Communicating computational workflows in a regulatory environment.

The volume of nucleic acid sequence data has exploded recently, amplifying the challenge of transforming data into meaningful information. Processing data can require an increasingly complex ecosystem of customized tools, which increases difficulty in communicating analyses in an understandable way yet is of sufficient detail to enable informed decisions or repeats. This can be of particular interest to institutions and companies communicating computations in a regulatory environment. BioCompute Objects (BCOs; an instance of pipeline documentation that conforms to the IEEE 2791-2020 standard) were developed as a standardized mechanism for analysis reporting. A suite of BCOs is presented, representing interconnected elements of a computation modeled after those that might be found in a regulatory submission but are shared publicly - in this case a pipeline designed to identify viral contaminants in biological manufacturing, such as for vaccines.

Consumption of sucralose- and acesulfame-potassium-containing diet soda alters the relative abundance of microbial taxa at the species level: findings of two pilot studies.

Sucralose and acesulfame-potassium consumption alters gut microbiota in rodents, with unclear effects in humans. We examined effects of three-times daily sucralose- and acesulfame-potassium-containing diet soda consumption for 1 (n = 17) or 8 (n = 8) weeks on gut microbiota composition in young adults. After 8 weeks of diet soda consumption, the relative abundance of Proteobacteria, specifically Enterobacteriaceae, increased; and, increased abundance of two Proteobacteria taxa was also observed after 1 week of diet soda consumption compared with sparkling water. In addition, three taxa in the Bacteroides genus increased following 1 week of diet soda consumption compared with sparkling water. The clinical relevance of these findings and effects of sucralose and acesulfame-potassium consumption on human gut microbiota warrant further investigation in larger studies. Clinical trial registration: NCT02877186 and NCT03125356.

A Retrospective Study Assessing the Clinical Outcomes After Cheilectomy and Subchondroplasty for Hallux Rigidus.

Introduction Hallux rigidus (HR) refers to osteoarthritis of the first metatarsal phalangeal joint, resulting in stiffness, pain, and limitation in daily function. Surgery of HR is indicated in those who have failed a trial of non-operative management and is typically divided into joint-preserving (JP) and joint-sacrificing procedures. Cheilectomy is the most commonly practiced JP procedure, often done in conjunction with associated procedures for HR. Our paper aims to report the clinical outcomes after cheilectomy and cheilectomy done with subchondroplasty (SCP) performed for HR. Methods All patients who underwent cheilectomy for HR between 2017 and 2022 were identified and had their outcomes evaluated at the time of this review. The patients had their pre-operative radiographs and clinical and operative notes analyzed for the grading of HR. Functional outcomes were assessed with the use of the visual analog scale (VAS) and American Orthopaedic Foot and Ankle Society (AOFAS) scores, as well as comparing the pre-operative and post-operative degree of dorsiflexion of the affected first metatarsophalangeal joint. This study was approved by the SingHealth Institutional Review Board (IRB) Institution with approval number 2021/2629. Results A total of 19 patients and 20 feet were included in our study at a mean follow-up of 29.8 months. There was an increase in dorsiflexion of the first MTP joint by 27.2 degrees (p-value = <0.0001). Patients who underwent cheilectomy alone (Group 1) had a mean improvement in VAS scores of 5.46 (p-value = <0.0001). Patients who underwent SCP of the first metatarsal head along with cheilectomy (Group 2) had an improvement in VAS scores by 5.78 (p-value = 0.0007). There was a mean improvement in AOFAS scores of 25.6 (p-value = <0.0001) for patients in Group 1. Patients in Group 2 had a mean improvement in AOFAS scores of 31.0 (p-value = 0.0003). Conclusion Both cheilectomy and cheilectomy performed with SCP for HR show good outcomes at short-term follow-up (mean 29.8 months). Cheilectomy is a viable alternative to arthrodesis for the surgical treatment of HR even in patients with higher grades. The use of SCP should be further explored as an adjunct in the surgical treatment of HR.

Anteromedial Impingement in Chronic Lateral Ankle Instability: A Comparison of MRI and Arthroscopic Findings.

Introduction Chronic lateral ankle instability (CLAI) is a known complication of ankle sprains, most commonly involving injury to the anterior talofibular ligament (ATFL). Growing evidence has shown an association between anteromedial (AM) impingement and CLAI. The purpose of this paper is to compare magnetic resonance imaging (MRI) with arthroscopic findings for the incidence of AM impingement in CLAI. Methods A retrospective study was performed by analyzing the radiological and operative reports of all patients who underwent an arthroscopic Broström-Gould procedure for CLAI between 2021 and 2022 at Changi General Hospital, Singapore. All patients who had a pre-operative MRI ankle scan performed and mention of the presence or absence of AM impingement in the operative notes were included in this study. Patients with concomitant fractures or systemic conditions affecting the same ankle were excluded. Results Ninety-seven patients were included in this study, 65 males and 32 females; 6.2% (6 of 97) of patients had a suggestion of AM impingement based on MRI findings, and 77.3% (75 of 97) of patients were noted to have AM impingement based on arthroscopic findings. Conclusion There is a high incidence of AM impingement associated with CLAI. AM impingement is often missed based on MRI findings. Arthroscopic Broström should be considered to address both issues of AM impingement and CLAI in the same setting.

Clinical Outcomes After Joint-Preserving and Joint-Sacrificing Surgery for Hallux Rigidus.

Introduction Hallux rigidus (HR) is a degenerative condition affecting the first metatarsal phalangeal joint, causing stiffness and pain. Surgery is indicated for those who have failed a trial of conservative management. The purpose of this paper is to evaluate the functional outcomes at short and medium term after surgery for HR. Methods All patients who underwent surgical treatment for HR between 2017 and 2022 at the time of this study were identified and invited to return for a follow-up evaluation. Outcomes were assessed by comparison of pre-operative and post-operative visual analogue scale (VAS) and American Orthopaedic Foot and Ankle Society (AOFAS) scores. Results A total of 26 patients were included in our study with a mean follow-up of 31 months. There was a mean improvement in VAS score by 5.6 (p-value < 0.0001) and 5.7 (p-value = 0.0012) in patients who underwent joint-preserving (JP) and joint-sacrificing (JS) surgery, respectively. Patients who underwent JP surgery had a mean increase of 28.1 points (p-value < 0.0001) in the AOFAS Hallux score, while patients who underwent JS surgery had a mean increase of 27.29 points (p-value = 0.0066). Conclusion Functional outcomes after surgical management for HR are good at short- and medium-term follow-up. Good outcomes are seen with both JP and JS procedures. JP procedures should be considered as a first-line surgical option for HR as it allows revision procedures if required.

Incidence of Injuries Associated With Anterior Talofibular Ligament Injury Based on the Reporting of Magnetic Resonance Imaging.

Introduction This paper aims to report the incidence of ligamentous, tendon, and other structural injuries associated with an anterior talofibular ligament (ATFL) injury based on magnetic resonance imaging (MRI) findings. Methods The reports of all patients who underwent surgical treatment for ATFL injury between 2021 and 2022 at Changi General Hospital and had preoperative MRI ankle scans performed were analyzed in this retrospective study. Patients who had a preoperative MRI ankle scan performed with specific reporting of the ATFL, calcaneofibular ligament (CFL), deltoid ligaments, peroneal tendons, and the presence of an osteochondral defect (OCD) were included in this study. Patients who underwent surgery but did not have a preoperative MRI ankle scan done or had ankle fractures or systemic conditions affecting the same ankle were excluded. Results Eighty-six patients were included in this study, of which 59 were males and 27 were females. About 73.3% (63 of 86) of patients had sustained injuries in association with ATFL injury, and 58.1% (50 of 86) of patients suffered an associated injury to the calcaneofibular ligament (CFL). There were injuries to the superficial and deep deltoid ligaments in 29.1% (25 of 86) and 44.2% (38 of 86) of patients, respectively. The peroneal tendons were also injured in 17.4% (15 of 86) of patients. Lastly, there were also associated OCDs found in 19.8% (17 of 86) of patients. Conclusion There is a high incidence of injuries associated with an ATFL injury. The CFL and deltoid ligament complex are the most commonly injured structures in association with the ATFL. One in five patients will also have an associated OCD. The ATFL tends to be the only structure that is commonly addressed during surgery. Repair of the ATFL only may thus lead to poorer outcomes and persistent pain, if the underlying cause is due to the other concurrent injuries. Clinical evaluation of the other structures should thus be thoroughly performed to allow the addressing of any concurrent injuries in the same surgical setting to achieve better outcomes.

Detection of acute dengue virus infection, with and without concurrent malaria infection, in a cohort of febrile children in Kenya, 2014-2019, by clinicians or machine learning algorithms.

Poor access to diagnostic testing in resource limited settings restricts surveillance for emerging infections, such as dengue virus (DENV), to clinician suspicion, based on history and exam observations alone. We investigated the ability of machine learning to detect DENV based solely on data available at the clinic visit. We extracted symptom and physical exam data from 6,208 pediatric febrile illness visits to Kenyan public health clinics from 2014-2019 and created a dataset with 113 clinical features. Malaria testing was available at the clinic site. DENV testing was performed afterwards. We randomly sampled 70% of the dataset to develop DENV and malaria prediction models using boosted logistic regression, decision trees and random forests, support vector machines, naïve Bayes, and neural networks with 10-fold cross validation, tuned to maximize accuracy. 30% of the dataset was reserved to validate the models. 485 subjects (7.8%) had DENV, and 3,145 subjects (50.7%) had malaria. 220 (3.5%) subjects had co-infection with both DENV and malaria. In the validation dataset, clinician accuracy for diagnosis of malaria was high (82% accuracy, 85% sensitivity, 80% specificity). Accuracy of the models for predicting malaria diagnosis ranged from 53-69% (35-94% sensitivity, 11-80% specificity). In contrast, clinicians detected only 21 of 145 cases of DENV (80% accuracy, 14% sensitivity, 85% specificity). Of the six models, only logistic regression identified any DENV case (8 cases, 91% accuracy, 5.5% sensitivity, 98% specificity). Without diagnostic testing, interpretation of clinical findings by humans or machines cannot detect DENV at 8% prevalence. Access to point-of-care diagnostic tests must be prioritized to address global inequities in emerging infections surveillance.

The Outcome of Modified Mini-Open Brostrom Gould Ankle Surgery on Chronic Ankle Instability.

Introduction  Modified Brostrom-Gould surgery (MBG) aims to repair the lateral ligaments of the ankle in patients with ligamentous laxity and chronic instability. Brostrom-Gould surgery-the Brostrom technique associated with Gould augmentation-is currently the gold standard surgical option for chronic ankle instability worldwide. Chronic lateral ankle instability caused by lateral ankle sprains is one of the most common sports-related injuries, and Brostrom-Gould surgery is commonly recommended as the operative treatment. While arthroscopic surgery is becoming the more heavily favored approach of choice, open Brostrom-Gould surgery is still pertinent for patients for whom arthroscopic repair is unsuitable. Aim This paper discusses a modified mini-open approach of the open Brostrom-Gould surgery with a smaller incision (1.5 cm) and aims to study the outcomes of this modified approach on patients' post-operative pain, stability, and functional outcome. Methods Forty-two patients were followed up for a mean of 2.6 years after undergoing modified mini-open Brostrom-Gould surgery. The Visual Analog Scale (VAS), the Foot and Ankle Outcome Score (FAOS), and Karlsson scores were used to monitor their post-operative recovery. The Wilcoxon signed-rank test and the SPSS Statistics (v.28.0.1) software were used for data management and analytics. Results The results showed a mean Karlsson score of 83.4, a mean FAOS score of 69.7, and a mean VAS score of 1.33. These results are comparable to studies conducted on conventional open Brostrom-Gould repair. Conclusion The modified mini-open Brostrom Gould provides a favorable functional outcome with a reduction in pain and suggests no decrease in efficacy with the modified approach. This is coupled with the added advantages of a smaller wound, better wound healing outcomes, and availability to patients not suited to arthroscopic repair.

A 14-year follow-up of ultrasound-detected urinary tract pathology associated with urogenital schistosomiasis in women living in the Msambweni region of coastal Kenya.

BACKGROUND: Complications of urogenital schistosomiasis include acute inflammatory and chronic fibrotic changes within the urogenital tract. Disease burden of this neglected tropical disease is often underestimated, as only active, urine egg-patent Schistosoma infection is formally considered. Previous studies have focussed on short-term effects of praziquantel treatment on urinary tract pathology, demonstrating that acute inflammation is reversible. However, the reversibility of chronic changes is less well studied. METHODS: Our study compared, at two time points 14 y apart, urine egg-patent infection and urinary tract pathology in a cohort of women living in a highly endemic area having intermittent praziquantel treatment(s). In 2014 we matched 93 women to their findings in a previous study in 2000. RESULTS: Between 2000 and 2014 the rate of egg-patent infection decreased from 34% (95% confidence interval [CI] 25 to 44) to 9% (95% CI 3 to 14). However, urinary tract pathology increased from 15% (95% CI 8 to 22) to 19% (95% CI 11 to 27), with the greatest increase seen in bladder thickening and shape abnormality. CONCLUSIONS: Despite praziquantel treatment, fibrosis from chronic schistosomiasis outlasts the presence of active infection, continuing to cause lasting morbidity. We suggest that future efforts to eliminate persistent morbidity attributable to schistosomiasis should include intensified disease management.

Surgical Treatment of Haglund's Deformity: A Systematic Review and Meta-Analysis.

Posterosuperior calcaneal prominence, also known as Haglund's deformity, can often lead to retrocalcaneal bursitis, a significant cause of posterior heel pain. Surgery is indicated for symptomatic patients, after a period of conservative treatment including analgesia, physiotherapy, activity, and shoe wear modification has failed. Surgical options include both open and endoscopic techniques, and typically involve excision of the retrocalcaneal bursa, resection of the calcaneal prominence, and debridement of the diseased Achilles tendon. This article aims to provide an evidence-based literature review for the surgical management of Haglund's deformity. A comprehensive evidence-based literature review of the PubMed database conducted in July 2021 identified 20 relevant articles assessing the efficacy of surgical modalities for Haglund's deformity. The 20 studies were assigned to a level of evidence (I-IV). Individual studies were reviewed to provide a grade of recommendation (A-C, I) according to the Wright classification in support of or against the surgical modality. Qualitative and quantitative analysis was performed for the 20 studies. The results show that both open and endoscopic surgical modalities are efficacious in the treatment of Haglund's deformity, significantly improving functional outcome scores such as American Orthopaedic Foot & Ankle Society (AOFAS) scores and patient satisfaction post-operatively. Endoscopic surgery appears to have the advantage of shorter operative times, lower complication rates, and better cosmesis. More studies are required to further validate and optimize these surgical techniques.

Defining elimination as a public health problem for schistosomiasis control programmes: beyond prevalence of heavy-intensity infections.

WHO's 2021-30 road map for neglected tropical diseases (NTDs) outlines disease-specific and cross-cutting targets for the control, elimination, and eradication of NTDs in affected countries. For schistosomiasis, the criterion for elimination as a public health problem (EPHP) is defined as less than 1% prevalence of heavy-intensity infections (ie, ≥50 Schistosoma haematobium eggs per 10 mL of urine or ≥400 Schistosoma mansoni eggs per g of stool). However, we believe the evidence supporting this definition of EPHP is inadequate and the shifting distribution of schistosomiasis morbidity towards more subtle, rather than severe, morbidity in the face of large-scale control programmes requires guidelines to be adapted. In this Viewpoint, we outline the need for more accurate measures to develop a robust evidence-based monitoring and evaluation framework for schistosomiasis. Such a framework is crucial for achieving the goal of widespread EPHP of schistosomiasis and to meet the WHO road map targets. We encourage use of overall prevalence of schistosome infection (instead of the prevalence of heavy-intensity infections), development of species-dependent and age-dependent morbidity markers, and construction of a standardised monitoring and evaluation protocol.

Dietary Intake and Pneumococcal Vaccine Response Among Children (5-7 Years) in Msambweni Division, Kwale County, Kenya.

Background: Vaccine and sufficient food availability are key factors for reducing pneumonia outbreaks in sub-Saharan Africa. Methods: In this study, the 10-valent pneumococcal conjugate vaccine (Synflorix® or PCV10) was administered to a child cohort (5-7 years old, n = 237) in Msambweni, Kenya, to determine relationships between dietary intake, nutritional/socioeconomic status of mothers/caregivers, and vaccine response. 7-day food frequency questionnaire (FFQ), dietary diversity score (DDS) and single 24-h dietary recall were used to address participants' dietary assessment and nutritional status. Individual food varieties were recorded and divided into 9 food groups as recommended by Food and Agriculture Organization. Anthropometric measurements, nasopharyngeal swabs and vaccine administration were performed at the initial visit. Participants were followed 4-8 weeks with a blood draw for pneumococcal IgG titers assessed by Luminex assay. Findings: Chronic malnutrition was prevalent in the cohort (15% stunting, 16% underweight). Unbalanced dietary intake was observed, with mean energy intake 14% below Recommended Dietary Allowances (1,822 Kcal) for 5-7 years age range. 72% of the daily energy was derived from carbohydrates, 18% from fats and only 10% from proteins. Poor anthropometric status (stunting/underweight) was associated with low socioeconomic/educational status and younger mother/caregiver age (p < 0.002). Limited intake of essential micronutrients (vitamins A, E, K) and minerals (calcium, potassium) associated with low consumption of fresh fruits, vegetables, and animal source foods (dairy, meat) was observed and correlated with poor vaccine response (p < 0.001). In contrast, children who consumed higher amounts of dietary fiber, vitamin B1, zinc, iron, and magnesium had adequate vaccine response (p < 0.05). Correlation between higher dietary diversity score (DDS), higher Vitamin E, K, Zinc intake and adequate vaccine response was also observed (p < 0.03). Interpretation: Overall, this study highlights ongoing food scarcity and malnutrition in Kenya and demonstrates the links between adequate socioeconomic conditions, adequate nutrient intake, and vaccine efficacy.

Improving anthelmintic treatment for schistosomiasis and soil-transmitted helminthiases through sharing and reuse of individual participant data.

The Infectious Diseases Data Observatory (IDDO, https://www.iddo.org) has launched a clinical data platform for the collation, curation, standardisation and reuse of individual participant data (IPD) on treatments for two of the most globally important neglected tropical diseases (NTDs), schistosomiasis (SCH) and soil-transmitted helminthiases (STHs). This initiative aims to harness the power of data-sharing by facilitating collaborative joint analyses of pooled datasets to generate robust evidence on the efficacy and safety of anthelminthic treatment regimens. A crucial component of this endeavour has been the development of a Research Agenda to promote engagement with the SCH and STH research and disease control communities by highlighting key questions that could be tackled using data shared through the IDDO platform. Here, we give a contextual overview of the priority research themes articulated in the Research Agenda-a 'living' document hosted on the IDDO website-and describe the three-stage consultation process behind its development. We also discuss the sustainability and future directions of the platform, emphasising throughout the power and promise of ethical and equitable sharing and reuse of clinical data to support the elimination of NTDs.

Review of 2022 WHO guidelines on the control and elimination of schistosomiasis.

Schistosomiasis is a helminthiasis infecting approximately 250 million people worldwide. In 2001, the World Health Assembly (WHA) 54.19 resolution defined a new global strategy for control of schistosomiasis through preventive chemotherapy programmes. This resolution culminated in the 2006 WHO guidelines that recommended empirical treatment by mass drug administration with praziquantel, predominately to school-aged children in endemic settings at regular intervals. Since then, school-based and community-based preventive chemotherapy programmes have been scaled-up, reducing schistosomiasis-associated morbidity. Over the past 15 years, new scientific evidence-combined with a more ambitious goal of eliminating schistosomiasis and an increase in the global donated supply of praziquantel-has highlighted the need to update public health guidance worldwide. In February, 2022, WHO published new guidelines with six recommendations to update the global public health strategy against schistosomiasis, including expansion of preventive chemotherapy eligibility from the predominant group of school-aged children to all age groups (2 years and older), lowering the prevalence threshold for annual preventive chemotherapy, and increasing the frequency of treatment. This Review, written by the 2018-2022 Schistosomiasis Guidelines Development Group and its international partners, presents a summary of the new WHO guideline recommendations for schistosomiasis along with their historical context, supporting evidence, implications for public health implementation, and future research needs.

Radiofrequency microtenotomy for plantar fasciitis: A systematic review and meta-analysis.

BACKGROUND: Currently, there is limited evidence on outcomes for plantar fascia radiofrequency microtenotomy. An evidence-based systematic review and meta-analysis for outcomes of radiofrequency microtenotomy for the treatment of plantar fasciitis was conducted. METHODS: A comprehensive evidence-based literature review of PubMed and Cochrane Databases was conducted in March 2019, which identified 11 relevant articles assessing the efficacy of plantar fascia radiofrequency microtenotomy. The studies were then assigned to a level of evidence (I-IV). Individual studies were reviewed to provide a grade of recommendation (A-C, I) according to the Wright classification in support of or against endoscopic plantar fascia release. Meta-analysis was performed for 7 of the studies that measured AOFAS scores. RESULTS: Based on the results of this evidence-based review, there was fair (grade B) evidence to support plantar fascia radiofrequency microtenotomy. There was a statistically significant mean increase of 40.9 in AOFAS scores post procedure. CONCLUSION: There was fair (grade B) evidence to recommend radiofrequency microtenotomy for plantar fasciitis. There is a need for more high quality level I randomized controlled trials with validated outcome measures to allow for stronger recommendations to be made. LEVEL OF EVIDENCE: Level II, systematic review of level II studies.

Paving the way for human vaccination against Rift Valley fever virus: A systematic literature review of RVFV epidemiology from 1999 to 2021.

BACKGROUND: Rift Valley fever virus (RVFV) is a lethal threat to humans and livestock in many parts of Africa, the Arabian Peninsula, and the Indian Ocean. This systematic review's objective was to consolidate understanding of RVFV epidemiology during 1999-2021 and highlight knowledge gaps relevant to plans for human vaccine trials. METHODOLOGY/PRINCIPAL FINDINGS: The review is registered with PROSPERO (CRD42020221622). Reports of RVFV infection or exposure among humans, animals, and/or vectors in Africa, the Arabian Peninsula, and the Indian Ocean during the period January 1999 to June 2021 were eligible for inclusion. Online databases were searched for publications, and supplemental materials were recovered from official reports and research colleagues. Exposures were classified into five groups: 1) acute human RVF cases, 2) acute animal cases, 3) human RVFV sero-surveys, 4) animal sero-surveys, and 5) arthropod infections. Human risk factors, circulating RVFV lineages, and surveillance methods were also tabulated. In meta-analysis of risks, summary odds ratios were computed using random-effects modeling. 1104 unique human or animal RVFV transmission events were reported in 39 countries during 1999-2021. Outbreaks among humans or animals occurred at rates of 5.8/year and 12.4/year, respectively, with Mauritania, Madagascar, Kenya, South Africa, and Sudan having the most human outbreak years. Men had greater odds of RVFV infection than women, and animal contact, butchering, milking, and handling aborted material were significantly associated with greater odds of exposure. Animal infection risk was linked to location, proximity to water, and exposure to other herds or wildlife. RVFV was detected in a variety of mosquito vectors during interepidemic periods, confirming ongoing transmission. CONCLUSIONS/SIGNIFICANCE: With broad variability in surveillance, case finding, survey design, and RVFV case confirmation, combined with uncertainty about populations-at-risk, there were inconsistent results from location to location. However, it was evident that RVFV transmission is expanding its range and frequency. Gaps assessment indicated the need to harmonize human and animal surveillance and improve diagnostics and genotyping. Given the frequency of RVFV outbreaks, human vaccination has strong potential to mitigate the impact of this now widely endemic disease.

Communicating regulatory high-throughput sequencing data using BioCompute Objects.

This project demonstrates the use of the IEEE 2791-2020 Standard (BioCompute Objects [BCO]) to enable the complete and concise communication of results from next generation sequencing (NGS) analysis. One arm of a clinical trial was replicated using synthetically generated data made to resemble real biological data and then two independent analyses were performed. The first simulated a pharmaceutical regulatory submission to the US Food and Drug Administration (FDA) including analysis of results and a BCO. The second simulated an FDA review that included an independent analysis of the submitted data. Of the 118 simulated patient samples generated, 117 (99.15%) were in agreement in the two analyses. This process exemplifies how a template BCO (tBCO), including a verification kit, facilitates transparency and reproducibility, thereby reinforcing confidence in the regulatory submission process.

Investigating the Radiological Outcomes of Syndesmosis Injuries in Ankle Fracture Patients After Suture Button Fixation.

Concomitant syndesmotic injury occurs in 10% of ankle fractures. Anatomic reduction and maintenance of this reduction is critical in ensuring ankle stability and preventing long-term complications. This is a retrospective cohort study aimed at evaluating the mid-term radiological outcomes of syndesmotic injuries in ankle fracture patients after surgical fixation with suture button device. The study group included 33 patients. Plain radiographs including anteroposterior, lateral and mortise views of the affected ankle were performed preoperatively, postoperatively and at 3-month follow-up. Anteroposterior views were used to measure the amount of tibiofibular overlap and tibiofibular clear space. Paired Student's t test and linear model regression were performed. Between the immediate postoperative and 3-month follow-up period, there was a mean decrease in tibiofibular overlap of 0.841 (±2.07) mm (p = .0259). There was a mean increase in tibiofibular clear space of 0.621 (±1.46) mm (p = .0201). In addition, we found significant correlation between fracture type and change in tibiofibular clear space (p = .047). Our study showed that there is statistically significant widening of the syndesmosis after suture button fixation at 3-month follow-up as evidenced by reduced tibiofibular overlap and increase in tibiofibular clear space. However, they remain within the maximum threshold for acceptable syndesmotic widening of 1.5 mm. Further correlation between radiological outcomes and patient function is needed to determine clinical significance of these changes.

Schistosoma Transmission in a Dynamic Seasonal Environment and its Impact on the Effectiveness of Disease Control.

BACKGROUND: A seasonal transmission environment including seasonal variation of snail population density and human-snail contact patterns can affect the dynamics of Schistosoma infection and the success of control interventions. In projecting control outcomes, conventional modeling approaches have often ignored seasonality by using simplified intermediate-host modeling, or by restricting seasonal effects through use of yearly averaging. METHODS: We used mathematical analysis and numerical simulation to estimate the impact of seasonality on disease dynamics and control outcomes, and to evaluate whether seasonal averaging or intermediate-host reduction can provide reliable predictions of control outcomes. We also examined whether seasonality could be used as leverage in creation of effective control strategies. RESULTS: We found models that used seasonal averaging could grossly overestimate infection burden and underestimate control outcomes in highly seasonal environments. We showed that proper intraseasonal timing of control measures could make marked improvement on the long-term burden reduction for Schistosoma transmission control, and we identified the optimal timing for each intervention. Seasonal snail control, implemented alone, was less effective than mass drug administration, but could provide additive impact in reaching control and elimination targets. CONCLUSIONS: Seasonal variation makes Schistosoma transmission less sustainable and easier to control than predicted by earlier modeling studies.

Procalcitonin Increase Is Associated with the Development of Critical Care-Acquired Infections in COVID-19 ARDS.

Secondary bacterial infection in COVID-19 patients is associated with increased mortality and disproportionately affects critically ill patients. This single-centre retrospective observational study investigates the comparative efficacy of change in procalcitonin (PCT) and other commonly available biomarkers in revealing or predicting microbiologically proven secondary infection in critical COVID-19 patients. Adult patients admitted to an intensive care unit (ICU) with confirmed SARS-CoV-2 infection between 9 March 2020 and 5 June 2020 were recruited to the study. For daily biomarker and secondary infection, laboratory-confirmed bloodstream infection (LCBI) and ventilator-associated pneumonia/tracheobronchitis (VAP/VAT) data were collected. We observed a PCT rise in 53 (81.5%) of the patients, a C-reactive protein (CRP) rise in 55 (84.6%) and a white blood cell count (WBC) rise in 61 (93.8%). Secondary infection was confirmed in 33 (50.8%) of the patients. A PCT rise was present in 97.0% of patients with at least one confirmed VAP/VAT and/or LCBI event. CRP and WBC rises occurred in 93.9% and 97.0% of patients with confirmed VAP/VAT and/or LCBI, respectively. Logistic regression analysis found that, when including all biomarkers in the same model, there was a significant association between PCT rise and the occurrence of LCBI and/or VAP/VAT (OR = 14.86 95%CI: 2.20, 342.53; p = 0.021). Conversely, no statistically significant relationship was found between either a CRP rise (p = 0.167) or a WBC rise (p = 0.855) and the occurrence of VAP/VAT and/or LCBI. These findings provide a promising insight into the usefulness of PCT measurement in predicting the emergence of secondary bacterial infection in ICU.