Patient ratings in exercise therapy for the management of tendinopathy: a systematic review with meta-analysis.

OBJECTIVE: To synthesise exercise therapy intervention data investigating patient rating outcomes for the management of tendinopathy. DESIGN: A systematic review and meta-analysis of randomized controlled trials investigating exercise therapy interventions and reporting patient rating outcomes. SETTING: Any setting in any country listed as very high on the human development index. PARTICIPANTS: People with a diagnosis of any tendinopathy of any severity or duration. INTERVENTIONS: Exercise therapy for the management of tendinopathy comprising five different therapy classes: 1) resistance; 2) plyometric; 3) vibration; 4) flexibility, and 5) movement pattern retraining modalities, were considered for inclusion. MAIN OUTCOME MEASURES: Outcomes measuring patient rating of condition, including patient satisfaction and Global Rating of Change (GROC). RESULTS: From a total of 124 exercise therapy studies, 34 (Achilles: 41%, rotator cuff: 32%, patellar: 15%, elbow: 9% and gluteal: 3%) provided sufficient information to be meta-analysed. The data were obtained across 48 treatment arms and 1246 participants. The pooled estimate for proportion of satisfaction was 0.63 [95%CrI: 0.53-0.73], and the pooled estimate for percentage of maximum GROC was 53 [95%CrI: 38-69%]. The proportion of patients reporting positive satisfaction and perception of change increased with longer follow-up periods from treatment onset. CONCLUSION: Patient satisfaction and GROC appear similar and are ranked moderately high demonstrating that patients generally perceive exercise therapies positively. Further research including greater consistency in measurement tools is required to explore and where possible, identify patient- and exercise-related moderating factors that can be used to improve person-centred care. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO ID=CRD42020168187 CONTRIBUTION OF PAPER.

Social injustice symposium: Urban, rural, and global disparities in access to care.

BACKGROUND: Barriers in access to pediatric surgical care are common in low- and middle-income countries (LMICs), but also exist in high-income countries, particularly in urban and rural areas. METHODS: This article describes "Disparities in Access to Care"-held within the Social Injustice Symposium at the 2020 American Pediatric Surgical Association (APSA) Annual Meeting. RESULTS: This symposium outlined disparities in access to care, illustrated by examples from pediatric trauma and neonatal surgery in U.S. urban, U.S. rural, and non-U.S. global locations (LMICs). Geographic and financial challenges were common to families from the rural U.S. and LMICs. In contrast, families in U.S. urban settings generally do not face geographic barriers, but are often economically and racially diverse and many face complex societal factors leading to poor outcomes. Systemic processes must be changed to improve pediatric surgical health outcomes. CONCLUSION: A comprehensive health system with an equal emphasis on supportive care and surgery is required in all settings. Global collaboration and partnerships can provide an avenue for advocacy and strategic innovation to improve quality of care. LEVEL OF EVIDENCE: Ⅴ.

Seventy years of data from the world's longest grazed and irrigated pasture trials.

Pastures are the most widespread land use, globally. The Winchmore trials were established in 1948-1949 in Canterbury, New Zealand and examined either different rates of phosphorus (P) fertiliser on the same irrigation schedule (Fertiliser trial), or different irrigation scheduling at the same rate of P application (Irrigation trial). About 96,000 records of soil chemistry and physical data and pasture yield and botanical composition are available along with nearly 7000 soil samples. These data have been used in 475 publications that have explored topics as diverse as: improvements in sheep, dairy and deer production; the efficacy and scheduling of irrigation; improvements in pasture and crop production; agronomic and environmental soil and water research; and entomology. In addition to above topics, these data are invaluable for calibrating models to predict long-term issues like the accumulation of soil carbon or contaminants like cadmium and informing policy on climate change and agricultural practices. The data and soil samples are available for use and may yet yield discoveries, unforeseen 70 years ago.

Constructing an ethical framework for priority allocation of pandemic vaccines.

BACKGROUND: Allocation of scarce resources during a pandemic extends to the allocation of vaccines when they eventually become available. We describe a framework for priority vaccine allocation that employed a cross-disciplinary approach, guided by ethical considerations and informed by local risk assessment. METHODS: Published and grey literature was reviewed, and augmented by consultation with key informants, to collate past experience, existing guidelines and emerging strategies for pandemic vaccine deployment. Identified ethical issues and decision-making processes were also included. Concurrently, simulation modelling studies estimated the likely impacts of alternative vaccine allocation approaches. Assembled evidence was presented to a workshop of national experts in pandemic preparedness, vaccine strategy, implementation and ethics. All of this evidence was then used to generate a proposed ethical framework for vaccine priorities best suited to the Australian context. FINDINGS: Published and emerging guidance for priority pandemic vaccine distribution differed widely with respect to strategic objectives, specification of target groups, and explicit discussion of ethical considerations and decision-making processes. Flexibility in response was universally emphasised, informed by real-time assessment of the pandemic impact level, and identification of disproportionately affected groups. Model outputs aided identification of vaccine approaches most likely to achieve overarching goals in pandemics of varying transmissibility and severity. Pandemic response aims deemed most relevant for an Australian framework were: creating and maintaining trust, promoting equity, and reducing harmful outcomes. INTERPRETATION: Defining clear and ethically-defendable objectives for pandemic response in context aids development of flexible and adaptive decision support frameworks and facilitates clear communication and engagement activities.

Priority allocation of pandemic influenza vaccines in Australia - Recommendations of 3 community juries.

BACKGROUND: Pandemic planning has historically been oriented to respond to an influenza virus, with vaccination strategy being a key focus. As the current COVID-19 pandemic plays out, the Australian government is closely monitoring progress towards development of SARS-CoV2 vaccines as a definitive intervention. However, as in any pandemic, initial supply will likely be exceeded by demand due to limited manufacturing output. METHODS: We convened community juries in three Australian locations in 2019 to assess public acceptability and perceived legitimacy of influenza pandemic vaccination distribution strategies. Preparatory work included literature reviews on pandemic vaccine allocation strategies and on vaccine allocation ethics, and simulation modelling studies. We assumed vaccine would be provided to predefined priority groups. Jurors were then asked to recommend one of two strategies for distributing remaining early doses of vaccine: directly vaccinate people at higher risk of adverse outcomes from influenza; or indirectly protect the general population by vaccinating primary school students, who are most likely to spread infection. RESULTS: Thirty-four participants of diverse backgrounds and ages were recruited through random digit dialling and topic-blinded social media advertising. Juries heard evidence and arguments supporting different vaccine distribution strategies, and questioned expert presenters. All three community juries supported prioritising school children for influenza vaccination (aiming for indirect protection), one by 10-2 majority and two by consensus. Justifications included that indirect protection benefits more people and is likely to be more publicly acceptable. CONCLUSIONS: In the context of an influenza pandemic, informed citizens were not opposed to prioritising groups at higher risks of adverse outcomes, but if resources and epidemiological conditions allow, achieving population benefits should be a strategic priority. These insights may inform future SARS-CoV-2 vaccination strategies.

Nano-scale morphology of cardiomyocyte t-tubule/sarcoplasmic reticulum junctions revealed by ultra-rapid high-pressure freezing and electron tomography.

Detailed knowledge of the ultrastructure of intracellular compartments is a prerequisite for our understanding of how cells function. In cardiac muscle cells, close apposition of transverse (t)-tubule (TT) and sarcoplasmic reticulum (SR) membranes supports stable high-gain excitation-contraction coupling. Here, the fine structure of this key intracellular element is examined in rabbit and mouse ventricular cardiomyocytes, using ultra-rapid high-pressure freezing (HPF, omitting aldehyde fixation) and electron microscopy. 3D electron tomograms were used to quantify the dimensions of TT, terminal cisternae of the SR, and the space between SR and TT membranes (dyadic cleft). In comparison to conventional aldehyde-based chemical sample fixation, HPF-preserved samples of both species show considerably more voluminous SR terminal cisternae, both in absolute dimensions and in terms of junctional SR to TT volume ratio. In rabbit cardiomyocytes, the average dyadic cleft surface area of HPF and chemically fixed myocytes did not differ, but cleft volume was significantly smaller in HPF samples than in conventionally fixed tissue; in murine cardiomyocytes, the dyadic cleft surface area was higher in HPF samples with no difference in cleft volume. In both species, the apposition of the TT and SR membranes in the dyad was more likely to be closer than 10 nm in HPF samples compared to CFD, presumably resulting from avoidance of sample shrinkage associated with conventional fixation techniques. Overall, we provide a note of caution regarding quantitative interpretation of chemically-fixed ultrastructures, and offer novel insight into cardiac TT and SR ultrastructure with relevance for our understanding of cardiac physiology.

Low-dose ipilimumab plus nivolumab combined with IL-2 and hyperthermia in cancer patients with advanced disease: exploratory findings of a case series of 131 stage IV cancers - a retrospective study of a single institution.

The 3-year overall survival (OS) rate of patients with previously treated or untreated stage III or IV melanoma has by now reached 63% using ipilimumab and nivolumab therapy. However, immune-related adverse events (irAEs) of grade 3 or 4 occurred in 59% of patients leading to discontinuation of therapy in 24.5% of patients and one death. Therapy with checkpoint inhibitors could be safer and more effective in combination with hyperthermia and fever inducing therapies. We conducted a retrospective analysis to test the safety and efficacy of a new combination immune therapy in 131 unselected stage IV solid cancer patients with 23 different histological types of cancer who exhausted all conventional treatments. Treatment consisted of locoregional- and whole-body hyperthermia, individually dose adapted interleukin 2 (IL-2) combined with low-dose ipilimumab (0.3 mg/kg) plus nivolumab (0.5 mg/kg). The objective response rate (ORR) was 31.3%, progression-free survival (PFS) was 10 months, survival probabilities at 6 months was 86.7% (95% CI, 81.0-92.8%), at 9 months was 73.5% (95% CI, 66.2-81.7%), at 12 months was 66.5% (95% CI, 58.6-75.4%), while at 24 months survival was 36.6% (95% CI:28.2%; 47.3%). irAEs of World Health Organization (WHO) Toxicity Scale grade 1, 2, 3, and 4 were observed in 23.66%, 16.03%, 6.11%, and 2.29% of patients, respectively. Our results suggest that the irAEs profile of the combined treatment is safer than that of the established protocols without compromising efficacy.

Global Research Alliance N2 O chamber methodology guidelines: Recommendations for air sample collection, storage, and analysis.

Certain aspects in the collection, handling, storage, and subsequent analysis of discrete air samples from non-steady-state flux chambers are critical to generating accurate and unbiased estimates of nitrous oxide (N2 O) fluxes. The focus of this paper is on air sample collection and storage in small vials (<12 ml) primarily for gas chromatography (GC) analysis. Sample integrity is assured through following simple procedures including storage under pressure and analysis within a few months of collection. Concurrent storage of standards in an identical manner to samples is recommended and allows the storage period to be reliably extended. In the laboratory, an autosampler is typically used in batch analysis of ∼200 sequentially analyzed samples by GC with an electron capture detector (ECD). Some comparisons are given between GC and alternatives including optical N2 O detectors that are increasingly being used for high-precision N2 O measurement. The importance of calibration and traceability of gas standards is discussed, where high-quality standards ensure the most accurate assessment of N2 O concentration and comparability between laboratories. The calibration allows a consistent and best estimate of flux to be derived.

Toward indicators of the performance of US Infrastructures under climate change risks.

Built infrastructures are increasingly disrupted by climate-related extreme events. Being able to monitor what climate change implies for US infrastructures is of considerable importance to all levels of decision-makers. A capacity to develop cross-cutting, widely applicable indicators for more than a dozen different kinds of infrastructure, however, is severely limited at present. The development of such indicators must be considered an ongoing activity that will require expansion and refinement. A number of recent consensus reports suggest four priorities for indicators that portray the impacts of climate change, climate-related extreme events, and other driving forces on infrastructure. These are changes in the reliability of infrastructure services and the implications for costs; changes in the resilience of infrastructures to climate and other stresses; impacts due to the interdependencies of infrastructures; and ongoing adaptation in infrastructures.

New anthropometric classification scheme of preoperative nutritional status in children: a retrospective observational cohort study.

OBJECTIVE: WHO uses anthropometric classification scheme of childhood acute and chronic malnutrition based on low body mass index (BMI) ('wasting') and height for age ('stunting'), respectively. The goal of this study was to describe a novel two-axis nutritional classification scheme to (1) characterise nutritional profiles in children undergoing abdominal surgery and (2) characterise relationships between preoperative nutritional status and postoperative morbidity. DESIGN: This was a retrospective observational cohort study. SETTING: The setting was 50 hospitals caring for children in North America that participated in the American College of Surgeons National Surgical Quality Improvement Program Paediatric from 2011 to 2013. PARTICIPANTS: Children >28 days who underwent major abdominal operations were identified. INTERVENTIONS/MAIN PREDICTOR: The cohort of children was divided into five nutritional profile groups based on both BMI and height for age Z-scores: (1) underweight/short, (2) underweight/tall, (3) overweight/short, (4) overweight/tall and (5) non-outliers (controls). MAIN OUTCOME MEASURES: Multiple variable logistic regressions were used to quantify the association between 30-day morbidity and nutritional profile groups while adjusting for procedure case mix, age and American Society of Anaesthesiologists class. RESULTS: A total of 39 520 cases distributed as follows: underweight/short (656, 2.2%); underweight/tall (252, 0.8%); overweight/short (733, 2.4%) and overweight/tall (1534, 5.1%). Regression analyses revealed increased adjusted odds of composite morbidity (35%) and reintervention events (75%) in the underweight/short group, while overweight/short patients had increased adjusted odds of composite morbidity and healthcare-associated infections (43%), and reintervention events (79%) compared with controls. CONCLUSION: Stratification of preoperative nutritional status using a scheme incorporating both BMI and height for age is feasible. Further research is needed to validate this nutritional risk classification scheme for other surgical procedures in children.

Patient blood management and the importance of the Transfusion Practitioner role to embed this into practice.

Patient blood management (PBM) is a widely established international initiative, with a multidisciplinary approach to reduce transfusion. The Transfusion Practitioner1 (TP) role is well embedded in the United Kingdom (UK) and Australia. The value of the TP in changing both culture and practice to implement an all-inclusive PBM approach to care will be discussed. The TP role was born from both a safety and haemovigilance culture, where the greatest identified risk to the patient undergoing a transfusion was human error. From this initial trigger for improved safety, the TP role has evolved to a multifaceted, highly specialised role, involved in both PBM and transfusion processes. As the transfusion paradigm shifted from product to patient, the TP role evolved to include PBM, with an emphasis on the patients and the impact transfusion has on them. A multidisciplinary team is required to drive both PBM and transfusion; the TP is recognised as a critical link in the multidisciplinary team. They are seen as a driving force for change, bridging the gap between the laboratory and clinical arenas. The TP plays a vital role in helping establish and embed PBM that improves patient and safety outcomes.

Hospital variation in rates of concurrent fundoplication during gastrostomy enteral access procedures.

BACKGROUND: This study aimed to determine whether (1) the propensity for concurrent fundoplication during gastrostomy varies among hospitals, and (2) postoperative morbidity differs among institutions performing fundoplication more or less frequently. METHODS: Children who underwent gastrostomy with or without concurrent fundoplication were identified in the American College of Surgeons National Surgical Quality Improvement Program Pediatric (ACS-NSQIP-P). A hierarchical multivariate regression modeled the excess effects that hospitals exerted over propensity for concurrent fundoplication adjusting for preoperative clinical variables. Hospitals were designated as low outliers (significantly lower-adjusted odds of concurrent fundoplication than the average hospital with similar patient mix), average hospitals, and high outliers based on their risk-adjusted concurrent fundoplication practice. The postoperative morbidity rates were compared among low-outlier, average, and high-outlier hospitals. RESULTS: Between 2011 and 2013, 3775 children underwent gastrostomy at one of 54 ACS-NSQIP-P participating hospitals. The mean hospital concurrent fundoplication rate was 11.7% (range 0-64%). There was no significant difference in unadjusted morbidity rate in children with concurrent fundoplication, 11.0% compared to 9.7% in children without concurrent fundoplication. After controlling for clinical variables, 8 hospitals were identified as low outliers (fundoplication rate of 0.4%) and 16 hospitals were identified as high outliers (fundoplication rate of 34.6%). The average unadjusted morbidity rate among hospitals with low, average, and high odds of concurrent fundoplication were 9.6, 10.6, and 8.4%, respectively. CONCLUSION: Hospitals vary significantly in propensity for concurrent fundoplication during gastrostomy yet postoperative morbidity does not differ significantly among institutions performing fundoplication more or less frequently.

Single visit surgery for pediatric ambulatory surgical procedures: a satisfaction and cost analysis.

BACKGROUND: Single visit surgery (SVS) consists of same-day pre-operative assessment and operation with telephone post-operative follow-up. This reduces family time commitment to 1 hospital trip rather than 2-3. We began SVS for ambulatory patients with clear surgical indications in 2013. We sought to determine family satisfaction, cost savings to families, and institutional financial feasibility of SVS. METHODS: SVS patients were compared to age/case matched conventional surgery (CS) patients. Satisfaction was assessed by post-operative telephone survey. Family costs were calculated as the sum of lost revenue (based on median income) and transportation costs ($0.50/mile). RESULTS: Satisfaction was high in both groups (98% for SVS vs. 93% for CS; p=0.27). 40% of CS families indicated that they would have preferred SVS, whereas no SVS families indicated preference for the CS option (p<0.001). Distance from the hospital did not correlate with satisfaction. Estimated cost savings for an SVS family was $188. Reimbursement, hospital and physician charges, and day-of-surgery cancellation rates were similar. CONCLUSIONS: SVS provides substantial cost savings to families while maintaining patient satisfaction and equivalent institutional reimbursement. SVS is an effective approach to low-risk ambulatory surgical procedures that is less disruptive to families, facilitates access to pediatric surgical care, and reduces resource utilization. TYPE OF STUDY: Cost Effectiveness Study. LEVEL OF EVIDENCE: Level II.

Structural and physico-chemical analysis of calcium/strontium substituted, near-invert phosphate based glasses for biomedical applications.

Neutron diffraction, 23Na and 31P NMR, and FTIR spectroscopy have been used to investigate the structural effects of substituting CaO with SrO in a 40P2O5·(16-x)CaO·20Na2O·24MgO·xSrO glass, where x is 0, 4, 8, 12 and 16mol%. The 31P solid-state NMR results showed similar amounts of Q1 and Q2 units for all of the multicomponent glasses investigated, showing that the substitution of Sr for Ca has no effect on the phosphate network. The M-O coordinations (M=Mg, Ca, Sr, Na) were determined for binary alkali and alkaline earth metaphosphates using neutron diffraction and broad asymmetric distributions of bond length were observed, with coordination numbers that were smaller and bond lengths that were shorter than in corresponding crystals. The Mg-O coordination number was determined most reliably as 5.0(2). The neutron diffraction results for the multicomponent glasses are consistent with a structural model in which the coordination of Ca, Sr and Na is the same as in the binary metaphosphate glass, whereas there is a definite shift of Mg-O bonds to longer distance. There is also a small but consistent increase in the Mg-O coordination number and the width of the distribution of Mg-O bond lengths, as Sr substitutes for Ca. Functional properties, including glass transition temperatures, thermal processing windows, dissolution rates and ion release profiles were also investigated. Dissolution studies showed a decrease in dissolution rate with initial addition of 4mol% SrO, but further addition of SrO showed little change. The ion release profiles followed a similar trend to the observed dissolution rates. The limited changes in structure and dissolution rates observed for substitution of Ca with Sr in these fixed 40mol% P2O5 glasses were attributed to their similarities in terms of ionic size and charge. STATEMENT OF SIGNIFICANCE: Phosphate based glasses are extremely well suited for the delivery of therapeutic ions in biomedical applications, and in particular strontium plays an important role in the treatment of osteoporosis. We show firstly that the substitution of strontium for calcium in bioactive phosphate glasses can be used to control the dissolution rate of the glass, and hence the rate at which therapeutic ions are delivered. We then go on to examine in detail the influence of Sr/Ca substitution on the atomic sites in the glass, using advanced structural probes, especially neutron diffraction. The environments of most cations in the glass are unaffected by the substitution, with the exception of Mg, which becomes more disordered.

Reframing climate change assessments around risk: recommendations for the US National Climate Assessment.

Climate change is a risk management challenge for society, with uncertain but potentially severe outcomes affecting natural and human systems, across generations. Managing climate-related risks will be more difficult without a base of knowledge and practice aimed at identifying and evaluating specific risks, and their likelihood and consequences, as well as potential actions to promote resilience in the face of these risks. We suggest three improvements to the process of conducting climate change assessments to better characterize risk and inform risk management actions.

Acylcarnitine Profiles Reflect Metabolic Vulnerability for Necrotizing Enterocolitis in Newborns Born Premature.

OBJECTIVE: To evaluate the association between newborn acylcarnitine profiles and the subsequent development of necrotizing enterocolitis (NEC) with the use of routinely collected newborn screening data in infants born preterm. STUDY DESIGN: A retrospective cohort study was conducted with the use of discharge records for infants born preterm admitted to neonatal intensive care units in California from 2005 to 2009 who had linked state newborn screening results. A model-development cohort of 94 110 preterm births from 2005 to 2008 was used to develop a risk-stratification model that was then applied to a validation cohort of 22 992 births from 2009. RESULTS: Fourteen acylcarnitine levels and acylcarnitine ratios were associated with increased risk of developing NEC. Each log unit increase in C5 and free carnitine /(C16 + 18:1) was associated with a 78% and a 76% increased risk for developing NEC, respectively (OR 1.78, 95% CI 1.53-2.02, and OR 1.76, 95% CI 1.51-2.06). Six acylcarnitine levels, along with birth weight and total parenteral nutrition, identified 89.8% of newborns with NEC in the model-development cohort (area under the curve 0.898, 95% CI 0.889-0.907) and 90.8% of the newborns with NEC in the validation cohort (area under the curve 0.908, 95% CI 0.901-0.930). CONCLUSIONS: Abnormal fatty acid metabolism was associated with prematurity and the development of NEC. Metabolic profiling through newborn screening may serve as an objective biologic surrogate of risk for the development of disease and thus facilitate disease-prevention strategies.

Retrospective forecasting of the 2010-2014 Melbourne influenza seasons using multiple surveillance systems.

Accurate forecasting of seasonal influenza epidemics is of great concern to healthcare providers in temperate climates, since these epidemics vary substantially in their size, timing and duration from year to year, making it a challenge to deliver timely and proportionate responses. Previous studies have shown that Bayesian estimation techniques can accurately predict when an influenza epidemic will peak many weeks in advance, and we have previously tailored these methods for metropolitan Melbourne (Australia) and Google Flu Trends data. Here we extend these methods to clinical observation and laboratory-confirmation data for Melbourne, on the grounds that these data sources provide more accurate characterizations of influenza activity. We show that from each of these data sources we can accurately predict the timing of the epidemic peak 4-6 weeks in advance. We also show that making simultaneous use of multiple surveillance systems to improve forecast skill remains a fundamental challenge. Disparate systems provide complementary characterizations of disease activity, which may or may not be comparable, and it is unclear how a 'ground truth' for evaluating forecasts against these multiple characterizations might be defined. These findings are a significant step towards making optimal use of routine surveillance data for outbreak forecasting.

Altered hippocampal function in major depression despite intact structure and resting perfusion.

BACKGROUND: Hippocampal volume reductions in major depression have been frequently reported. However, evidence for functional abnormalities in the same region in depression has been less clear. We investigated hippocampal function in depression using functional magnetic resonance imaging (fMRI) and neuropsychological tasks tapping spatial memory function, with complementing measures of hippocampal volume and resting blood flow to aid interpretation. METHOD: A total of 20 patients with major depressive disorder (MDD) and a matched group of 20 healthy individuals participated. Participants underwent multimodal magnetic resonance imaging (MRI): fMRI during a spatial memory task, and structural MRI and resting blood flow measurements of the hippocampal region using arterial spin labelling. An offline battery of neuropsychological tests, including several measures of spatial memory, was also completed. RESULTS: The fMRI analysis showed significant group differences in bilateral anterior regions of the hippocampus. While control participants showed task-dependent differences in blood oxygen level-dependent (BOLD) signal, depressed patients did not. No group differences were detected with regard to hippocampal volume or resting blood flow. Patients showed reduced performance in several offline neuropsychological measures. All group differences were independent of differences in hippocampal volume and hippocampal blood flow. CONCLUSIONS: Functional abnormalities of the hippocampus can be observed in patients with MDD even when the volume and resting perfusion in the same region appear normal. This suggests that changes in hippocampal function can be observed independently of structural abnormalities of the hippocampus in depression.