presentation, the phenotype evident on routine clinical blood and urine tests as well as more extensive analyses of blood and urine in research settings, recent genetic associations with TIH, and thoughts on management of the condition. Recent Findings Recent genetic and phenotyping analysis has suggested that prostaglandin E2 pathways in the collecting duct may have a role in the development of TIH in a subgroup of patients. Greater understanding of the molecular pathophysiology of TIH raises the prospect of pre-prescription TIH risk profiling and may offer novel insights into how TIH may be avoided, prevented and treated. Summary The rising prevalence of hypertension and the widespread use of thiazides mean that further understanding of TIH will continue to be a pressing issue for patients, physicians, and scientists alike for the foreseeable future.

Background Strongyloides stercoralis and hookworm are two soil-transmitted helminths (STH) that are highly prevalent in Cambodia. Strongyloides stercoralis causes long-lasting infections and significant morbidity but is largely neglected, while hookworm causes the highest public health burden among STH. The two parasites have the same infection route, i.e. skin penetration. The extent of co-distribution, which could result in potential high co-morbidities, is unknown in highly endemic settings like Cambodia. The aim of this study was to predict the spatial distribution of S. stercoralis-hookworm co-infection risk and to investigate determinants of co-infection in Preah Vihear Province, North Cambodia. Methods A cross-sectional survey was conducted in 2010 in 60 villages of Preah Vihear Province. Diagnosis was performed on two stool samples, using combined Baermann technique and Koga agar culture plate for S. stercoralis and Kato-Katz technique for hookworm. Bayesian multinomial geostatistical models were used to assess demographic, socioeconomic, and behavioural determinants of S. stercoralis-hookworm co-infection and to predict co-infection risk at non-surveyed locations. Results Of the 2576 participants included in the study, 48.6% and 49.0% were infected with S. stercoralis and hookworm, respectively; 43.8% of the cases were co-infections. Females, preschool aged children, adults aged 19–49 years, and participants who reported regularly defecating in toilets, systematically boiling drinking water and having been treated with anthelmintic drugs had lower odds of co-infection. While S. stercoralis infection risk did not appear to be spatially structured, hookworm mono-infection and co-infection exhibited spatial correlation at about 20 km. Co-infection risk was positively associated with longer walking distances to a health centre and exhibited a small clustering tendency. The association was only partly explained by climatic variables, suggesting a role for underlying factors, such as living conditions and remoteness. Conclusions Both parasites were ubiquitous in the province, with co-infections accounting for almost half of all cases. The high prevalence of S. stercoralis calls for control measures. Despite several years of school-based de-worming programmes, hookworm infection levels remain high. Mebendazole efficacy, as well as coverage of and compliance to STH control programmes should be investigated. Electronic supplementary material The online version of this article (10.1186/s13071-017-2604-8) contains supplementary material, which is available to authorized users.

Risk maps facilitate discussion among different stakeholders and provide a tool for spatial targeting of health interventions. We present maps documenting shrinking risk profiles after deworming with respect to soil-transmitted helminthiasis among schoolchildren from disadvantaged neighbourhoods in Port Elizabeth, South Africa. Children were examined for soil-transmitted helminth infections using duplicate Kato-Katz thick smears in March 2015, October 2015 and May 2016, and subsequently treated with albendazole after each survey. The mean infection intensities for Ascaris lumbricoides were 9,554 eggs per gram of stool (EPG) in March 2015, 4,317 EPG in October 2015 and 1,684 EPG in March 2016. The corresponding figures for Trichuris trichiura were 664 EPG, 331 EPG and 87 EPG. Repeated deworming shrank the risk of soil-transmitted helminthiasis, but should be complemented by other public health measures.