Insufficient Representation of Patients With Obesity in Randomized Controlled Trials Evaluating the Efficacy and Safety of Antimicrobials for Treatment of Skin and Skin Structure Infections: A Scoping Review.

Persons with obesity (PwO) represent approximately 50% of acute bacterial skin and skin structure infections (ABSSSIs) in the United States (US). There are currently insufficient data in PwO for drugs used for ABSSSIs. We conducted a scoping review of randomized controlled trials (RCTs) published between 2000 and 2022 to describe how frequently body size measures were reported. Weight and/or body mass index (BMI) were recorded in approximately 50% of the 69 RCTs. The average weights or BMIs were lower than US averages for most RCTs reporting data. None evaluated the impact of body size on outcomes in the original publication. Only 30% of newly approved drugs mention PwO representation in the prescribing information. More representative recruitment of PwO into RCTs is needed to help clinicians evaluate efficacy in these patients. We suggest that the Food and Drug Administration require companies to submit plans to ensure adequate PwO inclusion and that authors of RCTs report subgroup results based on body size.

Finding gaps in routine TB surveillance activities in Bangladesh.

BACKGROUND: TB was the leading cause of death from a single infectious pathogen globally between 2014 and 2019. Fine-scale estimates of TB prevalence and case notifications can be combined to guide priority-setting for strengthening routine surveillance activities in high-burden countries. We produce policy-relevant estimates of the TB epidemic at the second administrative unit in Bangladesh.METHODS: We used a Bayesian spatial framework and the cross-sectional National TB Prevalence Survey from 2015-2016 in Bangladesh to estimate prevalence by district. We used case notifications to calculate prevalence-to-notification ratio, a key metric of under-diagnosis and under-reporting.RESULTS: TB prevalence rates were highest in the north-eastern districts and ranged from 160 cases per 100,000 (95% uncertainty interval [UI] 80-310) in Jashore to 840 (UI 690-1020) in Sunamganj. Despite moderate prevalence rates, the Rajshahi and Dhaka Divisions presented the highest prevalence-to-notification ratios due to low case notifications. Resolving subnational disparities in case detection could lead to 26,500 additional TB cases (UI 8,500-79,400) notified every year.CONCLUSION: This study is the first to produce and map subnational estimates of TB prevalence and prevalence-to-notification ratios, which are essential to target prevention and treatment efforts in high-burden settings. Reaching TB cases currently missing from care will be key to ending the TB epidemic.

Sources of information during pregnancy and the early parenting period: Exploring the views of women and their partners.

OBJECTIVE: There are a wide variety of information sources available during pregnancy and the early parenting period, but limited understanding of their usefulness, particularly for partners. We explored the views of both women and their partners regarding sources of information, their frequency of use, and their preferred formats. DESIGN AND SETTING: Data were collected as part of a large cluster randomised controlled trial at a tertiary maternity hospital in 2015-2016, in Melbourne, Australia. The overall evaluation was of a parenting kit ('Growing Together'), an evidence-based information source for prospective and new parents covering the period from conception until one year postpartum. This paper uses data collected from women when their baby was two months of age, and women's partners when the baby was six months of age, via postal or online survey. PARTICIPANTS: Women were eligible if they booked for pregnancy care at The Royal Women's Hospital during the recruitment period, were having their first baby, able to read and speak English without an interpreter, and <30 weeks pregnant at their first hospital appointment (n = 1034). All eligible women were included unless they opted out. MEASUREMENTS AND FINDINGS: In total 92 women were excluded. Of the women sent the two-month survey, 42% (392/941) responded. Partner surveys were returned by 252/791 partners (32%). Respondents received information from a range of sources, most frequently face to face from health professionals through childbirth education or midwife discussion/education, followed by friends and family members. Information received from a health professional was also reported as being the most useful. For both women and their partners, the most important factor related to information was that it was from a trusted and reliable source. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Women and their partners highlighted the importance of quality and access to evidence based resources and information. The internet is frequently favoured by women and their partners due to its convenience, accessibility, and timely access to information. Overall, women and their partners reported information directly from a health care professional to be the most useful and health services should ensure that women and their partners have adequate access to their health care professional.

Adoption of adjuvant bisphosphonates for early breast cancer into standard clinical practice: Challenges and lessons learnt from comparison of the UK and Australian experience.

International guidelines recommend adjuvant bisphosphonates (BPs) for post-menopausal women with early breast cancer to reduce recurrence and mortality. However, globally, wide variation exists in their adoption. In the UK, adjuvant BPs were a recommendation in the breast cancer Clinical Reference Group service specification and were included as a priority for implementation by the national oncologists group UK Breast Cancer Group in November 2015, promoting national uptake, guidance and funding arrangements. In 2018, adjuvant BPs were recommended by the UKs National Institute for Health and Care Excellence. In Australia, adjuvant BPs are still 'off-label' and do not receive national reimbursement or endorsement. To date there has been no research into the prescribing habits of these agents in Australia. With the aim to gather data on adjuvant BPs prescribing practices, online surveys were developed and disseminated to breast oncologists in both countries between December 2018 and June 2019. Almost all of the UK oncologists prescribed adjuvant BPs, demonstrating that education, endorsement from professional bodies, presence of national guidelines and funding decisions have been critical to implementation. In contrast, only 48% of the Australian responders prescribed adjuvant BPs, while 83% reported that they would prescribe them if funding was available. Lack of local protocol guidance was also seen as a major barrier. This study was intended to assess the pathway taken for adjuvant BP implementation in the UK and how it might inform changes in Australian practice and also guide other countries with similar issues with the ultimate aim of improving the care of women with early breast cancer globally.

Blood, sweat, and tears: extraterrestrial regolith biocomposites with in vivo binders.

The proverbial phrase 'you can't get blood from a stone' is used to describe a task that is practically impossible regardless of how much force or effort is exerted. This phrase is well-suited to humanity's first crewed mission to Mars, which will likely be the most difficult and technologically challenging human endeavor ever undertaken. The high cost and significant time delay associated with delivering payloads to the Martian surface means that exploitation of resources in situ - including inorganic rock and dust (regolith), water deposits, and atmospheric gases - will be an important part of any crewed mission to the Red Planet. Yet there is one significant, but chronically overlooked, source of natural resources that will - by definition - also be available on any crewed mission to Mars: the crew themselves. In this work, we explore the use of human serum albumin (HSA) - a common protein obtained from blood plasma - as a binder for simulated Lunar and Martian regolith to produce so-called 'extraterrestrial regolith biocomposites (ERBs).' In essence, HSA produced by astronauts in vivo could be extracted on a semi-continuous basis and combined with Lunar or Martian regolith to 'get stone from blood', to rephrase the proverb. Employing a simple fabrication strategy, HSA-based ERBs were produced and displayed compressive strengths as high as 25.0 MPa. For comparison, standard concrete typically has a compressive strength ranging between 20 and 32 MPa. The incorporation of urea - which could be extracted from the urine, sweat, or tears of astronauts - could further increase the compressive strength by over 300% in some instances, with the best-performing formulation having an average compressive strength of 39.7 MPa. Furthermore, we demonstrate that HSA-ERBs have the potential to be 3D-printed, opening up an interesting potential avenue for extraterrestrial construction using human-derived feedstocks. The mechanism of adhesion was investigated and attributed to the dehydration-induced reorganization of the protein secondary structure into a densely hydrogen-bonded, supramolecular ß-sheet network - analogous to the cohesion mechanism of spider silk. For comparison, synthetic spider silk and bovine serum albumin (BSA) were also investigated as regolith binders - which could also feasibly be produced on a Martian colony with future advancements in biomanufacturing technology.

Reliability of stemless shoulder arthroplasty in rheumatoid arthritis: observation of early lysis around the humeral component.

PURPOSE: To evaluate whether stemless shoulder implants in rheumatoid arthritis (RA) patients provide comparable functional outcomes to patients with osteoarthritis or post-traumatic arthritis. In addition, the study assessed for differences in incidence of radiolucent lines or proximal humeral bone loss during radiographic follow-up. METHODS: Consecutive stemless shoulder arthroplasties performed in RA patients and a matched control group were retrospectively identified between February 2012 and 2018. Thirty-five patients were included in each group: 24 total shoulder arthroplasty (TSA) and 11 hemiarthroplasty (HA). Patients were evaluated annually using the Oxford Shoulder Score (OSS) and radiographically. RESULTS: The mean OSS significantly improved in all groups until 24 months. The mean improvement for RA TSA and HA patients at 24 months was 19.86 (95% CI 10.66-29.05, p = 0.0004) and 19.71 (95% CI 7.33-32.31, p = 0.0084), respectively. The mean improvement in the control TSA and HA patients at 24 months was 20.86 (95% CI 17-24.71, p = 0.0001) and 17.86 (95% CI 1.36-34.35, p = 0.0381), respectively. During the study period, two patients in the RA TSA group (8%), one patient in the control TSA group (4%) and one patient in the control HA group (9%) required revision. The proportion of progressive proximal humeral bone loss after TSA was 33% in the RA group and 13% in the control group. CONCLUSION: Stemless shoulder implants can provide significant improvement in functional scores in RA patients in the short term. However, early bone loss around the humeral implant is a concern and the authors recommend long-term clinical and radiological follow-up.

Non-covalent protein-based adhesives for transparent substrates-bovine serum albumin vs. recombinant spider silk.

Protein-based adhesives could have several advantages over petroleum-derived alternatives, including substantially lower toxicity, smaller environmental footprint, and renewable sourcing. Here, we report that non-covalently crosslinked bovine serum albumin and recombinant spider silk proteins have high adhesive strength on glass (8.53 and 6.28 MPa, respectively) and other transparent substrates. Moreover, the adhesives have high visible transparency and showed no apparent degradation over a period of several months. The mechanism of adhesion was investigated and primarily attributed to dehydration-induced reorganization of protein secondary structure, resulting in the supramolecular association of ß-sheets into a densely hydrogen-bonded network.

Global, Regional, and National Levels and Trends in Burden of Oral Conditions from 1990 to 2017: A Systematic Analysis for the Global Burden of Disease 2017 Study.

Government and nongovernmental organizations need national and global estimates on the descriptive epidemiology of common oral conditions for policy planning and evaluation. The aim of this component of the Global Burden of Disease study was to produce estimates on prevalence, incidence, and years lived with disability for oral conditions from 1990 to 2017 by sex, age, and countries. In addition, this study reports the global socioeconomic pattern in burden of oral conditions by the standard World Bank classification of economies as well as the Global Burden of Disease Socio-demographic Index. The findings show that oral conditions remain a substantial population health challenge. Globally, there were 3.5 billion cases (95% uncertainty interval [95% UI], 3.2 to 3.7 billion) of oral conditions, of which 2.3 billion (95% UI, 2.1 to 2.5 billion) had untreated caries in permanent teeth, 796 million (95% UI, 671 to 930 million) had severe periodontitis, 532 million (95% UI, 443 to 622 million) had untreated caries in deciduous teeth, 267 million (95% UI, 235 to 300 million) had total tooth loss, and 139 million (95% UI, 133 to 146 million) had other oral conditions in 2017. Several patterns emerged when the World Bank's classification of economies and the Socio-demographic Index were used as indicators of economic development. In general, more economically developed countries have the lowest burden of untreated dental caries and severe periodontitis and the highest burden of total tooth loss. The findings offer an opportunity for policy makers to identify successful oral health strategies and strengthen them; introduce and monitor different approaches where oral diseases are increasing; plan integration of oral health in the agenda for prevention of noncommunicable diseases; and estimate the cost of providing universal coverage for dental care.

An Epidemiological Study of Foot and Ankle Motocross Motorcycling Injuries in the United Kingdom.

BACKGROUND: Motocross is a recreational and competitive sport involving motorcycle racing on off-road circuits. Participants have enjoyed their sport worldwide for over 100 years. In the United Kingdom, there are over 200 clubs, with over 900 events annually. Unfortunately, little evidence exists on motocross injuries and their prevention. The aim of this study is to report and to quantify the different foot and ankle injuries observed in motocross. METHODS: Data was collected prospectively between August 2010 to August 2015 at our regional trauma unit, regardless of whether the sport was performed competitively or recreationally. RESULTS: Foot and ankle related injuries were identified in 210 patients (age range 4-78 years), with the majority being male participants (189, 90%). The majority of injuries occurred within the 21- to 30-year-old-age group. Most injuries were sustained around the start of the motocross season, in early spring and the summer months. A total of 76 patients (36%) required operative intervention. The most common injury was ankle fracture (49, 23%), followed by ankle sprain (44, 21%). CONCLUSION: This is the first epidemiological study in the United Kingdom documenting foot and ankle injuries in motocross. The frequency and severity of motocross-related injuries is presented. This may serve to provide recommendations and guidelines in the governing bodies of this sport. The surge in motocross popularity is correlates with an increase in injuries and inevitably the resources required to treat them. LEVEL OF EVIDENCE: Prospective descriptive epidemiological study. Level 1.

Utilizing general human movement models to predict the spread of emerging infectious diseases in resource poor settings.

Human mobility is an important driver of geographic spread of infectious pathogens. Detailed information about human movements during outbreaks are, however, difficult to obtain and may not be available during future epidemics. The Ebola virus disease (EVD) outbreak in West Africa between 2014-16 demonstrated how quickly pathogens can spread to large urban centers following one cross-species transmission event. Here we describe a flexible transmission model to test the utility of generalised human movement models in estimating EVD cases and spatial spread over the course of the outbreak. A transmission model that includes a general model of human mobility significantly improves prediction of EVD's incidence compared to models without this component. Human movement plays an important role not only to ignite the epidemic in locations previously disease free, but over the course of the entire epidemic. We also demonstrate important differences between countries in population mixing and the improved prediction attributable to movement metrics. Given their relative rareness, locally derived mobility data are unlikely to exist in advance of future epidemics or pandemics. Our findings show that transmission patterns derived from general human movement models can improve forecasts of spatio-temporal transmission patterns in places where local mobility data is unavailable.

Revision shoulder arthroplasty for failed surface replacement hemiarthroplasty.

PURPOSE: The aim of this study was to assess the reasons of failure of shoulder surface replacement hemiarthroplasty (SRH) and to evaluate the outcome of revision surgery. METHOD: The study group included 25 patients (26 shoulders) with failed SRHs. The mean time to revision surgery was 3.6 years. Their functional outcome was evaluated using adjusted Constant-Murley score at mean follow-up of 5.2 years (range 2-16 years). RESULT: Most common cause of failure was glenoid erosion (42%) and progressive failure of rotator cuff (31%). Median adjusted Constant-Murley score at mean follow-up of 5.2 years was 51.6. Median adjusted Constant-Murley score in patients who had primary diagnosis of osteoarthritis and had revision performed to anatomic TSA (14 shoulders) was 85 (range 40-100) at mean follow-up of 5 years compared to 36.3 (range 20-66.3) in the remaining patients at 5.4 years, p = 0.00008. CONCLUSION: Revision surgery for failed SRH can be technically challenging with variable results. Most common mode of failure was glenoid erosion. Functional outcomes are better in those with revision performed to anatomic TSA.

Travel time to health facilities in areas of outbreak potential: maps for guiding local preparedness and response.

BACKGROUND: Repeated outbreaks of emerging pathogens underscore the need for preparedness plans to prevent, detect, and respond. As countries develop and improve National Action Plans for Health Security, addressing subnational variation in preparedness is increasingly important. One facet of preparedness and mitigating disease transmission is health facility accessibility, linking infected persons with health systems and vice versa. Where potential patients can access care, local facilities must ensure they can appropriately diagnose, treat, and contain disease spread to prevent secondary transmission; where patients cannot readily access facilities, alternate plans must be developed. Here, we use travel time to link facilities and populations at risk of viral hemorrhagic fevers (VHFs) and identify spatial variation in these respective preparedness demands. METHODS AND FINDINGS: We used geospatial resources of travel friction, pathogen environmental suitability, and health facilities to determine facility accessibility of any at-risk location within a country. We considered in-country and cross-border movements of exposed populations and highlighted vulnerable populations where current facilities are inaccessible and new infrastructure would reduce travel times. We developed profiles for 43 African countries. Resulting maps demonstrate gaps in health facility accessibility and highlight facilities closest to areas at risk for VHF spillover. For instance, in the Central African Republic, we identified travel times of over 24 h to access a health facility. Some countries had more uniformly short travel times, such as Nigeria, although regional disparities exist. For some populations, including many in Botswana, access to areas at risk for VHF nationally was low but proximity to suitable spillover areas in bordering countries was high. Additional analyses provide insights for considering future resource allocation. We provide a contemporary use case for these analyses for the ongoing Ebola outbreak. CONCLUSIONS: These maps demonstrate the use of geospatial analytics for subnational preparedness, identifying facilities close to at-risk populations for prioritizing readiness to detect, treat, and respond to cases and highlighting where gaps in health facility accessibility exist. We identified cross-border threats for VHF exposure and demonstrate an opportunity to improve preparedness activities through the use of precision public health methods and data-driven insights for resource allocation as part of a country's preparedness plans.

In rats gestational iron deficiency does not change body fat or hepatic mitochondria in the aged offspring.

Mitochondrial dysfunction and resulting changes in adiposity have been observed in the offspring of animals fed a high fat (HF) diet. As iron is an important component of the mitochondria, we have studied the offspring of female rats fed complete (Con) or iron-deficient (FeD) rations for the duration of gestation to test for similar effects. The FeD offspring were ~12% smaller at weaning and remained so because of a persistent reduction in lean tissue mass. The offspring were fed a complete (stock) diet until 52 weeks of age after which some animals from each litter were fed a HF diet for a further 12 weeks. The HF diet increased body fat when compared with animals fed the stock diet, however, prenatal iron deficiency did not change the ratio of fat:lean in either the stock or HF diet groups. The HF diet caused triglyceride to accumulate in the liver, however, there was no effect of prenatal iron deficiency. The activity of the mitochondrial electron transport complexes was similar in all groups including those challenged with a HF diet. HF feeding increased the number of copies of mitochondrial DNA and the prevalence of the D-loop mutation, however, neither parameter was affected by prenatal iron deficiency. This study shows that the effects of prenatal iron deficiency differ from other models in that there is no persistent effect on hepatic mitochondria in aged animals exposed to an increased metabolic load.

Inferences about spatiotemporal variation in dengue virus transmission are sensitive to assumptions about human mobility: a case study using geolocated tweets from Lahore, Pakistan.

Billions of users of mobile phones, social media platforms, and other technologies generate an increasingly large volume of data that has the potential to be leveraged towards solving public health challenges. These and other big data resources tend to be most successful in epidemiological applications when utilized within an appropriate conceptual framework. Here, we demonstrate the importance of assumptions about host mobility in a framework for dynamic modeling of infectious disease spread among districts within a large urban area. Our analysis focused on spatial and temporal variation in the transmission of dengue virus (DENV) during a series of large seasonal epidemics in Lahore, Pakistan during 2011-2014. Similar to many directly transmitted diseases, DENV transmission occurs primarily where people spend time during daytime hours, given that DENV is transmitted by a day-biting mosquito. We inferred spatiotemporal variation in DENV transmission under five different assumptions about mobility patterns among ten districts of Lahore: no movement among districts, movement following patterns of geo-located tweets, movement proportional to district population size, and movement following the commonly used gravity and radiation models. Overall, we found that inferences about spatiotemporal variation in DENV transmission were highly sensitive to this range of assumptions about intra-urban human mobility patterns, although the three assumptions that allowed for a modest degree of intra-urban mobility all performed similarly in key respects. Differing inferences about transmission patterns based on our analysis are significant from an epidemiological perspective, as they have different implications for where control efforts should be targeted and whether conditions for transmission became more or less favorable over time. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1140/epjds/s13688-018-0144-x) contains supplementary material.

Do trials reduce uncertainty? Assessing impact through cumulative meta-analysis of neonatal RCTs.

OBJECTIVE: To assess the impact of the latest randomized controlled trial (RCT) to each systematic review (SR) in Cochrane Neonatal Reviews. STUDY DESIGN: We selected meta-analyses reporting the typical point estimate of the risk ratio for the primary outcome of the latest study (n=130), mortality (n=128) and the mean difference for the primary outcome (n=44). We employed cumulative meta-analysis to determine the typical estimate after each trial was added, and then performed multivariable logistic regression to determine factors predictive of study impact. RESULTS: For the stated primary outcome, 18% of latest RCTs failed to narrow the confidence interval (CI), and 55% failed to decrease the CI by ⩾20%. Only 8% changed the typical estimate directionality, and 11% caused a change to or from significance. Latest RCTs did not change the typical estimate in 18% of cases, and only 41% changed the typical estimate by at least 10%. The ability to narrow the CI by >20% was negatively associated with the number of previously published RCTs (odds ratio 0.707). Similar results were found in analysis of typical estimates for the outcomes of mortality and mean difference. CONCLUSION: Across a broad range of clinical questions, the latest RCT failed to substantially narrow the CI of the typical estimate, to move the effect estimate or to change its statistical significance in a majority of cases. Investigators and grant peer review committees should consider prioritizing less-studied topics or requiring formal consideration of optimal information size based on extant evidence in power calculations.

A Study To Assess The Prevalence Of Exercise-Induced Bronchoconstriction In Inter-County Hurling.

Exercise-Induced Bronchoconstriction (EIB) is an acute, transient airway narrowing occurring after exercise which may impact athletic performance. Studies report 10% of the general population and up to 90% of asthmatics experience EIB. Ninety-two players from three elite hurling squads underwent a spirometric field-based provocation test with real-time heart rate monitoring and lactate measurements to ensure adequate exertion. Players with a new diagnosis of EIB and those with a negative field-test but with a previous label of EIB or asthma underwent further reversibility testing and if negative, methacholine challenge. Eight (8.7%) of players had EIB, with one further athlete having asthma with a negative field test. Interestingly, only three out of 12 players who had previously been physician-labelled with EIB or asthma had their diagnosis objectively confirmed. Our study highlights the role of objective testing in EIB.

Global distribution and environmental suitability for chikungunya virus, 1952 to 2015.

Chikungunya fever is an acute febrile illness caused by the chikungunya virus (CHIKV), which is transmitted to humans by Aedes mosquitoes. Although chikungunya fever is rarely fatal, patients can experience debilitating symptoms that last from months to years. Here we comprehensively assess the global distribution of chikungunya and produce high-resolution maps, using an established modelling framework that combines a comprehensive occurrence database with bespoke environmental correlates, including up-to-date Aedes distribution maps. This enables estimation of the current total population-at-risk of CHIKV transmission and identification of areas where the virus may spread to in the future. We identified 94 countries with good evidence for current CHIKV presence and a set of countries in the New and Old World with potential for future CHIKV establishment, demonstrated by high environmental suitability for transmission and in some cases previous sporadic reports. Aedes aegypti presence was identified as one of the major contributing factors to CHIKV transmission but significant geographical heterogeneity exists. We estimated 1.3 billion people are living in areas at-risk of CHIKV transmission. These maps provide a baseline for identifying areas where prevention and control efforts should be prioritised and can be used to guide estimation of the global burden of CHIKV.

Simple antireflux technique for the cologastric anastomosis: complementary step in retrosternal colon interposition procedure.

Gastrocolic reflux is a troublesome symptom causing repeated aspiration or chocking in patients underwent retrosternal colon interposition. Various techniques were described to avoid such complication, however, they entail complicated technique that may jeopardize the viability of the graft or cause obstructing symptoms. A simple antireflux procedure is described here alleviating this problem. Over the last 7 years, 87 patients had gastrocolic antireflux procedure for cologastric anastomosis; 75 patients as a primary procedure (group 1) and 12 patients as a secondary procedure treating symptomatic reflux (group 2). The technique entails the creation of cologastric angle after finishing the cologastric anastomosis by applying three stitches between the colon and the stomach, thus tucking the colon to the stomach for 3-4 cm. Gastrocolic reflux was evaluated clinically and radiologically 3 months postoperatively. In group 1, three cases (4%) suffered symptomatic gastrocolic reflux, and seven cases (9.3%) had radiological asymptomatic mild reflux, while all patients in group 2 had complete alleviation of their symptoms with gastrogram showing no reflux. Gastrocolic reflux can be treated simply by creation of cologastric angle; however, controlled trial is needed to confirm its effectiveness in comparison to other described techniques.