Improving risk equalization for individuals with persistently high costs: Experiences from the Netherlands.

Health Policy. 2017 Nov;121(11):1169-1176

Authors: Eijkenaar F, van Vliet RCJA

Abstract
BACKGROUND: Risk-equalization (RE) models in competitive health insurance markets have become increasingly sophisticated. However, these models still have important imperfections. A specific problem in the Netherlands is that insurers are insufficiently compensated for individuals who can persistently be found in the right-end tail of the cost distribution.
OBJECTIVES: The goal of this study is to explore and evaluate options for improving compensation for persistently high-cost individuals in the Dutch basic health insurance.
METHODS: Prescription drugs claims (2012) and administrative data on costs and risk-characteristics (2010-2013) for the entire Dutch population are used to identify high-cost individuals and evaluate improvement options. These options - including new risk-classes and a form of risk-sharing - are evaluated in terms of insurers' incentives for risk-selection and efficiency.
RESULTS: Three significantly undercompensated high-cost groups are identified: users of specific expensive drugs for rare diseases, hemophilia-patients, and individuals whose costs are in the top-0.50% in 3 prior years. The improvement options effectively remove the undercompensations for these groups and lead to a considerable improvement in individual-level model fit. However, the options differ in terms of their (potential) effects on insurers' efficiency incentives.
CONCLUSIONS: Although this study provides useful insights in the possibilities for improving RE-models for persistently high-cost individuals, improving compensation remains challenging and dependent on the ongoing debate regarding coverage and reimbursement of expensive drugs.

PMID: 28942090 [PubMed - indexed for MEDLINE]

Long-term metabolic follow-up and clinical outcome of 35 patients with maple syrup urine disease.

J Inherit Metab Dis. 2017 Nov;40(6):783-792

Authors: Abi-Wardé MT, Roda C, Arnoux JB, Servais A, Habarou F, Brassier A, Pontoizeau C, Barbier V, Bayart M, Leboeuf V, Chadefaux-Vekemans B, Dubois S, Assoun M, Belloche C, Alili JM, Husson MC, Lesage F, Dupic L, Theuil B, Ottolenghi C, de Lonlay P

Abstract
BACKGROUND: Maple syrup urine disease (MSUD) is a rare disease that requires a protein-restricted diet for successful management. Little is known, however, about the psychosocial outcome of MSUD patients. This study investigates the relationship between metabolic and clinical parameters and psychosocial outcomes in a cohort of patients with neonatal-onset MSUD.
METHODS: Data on academic achievement, psychological care, family involvement, and biochemical parameters were collected from the medical records of neonatal MSUD patients treated at Necker Hospital (Paris) between 1964 and 2013.
RESULTS: Thirty-five MSUD patients with a mean age of 16.3 (2.1-49.0) years participated. Metabolic decompensations (plasma leucine >380 μmol/L) were more frequent during the first year of life and after 15 years, mainly due to infection and dietary noncompliance, respectively. Leucine levels increased significantly in adulthood: 61.5% of adults were independent and achieved adequate social and professional integration; 56% needed occasional or sustained psychological or psychiatric care (8/19, with externalizing, mood, emotional, and anxiety disorders being the most common). Patients needing psychiatric care were significantly older [mean and standard deviation (SD) 22.6 (7.7) years] than patients needing only psychological follow-up [mean (SD) 14.3 (8.9) years]. Patients with psychological follow-up experienced the highest lifetime number of decompensations; 45% of families had difficulty coping with the chronic disease. Parental involvement was negatively associated with the number of lifetime decompensations.
CONCLUSION: Adults had increased levels of plasma leucine, consistent with greater chronic toxicity. Psychological care was associated with age and number of decompensations. In addition, parental involvement appeared to be crucial in the management of MSUD patients.

PMID: 28905140 [PubMed - indexed for MEDLINE]

Small-Molecule Inhibitors Disrupt let-7 Oligouridylation and Release the Selective Blockade of let-7 Processing by LIN28.

Cell Rep. 2018 Jun 05;23(10):3091-3101

Authors: Wang L, Rowe RG, Jaimes A, Yu C, Nam Y, Pearson DS, Zhang J, Xie X, Marion W, Heffron GJ, Daley GQ, Sliz P

Abstract
LIN28 is an RNA-binding protein that regulates the maturation of the let-7 family of microRNAs by bipartite interactions with let-7 precursors through its two distinct cold shock and zinc-knuckle domains. Through inhibition of let-7 biogenesis, LIN28 functions as a pluripotency factor, as well as a driver of tumorigenesis. Here, we report a fluorescence polarization assay to identify small-molecule inhibitors for both domains of LIN28 involved in let-7 interactions. Of 101,017 compounds screened, six inhibit LIN28:let-7 binding and impair LIN28-mediated let-7 oligouridylation. Upon further characterization, we demonstrate that the LIN28 inhibitor TPEN destabilizes the zinc-knuckle domain of LIN28, while LI71 binds the cold shock domain to suppress LIN28's activity against let-7 in leukemia cells and embryonic stem cells. Our results demonstrate selective pharmacologic inhibition of individual domains of LIN28 and provide a foundation for therapeutic inhibition of the let-7 biogenesis pathway in LIN28-driven diseases.

PMID: 29874593 [PubMed - in process]

Berry syndrome: a rare cardiac malformation with extra-cardiac findings.

Sci China Life Sci. 2017 07;60(7):772-774

Authors: Li J, Yang Y, Duan X, Jin L, Zheng L, Zhang X, Wei H, Sun Y, Zhang X, Li P, Yang J, Ma N, Wang F

PMID: 28646472 [PubMed - indexed for MEDLINE]

Analysis of diagnosis and treatment of lipoblastomatosis.

Sci China Life Sci. 2017 07;60(7):778-780

Authors: Mo Z, Xie X, Wang H, Qin H, Han W, Li X

PMID: 28639103 [PubMed - indexed for MEDLINE]

The challenge and promise of rare disease diagnosis in China.

Sci China Life Sci. 2017 07;60(7):681-685

Authors: Ni X, Shi T

PMID: 28623543 [PubMed - indexed for MEDLINE]

Making a Notch in the Evolution of the Human Cortex.

Dev Cell. 2018 Jun 04;45(5):548-550

Authors: Bizzotto S, Walsh CA

Abstract
The unique structure and function of the human brain ultimately results from the action of evolution on the human genome. In a recent issue of Cell, Fiddes et al. (2018) and Suzuki et al. (2018) describe human-specific NOTCH2 paralogs that enhance neural progenitor proliferation and expand cortical neurogenesis.

PMID: 29870717 [PubMed - in process]

Establishment of New National Rare Disease (Nambyo) Registry and Registry Guidelines in Japan.

Stud Health Technol Inform. 2017;245:536-538

Authors: Mizushima H, Tanabe M, Sugamori Y, Sato Y, Ogata H

Abstract
A New legal structure for rare disease (nambyo) has been established in Japan this year, after 42 years of measures of nambyo. We have been accumulating registry for nambyo from 2003, however, as it was based on paper registration, quality was not enough. Our new registry system will be based under ISO13606 which is a new medical international standard. Authorized doctors can put in data On Line by the new system, which has data cleaning filter for accurate data entry. Patients will be supported their medical expense by authorization by this system, so the registry will be efficient.

PMID: 29295152 [PubMed - indexed for MEDLINE]

Das Myelosarkom der Hypophyse – eine Rarität eines isolierten Rezidivs einer akuten myeloischen Leukämie.

Rofo. 2018 Mar;190(3):273-274

Authors: Fleischmann T, Hilgendorf I, Franiel T

PMID: 29156477 [PubMed - indexed for MEDLINE]

37 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Rare Diseases"[Mesh] OR "orphan disease"

These pubmed results were generated on 2018/06/05

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

37 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Rare Diseases"[Mesh] OR "orphan disease"

These pubmed results were generated on 2018/06/05

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

6 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Rare Diseases"[Mesh] OR "orphan disease"

These pubmed results were generated on 2018/06/02

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

The value of Autoimmune Syndrome Induced by Adjuvant (ASIA) - Shedding light on orphan diseases in autoimmunity.

Autoimmun Rev. 2018 May;17(5):440-448

Authors: Segal Y, Dahan S, Sharif K, Bragazzi NL, Watad A, Amital H

Abstract
Autoimmune Syndrome Induced by Adjuvant (ASIA) is a definition aimed to describe the common etiological process at the root of five clinical entities sharing similar symptomatology: macrophagic myofasciitis syndrome (MMF), Gulf War Syndrome (GWS), sick building syndrome (SBS), siliconosis, and post vaccination autoimmune phenomena. ASIA illustrates the role of environmental immune stimulating agents, or adjuvants, in the instigation of complex autoimmune reactions among individuals bearing a genetic preponderance for autoimmunity. The value of ASIA lies first in the acknowledgment it provides for patients suffering from these as yet ill-defined medical conditions. Equally important is the spotlight it sheds for further research of these poorly understood conditions sharing a common pathogenesis. In this article we elaborate on the significance of ASIA, review the current evidence in support of the syndrome, and address recent reservations raised regarding its validity.

PMID: 29526630 [PubMed - indexed for MEDLINE]

Young Man Battles For His Life Against Rare Autoimmune Disease.

Manag Care. 2017 10;26(10):19-20

Authors: Calandra R

Abstract
The author's nephew suffers from a rare form of familial hemophagocytic lymphohistiocytosis. His organs shut down and he's placed in a medically induced coma. Meanwhile, costs mount to $4.9 million, most of it paid by an employer-sponsored health plan.

PMID: 29068294 [PubMed - indexed for MEDLINE]

Cutaneous leiomyosarcoma on the face.

An Bras Dermatol. 2018 Mar;93(2):262-264

Authors: Murback NDN, Takita LC, Castro BC, Hans Filho G

Abstract
Leiomyosarcoma is a rare skin tumor, most common in white men in the fifth to eighth decades of life. Primary tumors are classified in dermal or subcutaneous, that differ by clinical and prognostic features. They may appear on any site of the body, but are rare on the face. A 54-year-old female was admitted with a 5cm exophytic nodular lesion of 8 months duration on the right cheek, site of previous chronic radiodermatitis. Histopathology revealed spindle-shaped cell neoplasia, positive for smooth muscle actin on immunohistochemistry. Cutaneous leiomyosarcomas on the face are rare and may occur in previously irradiated areas. Immunohistochemistry is mandatory for an accurate diagnosis. Its similarity with other tumors may complicate the diagnosis, with delay expansion of the tumor.

PMID: 29723357 [PubMed - indexed for MEDLINE]

Multicystic peritoneal mesothelioma: A short review.

Curr Probl Cancer. 2017 Sep - Oct;41(5):340-348

Authors: Zhang CH, Yu JW, Luo M

Abstract
Multicystic peritoneal mesothelioma (MCPM) is a rare neoplasm, predominantly affecting female patients during their reproductive years. The lesion is usually distributed diffusely in the abdomen and pelvis, but the peritoneum of the pelvic organs is the most common site. MCPM is composed of fluid-filled translucent cysts, connected by varying amounts of fibrous tissue, and lined by a layer of mesothelial cells. Because of the rarity of this disease, the pathogenesis and natural history of MCPM remain poorly understood and continuously debated. Some authors consider it to be a reactive process for its association with prior surgery or abdominal inflammation. But its high rate of local-regional recurrence, as well as its malignant potential, suggests a neoplastic etiology. Preoperative diagnosis is often very difficult. Imaging methods, such as ultrasound, computed tomography, and magnetic resonance imaging, are of little value for an accurate diagnosis of MCPM. The definitive diagnosis relies on histologic examination of target lesions combined with immunohistochemical stains. There is no consensus on the clinical management of MCPM, although surgical removal remains the first-line treatment of choice. But no standards have been reached concerning which surgical options-traditional debulking surgery or more aggressive one-should be chosen. Alternative therapeutic approaches include hand-off treatment, hormonal supplementation, laser vaporization, and sclerotherapy, and they all come with uncertain results. Moreover, the lesions show no response to adjuvant chemotherapy and radiotherapy. This article aimed to focus on those controversial problems in pathogenesis, natural history, diagnosis, and treatment strategies to help medical workers to better understand this rare disease.

PMID: 28528021 [PubMed - indexed for MEDLINE]

[Healthcare services for people in Lower Saxony (Germany) suffering from a rare disease: Findings from a survey among medical professionals].

Z Evid Fortbild Qual Gesundhwes. 2016;113:36-44

Authors: Pauer F, Pflaum U, Lührs V, Frank M, Graf von der Schulenburg JM

Abstract
BACKGROUND: In the European Union, about 30 million people are affected by one of the 7,000 to 8,000 diseases being defined as rare. In Germany alone, an estimated 4 million people suffer from a rare disease. In many cases, therapeutic options and knowledge of specific rare diseases are strongly limited.
OBJECTIVE: The aim of this study was to identify the deficits and challenges confronting healthcare services for people suffering from a rare disease from the medical professional's perspective.
METHOD: As many as 530 medical professionals were invited to complete an online questionnaire, which was also available on the website of the General Medical Council of Lower Saxony. The questionnaire focused on questions in the following fields: structure of the medical care system; diagnosis and therapy; information sources and information exchange; and improvement of healthcare situation. Data were analyzed using IBM SPSS 22.
RESULT: We received 65 completed questionnaires. The evaluation indicates deficits in the medical services provided for people with a rare disease and shortcomings in the communication between clinical disciplines. In addition, diagnostic and therapeutic options are limited, and quality-tested information is rare.
CONCLUSION: Many of the identified deficits have already been addressed in the German national plan of action for people affected by rare diseases. Furthermore, newly discovered deficits have been evaluated. The German government implemented healthcare structures to improve healthcare services for people with rare diseases. However, budget deficits for specialized structures have occurred inhibiting the expansion of healthcare services. Moreover, many patients need systemic treatment requiring the further development of interdisciplinary care.

PMID: 27480187 [PubMed - indexed for MEDLINE]

8 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Rare Diseases"[Mesh] OR "orphan disease"

These pubmed results were generated on 2018/05/29

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

6 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Rare Diseases"[Mesh] OR "orphan disease"

These pubmed results were generated on 2018/05/25

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Genetic disorders and mortality in infancy and early childhood: delayed diagnoses and missed opportunities.

Genet Med. 2018 Apr 12;:

Authors: Wojcik MH, Schwartz TS, Yamin I, Edward HL, Genetti CA, Towne MC, Agrawal PB

Abstract
PurposeInfants admitted to a level IV neonatal intensive care unit (NICU) who do not survive early childhood are a population that is probably enriched for rare genetic disease; we therefore characterized their genetic diagnostic evaluation.MethodsThis is a retrospective analysis of infants admitted to our NICU between 1 January 2011 and 31 December 2015 who were deceased at the time of records review, with age at death less than 5 years.ResultsA total of 2,670 infants were admitted; 170 later died. One hundred six of 170 (62%) had an evaluation for a genetic or metabolic disorder. Forty-seven of 170 (28%) had laboratory-confirmed genetic diagnoses, although 14/47 (30%) diagnoses were made postmortem. Infants evaluated for a genetic disorder spent more time in the NICU (median 13.5 vs. 5.0 days; p = 0.003), were older at death (median 92.0 vs. 17.5 days; p < 0.001), and had similarly high rates of redirection of care (86% vs. 79%; p = 0.28).ConclusionGenetic disorders were suspected in many infants but found in a minority. Approximately one-third of diagnosed infants died before a laboratory-confirmed genetic diagnosis was made. This highlights the need to improve genetic diagnostic evaluation in the NICU, particularly to support end-of-life decision making.Genetics in Medicine advance online publication, 12 April 2018; doi:10.1038/gim.2018.17.

PMID: 29790870 [PubMed - as supplied by publisher]