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Pandemics, epidemics and food borne diseases have, for some at least, become key challenges for contemporary global society. They threaten progress in global health, compromise food security and, along with climate change and global terrorism, seem to usher in a state of emergency and a radically uncertain future. The central claim of Pathological Lives is that any solution offered to these kinds of emerging and often communicable diseases requires a broad based geographical scrutiny. The book marks an empirically and theoretically informed contribution to a world seemingly under constant microbiological threat, drawing together and extending empirically based geographical scholarship in human-environment relations, science and society, more than human geographies and spatial theory, to understand and evaluate efforts at making life more secure. The focus is on the food and farming sector, where the generation and subsequent transmission of disease can reach pandemic proportions. The authors review current approaches to biosecurity on making life safe within those sectors, analyse underlying drivers and logics to existing programmes and ask whether the resulting solutions can succeed. They follow farmers, retailers and regulators, amongst others, asking how pathological lives can be successfully 'regulated' without making life more dangerous as a result.

Biosecurity, as a response to threats from zoonotic, food-borne and emerging infectious diseases, implies and is often understood in terms of a spatial segregation of forms of life, a struggle to separate healthy life from diseased bodies. While an ensuing will to closure in the name of biosecurity is evident at various sites, things are, in practice and in theory, more intricate than this model would suggest. There are transactions and transformations that defy easily segmented spaces. Using multi-species ethnographic work across a range of sites, from wildlife reserves to farms and food processing plants, we argue for a shift of focus in biosecurity away from defined borderlines towards that of borderlands. The latter involves the detachment of borders from geographic territory and highlights the continuous topological interplay and resulting tensions involved in making life live. We use this spatial imagination to call for a different kind of biopolitics and for a shift in what counts as a biosecurity emergency. As a means to re-frame the questions concerning biosecurity, we argue for a change of discourse and practice away from disease 'breach points' towards the 'tipping points' that can arise in the intense foldings that characterise pathological lives.

Background The proximal tibia is one of the most challenging anatomic sites for extremity reconstructions after bone tumor resection. Because bone tumors are rare and large case series of reconstructions of the proximal tibia are lacking, we undertook this study to compare two major reconstructive approaches at two large sarcoma centers. Questions/purposes The purpose of this study was to compare groups of patients treated with endoprosthetic replacement or osteoarticular allograft reconstruction for proximal tibia bone tumors in terms of (1) limb salvage reconstruction failures and risk of amputation of the limb; (2) causes of failure; and (3) functional results. Methods Between 1990 and 2012, two oncologic centers treated 385 patients with proximal tibial resections and reconstruction. During that time, the general indications for those types of reconstruction were proximal tibia malignant tumors or bone destruction with articular surface damage or collapse. Patients who matched the inclusion criteria (age between 15 and 60 years old, diagnosis of a primary bone tumor of the proximal tibia treated with limb salvage surgery and reconstructed with endoprosthetic replacement or osteoarticular allograft) were included for analysis (n = 149). In those groups (endoprosthetic or allograft), of the patients not known to have reached an endpoint (death, reconstructive failure, or limb loss) before 2 years, 85% (88 of 104) and 100% (45 of 45) were available for followup at a minimum of 2 years. A total of 88 patients were included in the endoprosthetic group and 45 patients in the osteoarticular allograft group. Followup was at a mean of 9.5 (SD 6.72) years (range, 2–24 years) for patients with endoprosthetic reconstructions, and 7.4 (SD 5.94) years for patients treated with allografts (range, 2–21 years). The following variables were compared: limb salvage reconstruction failure rates, risk of limb amputation, type of failures according to the Henderson et al. classification, and functional results assessed by the Musculoskeletal Tumor Society system. Results With the numbers available, after competitive risk analysis, the probability of failure for endoprosthetic replacement of the proximal tibia was 18% (95% confidence interval [CI], 10.75–27.46) at 5 years and 44% (95% CI, 31.67–55.62) at 10 years and for osteoarticular allograft reconstruction was 27% (95% CI, 14.73–40.16) at 5 years and 32% (95% CI, 18.65–46.18) at 10 years. There were no differences in terms of risk of failures at 5 years (p = 0.26) or 10 years (p = 0.20) between the two groups. Fifty-one of 88 patients (58%) with proximal tibia endoprostheses developed a reconstruction failure with mechanical causes being the most prevalent (32 of 51 patients [63%]). A total of 19 of 45 osteoarticular allograft reconstructions failed (42%) and nine of 19 (47%) of them were caused by early infection. Ten-year risk of amputation after failure for endoprosthetic reconstruction was 10% (95% CI, 5.13–18.12) and 11% (95% CI, 4.01–22.28) for osteoarticular allograft with no difference between the groups (p = 0.91). With the numbers available, there were no differences between the groups in terms of the mean Musculoskeletal Tumor Society score (26.58, SD 2.99, range, 19–30 versus 27.52, SD 1.91, range, 22–30; p = 0.13; 95% CI, −2,3 to 0.32). Mean extension lag was more severe in the endoprosthetic group than the osteoarticular allograft group: 13.56° (SD 18.73; range, 0°–80°) versus 2.41° (SD 5.76; range, 0°–30°; p < 0.001; 95% CI, 5.8–16.4). Conclusions Reconstruction of the proximal tibia with either endoprosthetic replacement or osteoarticular allograft appears to offer similar reconstruction failures rates. The primary cause of failure for allograft was infection and for endoprosthesis was mechanical complications. We believe that the treating surgeon should have both options available for treatment of patients with malignant or aggressive tumors of the proximal tibia. (S)he might consider an allograft in a younger patient to achieve better extensor mechanism function, whereas in an older patient or one with a poorer prognosis where return to function and ambulation quickly is desired, an endoprosthesis may be advantageous. Level of Evidence Level III, therapeutic study.

Patient involvement in clinical trial design can facilitate the recruitment and retention of participants as well as potentially increase the uptake of the tested intervention and the impact of the findings on patient outcomes. Despite these benefits, patients still have very limited involvement in designing and conducting trials in nephrology. Many trials do not address research questions and outcomes that are important to patients, including patient-reported outcomes that reflect how patients feel and function. This limitation can undermine the relevance, reliability and value of trial-based evidence for decision-making in clinical practice and health policy. However, efforts to involve patients with kidney disease are increasing across all stages of the trial process from priority setting, to study design (including selection of outcomes and approaches to improve participant recruitment and retention) and dissemination and implementation of the findings. Harnessing the patient voice in designing trials can ensure that efforts and resources are directed towards patient-centred trials that address the needs, concerns and priorities of patients living with kidney disease with the aim of achieving transformative improvements in care and outcomes.Meaningful involvement of patients in clinical trial design could lead to improvements in participant recruitment and retention, the uptake of the tested intervention and the impact of the findings. Here, the authors discuss the involvement of patients at all stages of trial design.

Cardiopulmonary arrest in children is an uncommon event, and often fatal. Resuscitation is often attempted, but at what point, and under what circumstances do continued attempts to re-establish circulation become futile? The uncertainty around these questions can lead to unintended distress to the family and to the resuscitation team. To define the likely outcomes of cardiopulmonary resuscitation in children, within different patient groups, related to clinical features. MEDLINE, MEDLINE in-Process & Other non-Indexed Citations, EMBASE, Cochrane database of systematic reviews and Cochrane central register of trials, Database of Abstracts of Reviews of Effects (DARE), the Health Technology Assessment database, along with reference lists of relevant systematic reviews and included articles. Prospective cohort studies which derive or validate a clinical prediction model of outcome following cardiopulmonary arrest. Children or young people (aged 0 - 18 years) who had cardiopulmonary arrest and received an attempt at resuscitation, excluding resuscitation at birth. Risk of bias assessment developed the Hayden system for non-randomised studies and QUADAS2 for decision rules. Synthesis undertaken by narrative, and random effects meta-analysis with the DerSimonian-Laird estimator. More than 18,000 episodes in 16 data sets were reported. Meta-analysis was possible for survival and one neurological outcome; others were reported too inconsistently. In-hospital patients (average survival 37.2% (95% CI 23.7 to 53.0%)) have a better chance of survival following cardiopulmonary arrest than out-of-hospital arrests (5.8% (95% CI 3.9% to 8.6%)). Better neurological outcome was also seen, but data were too scarce for meta-analysis (17% to 71% 'good' outcomes, compared with 2.8% to 3.2%). Lack of consistent outcome reporting and short-term neurological outcome measures limited the strength of conclusions that can be drawn from this review. There is a need to collaboratively, prospectively, collect potentially predictive data on these rare events to understand more clearly the predictors of survival and long-term neurological outcome. PROSPERO 2013:CRD42013005102.

BackgroundLife course studies are designed to “collect once, use multiple times” for observational and, increasingly, interventional research. Core Outcome Sets (COS) are minimum sets developed for clinical trials by multi-stakeholder consensus methodologies. We aimed to synthesize published COS that might guide outcomes selection for early life cohorts with an interventional focus.MethodsWe searched PubMed, Medline, COMET, and CROWN for COS published before January 2021 relevant to four life stages (pregnancy, newborns, children <8 years, and parents (adults aged 18–50 years)). We synthesized core outcomes into overarching constructs.ResultsFrom 46 COS we synthesized 414 core outcomes into 118 constructs. “Quality of life”, “adverse events”, “medication use”, “hospitalization”, and “mortality” were consistent across all stages. For pregnancy, common constructs included “preterm birth”, “delivery mode”, “pre-eclampsia”, “gestational weight gain”, “gestational diabetes”, and “hemorrhage”; for newborns, “birthweight”, “small for gestational age”, “neurological damage”, and “morbidity” and “infection/sepsis”; for pediatrics, “pain”, “gastrointestinal morbidity”, “growth/weight”, “breastfeeding”, “feeding problems”, “hearing”, “neurodevelopmental morbidity”, and “social development”; and for adults, “disease burden”, “mental health”, “neurological function/stroke”, and “cardiovascular health/morbidity”.ConclusionThis COS synthesis generated outcome constructs that are of high value to stakeholders (participants, health providers, services), relevant to life course research, and could position cohorts for trial capabilities.ImpactWe synthesized existing Core Outcome Sets as a transparent methodology that could prioritize outcomes for lifecourse cohorts with an interventional focus.“Quality of life”, “adverse events”, “medication use”, “hospitalization”, and “mortality” are important outcomes across pregnancy, newborns, childhood, and early-to-mid-adulthood (the age range relevant to parents). Other common outcomes (such as “birthweight”, “cognitive function/ability”, “psychological health”) are also highly relevant to lifecourse research.This synthesis could assist new early life cohorts to pre-select outcomes that are of high value to stakeholders (participants, health providers, services), are relevant to lifecourse research, and could position them for future trials and interventional capability.

Background Primary aneurysmal bone cysts (ABCs) are benign, expansile bone lesions commonly treated with aggressive curettage with or without adjuvants such as cryotherapy, methacrylate cement, or phenol. It has been reported that occasionally these lesions heal spontaneously or after a pathologic fracture, and we observed that some ABCs treated at our center healed after biopsy alone. Because of this, we introduced a novel biopsy technique we call “curopsy,” which is a percutaneous limited curettage at the time of biopsy, obtaining the lining membrane from various quadrants of the cyst leading to consolidation (curopsy = biopsy with intention to cure). Questions/purposes We asked whether (1) a curopsy results in comparable likelihood of healing of the ABC compared with more aggressive approaches involving curettage, (2) the two approaches differ in terms of the likelihood of recurrence after treatment, and (3) the two approaches differ in terms of complications after surgery. Methods Between January 1, 1999 and June 30, 2012, 221 patients with a diagnosis of primary ABC were registered in our oncology database. Patients presenting with a pathologic fracture and those seeking a second opinion were excluded. One hundred ninety patients were included in the study. One hundred two (54%) were treated with curopsy and 88 (46%) were treated with curettage after a core needle biopsy. Complete followups were available for 88% (90 of 102) and 93% (80 of 88) of patients in those groups, respectively. During that period, a curopsy was performed for all patients with benign bone lesions with imaging suggestive of classic primary ABCs and for whom the core needle biopsy simply showed blood with no solid component. Curettage after a core needle biopsy was reserved for histologically confirmed primary ABCs, lesions with impending fractures, large lesions, if the ABC was thought to be a secondary disorder, and patients for whom the curopsy failed. All patients were followed up until consolidation of the lesion (mean, 9.6 weeks, range, 3–25 weeks, 95% CI, 8.32–10.9 for curopsy; mean, 11.4 weeks, range, 8–32 weeks, 95% CI, 10.6–12.3 for curettage). The median followup for all patients was 14 months (range, 6–36 months). Results Of the 102 patients who had curopsy and observation, 83 (81%) required no additional treatment and the lesion resolved. Of the 88 patients who underwent curettage (with or without adjuvant therapy) after core needle biopsy, the success rate was 90% (79 of 88). Local recurrences in both groups (curopsy or curettage) were treated successfully with additional curettage in all but one case. Curopsy in comparison to curettage provided a mean shorter healing time (9.6 versus 11.4, p = 0.01) but there was a higher local recurrence and need for additional intervention rate (18.6% versus 10.2%, p = 0.04). There were no differences in the complications between the treatment groups. Conclusions A curopsy is a novel biopsy technique that was successful in resolving ABCs in 81% of the patients in our study. Curopsy, as a biopsy technique, for ABCs needs consideration as it potentially minimizes the number of patients needing a second procedure (a core needle biopsy being the first) as is the current practice. Furthermore, it does not disadvantage the patient or surgeon should additional intervention be needed in the form of curettage with or without adjuvants. Level of Evidence Level III, therapeutic study. See the Instructions for Authors for a complete description of levels of evidence.

SONG aims to establish COS across the spectrum of chronic kidney disease and since 2014 has engaged over 9,000 participants (4,000 patients and caregivers and 5,000 health professionals) from over 100 countries to establish six COS for hemodialysis, peritoneal dialysis, transplantation, polycystic kidney disease, glomerular disease, and pediatric kidney disease [3–8]. The SONG methodological framework is based on COMET recommendations and involves the following: 1) a systematic review of outcomes reported in trials, 2) focus groups with a nominal group technique involving patients and caregivers, 3) stakeholder interviews, 4) a multiround, international online Delphi survey, and 5) consensus workshops. [...]participants individually rank outcomes and then discuss similarities and differences in priorities as a group. SONG-PKD (polycystic kidney disease), SONG-GD (glomerular disease), and SONG-PD (peritoneal dialysis) have each involved over 120 participants in at least 14 focus groups and from at least three countries in two or more languages [10,11] (Table 1).

Population pharmacokinetic (PK) models are widely used to inform drug development by pharmaceutical companies and facilitate drug evaluation by regulatory agencies. Developing a population PK model is a multi‐step, challenging, and time‐consuming process involving iterative manual model fitting and evaluation. A tool for fully automatic model development (AMD) of common population PK models is presented here. The AMD tool is implemented in Pharmpy, a versatile open‐source library for pharmacometrics. It consists of different modules responsible for developing the different components of population PK models, including the structural model, the inter‐individual variability (IIV) model, the inter‐occasional variability (IOV) model, the residual unexplained variability (RUV) model, the covariate model, and the allometry model. The AMD tool was evaluated using 10 real PK datasets involving the structural, IIV, and RUV modules in three sequences. The different sequences yielded generally consistent structural models; however, there were variations in the results of the IIV and RUV models. The final models of the AMD tool showed lower Bayesian Information Criterion (BIC) values and similar visual predictive check plots compared with the available published models, indicating reasonable quality, in addition to reasonable run time. A similar conclusion was also drawn in a simulation study. The developed AMD tool serves as a promising tool for fast and fully automatic population PK model building with the potential to facilitate the use of modeling and simulation in drug development.

Sunshine plays an important role in all aspects of life but there has been little social analysis of the sun and its place in our world. Recently experts have warned us that the sun's rays are dangerous. Yet, a suntan can still be taken as a sign of health. How did we arrive at this ambivalent relationship to the sun and what does this say about our changing attitudes to the human body and environment? Rise and Shine takes as its starting point a view of sunlight as part of our material and social culture. How did the use of sunlight to treat tuberculosis and rickets in the early twentieth century alter our relationship with the sun? When was suntan lotion invented? By drawing on a range of archival and historical sources, Rise and Shine traces the network of social and medical forces that constitute our current, sometimes problematic, relationship with sun and sunlight.