Age and the Residual Risk of Cardiovascular Disease following Low Density Lipoprotein-Cholesterol Exposure.

We believe that there is sufficient evidence from basic science, longitudinal cohort studies and randomised controlled trials which validates the low-density lipoprotein cholesterol (LDL-C) or lipid hypothesis. It is important that we can communicate details of the cardiovascular disease (CVD) risk reduction that the average patient could expect depending on the scale of LDL-C decrease following lipid lowering therapy. It is also essential that residual risk (ResR) of CVD be highlighted. To achieve this aim by using existing trial evidence, we developed mathematical models initially for relative risk reduction (RRR) and absolute risk (AR) reduction and then showed that despite optimising LDL-C levels, a considerable degree of ResR remains that is dependent on AR. Age is significantly associated with AR (odds ratio: 1.02, 95% confidence intervals: 1.01-1.04) as was previously demonstrated by analysing the Whickham study cohort using a logistic regression model (age remaining significant even when all the other significant risk factors such as sex, smoking, systolic blood pressure, diabetes and family history were included in the regression model). A discussion of a paper by Ference et al. provided detailed evidence of the relationship between age and AR, based on lifetime LDL-C exposure. Finally, we discussed non-traditional CVD risk factors that may contribute to ResR based on randomised controlled trials investigating drugs improving inflammation, thrombosis, metabolic and endothelial status.

From the European Medicines Agency to Project Orbis: new activities and challenges to facilitate UK oncology drug approval following Brexit.

The departure of the UK from the European Union (EU) and affiliated European regulatory bodies, including the European Medicines Agency, on Dec 31, 2020, has resulted in the Medicines and Healthcare products Regulatory Agency becoming an independent national regulator. This change has required a fundamental transformation of the UK drug regulatory landscape, creating both opportunities and challenges for future development of oncology drugs. New UK pharmaceutical policies have sought to make the UK an attractive market for drug development and regulatory review, by offering expedited review pathways coupled to strong collaborative relations with other leading international medicines regulators, outside of Europe. Oncology is a key global therapy area for both drug development and regulatory approval, and the UK Government has been keen to show regulatory innovation and international collaboration through approval of new cancer medicines. In this Policy Review, we examine the new UK regulatory frameworks, policies, and global collaborations affecting new oncology drug approvals after departure from the EU. We explore some of the challenges that might lie ahead as the UK creates new and independent regulatory review and approval processes for the next generation of cancer medicines.

A meta-ethnography of adult smokers' exploring the meanings of tobacco dependency medications adherence behaviours during smoking cessation.

AIMS: To synthesize the experiences and adherence of adult smokers' with tobacco dependence medications. DESIGN: Meta-ethnography. DATA SOURCES: Seven bibliographic databases were systematically searched until April 2016. REVIEW METHODS: A standardized appraisal tool evaluated the quality of the selected studies. RESULTS: Seven studies met the eligibility criteria. Three major themes described the experiences and adherence of adult smokers' with tobacco dependence medications; the psychosocial context, predilection for willpower and "natural" methods and a tendency to resist medications. CONCLUSION: The findings of this meta-ethnography are important to future clinical practice guideline development so health professionals contribute effectively to further reduction in smoking prevalence. Further research is needed to understand resistance to tobacco dependence medications and to inform the design of person-tailored interventions to improve tobacco dependence medication adherence that can be incorporated into smoking cessation interventions. IMPACT: Smoking causes more death and disability in the world than any other avoidable factor. Research on smoker perspectives on tobacco dependence medications is sparse. Tobacco dependency is a unique treatment context with specific adherence issues. Smokers are active decision-makers regarding tobacco dependence medications. Inconsistent adherence to tobacco dependency medication regimens was apparent. Implications for health professionals, healthcare policy and clinical practice guidelines regard the structure of consultations with smoking patients. It is critical for all health professionals to assess the person seeking to stop smoking and foresee the possible causes of non-adherence behaviour. Addressing non-adherence will to lead to more effective health communications and positively contribute to quality of smoking cessation care.

Risk Factors Associated with the Requirement for Pharmaceutical Intervention in the Hospital Setting: A Systematic Review of the Literature.

BACKGROUND: A number of methods exist for the risk assessment of hospital inpatients to determine the likelihood of patients experiencing drug-related problems (DRPs), including manual review of a patient's medication (medication reviews) and more complex electronic assessment using decision support alerts in electronic prescribing systems. A systematic review was conducted to determine the evidence base for potential risks associated with adult hospital inpatients that could not only lead to medication-related issues but might also be directly associated with pharmacist intervention. OBJECTIVES: The aims were to perform a systematic review of the literature in order to (1) identify all measurable risk factors associated with adult hospital inpatients that potentially lead to a pharmaceutical intervention; (2) critically evaluate the quality of the identified research; and (3) further subcategorise potential risk factors, so that pharmaceutical services may be targeted to patients "at risk" by identifying potential risk factors in a patient's electronic hospital record. METHODS: A systematic review, conducted in June 2013, searched ten medical literature databases for all papers identifying risks leading to pharmacist interventions or DRPs, adverse drug events (ADEs), adverse drug reactions, drug errors (where not included in the definition of an ADE), and medication-related problems. The search identified 7720 titles, from which 120 papers were sourced. A hand search of a further 11 journals was also performed. No date restrictions were imposed. All primary research and literature reviews were included. Summary articles were excluded with the exception of literature reviews. The inclusion of search outputs was validated by a third party pharmacy research graduate. RESULTS: From the 7720 titles, 38 publications met the inclusion criteria for the review. The ten most frequently reported risk factors associated with medication-related issues that may potentially lead to a hospital pharmaceutical intervention are as follows (ranked in descending order of frequency): prescription of certain drugs or classes of drugs, polypharmacy, elderly patients (defined as over 65 years), female gender, poor renal function, the presence of multiple comorbidities, length of patient stay, history of drug allergy or sensitivity, patient compliance issues, and poor liver function. The ten classes of drugs most frequently reported to be associated with medication-related issues leading to a hospital pharmaceutical intervention are as follows (ranked in descending order of frequency): intravenous antimicrobials, thrombolytics/anticoagulants, cardiovascular agents, central nervous system agents, corticosteroids, diuretics, chemotherapy, insulin/hypoglycaemics, opiates, and anti-epileptics. CONCLUSION: Review of the literature identified 38 papers, from which the ten most frequently reported risk factors linked with factors that are potentially associated with hospital pharmaceutical interventions (all definitions included) were identified. No papers were identified that demonstrated a direct causal relationship between a potential risk factor and hospital pharmaceutical interventions. All of the potential risk factors associated with problems with the use of medicines can be identified from patient records on admission to hospital. These risk factors may be used to identify patients at risk, with a view to targeting pharmaceutical intervention in order to minimise risks of problems with medicines and improve efficiency of clinical pharmacy services.

Influences on the decision to prescribe or administer anticholinergic drugs to treat death rattle: a focus group study.

BACKGROUND: The evidence supporting pharmacological treatment of death rattle is poor; yet, anticholinergic drugs feature in end-of-life care pathways and guidelines worldwide as a treatment option. AIM: This qualitative arm of a wider study aimed to explore important issues which health-care professionals associated with decision-making to prescribe or administer anticholinergics at the end of life. DESIGN: After purposive sampling, five focus groups were conducted. Discussions were audiotaped and transcribed verbatim. SETTING: Thirty medical and nursing personnel working in inpatient and community settings from two specialist palliative care units in the United Kingdom took part in the study. RESULTS: Thematic analysis of transcripts from audiotapes revealed perceived pressures to prescribe and/or administer anticholinergics from colleagues and carers, and drugs were often prescribed or administered in order to be seen to 'do something', although the benefit in terms of therapeutic response was considered minimal. Familiarity with drug regimens and dosing was often based on personal experience. The monitoring of side effects of anticholinergics at the end of life was recognised as problematic and had little influence on prescribing and administration. There was also an indication that patients and carers in the community were more likely to receive timely verbal preparation and explanation around death rattle than those cared for in an inpatient setting. CONCLUSION: The study raises questions about the routine inclusion of anticholinergic treatment in UK end of life care pathways for the treatment of death rattle.

Realizable protocols for optimal administration of drugs in mathematical models for anti-angiogenic treatment.

Two mathematical models for tumour anti-angiogenesis, one originally formulated by Hahnfeldt et al. (1999, Tumor development under angiogenic signaling: a dynamical theory of tumor growth, treatment response, and postvascular dormancy. Cancer Res., 59, 4770-4775) and a modification of this model by Ergun et al. (2003, Optimal scheduling of radiotherapy and angiogenic inhibitors. Bull. Math. Biol., 65, 407-424) are considered as optimal control problem with the aim of maximizing the tumour reduction achievable with an a priori given amount of angiogenic agents. For both models, depending on the initial conditions, optimal controls may contain a segment along which the dosage follows a so-called singular control, a time-varying feedback control. In this paper, for these cases, the efficiency of piecewise constant protocols with a small number of switchings is investigated. Through comparison with the theoretically optimal solutions, it will be shown that these protocols provide generally excellent suboptimal strategies that for many initial conditions come within a fraction of 1% of the theoretically optimal values. When the duration of the dosages are a priori restricted to a daily or semi-daily regimen, still very good approximations of the theoretically optimal solution can be achieved.

Prevalence of the use of cancer related self-tests by members of the public: a community survey.

BACKGROUND: Self-tests are those where an individual can obtain a result without recourse to a health professional, by getting a result immediately or by sending a sample to a laboratory that returns the result directly. Self-tests can be diagnostic, for disease monitoring, or both. There are currently tests for more than 20 different conditions available to the UK public, and self-testing is marketed as a way of alerting people to serious health problems so they can seek medical help. Almost nothing is known about the extent to which people self-test for cancer or why they do this. Self-tests for cancer could alter perceptions of risk and health behaviour, cause psychological morbidity and have a significant impact on the demand for healthcare. This study aims to gain an understanding of the frequency of self-testing for cancer and characteristics of users. METHODS: Cross-sectional survey. Adults registered in participating general practices in the West Midlands Region, will be asked to complete a questionnaire that will collect socio-demographic information and basic data regarding previous and potential future use of self-test kits. The only exclusions will be people who the GP feels it would be inappropriate to send a questionnaire, for example because they are unable to give informed consent. Freepost envelopes will be included and non-responders will receive one reminder. Standardised prevalence rates will be estimated. DISCUSSION: Cancer related self-tests, currently available from pharmacies or over the Internet, include faecal occult blood tests (related to bowel cancer), prostate specific antigen tests (related to prostate cancer), breast cancer kits (self examination guide) and haematuria tests (related to urinary tract cancers). The effect of an increase in self-testing for cancer is unknown but may be considerable: it may affect the delivery of population based screening programmes; empower patients or cause unnecessary anxiety; reduce costs on existing healthcare services or increase demand to investigate patients with positive test results. It is important that more is known about the characteristics of those who are using self-tests if we are to determine the potential impact on health services and the public.