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Based on Dr Colin Espie's 45 years of clinical and research experience, this expert manual for clinicians and healthcare professionals shows how best to assess insomnia and deliver effective treatment in everyday practice using cognitive and behavioural therapeutics (CBTx). The book provides in-depth background on the importance of sleep, the interactions between sleep and health, what insomnia is, and insomnia's negative impact on patients. Using detailed examples, metaphors, and practical guidance, it provides clear instructions on the evaluation of sleep complaints and on the why and how of selecting and providing a specific CBTx to suit the presenting patient. Delving beyond treating patients at the individual level, the book also considers how to develop an effective and efficient insomnia service at population scale.
The Accelerating COVID-19 Therapeutic Interventions and Vaccines Therapeutic-Clinical Working Group members gathered critical recommendations in follow-up to lessons learned manuscripts released earlier in the COVID-19 pandemic. Lessons around agent prioritization, preclinical therapeutics testing, master protocol design and implementation, drug manufacturing and supply, data sharing, and public–private partnership value are shared to inform responses to future pandemics.
This study examines how psychological aspects of vestibular disorders are currently addressed highlighting any national variation.
Method
An online survey was completed by 101 UK healthcare professionals treating vestibular disorders. The survey covered service configurations, attitudes towards psychological aspects and current clinical practice.
Results
Ninety-six per cent of respondents thought there was a psychological component to vestibular disorders. There was a discrepancy between perceived importance of addressing psychological aspects and low confidence to undertake this. Those with more experience felt more confident addressing psychological aspects. History taking and questionnaires containing one or two psychological items were the most common assessment approaches. Discussing symptoms and signposting were the most frequent management approaches. Qualitative responses highlighted the interdependence of psychological and vestibular disorders which require timely intervention. Barriers included limited referral pathways, resources and interdisciplinary expertise.
Conclusion
Although psychological distress is frequently identified, suitable psychological treatment is not routinely offered in the UK.
Drugs are a part of everyday life and may be defined as any pharmacologically active substance intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease (1). Whether a drug is a conventional medicine, a herbal remedy, or the caffeine in your coffee, drugs are an integral part of human existence and have been since ancient times. Drugs may be synthetic in origin or naturally derived from plants, animals, or biotechnology. A ‘medicine’ is a drug product containing one or more drugs in a formulation administered for a therapeutic purpose.
Ocrelizumab is an effective anti-CD20 therapy approved for Relapsing Remitting (RRMS) and Primary Progressive Multiple Sclerosis (PPMS). In clinical trials, a proportion of patients developed hypogammaglobulinemia which could contribute to infection risk. This study aimed to identify hypogammaglobulinemia and its risk factors and evaluate potentially associated serious infection risk in a real-world cohort of patients.
Methods:
All MS patients treated with ocrelizumab in a Quebec City MS clinic from January 2017 to August 2021 were included and detailed patient characteristics were collected by chart review. Levels of immunoglobulins (IgM, IgA and IgG) were assessed prior to each treatment. Serious infection was defined as an infection requiring hospitalization or emergency room treatment. Association between hypogammaglobulinemia and serious infection was analyzed.
Results:
A total of 266 patients (average follow-up 2.05 years) were included (87% RRMS). After 6 infusions, 32.8%, 3.5% and 4.2% of patients had at least one IgM, IgA and IgG hypogammaglobulinemia event respectively. Aside from pre-treatment hypogammaglobulinemia, there were no variables associated with on-treatment hypogammaglobulinemia. There was a total of 21 serious infections (3.36 and 12.33 per 100-person-years in RRMS and PPMS). Developing hypogammaglobulinemia during treatment was not associated with serious infection. A regression analysis did not show associations between serious infection and key disease characteristics.
Conclusion:
Similar to ocrelizumab extension studies, our cohort demonstrated a significant rate of hypogammaglobulinemia over time, mostly with IgM. No association was found between hypogammaglobulinemia and serious infection.
Alzheimer’s disease (AD) is a neurodegenerative disorder that accounts for 60%–70% of patients with dementia, and it is estimated that over one million Canadians will be living with dementia by 2030. Disease-modifying therapies (DMTs) targeting the underlying pathophysiology of AD are currently in development. Several models have demonstrated that the potential arrival of Alzheimer’s DMTs will most likely overwhelm the already-constrained Canadian healthcare system. Canada does not have a strategy to address the extensive requirements of using DMTs, including providing an early diagnosis of AD, confirming DMT eligibility via amyloid biomarkers, and conducting ongoing treatment monitoring. Thus, a multidisciplinary group of experts involved in AD care in Canada gathered to review (1) the current barriers to diagnosis and management of AD; (2) how existing clinic models, including those used in multiple sclerosis (MS), could be applied to address key barriers in AD; and (3) how to design and implement optimal care pathways in the future. The actions outlined in this review will help clinicians and healthcare systems improve readiness to integrate the use of disease-modifying therapies in Alzheimer’s disease, if such therapies are approved in Canada.
Alzheimer’s disease (AD) is experienced by > 600,000 Canadians. Disease-modifying therapies (DMTs) for earlier stages of disease are in development. Existing health system capacity constraints and the need for biomarker-driven diagnostics to confirm DMT eligibility are concerning. This study aimed to characterize the capacity gap related to early AD (eAD) treatment with DMTs in Canada.
Methods:
A capacity model was developed to simulate the flow of a patient from screening to treatment for eAD to quantify the gap between available and required healthcare resources and qualify the bottlenecks restricting the patient journey at a provincial and national level. The model inputs (epidemiological, human resource, and clinical) were evidence-based, healthcare professional-, and patient advocate-informed.
Results:
The model estimated that nationally < 2% of patients would have access to the required healthcare resources for treatment with a DMT. Eligibility assessment represented the step with the largest capacity gap across all provinces, with a wait list of about 382,000 Canadians one year following DMT introduction. The top three resource gaps included AD specialist time and positron emission tomography and magnetic resonance imaging exam slots. Sensitivity analysis showed that full reliance on cerebrospinal fluid for eligibility testing increased capacity for assessment by about 47,000 patients.
Conclusion:
This model highlights that the Canadian health system is critically under-resourced to diagnose, assess, and treat patients with eAD with DMT. It underscores an urgent need for national policy and provincial resource allocation to close the gap.
Metallic nanoparticles from different natural sources exhibit superior therapeutic options as compared to the conventional methods. Selaginella species have attracted special attention of researchers worldwide due to the presence of bioactive molecules such as flavonoids, biflavonoids, triterpenes, steroids, saponins, tannins and other secondary metabolites that exhibit antimicrobial, antiplasmodial, anticancer and anti-inflammatory activities. Environment friendly green synthesised silver nanoparticles from Selaginella species provide viable, safe and efficient treatment against different fungal pathogens.
Objective
This systematic review aims to summarise the literature pertaining to superior antifungal ability of green synthesised silver nanoparticles using plant extracts of Selaginella spp. in comparison to both aqueous and ethanolic raw plant extracts by electronically collecting articles from databases.
Methods
The recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis were taken into consideration while preparing this review. The titles and abstracts of the collected data were stored in Endnote20 based on the inclusion and exclusion criteria. The search strategy included literature from established sources like PubMed, Google Scholar and Retrieval System Online using subject descriptors.
Results
The search yielded 60 articles with unique hits. After removal of duplications, 46 articles were identified, 40 were assessed and only seven articles were chosen and included in this review based on our eligibility criteria.
Conclusion
The physicochemical and preliminary phytochemical investigations of Selaginella suggest higher drug potency of nanoparticles synthesised from plant extract against different diseases as compared to aqueous and ethanolic plant extracts. The study holds great promise as the synthesis of nanoparticles involves low energy consumption, minimal technology and least toxic effects.
The British Thyroid Association and American Thyroid Association guideline definitions for low-risk differentiated thyroid cancers are susceptible to differing interpretations, resulting in different clinical management in the UK.
Objective
To explore the national effect of these guidelines on the management of low-risk differentiated thyroid cancers.
Methods
Anonymised questionnaires were sent to multidisciplinary teams performing thyroidectomies in the UK. Risk factors that multidisciplinary teams considered important when managing low-risk differentiated thyroid cancers were established.
Results
Most surgeons (71 out of 75; 94.7 per cent) confirmed they were core multidisciplinary team members. More than 80 per cent of respondents performed at least 30 hemi- and/or total thyroidectomies per annum. A majority of multidisciplinary teams (50 out of 75; 66.7 per cent) followed British Thyroid Association guidelines. Risk factors considered important when managing low-risk differentiated thyroid cancers included: type of tumour histology findings (87.8 per cent), tumour size of greater than 4 cm (86.5 per cent), tumour stage T3b (85.1 per cent) and central neck node involvement (85.1 per cent). Extent of thyroid surgery (e.g. hemi- or total thyroidectomy) was highly variable for low-risk differentiated thyroid cancers.
Conclusion
Management of low-risk differentiated thyroid cancers is highly variable, leading to a heterogeneous patient experience.
Chapter 14 describes the biotechnological applications of recombinant DNA technology. The range of disciplines that contribute to biotechnology is outlined to illustrate the scale and scope of the sector. Production of proteins is one key area where cloned genes can be expressed to produce high-value products for use in a variety of applications, and the types of systems used for protein production are discussed. Protein engineering by methods such as rational design and directed evolution has enabled customised proteins to be developed for specific applications. The requirements for transition from laboratory-scale research and development to industrial production at a commercially viable level are outlined, and the contribution of the biotechnology sector in managing the COVID-19 pandemic is discussed.
Treatment for tinnitus focuses on supportive therapies. Long waiting times in the National Health Service encourage telemedicine options as an alternative. This study aimed to review the literature on telemedicine in the management of tinnitus and analyse its impact on the burden of tinnitus, long-term, anxiety, depression, insomnia and quality of life.
Method
PubMed, Embase, Cochrane Library, Google Scholar, Scopus and Web of Science were searched. English randomised, controlled trials with adult participants suffering from tinnitus were included. A random effects model looking at standardised mean differences between intervention and control groups was utilised.
Results
Eleven randomised, controlled trials were included. Nine studies looked at internet-based cognitive behavioural therapy. A z-value of 9.87 (p < 0.00001; I2 = 21 per cent) showed telemedicine approaches may be better at reducing tinnitus burden compared with passive controls.
Conclusion
Telemedicine options have multiple benefits, but more research will be needed to conclusively say they are better than alternatives.
Pancreatic ductal adenocarcinoma (PDAC) is usually diagnosed at an advanced, incurable, stage and has an extremely poor prognosis. Systemic chemotherapy represents the standard treatment either in the pre-operative, adjuvant and palliative setting, which is associated with only modest improvement in survival. More recently, advances in cancer genomic sequencing have unravelled the molecular heterogeneity of PDAC and identified small patient subgroups harbouring unique actionable aberrations in BRCA, NTRK, NRG1 and mismatch repair genes paving the way to a more personalised approach for this tumour. However, the evolution of PDAC treatment towards a successful precision approach presents many challenges. In this review, we discuss the current standard treatments of PDAC, from early stage to advanced disease, and we illustrate the opportunities and challenges of precision medicine for this deadly cancer.
Cardiovascular diseases (CVDs) are complex in their aetiology, arising due to a combination of genetics, lifestyle and environmental factors. By nature of this complexity, different CVDs vary in their molecular mechanisms, clinical presentation and progression. Although extensive efforts are being made to develop novel therapeutics for CVDs, genetic heterogeneity is often overlooked in the development process. By considering molecular mechanisms at an individual and ancestral level, a richer understanding of the influence of environmental and lifestyle factors can be gained and more refined therapeutic interventions can be developed. It is therefore expedient to understand the molecular and clinical heterogeneity in CVDs that exists across different populations. In this review, we highlight how the mechanisms underlying CVDs vary across diverse population ancestry groups due to genetic heterogeneity. We then discuss how such genetic heterogeneity is being leveraged to inform therapeutic interventions and personalised medicine, highlighting examples across the CVD spectrum. Finally, we present an overview of how polygenic risk scores and Mendelian randomisation can foster more robust insight into disease mechanisms and therapeutic intervention in diverse populations. Fulfilment of the vision of precision medicine requires more exhaustive leveraging of the genetic variability across diverse ancestry populations to improve our understanding of disease onset, progression and response to therapeutic intervention.
Precision Medicine is an approach to disease treatment and prevention taking into account individual genetic, environmental, therapeutic and lifestyle variability for each person. This holistic approach to therapeutics is intended to enhance drug efficacy and safety not only across healthcare systems but for individual patients. While weight and to some extent gestational age have been considered in determining drug dosing in children, historically other factors including genetic variability have not been factored into therapeutic decision making. As our knowledge of the role of ontogeny and genetics in determining drug efficacy and safety has expanded, these insights have provided new opportunities to apply principles of Precision Medicine to the care of infants, children and youth. These opportunities are most likely to be achieved first in select sub-groups of children. While there are many challenges to the successful implementation of Precision Medicine in children including the need to ensure that Precision Medicine enhances rather than reduces equity in children’s health care rather, there are many more opportunities. Research, advocacy, planning and teamwork are required to move Precision Medicine forward in children in pursuit of the common goal of safe and effective drug therapy.
Vestibular migraine is in the process of recognition as an individual clinical entity. At present, no guidelines exist for its management. This study aimed to conduct a systematic review and meta-analysis to determine the effectiveness of available prophylactic medication.
Method
A literature search was performed using PubMed, Ovid and Embase databases. Qualitative and quantitative analysis were performed as well as risk of bias analysis. Meta-analysis for the mean differences for pre- and post-treatment impact based on Dizziness Handicap Inventory and Vertigo Symptom Scale were performed. Proportionate transformation meta-analysis for the successful event rate based on complete symptoms control was explored.
Results
Thirteen publications were identified: 3 were randomised, controlled trials and 10 were non-randomised, controlled trials. Propranolol and venlafaxine improved the Vertigo Symptom Scale score by −13.31 points and −4.16 points, respectively, and the Dizziness Handicap Inventory score by −32.24 and −21.24, respectively. Only propranolol achieved statistically significant impact with 60 per cent of patients achieving complete symptom control.
Conclusion
Propranolol should be offered as the first-line treatment for vestibular migraine followed by venlafaxine. Amitriptyline, flunarizine and cinnarizine showed a trend for symptom improvement, but this was not statistically significant.
Mortality remains a substantial problem after acute ischemic stroke, despite advances in acute stroke treatment over the past three decades. Mortality is particularly high among patients with Total Anterior Circulation Stroke (TACS), generally representing patients with middle cerebral artery occlusions. Notably however, these patients also stand to benefit most from new therapies including endovascular thrombectomy (EVT). In this study, we aimed to examine temporal trends in, and factors associated with, 30-day in-hospital mortality after TACS.
Methods:
Information on all patients with community-onset TACS from 1994 through 2019 was extracted from a prospective acute stroke registry. Multivariate analysis was performed on the primary outcome of 30-day in-hospital mortality, as well as secondary functional outcomes.
Results:
We studied 1106 patients hospitalized for community-onset TACS, 456 (41%) of whom experienced 30-day in-hospital mortality. Over the 25 years of observation, 30-day in-hospital mortality rose and then fell. Increased odds of mortality was associated with age and stroke severity. Decreased odds of mortality was associated with alteplase therapy and EVT, as well as presentation to hospital more than 12 hours after stroke onset. Treatment with alteplase, EVT, or both was associated with higher odds of functional independence and discharge home, and shorter lengths of stay in acute care.
Conclusions:
Patients receiving alteplase, EVT, or both had lower 30-day in-hospital mortality and better functional outcomes than those who were untreated. These observational data demonstrate the benefits of recanalization therapy in routine clinical practice.
Early-stage drug development efforts for Alzheimer’s disease (AD) therapeutics often occur within academia and start-up companies and are often supported by National Institutes of Health (NIH) funding. The National Institute on Aging’s (NIA’s) seed funding through the Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs provide innovators with non-dilutive funding that supports key early-stage drug developments. Since 2015, the NIA small business funding programs have become a valuable source of seed funding available that enabled start-up companies to reach critical value inflection points. This chapter includes examples of five companies that received NIA small business funding at the preclinical stage of development and advanced their innovations to clinical trials: AgeneBio, Alector, Avid Radiopharmaceuticals, Cognition Therapeutics and Tetra Therapeutics. The NIH and NIA have launched several strategic initiatives and funding opportunities to enable small businesses to reach key value inflection points.
The path to approvability of drugs created for Alzheimer’s disease (AD) dementia, mild cognitive impairment, or associated symptoms of AD is long and expensive, involving the study sponsor, the registration authorities, a clinical research organization, and the performance site. The key to successful AD trials is the performance site, the individual investigators, the recruited subjects, and the quality of the data generated. Performance sites include academic medical centers, a division within a large multi-specialty group, and for-profit clinical trial companies. All performance sites have common elements. These include the staff (investigator, coordinator, rater/neuropsychologist, and manager), access to study participants for enrollment, appropriate training of staff, regulatory oversight (investigational review board ), and the ancillary services. Types of studies that are available include therapeutic (medication or device), longitudinal observational, and imaging. Different types of studies have different requirements for staff or infrastructure, some easy to deploy, others not. In this chapter we will describe the elements of a successful AD clinical trial site.