Evaluation of Central Sensitisation in Bladder Pain Syndrome: A Systematic Review.

INTRODUCTION AND HYPOTHESIS: Bladder pain syndrome (BPS) is a debilitating condition characterised by exaggerated bladder sensations and altered bladder function. It is still unknown whether the condition is a peripheral sensory problem or due to abnormal central sensory processing as seen in central sensitisation. This systematic review, which followed a published and Prospective Register of Systematic Reviews-registered protocol (CRD42021229962), is aimed at establishing the scope of central sensitisation in patients with BPS to aid optimal management and treatment. METHODS: Four databases were searched, and appraisal of the identified studies was conducted by two independent reviewers based on eligibility criteria: patients with BPS being investigated for central sensitisation with or without comparison of controls, English-language articles, full text and publication in a peer-reviewed journal. The Methodological Index for non-Randomised Studies was used to determine study quality. We identified 763 papers in total, with 15 studies included in the final analysis. All studies were observational and had a low risk of bias. Measures included in the evaluation of CS were questionnaires, urodynamics, and quantitative sensory testing methods. RESULTS: There was evidence of central sensitisation in patients with BPS in all papers evaluated (15 out of 15). In addition, more significant central sensitisation correlated with severe disease presentation (3 out of 3 papers) and concomitant chronic pain conditions (5 out of 5 papers). CONCLUSIONS: Central sensitisation plays an integral role in BPS patient pathology. Many secondary measures are used to evaluate this condition. Stratification of patients based on their pathology (peripheral, central or a combination of the two) will aid in implementing an individualised management strategy.

Clinical Trial Endpoints and Their Clinical Meaningfulness in Early Stages of Alzheimer's Disease.

As the focus of Alzheimer's disease (AD) therapeutic development shifts to the early stages of the disease, the clinical endpoints used in drug trials, and how these might translate into clinical practice, are of increasing importance. The clinical meaningfulness of trial outcome measures is often unclear, with a lack of conclusive evidence as to how these measures correlate to changes in disease progression and treatment response. Clarifying this would benefit all, including patients, care partners, primary care providers, regulators, and payers, and would enhance our understanding of the relationship between clinical trial endpoints and assessments used in everyday practice. At present, there is a wide range of assessment tools used in clinical trials for AD and substantial variability in measures selected as endpoints across these trials. The aim of this review is to summarize the most commonly used assessment tools for early stages of AD, describe their use in clinical trials and clinical practice, and discuss what might constitute clinically meaningful change in these measures in relation to disease progression and treatment response.

Diagnosis of Early Alzheimer's Disease: Clinical Practice in 2021.

Alzheimer's disease is a progressive, irreversible neurodegenerative disease impacting cognition, function, and behavior. Alzheimer's disease progresses along a continuum from preclinical disease, to mild cognitive and/or behavioral impairment and then Alzheimer's disease dementia. Recently, clinicians have been encouraged to diagnose Alzheimer's earlier, before patients have progressed to Alzheimer's disease dementia. The early and accurate detection of Alzheimer's disease-associated symptoms and underlying disease pathology by clinicians is fundamental for the screening, diagnosis, and subsequent management of Alzheimer's disease patients. It also enables patients and their caregivers to plan for the future and make appropriate lifestyle changes that could help maintain their quality of life for longer. Unfortunately, detecting early-stage Alzheimer's disease in clinical practice can be challenging and is hindered by several barriers including constraints on clinicians' time, difficulty accurately diagnosing Alzheimer's pathology, and that patients and healthcare providers often dismiss symptoms as part of the normal aging process. As the prevalence of this disease continues to grow, the current model for Alzheimer's disease diagnosis and patient management will need to evolve to integrate care across clinical disciplines and the disease continuum, beginning with primary care. This review summarizes the importance of establishing an early diagnosis of Alzheimer's disease, related practical 'how-to' guidance and considerations, and tools that can be used by healthcare providers throughout the diagnostic journey.

The challenge of using routinely collected data to compare hospital admission rates by ethnic group: a demonstration project in Scotland.

BACKGROUND: Recording patients' ethnic group supports efforts to achieve equity in health care provision. Before the Equality Act (2010), recording ethnic group at hospital admission was poor in Scotland but has improved subsequently. We describe the first analysis of the utility of such data nationally for monitoring ethnic variation. METHODS: We analysed all in-patient or day case hospital admissions in 2013. We imputed missing data using the most recent ethnic group recorded for a patient from 2009 to 2015. For episodes lacking an ethnic code, we attributed known ethnic codes proportionately. Using the 2011 Census population, we calculated rates and rate ratios for all-cause admissions and ischaemic heart diseases (IHDs) directly standardized for age. RESULTS: Imputation reduced missing ethnic group codes from 24 to 15% and proportionate redistribution to zero. While some rates for both all-cause and IHD admissions appeared plausible, unexpectedly low or high rates were observed for several ethnic groups particularly amongst White groups and newly coded groups. CONCLUSIONS: Completeness of ethnicity recoding on hospital admission records has improved markedly since 2010. However the validity of admission rates based on these data is variable across ethnic groups and further improvements are required to support monitoring of inequality.

Addressing the quality of life needs of older patients with cancer: a SIOG consensus paper and practical guide.

Around 60% of people living with cancer are aged 65 years or older. Older cancer patients face a unique set of age-associated changes, comorbidities and circumstances that impact on their quality of life (QoL) in ways that are different from those affecting younger patients. A Task Force of the International Society of Geriatric Oncology recommends and encourages all healthcare professionals involved in cancer care to place greater focus on the QoL of older people living with cancer. This paper summarizes current thinking on the key issues of importance to addressing QoL needs of older cancer patients and makes a series of recommendations, together with practical guidance.

Resistance Analyses of Japanese Hepatitis C-Infected Patients Receiving Sofosbuvir or Ledipasvir/Sofosbuvir Containing Regimens in Phase 3 Studies.

High rates of sustained virologic response (SVR) has been achieved in Japanese patients with chronic hepatitis C virus (HCV) genotype (GT)1 and GT2 infection treated with ledipasvir/sofosbuvir (LDV/SOF) ±ribavirin (RBV) and SOF+RBV, respectively. We evaluated the effect of baseline HCV NS5A and NS5B resistance-associated variants (RAVs) on treatment outcome and characterized variants at virologic failure. Baseline deep sequencing for NS5A and NS5B genes was performed for all GT1 patients. Deep sequencing of NS5A (GT1 only) and NS5B (GT1 and GT2) was performed for patients who failed treatment or discontinued early with detectable HCV RNA (i.e., >25 IU/mL). In patients with HCV GT1 infection, 22.3% (GT1a: 2/11; GT1b: 74/330) had ≥1 baseline NS5A RAV. The most frequent NS5A RAVs in GT1b were Y93H (17.9%, 59/330) and L31M (2.4%, 8/330). Despite the presence of NS5A RAVs at baseline, 100% and 97% of patients achieved SVR12, compared with 100% and 99% for those with no NS5A RAVs with LDV/SOF and LDV/SOF+RBV, respectively. All patients with NS5B RAVs at baseline achieved SVR12. Of the 153 patients with GT2 infection (GT2a 60.1%, GT2b 39.9%), 3.3% (5/153) experienced viral relapse. No S282T or other NS5B RAVs were detected at baseline or relapse; no change in susceptibility to SOF or RBV was observed at relapse. In conclusion, LDV/SOF and SOF+RBV demonstrate a high barrier to resistance in Japanese patients with HCV GT1 and GT2 infection. The presence of baseline NS5A RAVs did not impact treatment outcome in GT1 Japanese patients treated with LDV/SOF for 12 weeks.

A phase 3b study of sofosbuvir plus ribavirin in treatment-naive and treatment-experienced Korean patients chronically infected with genotype 2 hepatitis C virus.

In Korea, patients with chronic hepatitis C virus (HCV) infection are typically treated with pegylated interferon-alpha plus ribavirin, but interferons are contraindicated in many patients and are often poorly tolerated, particularly by the elderly and those with advanced liver disease. No interferon-free treatment regimens are approved in Korea. Sofosbuvir is an oral nucleotide analog inhibitor of the HCV nonstructural 5B RNA polymerase. It is approved in the USA, European Union and Japan for treating a number of HCV genotypes, including genotype 2. Genotype 2 has a seroprevalence of 38-46% in Korea. This single-arm, phase 3b study (NCT02021643) examined the efficacy and safety of sofosbuvir plus ribavirin (12-week duration) in chronic genotype 2 HCV-infected treatment-naive and treatment-experienced Korean patients with and without cirrhosis. The proportion of patients with sustained virologic response 12 weeks after treatment discontinuation (SVR12) was 97% (125/129), with 96% (101/105) of treatment-naive and 100% (24/24) of treatment-experienced patients achieving SVR12. Two patients experienced virologic failure (n = 1, on-treatment failure; n = 1, relapse). No patient discontinued study treatment due to an adverse event (AE). The most common treatment-emergent AEs were headache (18%, 23/129) and pruritus (15%, 19/129). Few patients had grade 3 AEs (5%, 6/129) or grade 3 laboratory abnormalities (12%, 15/129). No grade 4 AE was reported. These data suggest that 12 weeks of treatment with the all-oral, interferon-free regimen of sofosbuvir plus ribavirin is effective and well tolerated in Korean patients with chronic genotype 2 HCV infection.

Regulation and registration as drivers of continuous professional competence for Irish pre-hospital practitioners: a discussion paper.

BACKGROUND: The regulatory body responsible for the registration of Irish pre-hospital practitioners, the Pre-Hospital Emergency Care Council (PHECC), identified the need to implement a continuing professional competence (CPC) framework. The first cycle of CPC (focused on emergency medical technicians) commenced in November 2013 creating for the first time a formal relationship between continuing competence and registration to practice. AIMS: To review current literature and to describe benefits and challenges relevant to CPC, regulation, registration and their respective contributions to professionalism of pre-hospital practitioners: advanced paramedics, paramedics and emergency medical technicians. METHODS: Online search of cumulative index to nursing and allied health literature (CINAHL Plus with Full Text), Allied and Complementary Medicine (AMED) and 'Pubmed' databases using: 'Continuous Professional Development'; 'Continuous Professional Development'; 'emergency medical technician'; 'paramedic'; 'registration'; 'regulation'; and "profession' for relevant articles published since 2004. Additional policy documents, discussion papers, and guidance documents were identified from bibliographies of papers found. RESULTS: Reports, governmental policies for other healthcare professions, and professional developments internationally for allied professions (e.g., nursing, physiotherapy and medicine) link maintenance of competence with requirements for registration to practice. CONCLUSION: We suggest that evolving professionalisation of Irish paramedics should be affirmed through behaviours and competencies that incorporate adherence to professional codes of conduct, reflective practice, and commitment to continuing professional development. While the need for ambulance practitioner CPD was identified in Ireland almost a decade ago, PHECC now has the opportunity to introduce a model of CPD for paramedics linking competence and professionalism to annual registration.

Sofosbuvir plus ribavirin for the treatment of patients with chronic genotype 1 or 6 hepatitis C virus infection in Hong Kong.

BACKGROUND: In Hong Kong, most patients with hepatitis C virus (HCV) have either genotype 6a or 1b infection. AIM: To evaluate the efficacy and safety of sofosbuvir with ribavirin in treatment-naïve patients in Hong Kong with HCV genotype 1 or 6. METHODS: In an open-label study, patients were randomised to sofosbuvir 400 mg once daily plus ribavirin 1000-1200 divided twice daily for 12 (n = 10), 16 (n = 11) or 24 (n = 10) weeks. The primary endpoint was the percentage of patients with HCV RNA < LLOQ (lower limit of quantification, 25 IU/mL) 12 weeks after cessation of therapy (SVR12). RESULTS: All 31 patients (20 HCV genotype 1 and 11 genotype 6) had HCV RNA < LLOQ by Week 4 of treatment and at their last on-treatment visit. SVR12 rates were high in all treatment groups: 100% (10/10) for 12 weeks, 100% (11/11) for 16 weeks and 90% (9/10) for 24 weeks of therapy. The only patient who did not reach SVR12 had genotype 1 HCV and relapsed at post-treatment Week 4. Sofosbuvir with ribavirin was generally well tolerated. The most common adverse events were malaise (13%) and upper respiratory tract infection (13%), followed by anaemia (10%). No patients experienced serious adverse events. One patient discontinued treatment at Week 16 because of an adverse event. The event, upper respiratory tract infection, was not considered treatment related by the investigator. This subject achieved SVR12. CONCLUSIONS: The all-oral regimen sofosbuvir plus ribavirin is effective in treatment-naïve patients in Hong Kong with genotype 1 or 6 HCV. TRIAL REGISTRATION NUMBER: NCT02021643.

Two Case Reports of Resensitization to Previous Chemotherapy with the Novel Hypoxia-Activated Hypomethylating Anticancer Agent RRx-001 in Metastatic Colorectal Cancer Patients.

The development of chemoresistance is a persistent problem during the treatment of cancer. Although reversion or modification of acquired chemoresistance has been previously observed, no systematic exploration has been undertaken. Here, we report a case study of 2 male patients, 62 and 66 years old, both with histologically proven, radiologically progressing, extensively pretreated, metastatic and refractory (≥2 conventional regimens and drug therapy) colorectal adenocarcinoma that was previously treated with FOLFIRI. The patients were resensitized to FOLFIRI after exposure to RRx-001 in the context of a phase-1 study. RRx-001 is a novel, hypomethylating and free-radical-inducing anticancer agent that activates nitrite reduction to NO under hypoxia and has an impact on epigenetic pathways. The repression of DNA methyltransferase 1 by RRx-001 may lead to demethylation and reexpression of silenced tumor suppressor genes, leading to resensitization. These examples provide insight into a nascent strategy to improve the prognosis in heavily pretreated cancer patients and suggest routes for further exploration.

Salivary gland progenitor cell biology provides a rationale for therapeutic salivary gland regeneration.

An irreversible loss of salivary gland function often occurs in humans after removal of salivary tumors, after therapeutic radiation of head and neck tumors, as a result of Sjögren's syndrome and in genetic syndromes affecting gland development. The permanent loss of gland function impairs the oral health of these patients and broadly affects their quality of life. The regeneration of functional salivary gland tissue is thus an important therapeutic goal for the field of regenerative medicine and will likely involve stem/progenitor cell biology and/or tissue engineering approaches. Recent reports demonstrate how both innervation of the salivary gland epithelium and certain growth factors influence progenitor cell growth during mouse salivary gland development. These advances in our understanding suggest that developmental mechanisms of mouse salivary gland development may provide a paradigm for postnatal regeneration of both mice and human salivary glands. Herein, we will discuss the developmental mechanisms that influence progenitor cell biology and the implications for salivary gland regeneration.

Parasympathetic innervation maintains epithelial progenitor cells during salivary organogenesis.

The maintenance of a progenitor cell population as a reservoir of undifferentiated cells is required for organ development and regeneration. However, the mechanisms by which epithelial progenitor cells are maintained during organogenesis are poorly understood. We report that removal of the parasympathetic ganglion in mouse explant organ culture decreased the number and morphogenesis of keratin 5-positive epithelial progenitor cells. These effects were rescued with an acetylcholine analog. We demonstrate that acetylcholine signaling, via the muscarinic M1 receptor and epidermal growth factor receptor, increased epithelial morphogenesis and proliferation of the keratin 5-positive progenitor cells. Parasympathetic innervation maintained the epithelial progenitor cell population in an undifferentiated state, which was required for organogenesis. This mechanism for epithelial progenitor cell maintenance may be targeted for organ repair or regeneration.

Evolving attitudes to Alzheimer's disease among the general public and caregivers in Europe: findings from the IMPACT survey.

Understanding and appreciating the awareness of, and attitudes towards, Alzheimer's disease (AD) in the general public is of paramount importance to those charged with the development of health care policy. Furthermore, it is essential that this policy be formulated with consideration given to both the attitudes of the general population and to those within society more directly affected by AD; namely, the caregivers of patients with the disease. In the IMPACT survey, approximately 1000 members of the general public and 250 caregivers in 5 European countries (France, Germany, Italy, Spain, and the United Kingdom) completed a 30-minute, Web-based questionnaire. In this article, we compare and contrast the attitudes and opinions of these populations in an attempt to define specific themes. Indeed, caregivers were more concerned about consequences of growing old and were more fearful of AD than general public respondents, although a high proportion in both groups acknowledged the significant impact of the disease. Similarly, although most respondents in the 2 groups recognised that early signs and symptoms of AD are difficult to detect, caregivers were more skeptical of the abilities of both primary physicians and specialists to detect these early signs and symptoms. In terms of treatment, caregivers were less convinced of the effectiveness of treatment beyond the early stages of AD and more likely to agree that current treatments are associated with side effects. Respondents in both groups had a negative view of their government's investment in AD, but caregivers, particularly those in France, Spain and the United Kingdom, were more likely to feel that their government acts as a barrier to treatment. Some survey respondents from the 2 groups also had a negative view of their governments' attempts to raise awareness of AD and make its treatment a high priority. Overall, comparison of responses from these 2 groups suggests that caregivers' personal experiences of AD profoundly affect their attitudes and perceptions surrounding the disease.

Assessing attitudes and behaviours surrounding Alzheimer's disease in Europe: key findings of the Important Perspectives on Alzheimer's Care and Treatment (IMPACT) survey.

The Important Perspectives on Alzheimer's Care and Treatment (IMPACT) survey is an assessment in Europe of the attitudes of caregivers, physicians, the general public and payors towards Alzheimer's disease and dementia. This was an Internet-based questionnaire study, which sought to determine the opinion and perception of responders on issues relating to ageing and dementia. There were additional questions for caregivers on the impact of caregiving on their life. Responses were analysed from 949 members of the general public, 500 physicians (generalists and specialists), 250 caregivers and 50 payors from 5 countries--France, Germany, Italy, Spain and the United Kingdom. The survey highlighted the difficulty of diagnosing dementia, especially in the initial stages of the disease. The average time from first noticing symptoms to diagnosis varied from 36 to 63 weeks. Caregivers and the general public felt they had insufficient information about the benefits of treatment and care, although more than half the general public, caregiver and physician responders agreed that early treatment could delay the progression of the disease. The majority of respondents recognised the devastating effects of AD on caregivers and families, and a majority of caregivers, the general public and physicians agreed that their governments fail to view AD as a health care priority. This study occurs roughly 5 years after a similar survey, and provides a timely update. Despite some important differences between the methodologies used in these surveys, diagnosis of dementia is still a key issue, especially amongst generalists, as is the provision of information and support to caregivers. Despite the prevalence of AD in the ageing population of Europe, the perception within each of the 5 countries surveyed is that AD is not viewed as a health care priority.

Clinical practice patterns of generalists and specialists in Alzheimer's disease: what are the differences, and what difference do they make?

Optimising the roles played by both generalists and specialists in the diagnosis and treatment of Alzheimer's disease (AD) could have a major impact on the quality and cost of patient care. Therefore, one aim of the IMPACT survey was to characterise the similarities and differences between these 2 categories of physicians, in 5 different European countries, across a number of domains relevant to the medical care of people at risk for AD and those with the disease. Physician respondents comprised 250 generalists and 250 specialists from 5 European countries--France, Germany, Italy, Spain, and the United Kingdom. A substantial majority of generalists were either general practitioners or family physicians; the majority of specialists were neurologists. In April and May 2009, physician respondents completed a 30-minute, Web-based questionnaire during which they were presented with a number of multiple-choice-type questions concerning their knowledge of AD, approach to diagnosis and treatment of AD and experience of providing care for people with dementia. Generalists reported that 45% of their AD patients had mild symptoms at the initial visit compared with 60% for specialists (P < 0.001). Specialists claimed that they diagnose patients with AD themselves in 65% of cases versus 33% for generalists (P < 0.001). The main prescription treatment options employed were AD-specific medication (90%) and medication for mood or behaviour (78%). A similar percentage of generalists and specialists (77% and 75%) initiate drug treatment within 1 month of diagnosis. Overall, there were more similarities than differences between specialists and generalists regarding a broad spectrum of issues relating to AD; differences between countries appear to be greater than differences between physician groups.

Assessing physician attitudes and perceptions of Alzheimer's disease across Europe.

Given the important role that physicians play in clinical care, disease advocacy, national health policy making and clinical research, the IMPACT survey sought to assess the attitudes and perceptions of physicians in 3 general categories: diagnosis and treatment of Alzheimer's disease (AD); caregivers and families of patients with AD; and the role of government in dealing with this disease and its consequences. Survey respondents comprised a total of 250 generalists and 250 specialists (neurologists, geriatricians, neuro-psychiatrists, psychiatrists and psychogeriatricians) from France, Germany, Italy, Spain and the United Kingdom. Physicians were aged 25 to 69 years, in practice for between 5 and 30 years and currently spending more than 50% of their time in direct patient care. Results showed that a sizable majority of physicians throughout Europe, specialists and generalists alike, agree that: 1) AD is underdiagnosed and undertreated; 2) patients and families are not prepared to recognise the early symptoms of the disease; 3) early treatment can help to slow the progression of the disease; and 4) more effective treatments are needed. Attitudes were statistically significantly different between some groups of physicians regarding disclosure of the diagnosis of AD, the benefits of lifestyle modification, and the value of AD-specific medication in patients whose symptoms are worsening. Differences in attitudes and perceptions of AD between specialists and generalists were limited; differences between countries were more common and of greater magnitude, particularly with respect to barriers to the use of prescription medications.

Screening for cognitive impairment, Alzheimer's disease and other dementias: opinions of European caregivers, payors, physicians and the general public.

The IMPACT survey queried physicians, caregivers, payors and members of the general public from 5 European countries (France, Germany, Italy, Spain and the United Kingdom) regarding their opinions towards screening for Alzheimer's disease (AD) as part of a 30-minute Web-based questionnaire conducted between April and May 2009. A larger proportion of caregivers (84%) and members of the general public (80%) than of physicians (56%) or payors (40%) viewed routine screening for AD as extremely or very important (P < 0.001 for caregivers or general public vs physicians or payors). When asked if everyone should be routinely screened for AD at age 65, a smaller proportion of physicians (42%) and payors (44%) than members of the general public (81%) or caregivers (80%) agreed (P < 0.001 for caregivers or general public vs physicians or payors). These opinions were generally consistent across the 5 countries for each respondent group. A notable exception was physician respondents from Italy, where most generalists and specialists actually favoured screening. Overall, generalists had a more positive attitude towards screening than specialists. The most frequently cited reason given by those who did not favour routine screening at age 65 was screening inaccuracy. This article discusses these results in relation to what screening is, when to screen and the barriers to screening. Despite the majority of IMPACT respondents being in favour of screening for AD, the evidence to support the introduction of population screening for cognitive impairment is not available; however, the importance of optimal identification of AD and other dementias in primary care should be a priority for community health professionals and payors. In order to do this effectively, further work is required to identify good assessment guidelines for use during opportunistic screening for cognitive impairment in primary care.

Implications of the Impact Survey for payors across Europe.

People involved with development of health care policy must be appreciative of the social and economic challenges that will likely develop as a result of the rise in Alzheimer's disease (AD) as the 21st century progresses. Their attitudes, perceptions and understanding regarding AD were captured in the IMPACT survey, a 30-minute Web-based questionnaire. Fifty health policy managers and decision-makers (payors) were recruited, 10 each from 5 European countries--France, Germany, Italy, Spain and the United Kingdom. Most payors felt that AD was underdiagnosed and undertreated in their country (80% and 68%, respectively). Half of all payors felt that their government did not invest enough in treating AD, and 30% felt their government hindered access to drug therapy. Payors believed that treatment should be initiated as early as possible after a diagnosis of AD (82%), and that early treatment can delay progression of the disease (82%). Even more than caregivers, payors agreed that AD can have devastating effects on the family of the sufferer (90% vs 75%; P<0.05). Payors more often cited cancer, stroke and heart disease than AD as affecting their budgets, but cited AD more often than depression, diabetes, HIV/AIDs and arthritis. Cost savings were seen as the most important factor regarding policy decisions. These attitudes of the surveyed payors towards AD and the patients and caregivers affected by it suggest that they may advocate for national and international policies that will facilitate earlier diagnosis and improved access to treatment.

Physicians and caregivers: ready and waiting for increased participation in clinical research.

Progressive development of pharmacotherapy for Alzheimer's disease (AD) as well as non-pharmacological treatments is critically dependent on the timely recruitment of appropriate subjects for clinical trials. Accordingly, the IMPACT survey sought to determine the level of awareness of clinical trials and the willingness to foster patient involvement/participation in research studies. IMPACT survey participants were recruited via the Internet in equal numbers from 5 European countries-France, Germany, Italy, Spain and the United Kingdom. During April and May 2009, 250 caregivers and 500 physicians who agreed to participate in this market-based survey completed a 30-minute Web-based questionnaire that included items concerning awareness of clinical research and willingness to facilitate participation of AD patients in such research. Awareness of local clinical trials amongst both caregivers (24% overall; range by country, 14% to 34%) and physicians (19% overall; range by country, 13% to 30%) was found to be low in all countries surveyed. In contrast, the willingness of physicians to refer patients to, and caregivers to support their participation in, clinical trials was extremely high (98% and 81%, respectively). These results strongly indicate that physicians and caregivers are ready and waiting to become more involved in clinical research. Initiatives to increase awareness of clinical trials amongst caregivers and physicians and to conduct clinical trials within the geographical area of as many potential participants as possible should result in much more effective patient recruitment to AD clinical trials.