The Burden of X-Linked Retinitis Pigmentosa on Patients and Society: A Narrative Literature Review.

X-linked retinitis pigmentosa (XLRP) is a severe form of retinitis pigmentosa (RP), a rare, inherited retinal degenerative disorder, that causes blindness. The aim of this literature review was to identify what is currently known about the burden of XLRP. Literature databases were searched for articles describing the clinical, humanistic, or economic burden of XLRP or RP in the US, Japan, France, Germany, Italy, Spain, and the UK, published in English between 2014 and 2019; gray literature and cited references were reviewed. Literature describing XLRP is limited as this is an ultra-rare condition; findings relating to burden of RP have been reported with interpretation of how burden differs for XLRP. In XLRP, night blindness usually presents in the first decade of life, followed by loss of peripheral and then central vision; legal blindness is reported at a median of 45 years in affected males (vs median 70 years for RP). There is limited evidence of humanistic or economic burden specific to XLRP; one study identified greater vision-related activity limitations in patients with XLRP compared with the wider RP population. Qualitative studies describe increased humanistic burden for people living with RP; difficulty undertaking everyday tasks (driving, hobbies, reading), psychosocial burden and barriers to work and career. People described the emotional impact of dealing with progression of RP, ongoing social and physical challenges, and the impact of RP on relationships. The economic burden of RP is associated with lost productivity, greater healthcare costs and increasing requirement for formal and informal care. In summary, XLRP remains an untreatable condition that can impact people from childhood. The humanistic burden of RP has been shown to increase as the disease progresses; hence, in XLRP the earlier onset and earlier progression to blindness during prime working years may mean a comparatively greater lifetime burden of disease.

Testing for minimal residual disease in adults with acute lymphoblastic leukemia in Europe: a clinician survey.

BACKGROUND: In acute lymphoblastic leukemia (ALL), the presence of minimal residual disease (MRD) after induction/consolidation chemotherapy is a strong prognostic factor for subsequent relapse and mortality. Accordingly, European clinical guidelines and protocols recommend testing patients who achieve a complete hematological remission (CR) for MRD for the purpose of risk stratification. The aim of this study was to provide quantitative information regarding real-world clinical practice for MRD testing in five European countries. METHODS: A web-based survey was conducted in March/April 2017 in France, Germany, Italy, Spain, and the UK. The survey was developed after consultation with specialist clinicians and a review of published literature. Eligible clinicians (20 per country; 23 in Spain) were board-certified in hemato-oncology or hematology, had at least five years' experience in their current role after training, had treated at least two patients with B-cell precursor ALL in the 12 months before the survey or at least five patients in the last five years, and had experience of testing for MRD in clinical practice. RESULTS: MRD testing is now standard practice in the treatment of adult ALL across the five European countries, with common use of recent treatment protocols which specify testing. Respondents estimated that, among clinicians in their country who conduct MRD testing, 73% of patients in first CR (CR1) and 63% of patients in second or later CR (CR2+) are tested for MRD. The median time point reported as most commonly used for the first MRD test, to establish risk status and to determine a treatment plan was four weeks after the start of induction therapy. The timing and frequency of tests is similar across countries. An average of four or five post-CR1 tests per patient in the 12 months after the first MRD test were reported across countries. CONCLUSIONS: This comprehensive study of MRD testing patterns shows consistent practice across France, Germany, Italy, Spain, and the UK with respect to the timing and frequency of MRD testing, aligning with use of national protocols. MRD testing is used in clinical practice also in patients who reach CR2 + .

Identification and Management of Statin-Associated Symptoms in Clinical Practice: Extension of a Clinician Survey to 12 Further Countries.

PURPOSE: Statins are the first-choice pharmacological treatment for patients with hypercholesterolemia and at risk for cardiovascular disease; however, a minority of patients experience statin-associated symptoms (SAS) and are considered to have reduced statin tolerance. The objective of this study was to establish how patients with SAS are identified and managed in clinical practice in Austria, Belgium, Colombia, Croatia, the Czech Republic, Denmark, Portugal, Switzerland, Russia, Saudi Arabia, Turkey, and the United Arab Emirates. METHODS: A cross-sectional survey was conducted (2015-2016) among clinicians (n = 60 per country; Croatia: n = 30) who are specialized/experienced in the treatment of hypercholesterolemia. Participants were asked about their experience of patients presenting with potential SAS and how such patients were identified and treated. RESULTS: Muscle-related symptoms were the most common presentation of potential SAS (average: 51%; range across countries [RAC] 17-74%); other signs/symptoms included persistent elevation in transaminases. To establish whether symptoms are due to statins, clinicians required rechallenge after discontinuation of statin treatment (average: 77%; RAC 40-90%); other requirements included trying at least one alternative statin. Clinicians reported that half of high-risk patients with confirmed SAS receive a lower-dose statin (average: 53%; RAC 43-72%), and that most receive another non-statin lipid-lowering therapy with or without a concomitant statin (average: 65%; RAC 52-83%). CONCLUSIONS: The specialists and GPs surveyed use stringent criteria to establish causality between statin use and signs or symptoms, and persevere with statin treatment where possible.

Identification and management of patients with statin-associated symptoms in clinical practice: A clinician survey.

BACKGROUND AND AIMS: Discontinuation of statin therapy by patients with hypercholesterolemia because of the onset of side-effects (statin-associated symptoms [SAS]) increases the risk of cardiovascular morbidity and mortality. We aimed to understand how patients with SAS, particularly those with statin-associated muscle symptoms (SAMS), are identified and managed in the outpatient setting. METHODS: A web-based survey involving 60 clinicians in each of 12 countries and 90 clinicians in the US was conducted. Clinicians answered questions about the diagnostic criteria, estimated incidence of SAS, and choice of treatment for patients with SAS. RESULTS: Overall, 810 clinicians (78% cardiologists) completed the survey. An average of 72% of patients with potential SAS were reported to present with muscle-related symptoms (range across countries [RAC] 50-87%) that could be SAMS. Clinicians took a range of steps to confirm SAMS in these patients, including discontinuation of statin (average 59%; RAC 48-67%); re-challenge with ≥ 2 statins (average 74%; RAC 60-85%); modification of statin regimen (average 76%; RAC 65-85%); or a combination of these steps. Overall, 6% of patients with hypercholesterolemia were estimated to eventually have SAS (RAC 2-12%). In patients with SAS, on average 52% continued to receive a low-dose statin, usually with other lipid-lowering therapies (LLT). Of the remaining 49%, 38% received alternative LLT only; 11% did not receive any LLT. CONCLUSION: There is some consistency and stringency in clinical practice for identifying patients with SAS; however, a structured work-up for identification, followed by a defined therapeutic algorithm, may improve their management.

The burden and impact of severe and long-term sequelae of meningococcal disease.

This review describes current knowledge on the severity and long-term sequelae of meningococcal disease (MD) specifically. The literature databases Medline and Embase were used by combining search terms for MD and Neisseria meningitidis with terms for severity, mortality and sequelae. Case fatality for sufferers of MD remains high, typically 5-10%, despite the best medical care. Long-term sequelae in survivors may include physical, neurological, cognitive, behavioral and psychological consequences, such as hearing loss, amputations, skin scarring and neurodevelopmental deficits. A significantly lower quality of life is seen in survivors of MD compared with unaffected controls, with detrimental effects of childhood MD continuing into adulthood. MD carries a substantial risk of long-term sequelae and mortality. This should be recognized by physicians treating patients with this disease and lends support for the implementation of preventative measures such as vaccination.

The changing epidemiology of meningococcal disease in North America 1945-2010.

The epidemiology of Invasive Meningococcal Disease (IMD) is distinct in the United States and Canada compared with other countries. This review describes the incidence, mortality and vaccination strategies relevant to IMD in these countries over the past 65 y. The incidence of IMD has remained consistently low in both countries during this period. Serogroup B and serogroup C have been the most prominent disease-causing serogroups. Notably, serogroup Y has recently become an important cause of IMD in the USA, but has not been as prominent in Canada. Periodic rises in incidence have been characterized by local outbreaks that have raised public concern, especially those caused by serogroup C in Canada, and serogroup B in the USA. Case fatality rates have remained consistent at around 10-20%, but vary by age and serogroup. Recent outbreaks have led to the introduction of vaccination programs for both outbreak control and routine immunization.

Changing epidemiology of meningococcal disease in Europe from the mid-20th to the early 21st Century.

The epidemiology of meningococcal disease in Europe since 1945 has shown fluctuations in incidence, serogroup distribution and case-fatality rate. Outbreaks and epidemics driven by the introduction of new virulent strains into Europe have occurred unpredictably. Epidemics associated with serogroups A and B have occurred in all regions of the continent. Additionally, there have been periods of increased outbreak frequency, such as those associated with serogroup C in the 1980s and 1990s, against an endemic disease incidence of around one to two cases per 100,000 population. Serogroup W135 disease was observed in the 1970s and again in 2000, while serogroup Y has recently emerged in Sweden and the Czech Republic. This article describes the changing epidemiology of meningococcal disease in Europe. An understanding of this is important for informed decision-making about different meningococcal vaccines that may be considered for use in Europe.