Opioid use disorder in cancer patients.

PURPOSE OF REVIEW: The misuse of opioids has increased significantly in recent decades. Historically, cancer patients have not been considered at risk of opioid misuse. However, cancer pain is common, and opioids are often prescribed. Guidelines addressing opioid misuse often exclude cancer patients. Given that misuse is associated with significant harm and a reduction in quality of life, it is important to understand the risk of opioid misuse in cancer patients and how we can recognise and treat it. RECENT FINDINGS: Early cancer diagnoses and treatments have improved cancer survival rates, leading to a larger population of cancer patients and survivors. Opioid use disorder (OUD) may precede a cancer diagnosis or may develop during or after treatment. The effect of OUD extends from an individual patient to a societal level. This review examines the increasing incidence of OUD in cancer patients, ways to identify patients with OUD such as behaviour change and screening scales, prevention of OUD such as limited and targeted opioid prescriptions, and evidence-based treatment suggestions for OUD. SUMMARY: OUD in cancer patients has only relatively recently been recognised as a growing problem. Early identification, involvement of the multidisciplinary team, and treatment can reduce the negative impact of OUD.

Apnoeic oxygenation in morbid obesity: a randomised controlled trial comparing facemask and high-flow nasal oxygen delivery.

BACKGROUND: Obesity is a risk factor for airway-related incidents during anaesthesia. High-flow nasal oxygen has been advocated to improve safety in high-risk groups, but its effectiveness in the obese population is uncertain. This study compared the effect of high-flow nasal oxygen and low-flow facemask oxygen delivery on duration of apnoea in morbidly obese patients. METHODS: Morbidly obese patients undergoing bariatric surgery were randomly allocated to receive either high-flow nasal (70 L min-1) or facemask (15 L min-1) oxygen. After induction of anaesthesia, the patients were apnoeic for 18 min or until peripheral oxygen saturation decreased to 92%. RESULTS: Eighty patients were studied (41 High-Flow Nasal Oxygen, 39 Facemask). The median apnoea time was 18 min in both the High-Flow Nasal Oxygen (IQR 18-18 min) and the Facemask (inter-quartile range [IQR], 4.1-18 min) groups. Five patients in the High-Flow Nasal Oxygen group and 14 patients in the Facemask group desaturated to 92% within 18 min. The risk of desaturation was significantly lower in the High-Flow Nasal Oxygen group (hazard ratio=0.27; 95% confidence interval [CI], 0.11-0.65; P=0.007). CONCLUSIONS: In experienced hands, apnoeic oxygenation is possible in morbidly obese patients, and oxygen desaturation did not occur for 18 min in the majority of patients, whether oxygen delivery was high-flow nasal or low-flow facemask. High-flow nasal oxygen may reduce desaturation risk compared with facemask oxygen. Desaturation risk is a more clinically relevant outcome than duration of apnoea. Individual physiological factors are likely to be the primary determinant of risk rather than method of oxygen delivery. CLINICAL TRIAL REGISTRATION: NCT03428256.

Neuromodulation techniques for cancer pain management.

PURPOSE OF REVIEW: Advanced pain management techniques may be indicated in 5-15% of cancer patients. Despite this, a recent review identified that, over the course of 1 year in England, only 458 patients received a procedure intended to provide analgesia and only 30 patients had intrathecal drug delivery (ITDD) devices implanted. This article describes the emerging evidence for ITDD in cancer pain and provides a narrative review of other neuromodulatory techniques (including spinal cord stimulation, peripheral nerve stimulation and acupuncture), approaches that might be employed to address this area of significant unmet clinical need. RECENT FINDINGS: Numerous studies have been published within the last year reporting positive outcomes associated with ITDD in cancer pain management. Neuromodulation represents an important strategy in the management of persistent pain. Whilst the nonmalignant pain evidence-base is rapidly growing, it remains sparse for cancer pain management. The growing cohort of cancer survivors may significantly benefit from neuromodulatory techniques. SUMMARY: ITDD and other neuromodulatory techniques for cancer pain management appear underutilised in the UK and offer the prospect of better treatment for cancer patients with refractory pain or intolerable side-effects from systemic analgesics.

Human bony labyrinth is an indicator of population history and dispersal from Africa.

The dispersal of modern humans from Africa is now well documented with genetic data that track population history, as well as gene flow between populations. Phenetic skeletal data, such as cranial and pelvic morphologies, also exhibit a dispersal-from-Africa signal, which, however, tends to be blurred by the effects of local adaptation and in vivo phenotypic plasticity, and that is often deteriorated by postmortem damage to skeletal remains. These complexities raise the question of which skeletal structures most effectively track neutral population history. The cavity system of the inner ear (the so-called bony labyrinth) is a good candidate structure for such analyses. It is already fully formed by birth, which minimizes postnatal phenotypic plasticity, and it is generally well preserved in archaeological samples. Here we use morphometric data of the bony labyrinth to show that it is a surprisingly good marker of the global dispersal of modern humans from Africa. Labyrinthine morphology tracks genetic distances and geography in accordance with an isolation-by-distance model with dispersal from Africa. Our data further indicate that the neutral-like pattern of variation is compatible with stabilizing selection on labyrinth morphology. Given the increasingly important role of the petrous bone for ancient DNA recovery from archaeological specimens, we encourage researchers to acquire 3D morphological data of the inner ear structures before any invasive sampling. Such data will constitute an important archive of phenotypic variation in present and past populations, and will permit individual-based genotype-phenotype comparisons.

Post-herpetic neuralgia - a review of current management and future directions.

INTRODUCTION: Post-herpetic neuralgia (PHN) is common and treatment is often suboptimal with less than half of patients achieving adequate 50% pain relief. As an area of unmet clinical need and as an archetype of neuropathic pain, it deserves the attention of clinicians and researchers. Areas covered: This review summarises the epidemiology, pathophysiology, risk factors and clinical features of varicella infection. It describes the current and possible future management strategies for preventing varicella infection and reactivation and for treating PHN. Expert opinion: A highly successful Varicella Zoster (VZV) vaccine has not been universally adopted due to fears that it may increase Herpes Zoster (HZ) incidence - and thus PHN - in older, unvaccinated generations. This is a controversial theory but advances in the efficacy of vaccines against HZ may allay these fears and encourage more widespread adoption of the VZV vaccine. Treatment of PHN, as for any neuropathic pain, must be multidisciplinary and multimodal. Advances in sensory phenotyping technology and genomics may allow more individualised treatment. Traditional research methodologies are ill-suited to assess the kind of complex interventions that are necessary to achieve better clinical outcomes in this challenging field.

Head injury patterns in helmeted and non-helmeted cyclists admitted to a London Major Trauma Centre with serious head injury.

BACKGROUND: Cycle use across London and the UK has increased considerably over the last 10 years. With this there has been an increased interest in cycle safety and injury prevention. Head injuries are an important cause of mortality and morbidity in cyclists. This study aimed to ascertain the frequency of different head injury types in cyclists and whether wearing a bicycle helmet affords protection against specific types of head injury. METHODS: A retrospective observational study of all cyclists older than 16 years admitted to a London Major Trauma Centre between 1st January 2011 and 31st December 2015 was completed. A cohort of patients who had serious head injury was identified (n = 129). Of these, data on helmet use was available for 97. Comparison was made between type of injury frequency in helmeted and non-helmeted cyclists within this group of patients who suffered serious head injury. RESULTS: Helmet use was shown to be protective against intracranial injury in general (OR 0.2, CI 0.07-0.55, p = 0.002). A protective effect against subdural haematoma was demonstrated (OR 0.14, CI 0.03-0.72, p = 0.02). Wearing a helmet was also protective against skull fractures (OR 0.12, CI 0.04-0.39, p<0.0001) but not any other specific extracranial injuries. This suggests that bicycle helmets are protective against those injuries caused by direct impact to the head. Further research is required to clarify their role against injuries caused by shearing forces. CONCLUSIONS: In a largely urban environment, the use of cycle helmets appears to be protective for certain types of serious intra and extracranial head injuries. This may help to inform future helmet design.

Individual-based modelling of population growth and diffusion in discrete time.

Individual-based models (IBMs) of human populations capture spatio-temporal dynamics using rules that govern the birth, behavior, and death of individuals. We explore a stochastic IBM of logistic growth-diffusion with constant time steps and independent, simultaneous actions of birth, death, and movement that approaches the Fisher-Kolmogorov model in the continuum limit. This model is well-suited to parallelization on high-performance computers. We explore its emergent properties with analytical approximations and numerical simulations in parameter ranges relevant to human population dynamics and ecology, and reproduce continuous-time results in the limit of small transition probabilities. Our model prediction indicates that the population density and dispersal speed are affected by fluctuations in the number of individuals. The discrete-time model displays novel properties owing to the binomial character of the fluctuations: in certain regimes of the growth model, a decrease in time step size drives the system away from the continuum limit. These effects are especially important at local population sizes of <50 individuals, which largely correspond to group sizes of hunter-gatherers. As an application scenario, we model the late Pleistocene dispersal of Homo sapiens into the Americas, and discuss the agreement of model-based estimates of first-arrival dates with archaeological dates in dependence of IBM model parameter settings.

Nonclinical dose formulation: out of specification investigations.

Nonclinical safety studies are required to follow applicable Good Laboratory Practice (GLP) regulations. Nonclinical dose formulations are required to be analyzed to confirm the analyte concentration, homogeneity, and stability. Analytical samples that fall outside of the acceptance criteria are considered out of specification (OOS), and an investigation should be conducted. The US FDA has issued a guidance document for GMP studies on conducting OOS investigations. However, no regulatory guidance has been issued regarding nonclinical safety study (GLP) OOS investigations, which often vary in regard to content, assessment, and impact statements. There is opportunity to improve the quality of OOS investigations by defining expectations and providing guidance in several areas including root cause assessment, impact statements, and acceptable paths forward. This paper will provide recommendations of best practices for nonclinical dose formulation OOS investigations.

A bidirectional interface growth model for cranial interosseous suture morphogenesis.

Interosseous sutures exhibit highly variable patterns of interdigitation and corrugation. Recent research has identified fundamental molecular mechanisms of suture formation, and computer models have been used to simulate suture morphogenesis. However, the role of bone strain in the development of complex sutures is largely unknown, and measuring suture morphologies beyond the evaluation of fractal dimensions remains a challenge. Here we propose a morphogenetic model of suture formation, which is based on the paradigm of Laplacian interface growth. Computer simulations of suture morphogenesis under various boundary conditions generate a wide variety of synthetic sutural forms. Their morphologies are quantified with a combination of Fourier analysis and principal components analysis, and compared with natural morphological variation in an ontogenetic sample of human interparietal suture lines. Morphometric analyses indicate that natural sutural shapes exhibit a complex distribution in morphospace. The distribution of synthetic sutures closely matches the natural distribution. In both natural and synthetic systems, sutural complexity increases during morphogenesis. Exploration of the parameter space of the simulation system indicates that variation in strain and/or morphogen sensitivity and viscosity of sutural tissue may be key factors in generating the large variability of natural suture complexity.

A morphogenetic model of cranial pneumatization based on the invasive tissue hypothesis.

The interpretation of patterns of cranial pneumatization in terms of evolution, development, and function is controversial, because these structures exhibit extreme diversity and variability among and within taxa. However, there is general consensus that air-filled spaces are formed by invasion of mucous epithelial tissue from the nasopharyngeal cavity into the surrounding cranial bones. This investigation presents a morphogenetic model of pneumatization, which combines empirical data about epithelial growth with physical concepts of surface growth. The study develops a model that defines growth equations with a minimum number of system parameters to simulate the invasion of mucous tissue and air-filled spaces into the cancellous compartment of cranial bones. Computer simulations show that tuning a small set of model parameters permits generation of a wide diversity of morphologies mimicking natural air-filled spaces. Comparison of virtual with actual morphologies yields new insights into possible factors controlling the process of cranial pneumatization.