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Background: Prurigo nodularis (PN) is a rare chronic inflammatory skin disease with a high disease burden, but data on clinical and economic burden are still scarce. Objective: To describe the real-world epidemiologic, clinical and therapeutic characteristics and related economic burden of patients with PN compared to a benchmark population in Germany. Methods: This retrospective study was based on an excerpt of German Statutory Health Insurance data of patients with an initial PN diagnosis between 2012 and 2016. PN cohort contained no record of PN in eight quarters before the index quarter and was followed up for eight quarters (unless deceased). Benchmark cohort without PN was calculated using direct standardization and 1:1 matching to PN cohort. Results: Out of 4,536,002 insured patients, 2309 incident patients with PN were identified and matched to the benchmark cohort out of 3,018,382 patients without PN. Patients were mostly between 45 and 80 years when diagnosed with PN. Higher comorbidity rates were reported for PN than benchmark, with a rising disease burden at follow-up. Most patients with PN (91.3%) were diagnosed outpatient and had >50% more outpatient visits than the benchmark cohort. Hospitalization rates were higher in PN (53.9%) versus benchmark (35.1%), yielding twice longer mean hospital stays for PN (12 days) compared to benchmark (6 days) (p < 0.001). The most common initial therapy for patients with PN was topical corticosteroids (47.6%); ≥10% of patients were treated with antidepressants, antihistamines or systemic corticosteroids. Therapy rates were higher for PN compared to benchmark (p < 0.001). Mean initial costs were twofold higher in PN versus benchmark for outpatient, inpatient and drugs. During follow-up, an increase of >70% in mean PN costs compared to benchmark was identified for outpatient, inpatient and concomitant treatments (p < 0.001). Conclusion: This study highlights the significantly higher clinical and economic burden incurred by PN compared to benchmark patients in Germany, reflecting the unmet medical need for PN. [ABSTRACT FROM AUTHOR]

Introduction: Validated patient report tools for quantifying patient experiences of itch in prurigo nodularis (PN) are limited. This study aimed to evaluate the validity of the 11-point peak pruritus numerical rating scale (PP NRS) as a single-item patient-reported outcome (PRO) measure for assessing itch severity in PN. Methods: Content validity of the PP NRS was evaluated through qualitative interviews with adults with PN. The PP NRS was then psychometrically evaluated using data from a placebo-controlled trial of nemolizumab in adults with PN, during which patients completed the PP NRS daily. Meaningful within-patient change was estimated from the qualitative interviews and by anchor- and distribution-based analyses of trial data. Results: The interview participants (N = 21) all understood the PP NRS and reported itch as their worst symptom overall. The PP NRS showed good test–retest reliability and demonstrated convergent validity and known-groups validity. PP NRS scores improved more in patients classified as "improved" on other clinical outcome measures than in those classified as "worsened/unchanged". Triangulation of the different estimates identified a 2- to 5-point decrease in PP NRS score as a meaningful within-patient change threshold. Conclusion: The PP NRS is a content-valid and reliable PRO measure for quantifying itch severity in adults with PN in clinical trials. Trial Registration Number: NCT03181503. Plain Language Summary: Prurigo nodularis is a skin disease where the skin becomes inflamed and very itchy. Itching and scratching can ruin the lives of people with prurigo nodularis. For doctors to know how well treatments for prurigo nodularis are working, they need to be able measure how bad their patients' itching is. Here we tested whether a tool called the peak pruritus numeric rating scale (PP NRS) can be used to reliably measure itching in patients with prurigo nodularis. The PP NRS asks patients to rate their itch "at the worst moment during the previous 24 h" on a scale from 0 ("no itch") to 10 ("worst itch imaginable"). We interviewed 21 patients with prurigo nodularis. Overall, itch was their worst symptom. They were able to use the PP NRS with few or no problems. To further explore whether the PP NRS can be used by patients with prurigo nodularis, we also obtained data from a clinical study. In this clinical study, patients with prurigo nodularis received a drug that might one day be used to treat their disease. They completed the PP NRS daily during the time they received the drug. When we analyzed the data from the clinical study, we found that the PP NRS has the properties a tool like this needs to be useful. We also concluded that a decrease of 2–5 points on the PP NRS scale would be a meaningful improvement in itching for patients with prurigo nodularis. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis (AD) is associated with chronic pruritus, skin pain, sleep deprivation, depression, and anxiety, which may lead to decreased physical activity (PA). Objective: The aim of the study is to elucidate the impact of disease and itch severity on PA in adult AD. Methods: This is a prospective dermatology practice-based study of 955 AD patients (ages 18-97 years). Results: In multivariable logistic regression models controlling for age, sex, race/ethnicity, and asthma history, patient-reported global AD severity (PtGA), Patient-Oriented Eczema Measure, Eczema Area and Severity Index (EASI), and Investigator's Global Assessment (IGA) were associated with itch impairing light PA, moderate PA, and vigorous PA, as well as higher Patient-Reported Outcomes Measurement Information System Itch Questionnaire PA T-scores. Higher objective Scoring AD (O-SCORAD) was associated with itch impairing moderate PA. In bivariable analyses, performing greater than or equal to 30 minutes of light PA greater than or equal to 1 day a week was decreased with higher PtGA, Patient-Oriented Eczema Measure, and EASI; greater than or equal to 30 minutes of moderate PA greater than or equal to 1 day a week was decreased with PtGA, EASI, O-SCORAD, and IGA; and greater than equal to 30 minutes of vigorous PA was decreased with patient-reported AD severity, EASI, O-SCORAD, and IGA. In multivariable logistic regression models, the impact of itch on PA was inversely associated with light PA, moderate PA, and vigorous PA. Conclusion: Adult AD patients with more severe disease have decreased levels of PA secondary to itch. [ABSTRACT FROM AUTHOR]

Purpose: Establishing a meaningful within-individual change (MWIC) threshold is a key aspect for interpreting scores used as endpoints for evaluating treatment benefit. A new patient-reported outcome (PRO), a sleep disturbance numerical rating scale (SD NRS), was developed in adults and adolescents with moderate-to-severe atopic dermatitis (AD). This research aims to establish a MWIC threshold of the SD NRS score in the context of a drug development program. Methods: An explanatory sequential mixed-methods design was used to address the research objective. This mixed-methods design used phase IIb data and a stand-alone qualitative study. Quantitative anchor-based and distribution-based approaches supported by qualitative-based approaches were conducted, and results were triangulated to determine preliminary MWIC thresholds of the SD NRS score. Results: Triangulation of results from both quantitative and qualitative approaches suggested that a 2- to 6-point decrease in the SD NRS score change constitutes a preliminary range of MWIC threshold estimates. Conclusion: This research determined MWIC threshold estimates for the SD NRS score in both adolescents and adults with moderate-to-severe AD using an explanatory sequential mixed-methods design. This mixed-methods design provides interesting insights for establishing MWIC thresholds of a PRO score in the context of a drug development program. [ABSTRACT FROM AUTHOR]

Background: Sleep disturbance (SD) is common in atopic dermatitis (AD). Weexamined the longitudinal course ofSD and relationship with itch in AD patients. Methods: A prospective, dermatology practice--based study was performed (N = 1295) where patients were assessed at baseline and follow-up visits. Results: At baseline, 16.9% of the patients had severe SD based on Patient-Reported Outcomes Information System (PROMIS) SD T scores, 19.1% had difficulty falling asleep, 22.9% had difficulty staying asleep, and 34.2% had SD from AD. A total of 31.4% of the patients with difficulty staying asleep at baseline experienced persistent difficulties (for 3 followups or more). Only 17.7% with baseline difficulty falling asleep had persistent disturbance. Despite significant fluctuation in sleep scores, SD generally improved over time. Of the patients facing baseline SD from AD, 31.5% experienced SD at the first visit, and only 12.3% experienced persistent SD at the second follow-up visit. Predictors of increased PROMIS sleep-related impairment T scores over time included baseline PROMIS sleep-related impairment T scores (0.74 [0.68--0.80]), having 3 to 6 nights of itch (2.22 [0.85--3.59]), and severe/very severe AD (4.40 [2.60--6.20]). Conclusions: A significant proportion of adult AD patients, particularly those with moderate-severe AD and frequent itch, had baseline SD. Although sleep scores generally improved over time, many patients experienced a fluctuating or persistent course. [ABSTRACT FROM AUTHOR]

Background: Prurigo nodularis is a debilitating skin condition that is classified as rare by the Genetic and Rare Diseases Information Center (GARD) and the National Organization for Rare Diseases (NORD). There are currently no estimates of the prevalence of prurigo nodularis in England. Objectives: We aimed to address this data gap by describing the epidemiology of prurigo nodularis in a representative dataset derived from the English National Health Service. Methods: The study utilized data from the Clinical Practice Research Datalink linked to Hospital Episode Statistics inpatient data. Patients with a diagnosis of prurigo nodularis were selected by clinical code in the primary care or inpatient datasets. Case definition was based on a minimum of two distinct diagnoses to maximize specificity. Point prevalence was calculated for the midpoint of 2018 and incidence rates from 2008 to 2018 were presented. For those classified as incident cases, demographic and clinical characteristics were reported. In sensitivity analyses the case definition was modified to relax the multiple diagnosis criteria and to restrict cases to those diagnosed within a maximum of 4 or 10 years of the midpoint prevalence date. Results: Overall, 11 656 patients within the dataset had at least one prurigo nodularis diagnosis. Following application of the relevant inclusion criteria, 2743 patients formed the point prevalent cohort; the estimated prevalence was 3·27 patients per 10 000 population [95% confidence interval (CI) 3·15–3·40]. In sensitivity analyses the estimated prevalence ranged from 2·24 (95% CI 2·14–2·34) to 6·98 (95% CI 6·80–7·16). Incidence over the study period was 2·88 per 100 000 patient‐years. Comorbidity was relatively high in this population, notably for atopic dermatitis (52·2%), depression (41·1%) and anxiety (35·4%). Conclusions: This study supports the NORD/GARD classification of prurigo nodularis as a rare disease with a prevalence of 3·27 patients per 10 000 population, which equates to 18 471 patients living with the disease in England in 2018. The relatively high prevalence of comorbidity observed for these patients may increase the complexity of management. [ABSTRACT FROM AUTHOR]

A study published in the British Journal of Dermatology examined the severity and impact of pruritus (itching) in prurigo nodularis (PN), a chronic inflammatory skin disease. The study focused on a diverse cohort of patients in the United States, including a predominantly African American population. The results showed that patients with PN experienced severe pruritus, reduced quality of life, and a significant mental health burden. The study also found that Black patients reported higher disease severity and itch-specific burden on quality of life compared to White patients. The findings highlight the need for screening and treatment of mental health conditions in this vulnerable population. [Extracted from the article]

Itch is a complex symptom that is both common and burdensome in atopic dermatitis (AD). Yet, little is known about the longitudinal course of itch in AD. A prospective, dermatology practice-based study was performed of adults with AD (n = 463). Patients were assessed at baseline and approximately 6, 12, 18 and 24 months. Itch was assessed using Numeric Rating Scale (NRS) average and worst-itch scores, and frequency of itch in the past week. Repeated-measures regression models were constructed to examine itch over time. Overall, 31.5% and 22.5% had moderate (4–6) or severe (7–10) NRS average-itch scores; 27.4% and 36.4% had moderate (4–6) or severe (7–10) NRS worst-itch scores; 12.7% and 62.0% had itch from eczema 3–4 and ≥ 5 days in the past week; 27.4% and 45.1% reported sometimes and often/almost always having itch, respectively. Among patients with baseline moderate (4–6) or severe (7–10) NRS average-itch scores, 21.2% and 16.3% continued to have moderate or severe scores at ≥ 1 follow-up visits. In repeated-measures regression models, persistent NRS average-itch scores were associated with baseline NRS average-itch [adjusted β (95% CI): 0.75 (0.68, 0.82)] and food allergy [− 0.45 (− 0.84, − 0.07)]. Persistent NRS worst-itch was associated with baseline worst-itch NRS [0.73 (0.66, 0.80)] and Medicaid insurance [1.06 (0.17, 1.94)]. AD patients had a heterogeneous longitudinal course with fluctuating and complex overlapping patterns of average- and worst-itch intensity, and frequency. [ABSTRACT FROM AUTHOR]

Supplemental digital content is available in the text. Background: Itch is a complex and burdensome symptom in atopic dermatitis (AD). Severity of scratching/excoriation (SCORAD-scratch) has been found to be a valid measure of itch in AD. However, little is known about the longitudinal course of scratching/excoriations in AD. Methods: A prospective, dermatology practice–based study was performed of adults with AD (N = 399). The patients were assessed at baseline and approximately 6, 12, 18, and 24 months. Results: Severity of excoriations correlated best with the Numerical Rating Scale–worst itch (Spearman correlation, ρ = 0.50), followed by a Patient-Reported Outcome Measurement Information System Itch Questionnaire–scratching behavior T score (ρ = 0.48), Numerical Rating Scale–average itch (ρ = 0.41), relative frequency of itch (ρ = 0.36), and frequency of itch from eczema (ρ = 0.29, all P < 0.0001). Scratching severity showed good reliability (intraclass correlation coefficient range = 0.62–0.69). Overall, 30.6% and 5.5% had moderate (2) or severe (3) SCORAD-scratch scores. Among patients with baseline moderate (2) or severe (3) SCORAD-scratch scores, 18.9% and 13.6% continued to have moderate or severe scores at 1 or more follow-up visits. In repeated-measures regression models, persistent SCORAD-scratch scores were associated with baseline severity of excoriations (adjusted β [95% confidence interval] = 0.51 [0.37 to 0.65]), Medicaid insurance (−0.35 [−0.65 to −0.04]), and Eczema Area and Severity Index scores (0.03 [0.02 to 0.04]). Conclusions: Adult AD patients had a heterogeneous longitudinal course with fluctuating severity of excoriations. [ABSTRACT FROM AUTHOR]

Background: Few outcome measures were validated for assessing depressive symptoms in AD. Patient Health Questionnaire-9 (PHQ9) and the abridged PHQ2 are established patient-reported outcome measures of depressive symptoms. Objective: We sought to examine the measurement properties of PHQ9 and PHQ2 in adult AD. A prospective dermatology-practice based study of 458 AD patients (age 18-97 years) was conducted. Results: PHQ9 strongly correlated with Dermatology Life Quality Index, Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep-Disturbance and Sleep-Related Impairment, and PROMIS Itch Questionnaire Mood and Sleep (PIQ-MS), and moderately correlated with Patient-Oriented Eczema Measure, Numeric Rating Scale (NRS) average-itch, NRS-sleep, Eczema Area and Severity Index, Scoring AD and Rajka-Langeland scores. PHQ2 had significantly weaker correlations than PHQ9 with PROMIS SD, SRI and PIQ-MS, but similar correlations with other outcomes. PHQ9 and PHQ2 had good discriminant validity. Changes from baseline in PHQ9 and PHQ2 were poorly or weakly correlated with changes of the other outcome measures. There was no differential item functioning of PHQ items. PHQ9 showed good reliability (intraclass correlation coefficient range: 0.80-0.87). PHQ2 had slightly lower reliability (0.76-0.82). Conclusions: PHQ9 and PHQ2 had similar measurement properties, but PHQ2 was more feasible to assess depressive symptoms in AD. [ABSTRACT FROM AUTHOR]

Introduction: Prurigo nodularis (PN) is a chronic inflammatory skin disease characterized by intensely pruritic, hyperkeratotic nodules distributed on the trunk and extensor surfaces of the extremities. PN has a profoundly negative impact on sleep and quality of life in patients with PN. There are currently no U.S. Food and Drug Administration-approved agents and patients are often recalcitrant to current therapies, highlighting the importance of further research into this severely debilitating condition. Areas covered: A PubMed search was conducted to find available literature on the pathophysiology and clinical management of PN. In this review article, we discuss the current understanding of the pathophysiology, recommended diagnostic approach, and treatment options available for PN. Expert opinion/commentary: PN is an extremely difficult condition to treat, because there is a lack of effective therapies available due to our limited understanding of its pathophysiology. Currently, available treatment options are often multimodal due to the intersection of neuroimmune etiologic factors in the pathogenesis of PN. Fortunately, as our knowledge of PN expands, novel treatments targeting specific molecular biomarkers of PN are emerging, providing hope to this long-suffering patient population. [ABSTRACT FROM AUTHOR]

Prurigo nodularis is an itchy skin disease with unknown epidemiology. This study aimed to describe the epidemiology of prurigo nodularis compared with that of psoriasis. The German sickness fund claims database, with 2,783,175 continuously insured patients, included 1,720 patients diagnosed with prurigo nodularis and 51,390 with psoriasis. Patients with prurigo nodularis were averagely 8 years older than psoriasis patients and more often were women (p < 0.001). Annual incidence was a constant 0.02% in prurigo nodularis, and decreased steadily from 0.53 to 0.42% in psoriasis; cumulative incidence was 0.1% for prurigo nodularis and 1.9% for psoriasis. Prevalence was 0.1% for prurigo nodularis and 4.7% for psoriasis, with a one-year mortality of 5.4% for prurigo nodularis and 1.2% for psoriasis (p < 0.001). The most frequent preexisting comorbidities in patients with prurigo nodularis were inflammatory dermatoses and depression. This epidemiological study found a low prevalence of prurigo nodularis, manifesting different demographics and comorbidities compared with psoriasis. [ABSTRACT FROM AUTHOR]

Supplemental digital content is available in the text. Background: The ideal patient-reported outcome measure to assess sleep disturbance in atopic dermatitis (AD) has not been determined. Objective: We sought to determine the measurement properties of the Patient-Reported Outcomes Measurement Information System® (PROMIS®) Itch Questionnaire Mood and Sleep (PIQ-MS), Sleep Disturbance (SD), Sleep-Related Impairment (SRI), and Epworth Sleepiness Scale (ESS) in adults with AD. Methods: A prospective dermatology practice-based study was performed using questionnaires and evaluation by a dermatologist (n=611). Results: PIQ-MS, PROMIS SD, SRI, and ESS had good convergent validity with intensity and frequency of sleep disturbance, Patient-Oriented Eczema Measure, Eczema Area and Severity Index, total and objective-Scoring AD, Numerical Rating Scale of worst-itch and average-itch, and Dermatology Life Quality Index. PIQ-MS had significantly better correlations with other severity measures than the other sleep measures (Fisher z-scores, P ≤0.007). PIQ-MS, and to lesser extent PROMIS SD, PROMIS SRI and ESS had good discriminant validity. All four sleep assessments showed fair responsiveness to change of severity of sleep-disturbance, AD and itch. PIQ-MS had the best reliability. PIQ-MS, PROMIS SD, SRI and ESS showed good internal consistency and were feasible for use in clinical practice. Conclusions: PIQ-MS, followed by PROMIS SD, had the best construct validity and reliability in adult AD. [ABSTRACT FROM AUTHOR]

Most patients with mycosis fungoides are diagnosed with early-stage disease. However, prevalence of early-stage disease is unknown, and evidence of its burden is scarce. The aim of this study is to estimate the prevalence of early-stage mycosis fungoides, how long patients live with early-stage disease and to characterise these patients. Data were obtained from 4 key publications and from US cancer registries (Surveillance, Epidemiology and End Results Program; SEER). The derived incidence of early-stage mycosis fungoides was 0.26/100,000 (UK), 0.29/100,000 (US) and 0.38/100,000 (US-SEER) and the prevalence was 4.8/100,000 (UK), 5.2/100,000 (US) and 6.6/100,000 (US-SEER). Early-stage disease may last for 18 years. From SEER registries, 3,132 were diagnosed at early stage (mostly stage IA). Median age at diagnosis was 58 years. Compared with stage IA, the relative risk of death was 1.3 for stage IB and 3.5 for stage IIA. We confirm the rarity of early-stage mycosis fungoides, a differential prognosis and the potential for elevated burden of disease. [ABSTRACT FROM AUTHOR]

Objective: Post-stroke spasticity (PSS) is a common complication following stroke. This study describes the differences in healthcare resource utilization between patients who do and do not develop PSS in the UK.Methods: Adults registered in The Health Improvement Network database with a recorded stroke between 2007 and 2011 were included. PSS was identified through Read codes; machine learning was used to retrospectively identify unrecorded PSS events. Patients with diagnosed or predicted PSS in the 12 months after stroke were matched to those with no PSS on age, sex, number of strokes, socioeconomic status, and comorbidities using the nearest neighbor algorithm. Utilization and costs associated with general practitioner visits, nurse visits, hospitalizations, referrals to specialists, laboratory tests, and medications in the 12 months after stroke were compared.Results: Overall, 2,951 PSS cases were matched to 37,753 controls. During the first year, more PSS cases visited a physiotherapist (19% vs 7%) and occupational therapist (12% vs 5%) compared to controls. A greater proportion of cases were also referred to specialists (76% vs 64%) and hospitalized (33% vs 9%) compared to controls. Medication for spasticity was, on average, 14.68 prescriptions for cases and 5.64 for controls. Total mean costs per patient were £1,270 (standard deviation [SD] = 772) and £635 (SD = 273) for cases and controls, respectively.Conclusion: Costs after stroke for patients developing PSS are twice as high compared to patients who do not develop it, with the major driver being the number of hospital admissions. This highlights the need for better recording and closer management of PSS. [ABSTRACT FROM AUTHOR]

Introduction: Well- or moderately differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are often slow-growing, and some patients with unresectable, asymptomatic, non-functioning tumors may face the choice between watchful waiting (WW), or somatostatin analogues (SSA) to delay progression. We developed a comprehensive multi-criteria decision analysis (MCDA) framework to help patients and physicians clarify their values and preferences, consider each decision criterion, and support communication and shared decision-making.Methods: The framework was adapted from a generic MCDA framework (EVIDEM) with patient and clinician input. During a workshop, patients and clinicians expressed their individual values and preferences (criteria weights) and, on the basis of two scenarios (treatment vs WW; SSA-1 [lanreotide] vs SSA-2 [octreotide]) with evidence from a literature review, expressed how consideration of each criterion would impact their decision in favor of either option (score), and shared their knowledge and insights verbally and in writing.Results: The framework included benefit-risk criteria and modulating factors, such as disease severity, quality of evidence, costs, and constraints. Overall and progression-free survival being most important, criteria weights ranged widely, highlighting variations in individual values and the need to share them. Scoring and considering each criterion prompted a rich exchange of perspectives and uncovered individual assumptions and interpretations. At the group level, type of benefit, disease severity, effectiveness, and quality of evidence favored treatment; cost aspects favored WW (scenario 1). For scenario 2, most criteria did not favor either option.Conclusions: Patients and clinicians consider many aspects in decision-making. The MCDA framework provided a common interpretive frame to structure this complexity, support individual reflection, and share perspectives.Funding: Ipsen Pharma. [ABSTRACT FROM AUTHOR]

Dear Editor, Prurigo nodularis (PN) is a chronic inflammatory skin disease characterized by intensely pruritic, hyperkeratotic nodules.1,2 Previous studies have demonstrated an association between PN and substance use disorders (SUDs),3 and more specifically, with alcohol use.4 However, less is known about the association between PN and other subtypes of SUDs, such as opioid, cannabis and cocaine use disorders. We also adjusted for comorbid musculoskeletal disorders in analyses for opioid use disorder, as opioids are more commonly prescribed for such disorders. We then compared rates of comorbid SUDs among hospitalizations with a diagnosis of PN to those without a diagnosis of PN. [Extracted from the article]

Endpoints related to tumor progression are commonly used in clinical trials of novel therapeutic agents for neuroendocrine tumors (NETs). Whether improved tumor control translates into improved overall survival (OS), however, is uncertain. We assessed associations between tumor progression endpoints and OS in observational cohorts of patients with advanced neuroendocrine tumors treated with somatostatin analogs or with everolimus. We identified 440 patients with advanced NET who had received treatment with single-agent somatostatin analogs and 109 patients treated with everolimus, all of whom were treated at our institution and were evaluable for both tumor progression and survival. We assessed associations between progression-free survival (PFS) and OS by using the Kendall tau test, and we assessed associations between tumor progression and OS by using a landmark analysis. In the 440 patients treated with somatostatin analogs, we observed a significant correlation between PFS and OS by using the Kendall tau test (0.31; p< .0001). Additionally, the development of progressive disease was associated with OS in a landmark analysis, at landmark times of 6, 12, 18, and 24 months. In the 109 patients treated with everolimus, we similarly observed a significant correlation between PFS and OS by using the Kendall tau test (0.44; p < .0001) and associations between progressive disease and OS by using a landmark analysis at 3, 6, and 12 months. In these observational cohorts of patients with meta-static NET treated with single-agent somatostatin analogs or everolimus, longer times to disease progression and longer PFS were both associated with improved OS. Our findings support the continued use of disease progression endpoints in NET clinical trials. [ABSTRACT FROM AUTHOR]

Background: Helcococcus kunzii is a facultative anaerobic bacterium that was first described by Collins et al. in 1993, and was initially considered as a commensal of the human skin, in particular of lower extremities. Human infections caused by H. kunzii remain rare with only a few cases published in the pubmed database. Nevertheless recent reports indicate that this microorganism has to be considered as an opportunistic pathogen that can be involved in severe infections in human. To the best of our knowledge, we describe here the first known case of infectious endocarditis caused by H. kunzii. Case presentation: A 79 year-old man reporting severe polyvascular medical history attended the emergency ward for rapid deterioration of his general state of health. After physical examination and paraclinical investigations, the diagnosis of infectious endocarditis on native mitral valve caused by Helcococcus kunzii was established based on Dukes criteria. MALDI-TOF mass spectrometry and 16S rDNA sequencing allowed an accurate identification to the species level of Helcococcus kunzii. The patient was successfully treated by a medico-surgical approach. The treatment consisted in intravenous amoxicillin during four weeks and mitral valve replacement with a bioprosthestic valve. After an in depth review of patient's medical file, the origin of infection remained unknown. However, a cutaneous portal of entry cannot be excluded as the patient and his General Practitioner reported chronic ulcerations of both feet. Conclusions: We describe here the first case of endocarditis caused by H. kunzii in an elderly patient with polyvascular disease. This report along with previous data found in the literature emphasizes the invasive potential of this bacterial species as an opportunistic pathogen, in particular for patient with polyvascular diseases. MALDI-TOF mass spectrometry and 16S rDNA sequencing are reliable tools for H. kunzii identification. We also sequenced in this work H.kunzii type strain 103932T CIP and deposited in the Genbank under accession number KM403387. We noticed a 14 base difference between our sequence and the original sequence deposited by Collins et al. under Genbank accession number X69837. Hopefully, the spread of next generation sequencing tools would lead to a more accurate classification of clinical strains. [ABSTRACT FROM AUTHOR]

Purpose: Cervical dystonia (CD) is a hypertonic condition caused by damage to the central nervous system. Very few studies have assessed the overall economic burden of the disease. The objective of this study was to describe the utilization of health care resources of patients with CD in the UK primary care setting, using a large population-based database. Patients and methods: Adults with a first diagnosis of CD between January 1, 2007 and January 31, 2011, who were registered to a general practitioner (GP) practice contributing to The Health Improvement Network (THIN), were included. Sociodemographic and clinical characteristics were assessed at the time of diagnosis. Health care resource utilization and pharmacological treatment were investigated at the end of the first and second year after diagnosis. Results: Overall, 4,024 newly diagnosed patients with CD were identified, with average age at diagnosis of 45 years old; 65.3% were female. Depression in the year prior to diagnosis was the most common comorbidity. Primary care utilization was high in the first year, with 99.2% of patients visiting their GP (on average 6.2 times), and 43% visiting a nurse (on average 2.5 times). Patients were most commonly referred to an orthopedic surgeon, and 15.9% reported at least one physiotherapy visit. In the second year, utilization was similar. Prescriptions of at least one of the investigated treatments were found in 82.0% and 45.3%, in the first and second year, respectively. Conclusion: Findings suggest a high number of new CD cases are being identified in primary care, but not all will be referred to secondary care. Health care resource utilization was compared with that of all patients registered in THIN, which is representative of the UK, and the adjusted usage of primary care resources was found to be similar to that of the THIN population. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to determine the most cost-effective time point for initiation of irbesartan treatment in hypertensive patients with type 2 diabetes and renal disease.Research Design and Methods: This study was a Markov model-simulated progression from microalbuminuria to overt nephropathy, doubling of serum creatinine, end-stage renal disease, and death in hypertensive patients with type 2 diabetes. Two irbesartan strategies were created: early irbesartan 300 mg daily (initiated with microalbuminuria) and late irbesartan (initiated with overt nephropathy). These strategies were compared with control, which consisted of antihypertensive therapy with standard medications (excluding ACE inhibitors, other angiotensin-2 receptor antagonists, and dihydropyridine calcium channel blockers) with comparable blood pressure control, initiated at microalbuminuria. Transition probabilities were taken from the Irbesartan in Reduction of Microalbuminuria-2 study, Irbesartan in Diabetic Nephropathy Trial, and other published sources. Costs and life expectancy, discounted at 3% yearly, were projected over 25 years for 1,000 simulated patients using a third-party payer perspective in a U.S. setting.Results: Compared with control, early and late irbesartan treatment in 1,000 patients were projected to save (mean +/- SD) 11.9 +/- 3.3 million dollars and 3.3 +/- 2.7 million dollars, respectively. Early use of irbesartan added 1,550 +/- 270 undiscounted life-years (discounted 960 +/- 180), whereas late irbesartan added 71 +/- 40 life-years (discounted 48 +/- 27) in 1,000 patients. Early irbesartan treatment was superior under a wide-range of plausible assumptions.Conclusions: Early irbesartan treatment was projected to improve life expectancy and reduce costs in hypertensive patients with type 2 diabetes and microalbuminuria. Later use of irbesartan in overt nephropathy is also superior to standard care, but irbesartan should be started earlier and continued long term. [ABSTRACT FROM AUTHOR]

Background: The clinical manifestations of atherothrombotic disease include ischaemic heart disease (including myocardial infarction [MI]) and cerebrovascular disease (including ischaemic stroke [IS]). Although costs generated by the clinical manifestations of atherothrombotic disease represent an important economic burden for any healthcare system, very few economic comparative data are available.Objective: To: (i) assess management costs of the different practice patterns for acute and chronic phases for MI, IS and peripheral arterial disease (PAD) in eight European countries; and (ii) to simulate the cost of managing a patient with an atherothrombotic disease for 2 years in Europe.Study Perspective: Healthcare system.Methods: Firstly, the medical costs of managing MI and IS were analysed during the acute phase and subsequent 6-month periods over a total of 2 years. In each case, a decision tree was designed to indicate resource use. Assumptions concerning patient management and resource use were based on currently available local and international literature, official national statistics and local expert opinions (Delphi panel). Costs were assessed using diagnosis-related groups (Austria, Italy, Portugal and Sweden), or hospital databases and national tariffs (Belgium, France, Spain and Switzerland). Secondly, these costs were correlated to data from a large randomised clinical trial to estimate the overall cost per patient with atherothrombotic disease over a 2-year period.Results: For MI, there was a 2-fold difference in costs between the eight countries (euro9512-18 293), with 47-76% of costs devoted to acute management, 14-48% to follow-up management during the first year, and 4-17% to follow-up during the second year. For IS, there was a 10-fold difference (euro5607-56 370), with 18-75% devoted to follow-up for the years 1995-1997.Conclusions: There are differences in the overall costs and cost breakdown in the clinical management patterns of MI and IS in Europe. These differences seem to arise as a result of local treatment pattern specificities as well as the availability of specific and well-adapted structures for patients' rehabilitation. Further studies are necessary to fully explain these differences. The assessment of the total medical costs of managing an atherothrombotic patient over a 2-year period (MI, IS, established PAD) has to take into account the risk of ischaemic events in different vascular areas (MI, IS or major leg ischaemia). [ABSTRACT FROM AUTHOR]

The objective was to estimate the cost‐of‐illness of grades 1 and 2 metastatic gastroenteropancreatic neuroendocrine tumours (GEP‐NETs) in Sweden in 2013 in a population‐based study including all patients diagnosed between 2005 and 2013. Data were obtained from national registers, and patients who utilised healthcare resources due to metastatic GEP‐NETs in 2013 were included. The study included 478 patients (mean age 64 [SD=11] years, 51% men). The majority (80%) had small intestinal NET, 10% had pancreatic NET, and 41% had carcinoid syndrome. The total cost‐of‐illness was €12,189,000 in 2013, of which direct costs constituted 77% and costs from production loss constituted 22%. The largest contributor to the direct medical costs was prescription drugs (54%; primarily somatostatin analogues [91% of the total drug cost]). Production loss due to sickness absence constituted 52% of the total costs of production loss. The total annual cost per patient was €25,500. By patient group, the cost was €24,800 (95% CI €21,600–€28,100) for patients with small intestinal NET, €37,300 (95% CI €23,300–€51,300) for those with pancreatic NET and €18,600 (95% CI €12,600–€24,500) for patients with other GEP‐NETs. To conclude, the total annual cost of grades 1 and 2 metastatic GEP‐NETs in Sweden was €25,500 per patient and year. [ABSTRACT FROM AUTHOR]

INTRODUCTION:Advanced or metastatic renal cell-carcinoma (RCC) is associated with poor health outcomes; in particular in those whose disease progressed after first line treatment. A literature review was conducted to elucidate evidence on health-related utility associated with advanced and metastatic RCC.METHODS:A systematic literature search from 2006 onwards (date of search: July 2016) was conducted for studies evaluating health-related quality of life (QoL) and utility outcomes. Searches included Medline, Embase, National Health Service (NHS) Economic Evaluation Database and HTA Database and were supplemented by free internet search for key European Health Technology Assessment reports. Publications were limited to 2006 onwards as previous research (1) revealed no prior relevant evidence.RESULTS:The search yielded 4,178 records. The selection process revealed seventy-eight relevant publications. Generic EuroQol (EQ)-5D scale was most commonly used. Health-state utilities were assessed for specific treatments and at different time points. Mean reported value for patients after failure of one prior systemic therapy ranged from .79 - .62. For patients without progression (on and off-treatment) reported utility values were in range from .80 – .63. Utility in stable patients with adverse events ranged from .71 - .47. For patients with progressive diseases, utility was reported from .71 - .36. Utility for interventions due to skeletal-related events in patients with bone metastasis was reported to range between .46 and .15.CONCLUSIONS:Identified evidence confirms advanced or metastatic RCC leads to significant detriment to patients health-related utility. Further research efforts are warranted to assess health-state utility beyond clinical trial assessment. [ABSTRACT FROM PUBLISHER]

INTRODUCTION:Re-purposing of established products (EPs) – defined as marketed for 8 years or more – may represent a high value for patients and society. It has been recognized by the European Commission as an important factor contributing to greater access to new therapies. Due to a lower development cost, it could also represent a cost-effective alternative and help to reduce pressure on healthcare budgets. However, it is perceived that no financial incentives exist for the pharmaceutical industry to invest in new indications for EPs. The objective of this research was to review current European regulations and propose strategies stimulating development in this field.METHODS:We performed a targeted literature review and held two international expert panel workshops to discuss current policies and their implications, and issue recommendations for changes.RESULTS:Within the current regulatory framework EPs face price cuts due to generic competition, reference pricing (RP), price re-negotiations or systematic price cuts, after a period of marketing presence. Extension of indications does not permit to increase or maintain the price. Generic substitution regardless of indication poses another challenge. Limited incentives in the form of an additional year of market protection exists only for new indication(s) registered within the first 8 years following initial approval. The expert panel proposed several strategies to stimulate development in this field, including: (i) extending the period in which registering a new indication results in additional market protection beyond 8 years and extending the duration of additional market protection; (ii) delaying inclusion in RP for EPs with a new value adding indication; (iii) establishing a differential pricing by indication; (iv) preventing temporarily generic substitution when an EP is prescribed for a new indication.CONCLUSIONS:Current regulations represent a serious disincentive to develop new indications for EPs. Regulatory and pricing policy changes are needed to stimulate development in this important field. [ABSTRACT FROM PUBLISHER]

Background: Many established products (EPs – marketed for eight years or more) are widely used off-label despite little evidence on benefit–risk ratio. This exposes patients to risks related to safety and lack of efficacy, and healthcare providers to liability. Introducing new indications for EPs may represent a high societal value; however, manufacturers rarely invest in R&D for EPs. The objective of this research was to describe incentives and disincentives for developing new indications for EPs in Europe and to investigate consequences of current policies. Methods: Targeted literature search and expert panel meetings. Results: Within the current European-level and national-level regulatory framework there are limited incentives for development of new indications with EPs. Extension of indication normally does not allow the price to be increased or maintained, the market protection period to be extended, or exclusion from a reference price system. New indication frequently triggers re-evaluation, resulting in price erosion, regardless of the level of added value with the new indication. In consequence, manufacturers are more prone to undertake R&D efforts at early to mid-stage of product life cycle rather than with EPs, or to invest in new chemical entities, even in therapeutic areas with broad off-label use. This represents a potentially missed opportunity as developing new indications for EPs offers an alternative to off-label use or lengthy and expensive R&D for new therapies, opens new opportunities for potentially cost-effective treatment alternatives, as well as greater equity in patients’ access to treatment options. Conclusion: There are potential benefits from the development of new indications for EPs that are currently not being realized due to a lack of regulatory and pricing incentives in Europe. Incentives for orphan or paediatric drugs have proven to be effective in promoting R&D. Similarly, incentives to promote R&D in EPs should be developed, for the benefit of patients and healthcare systems. [ABSTRACT FROM PUBLISHER]

Background: Helcococcus kunzii is a facultative anaerobic bacterium that was first described by Collins et al. in 1993, and was initially considered as a commensal of the human skin, in particular of lower extremities. Human infections caused by H. kunzii remain rare with only a few cases published in the pubmed database. Nevertheless recent reports indicate that this microorganism has to be considered as an opportunistic pathogen that can be involved in severe infections in human. To the best of our knowledge, we describe here the first known case of infectious endocarditis caused by H. kunzii.Case Presentation: A 79 year-old man reporting severe polyvascular medical history attended the emergency ward for rapid deterioration of his general state of health. After physical examination and paraclinical investigations, the diagnosis of infectious endocarditis on native mitral valve caused by Helcococcus kunzii was established based on Dukes criteria. MALDI-TOF mass spectrometry and 16S rDNA sequencing allowed an accurate identification to the species level of Helcococcus kunzii. The patient was successfully treated by a medico-surgical approach. The treatment consisted in intravenous amoxicillin during four weeks and mitral valve replacement with a bioprosthestic valve. After an in depth review of patient's medical file, the origin of infection remained unknown. However, a cutaneous portal of entry cannot be excluded as the patient and his General Practitioner reported chronic ulcerations of both feet.Conclusions: We describe here the first case of endocarditis caused by H. kunzii in an elderly patient with polyvascular disease. This report along with previous data found in the literature emphasizes the invasive potential of this bacterial species as an opportunistic pathogen, in particular for patient with polyvascular diseases. MALDI-TOF mass spectrometry and 16S rDNA sequencing are reliable tools for H. kunzii identification. We also sequenced in this work H.kunzii type strain 103932T CIP and deposited in the Genbank under accession number KM403387. We noticed a 14 base difference between our sequence and the original sequence deposited by Collins et al. under Genbank accession number X69837. Hopefully, the spread of next generation sequencing tools would lead to a more accurate classification of clinical strains. [ABSTRACT FROM AUTHOR]