A literature review to understand the burden of disease in people living with tumour-induced osteomalacia.

This study reviews publications to describe the signs, symptoms and impact of tumour-induced osteomalacia (TIO) on patients' burden of disease. TIO is associated with a spectrum of signs and symptoms imposing a significant clinical burden, but the psychosocial impact of this rare disease has been poorly researched so far. INTRODUCTION: To describe the signs, symptoms and impacts of tumour-induced osteomalacia (TIO) and summarise the state of research on the burden of disease of this ultra-rare condition. METHODS: A targeted literature review was conducted in PubMed using pre-defined search terms. Relevant articles published between 1980 and 2021 were screened for inclusion. Seventy records were selected for analysis. Data were extracted and grouped into categories and sub-categories to identify recurrent signs, symptoms and impacts of TIO and describe the burden on patients. Chord diagrams were created to analyse the relationships between different TIO outcomes and characterise the presentation of TIO. RESULTS: Although the number of articles on TIO published have been increasing over the past 20 years, most studies were case reports and case series (n = 65/70) and only few were studies with higher quality of evidence (n = 5/70). Most articles were based on data reported by clinicians (n = 67/70). Patients with TIO experienced a combination of outcomes including chronic pain, weakness, skeletal-related manifestations and limitations in mobility. Only a few studies (n = 2/70) analysed the burden of TIO on the emotional wellbeing and on the work life of the patient. CONCLUSION: Patients with TIO present with a spectrum of signs and symptoms that impose a significant burden. The impact on the psychosocial wellbeing of patients should be further investigated, as this has been poorly researched so far. Studies with high quality of evidence should be designed to further the understanding of the burden of disease of TIO from the patient's perspective.

Musculoskeletal Features in Adults With X-linked Hypophosphatemia: An Analysis of Clinical Trial and Survey Data.

CONTEXT: Patients with X-linked hypophosphatemia (XLH) experience multiple musculoskeletal manifestations throughout adulthood. OBJECTIVE: To describe the burden of musculoskeletal features and associated surgeries across the lifespan of adults with XLH. METHODS: Three groups of adults were analyzed: subjects of a clinical trial, participants in an online survey, and a subgroup of the online survey participants considered comparable to the clinical trial subjects (according to Brief Pain Inventory worst pain scores of ≥ 4). In each group, the adults were categorized by age: 18-29, 30-39, 40-49, 50-59, and ≥ 60 years. Rates of 5 prespecified musculoskeletal features and associated surgeries were investigated across these age bands for the 3 groups. RESULTS: Data from 336 adults were analyzed. In all 3 groups, 43% to 47% had a history of fracture, with the proportions increasing with age. The overall prevalence of osteoarthritis was > 50% in all 3 groups, with a rate of 23% to 37% in the 18- to 29-year-old group, and increasing with age. Similar patterns were observed for osteophytes and enthesopathy. Hip and knee arthroplasty was reported even in adults in their 30s. Spinal stenosis was present at a low prevalence, increasing with age. The proportion of adults with ≥ 2 musculoskeletal features was 59.1%, 55.0%, and 61.3% in the clinical trial group, survey group, and survey pain subgroup, respectively. CONCLUSION: This analysis confirmed high rates of multiple musculoskeletal features beginning as early as age 20 years among adults with XLH and gradually accumulating with age.

Burden of cytomegalovirus DNAemia among pediatric renal transplant patients on antiviral prophylaxis: A hospital-based analysis.

INTRODUCTION: We examined the burden of CMV DNAemia and time to such events among renal transplant patients receiving CMV prophylaxis. We targeted the first year after transplantation, with the primary focus being on the first 3 months. METHODS: We conducted a retrospective review of renal transplant patients (<18 years) who were transplanted and followed at our center between January 2007, and December 2017. Clinical and laboratory data were obtained from the medical records and laboratory databases. RESULTS: Among 141 patients, the median age at transplant was 12.7 years (range 0.87-17.83 years). CMV DNAemia was detected in 33 of 77 patients eligible for prophylaxis (42.9%; 95% CI 31.6-54.6) during the first post-transplant year. Proportionately more D+R- patients were present among patients with DNAemia compared with those without DNAemia (15/38, 39.5% vs 16/103, 15.5%, P = .005). Median time to first positivity was 134 days (range 0-304 days). Eight patients had a positive PCR during the first 3 months (5.7% of all patients). Among those eligible for prophylaxis, 6.5% had DNAemia during the first 3 months while on prophylaxis. Among patients whose first positive PCR was after 3 months post-transplant, the median time to positivity was 52 days (range 13-214 days) after the end of prophylaxis. CONCLUSIONS: Breakthrough CMV DNAemia was documented among children receiving antiviral prophylaxis. While routine monitoring while on prophylaxis might not be warranted for the majority of patients, studies are needed to determine the optimal indications for CMV PCR testing while on prophylaxis.

Exploring the Burden of X-Linked Hypophosphataemia: An Opportunistic Qualitative Study of Patient Statements Generated During a Technology Appraisal.

INTRODUCTION: Capturing the patient experience of living with a rare disease such as X-linked hypophosphataemia (XLH) is critical for a holistic understanding of the burden of a disease. The complexity of the disease coupled with the limited population makes elicitation of the patient burden methodologically challenging. This study used qualitative information direct from patient and caregiver statements to assess the burden of XLH. METHODS: A thematic analysis was conducted on statements received during a National Institute for Health and Care Excellence (NICE) online public open consultation from 15 June to 6 July 2018. Researchers and clinical experts generated themes and codes based on expected aspects of XLH burden. Statements were independently coded by two reviewers, adding additional codes as required, and analysed by frequency and co-reporting across age groups. RESULTS: The majority of responses were submitted from UK-based patients with some from the USA and Australia, and the statements related to children, adolescents and adults. The findings suggest that the greatest burden experienced by children is associated with conventional therapy, co-reported with dosing regimen, adherence, distress and pain. During adolescence, the burden becomes increasingly complex and multi-factorial, with an increasing psychological burden. In adults, conventional therapy co-reported with bone deformity and orthopaedic surgery, as well as pain, mobility, fatigue and dental problems, featured highly. DISCUSSION: Whilst our study was opportunistic in nature, it has highlighted the clear and distinctive evolution of the burden of XLH, transitioning from being therapy-oriented in childhood to multi-factorial in adolescence, and finally to adulthood with its high impact on need for other interventions, function and mobility. This qualitative thematic analysis enhances the understanding of the symptom and treatment burden of XLH.

Using Community Feedback to Improve Community Interventions: Results From the Deep South Network for Cancer Control Project.

The Deep South Network for Cancer Control (DSNCC), initiated in 2000, is a dual-state, community-based participatory research infrastructure composed of academic and community partners committed to reducing cancer disparities among underserved African Americans in 12 designated counties of the Alabama Black Belt and the Mississippi Delta, 2 historically underserved areas of the country. Local residents trained as Community Health Advisors as Research Partners implemented a 3-tier community action plan (CAP) focused on promoting cancer screening, physical activity, and nutrition. Breast, cervical and colorectal cancer screening, healthy eating habits, and physical activity levels increased among many, but not all, African American women in the 12-county DSNCC coverage area. Seeking to improve our reach to include participants who reported they had never heard of the DSNCC or participated in the CAP, we conducted in-depth conversations with community residents about reasons for selective nonparticipation and ways to improve participation in the DSNCC community health interventions. Three patterns and their associated themes described ways to improve the penetration of CAP strategies and tailor them to effectively reach underserved African Americans in the intervention counties. We conclude with lessons learned for future interventions.

Bridging Functional and Structural Cardiotoxicity Assays Using Human Embryonic Stem Cell-Derived Cardiomyocytes for a More Comprehensive Risk Assessment.

More relevant and reliable preclinical cardiotoxicity tests are required to improve drug safety and reduce the cost of drug development. Current in vitro testing strategies predominantly take the form of functional assays to predict the potential for drug-induced ECG abnormalities in vivo. Cardiotoxicity can also be structural in nature, so a full and efficient assessment of cardiac liabilities for new chemical entities should account for both these phenomena. As well as providing a more appropriate nonclinical model for in vitro cardiotoxicity testing, human stem cell-derived cardiomyocytes offer an integrated system to study drug impact on cardiomyocyte structure as well as function. Employing human embryonic stem cell-derived cardiacmyocytes (hESC-CMs) on 3 assay platforms with complementary insights into cardiac biology (multielectrode array assay, electrophysiology; impedance assay, cell movement/beating; and high content analysis assay, subcellular structure) we profiled a panel of 13 drugs with well characterized cardiac liabilities (Amiodarone, Aspirin, Astemizole, Axitinib, AZT, Bepridil, Doxorubicin, E-4031, Mexiletine, Rosiglitazone, Sunitinib, Sibutramine, and Verapamil). Our data show good correlations with previous studies and reported clinical observations. Using multiparameter phenotypic profiling techniques we demonstrate the dynamic relationship that exists between functional and structural toxicity, and the benefits of this more holistic approach to risk assessment. We conclude by showing for the first time how the advent of transparent MEA plate technology enables functional and structural cardiotoxic responses to be recorded from the same cell population. This approach more directly links changes in morphology of the hESC-CMs with recorded electrophysiology signatures, offering even greater insight into the wide range of potential drug impacts on cardiac physiology, with a throughput that is more amenable to early drug discovery.

Long-term disease history, clinical symptoms, health status, and healthcare utilization in patients suffering from Lambert Eaton myasthenic syndrome: Results of a patient interview survey in Germany.

INTRODUCTION: The burden of disease in Lambert-Eaton myasthenic syndrome (LEMS) patients is unclear. This study focused on the patient's perspective to obtain patient-reported information on clinical symptoms, burden of illness, impact of LEMS on activities of daily living (ADL), and management of LEMS. METHODS: Semi-structured, face-to-face interviews with LEMS patients from two specialized centres in Germany between September and December 2010. RESULTS: Twelve patients participated; mean age 66.7 ± 9.8 years. First symptoms occurred at age 52.5 ± 14.0 years. Mean time between first symptoms and diagnosis was 4.4 ± 6.2 years. Patients reported neuromuscular, cranial, and autonomic symptoms plus general fatigue. Two-thirds of patients reported 10 or more symptoms. The most frequent symptoms were leg weakness (91.7%) and general fatigue (83.3%). Restrictions in ADL were reported always or often in 75% of patients. Over half of the patients (n = 7) reported poor or very poor health status. Mean EQ-5D utility scores were 0.34 ± 0.35, with little day-to-day variation. Patients visited a number of different clinicians; most had been hospitalized at some point in the course of their disease. The most frequent drug treatments were 3,4-diaminopyridine (3,4-DAP) (83.3%) and pyridostigmine (41.5%). The study has several limitations, including small sample size and the potential influence of recall bias. CONCLUSION: LEMS patients report long individual disease histories. Most patients suffer multiple symptoms which are frequently severe and troublesome, and almost all are restricted in ADL with poor health status. There is high utilization of healthcare resources from diagnosis to ongoing treatment. Physicians should be aware of this rare disease to ensure that patients receive an early diagnosis and prompt and appropriate treatment.

Inhaled corticosteroids for asthma: impact of practice level device switching on asthma control.

BACKGROUND: As more inhaled corticosteroid (ICS) devices become available, there may be pressure for health-care providers to switch patients with asthma to cheaper inhaler devices. Our objective was to evaluate impact on asthma control of inhaler device switching without an accompanying consultation in general practice. METHODS: This 2-year retrospective matched cohort study used the UK General Practice Research Database to identify practices where ICS devices were changed without a consultation for > or =5 patients within 3 months. Patients 6-65 years of age from these practices whose ICS device was switched were individually matched with patients using the same ICS device who were not switched. Asthma control over 12 months after the switch was assessed using a composite measure including short-acting beta-agonist and oral corticosteroid use, hospitalizations, and subsequent changes to therapy. RESULTS: A total of 824 patients from 55 practices had a device switch and could be matched. Over half (53%) of device switches were from dry powder to metered-dose inhalers. Fewer patients in switched than matched cohort experienced successful treatment based on the composite measure (20% vs. 34%) and more experienced unsuccessful treatment (51% vs. 38%). After adjusting for possible baseline confounding factors, the odds ratio for treatment success in the switched cohort compared with controls was 0.29 (95% confidence interval [CI], 0.19 to 0.44; p < 0.001) and for unsuccessful treatment was 1.92 (95% CI, 1.47 to 2.56; p < 0.001). CONCLUSION: Switching ICS devices without a consultation was associated with worsened asthma control and is therefore inadvisable.

An investigation of nurse educator's perceptions and experiences of undertaking clinical practice.

Educational policy (DOH, 1999. Making a difference: strengthening the nursing, midwifery and health visiting contribution to health and healthcare. Department of Health, London; UKCC, 1999. Fitness for Practice. United Kingdom Central Council for Nursing, Midwifery and Health Visiting, London; Nursing and Midwifery Council, 2006. Standards to support learning and assessment in practice. Nursing and Midwifery Council, London) and current nursing literature (Griscti, O., Jacono, B., Jacono, J., 2005. The nurse educator's clinical role. Journal of Advanced Nursing 50 (1), 84-92; Owen, S., Ferguson, K., Baguley, I., 2005. The clinical activity of mental health nurse lecturers. Journal of Psychiatric and Mental Health Nursing 12, 310-316), place increasing emphasis on nurse educators undertaking clinical practice to facilitate their clinical confidence and competence. This study investigated nurse educators' perceptions and experiences of undertaking clinical practice. A qualitative design and descriptive, exploratory approach were used. A purposive sample of 11 nurse educators in one nursing department, took part in two focus group interviews, one with 5 and the other with 6 respondents, to identify and discuss their perceptions and experiences of undertaking clinical practice. A process of thematic content analysis revealed three broad themes relating to the meaning and importance of clinical practice, perceived benefits and barriers which are examined and discussed. The paper concludes that despite policy recommendations, barriers highlighted in this study such as insufficient time, heavy workload and a lack of valuing of the clinical role have been raised over the past few decades. The effect of undertaking clinical practice, particularly on the quality of teaching is argued to be valuable armoury in the battle to secure sufficient resources to support engagement in clinical practice. Financial and organisational commitment; valuing of clinical practice and research evidence are crucial to realising clinical practice for nurse educators. Alternative interpretations of what may constitute the clinical role such as joint research projects and supporting and supervising students are offered, which need to be assessed against clear, specific and realistic aims for the clinical role of the nurse educator.

The burden of allergic rhinitis as reported by UK patients compared with their doctors.

This paper presents the results for the UK from a prospective, cross-sectional, international survey to identify perceptions of symptoms and the impact of disease in allergic rhinitis (AR). Data were recorded by 124 patients and matched with data from their primary care physicians or specialists. According to the physicians' assessments, a large proportion of patients presenting for routine care had moderate or severe disease (56.5%), persistent disease (52.0%) and comorbidities such as asthma (38.7%). Compared with the physicians' assessments, patients considered that their condition was more severe (p < 0.001). At the time of the survey, 58.1% of patients reported suffering from nasal and ocular symptoms, and these symptoms were moderate or severe in nature in 41.1% of patients. Most patients (75.0%) reported some impact of the symptoms of AR on daily activities, and health-related quality of life (HRQoL) was negatively correlated with disease severity and the number of symptom-free days in the previous 4 weeks. This survey highlights the unmet needs of many UK patients who suffer a high symptom burden and impaired health-related quality of life. Overall, there was a poor correlation between patients and physicians in the reporting of disease severity.

Patient preferences for asthma therapy: a discrete choice experiment.

AIM: This study was designed to capture patient preferences for different aspects of asthma treatment from people with asthma in the UK, the Netherlands and Spain. METHODS: Asthma patients from the UK (n=124), the Netherlands (n=269) and Spain (n=86) participated in the survey. Patients' preferences and willingness to pay for a particular number of preventer inhalers, in relation to days per week with symptoms, days requiring reliever medication, risk of side effects, and requirement for a visit to their general practitioner (GP) or the Emergency Room (ER), were recorded. RESULTS: Participants were willing to pay euro 35/month to avoid a day with symptoms, euro 109/month to avoid asthma attacks that required emergency visits to their GP or the ER, and euro 94/month to achieve total avoidance of asthma symptoms compared with their current state. CONCLUSIONS: This study presents European data regarding the importance to patients of different attributes of asthma and its treatment. Study participants placed high values on the avoidance of symptoms, and asthma attacks requiring medical attendance.

Defining COPD exacerbations: impact on estimation of incidence and burden in primary care.

AIMS: To investigate the impact of definition on the incidence of chronic obstructive pulmonary disease (COPD) exacerbations in primary care. METHODS: In a one-year prospective, observational study, data from diary cards were used to determine the incidence of symptom- and healthcare-defined exacerbations. One hundred and twenty seven patients completed > or =80% of days in the diary card and were included in the analysis. RESULTS: Incidence of COPD exacerbation varied according to definition. Mean yearly rates were 2.3 for symptom- and 2.8 for healthcare-defined exacerbations. Although patients with FEV(1) <50% had a higher mean yearly rate of healthcare-defined exacerbations than those with FEV(1) > or =50% (3.2 vs 2.3; p=0.003), patients with less severe disease reported recurrent exacerbations. There was limited agreement between symptom- and healthcare-defined exacerbations. CONCLUSION: Lung function does not appear to be a valid criterion for assigning COPD management directed at patients with recurrent exacerbation.

One-year clinical outcomes for Louisiana residents diagnosed with type 2 diabetes and hypertension.

PURPOSE: To identify patient outcomes for residents with a dual diagnosis of diabetes and hypertension under the care of nurse practitioners and physicians in joint or collaborative practice in Louisiana. DATA SOURCES: A retrospective review of records of 115 patients by 15 NPs across the state (response rate 30%) that examined clinical outcomes after 1 year for 14 indexes of care as well as standards of treatment for both diabetes and hypertension. CONCLUSIONS: Significant clinical outcomes for body mass index, blood pressure, hemoglobin A1c, fasting glucose, and total cholesterol levels were found. Clinical outcomes were correlated with healthcare interventions including appropriate medications, use of diabetes educators, and home glucose monitoring as well as total number of visits to the healthcare provider. IMPLICATIONS FOR PRACTICE: Improved outcomes for patients with a dual diagnosis of diabetes and hypertension can be enhanced by the use of diabetes educators, home glucose monitoring, and frequent visits to the healthcare providers. More research is needed to measure the contribution of NPs to improved health outcomes.

Breast health information needs of women from minority ethnic groups.

BACKGROUND: For women from minority ethnic groups to make informed decisions about their health, and particularly about whether to participate in breast cancer screening programmes, access to a range of appropriately designed high quality, culturally-specific and sensitive health information is needed. AIMS: Through a critical review of the literature, this paper aims to determine the breast health and breast cancer screening information needs of women from minority ethnic groups and to discuss the implications of cultural difference for nurses in relation to the development and dissemination of health information. METHODS: A critical review of the research literature published in English between 1996 and 2002 was conducted. Electronic and the relevant Cochrane Collaboration databases were searched using a range of search terms to retrieve literature specifically relevant to the aims of the review. The use of personal contacts and posting a request for information on the mailing list at minority-ethnic-health@jiscmail.ac.uk facilitated the retrieval of grey literature. All references retrieved were entered on a bibliographic database. The title and abstract of each was examined to assess it for inclusion in the review. FINDINGS: There was little published information about specific breast cancer screening information needs from the perspective of women from minority ethnic groups. In comparison with the indigenous population, the information needs of people from minority ethnic groups differ in relation to their cultural beliefs and values and the effects of these on health care practices. Inadequate knowledge about breast health and breast cancer screening may be a consequence of the provision of insufficient or culturally inappropriate information. CONCLUSIONS: There is a dearth of research highlighting breast health and breast cancer screening information needs of women from minority ethnic groups. In providing information, their needs appear to have been an 'add on'. Health care professionals' lack of understanding about cultural beliefs, values and knowledge, together with racial stereotyping and misconceptions about cancer in minority ethnic groups, pose challenges to information dissemination. Health care professionals need to work collaboratively with women from minority ethnic groups, identifying culturally-specific beliefs and values about breast cancer, breast cancer risk and screening, in order to develop appropriate and acceptable information and dissemination strategies.