Scrofuloderma.

JAMA Dermatol. 2019 May 01;155(5):610

Authors: Oberhelman S, Watchmaker J, Phillips T

PMID: 30942835 [PubMed - indexed for MEDLINE]

Compartment Syndrome of the Forearm Following Dermofasciectomy-A Rare and Devastating Complication.

J Hand Surg Asian Pac Vol. 2019 Dec;24(4):491-493

Authors: Jones CD, Addison PR, Lam WL, Davidson DM

Abstract
We present a case of compartment syndrome of the forearm following harvesting of a full thickness skin graft from the medial forearm for a double digit dermofasciectomy. The patient underwent forearm fasciectomy followed by multiple surgical debridements. At 18 months, despite intensive physiotherapy, the patient was left with a very significant residual functional deficit. This case highlights a previously undescribed but devastating complication of closure of a forearm skin graft donor site.

PMID: 31690199 [PubMed - indexed for MEDLINE]

The oncology crisis in sub-Saharan Africa-the answer is clear and simple.

Surgery. 2019 12;166(6):1196-1197

Authors: Tarpley JL

PMID: 31444007 [PubMed - indexed for MEDLINE]

Moving Towards Accountability for Reasonableness - A Systematic Exploration of the Features of Legitimate Healthcare Coverage Decision-Making Processes Using Rare Diseases and Regenerative Therapies as a Case Study.

Int J Health Policy Manag. 2019 07 01;8(7):424-443

Authors: Wagner M, Samaha D, Casciano R, Brougham M, Abrishami P, Petrie C, Avouac B, Mantovani L, Sarría-Santamera A, Kind P, Schlander M, Tringali M

Abstract
BACKGROUND: The accountability for reasonableness (A4R) framework defines 4 conditions for legitimate healthcare coverage decision processes: Relevance, Publicity, Appeals, and Enforcement. The aim of this study was to reflect on how the diverse features of decision-making processes can be aligned with A4R conditions to guide decision-making towards legitimacy. Rare disease and regenerative therapies (RDRTs) pose special decision-making challenges and offer therefore a useful case study.
METHODS: Features operationalizing each A4R condition as well as three different approaches to address these features (cost-per-QALY-focused and multicriteria-based) were defined and organized into a matrix. Seven experts explored these features during a panel run under the Chatham House Rule and provided general and RDRT-specific recommendations. Responses were analyzed to identify converging and diverging recommendations.
RESULTS: Regarding Relevance, recommendations included supporting deliberation, stakeholder participation and grounding coverage decision criteria in normative and societal objectives. Thirteen of 17 proposed decision criteria were recommended by a majority of panelists. The usefulness of universal cost-effectiveness thresholds to inform allocative efficiency was challenged, particularly in the RDRT context. RDRTs raise specific issues that need to be considered; however, rarity should be viewed in relation to other aspects, such as disease severity and budget impact. Regarding Publicity, panelists recommended transparency about the values underlying a decision and value judgements used in selecting evidence. For Appeals, recommendations included a life-cycle approach with clear provisions for re-evaluations. For Enforcement, external quality reviews of decisions were recommended.
CONCLUSION: Moving coverage decision-making processes towards enhanced legitimacy in general and in the RDRT context involves designing and refining approaches to support participation and deliberation, enhancing transparency, and allowing explicit consideration of multiple decision criteria that reflect normative and societal objectives.

PMID: 31441279 [PubMed - indexed for MEDLINE]

Strategies for eliciting and synthesizing evidence for guidelines in rare diseases.

BMC Med Res Methodol. 2019 03 28;19(1):67

Authors: Pai M, Yeung CHT, Akl EA, Darzi A, Hillis C, Legault K, Meerpohl JJ, Santesso N, Taruscio D, Verhovsek M, Schünemann HJ, Iorio A

Abstract
BACKGROUND: Rare diseases are a global public health priority. Though each disease is rare, when taken together the thousands of known rare diseases cause significant morbidity and mortality, impact quality of life, and confer a social and economic burden on families and communities. These conditions are, by their nature, encountered very infrequently by individual clinicians, who may feel unprepared to address their diagnosis and treatment. Clinical practice guidelines are necessary to support clinical and policy decisions. However, creating guidelines for rare diseases presents specific challenges, including a paucity of high certainty evidence to inform panel recommendations.
METHODS: This paper draws from the authors' experience in the development of clinical practice guidelines for three rare diseases: hemophilia, sickle cell disease, and catastrophic antiphospholipid syndrome.
RESULTS: We have summarized a number of strategies for eliciting and synthesizing evidence that are compatible with the rigorous, internationally accepted standards for guideline development set out by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. These strategies include: use of pre-existing and ad hoc qualitative research, use of systematic observation forms, use of registry data, and thoughtful use of indirect evidence. Their use in three real guideline development efforts, as well as their theoretical underpinnings, are discussed. Avenues for future research to improve clinical practice guideline creation for rare diseases - and any disease affected by a relative lack of evidence - are also identified.
CONCLUSIONS: Rigorous clinical practice guidelines are needed to improve the care of the millions of people worldwide who suffer from rare diseases. Innovative evidence elicitation and synthesis methods will benefit not only the rare disease community, but also individuals with common diseases who have rare presentations, suffer rare complications, or require nascent therapies. Further refinement and improved uptake of these innovative methods should lead to higher quality clinical practice guidelines in rare diseases.

PMID: 30922227 [PubMed - indexed for MEDLINE]

Acquired Pili Torti.

JAMA Dermatol. 2019 Apr 01;155(4):488

Authors: Evans JB, Hastings JG, Kaffenberger BH

PMID: 30810707 [PubMed - indexed for MEDLINE]

Guidelines for uveal melanoma: a critical appraisal of systematically identified guidelines using the AGREE II and AGREE-REX instrument.

J Cancer Res Clin Oncol. 2020 Feb 08;:

Authors: Steeb T, Hayani KM, Förster P, Liegl R, Toussaint F, Schlaak M, Berking C, Heppt MV

Abstract
PURPOSE: Clinical practice guidelines provide recommendations for the management of diseases. In orphan conditions such as uveal melanoma (UM), guideline developers are challenged to provide practical and useful guidance even in the absence of high-quality evidence. Here, we assessed the methodological quality and identified deficiencies of international guidelines on UM as a base for future guideline development.
METHODS: A systematic search was carried out in guideline databases, Medline and Embase until 27th May 2019 for guidelines on UM published between 2004 and 2019. Five independent reviewers assessed the methodological quality of the identified guidelines using the instruments "Appraisal of Guidelines for Research and Evaluation II" (AGREE II) and AGREE-REX (Recommendation EXcellence). Descriptive analysis was performed and subgroup differences were explored with the Kruskal-Wallis (H) test. The relationship between the individual domains and items of the instruments were examined using Spearman's correlation.
RESULTS: Five guidelines published from 2014 to 2018 by consortia of the United States of America, Canada and the United Kingdom (UK) were included. The highest scores were obtained by the UK guideline fulfilling 48-86% of criteria in AGREE II and 30-60% for AGREE-REX. All guidelines showed deficiencies in the domains "editorial independence", "applicability", and "recommendation". Subgroup differences were identified only for the domain "editorial independence".
CONCLUSION: The UK guideline achieved the highest scores with both instruments and may serve as a basis for future guideline development in UM. The domains "editorial independence", "recommendation", and "applicability" were identified as methodological weaknesses and require particular attention and improvement in future guidelines.

PMID: 32036455 [PubMed - as supplied by publisher]

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 2020/02/08

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 2020/02/08

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.

7 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 2020/02/07

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.

7 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 2020/02/07

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.

27 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 2020/02/06

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.

22 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 2020/02/05

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.

Defining orphan conditions in the context of the European orphan regulation: challenges and evolution.

Nat Rev Drug Discov. 2019 07;18(7):479-480

Authors: O'Connor DJ, Sheean ME, Hofer MP, Tsigkos S, Mariz S, Fregonese L, Larsson K, Hivert V, Westermark K, Naumann-Winter F, Stoyanova-Beninska V, Barišić I, Capovilla G, Magrelli A, Sepodes B

PMID: 30940922 [PubMed - indexed for MEDLINE]

[Drugs for rare diseases: the blessing of being orphans.]

Recenti Prog Med. 2019 05;110(5):221-229

Authors: Costa E, Schieppati A, Luzzatto L, Remuzzi G

Abstract
The incentives provided by Orphan Drugs Regulations have promoted the development of drugs that effectively ameliorate the course of serious conditions that had previously been neglected. However, the treatment of each individual patient with any of these drugs - the so-called 'orphan drugs' - is so expensive, that the total burden for publicly funded Health care Service is enormous and may become unsustainable. Italy is no exception, if it is to abide by its basic tenet of providing access to essential medicines - free of charge - to the entire population. We do not see any glimpses of improvement on the horizon: therefore we suggest that radical change must be introduced. First, price negotiation ought to take place at the European level, not at the member state level. Second, pricing should take into account not only value for patients, but also costs of research and development (R&D) plus production. Italian Medicines Agency (AIFA) should also support research focused on optimizing the effective use of orphan drugs in clinical practice. The challenges are complex: but AIFA is recognized as an authoritative body, and may be able to coagulate the agreement of other regulatory agencies for the ultimate purpose of achieving, for each of the orphan drugs a more reasonable 'European price'.

PMID: 31140454 [PubMed - indexed for MEDLINE]

Basaloid nasopharyngeal carcinoma: A population-based analysis of a rare tumor.

Laryngoscope. 2019 12;129(12):2727-2732

Authors: Unsal AA, Booth JR, Rossi NA, Byrd JK, Kountakis SE

Abstract
OBJECTIVES: Basaloid nasopharyngeal carcinoma (BNPC) is an extremely rare malignancy with a paucity of cases reported in the literature. This analysis represents the largest cohort of BNPC to date.
STUDY DESIGN: Retrospective population-based analysis.
METHODS: The Surveillance, Epidemiology, and End Results registry from 2001 to 2015 was utilized to extract a total of 82 cases of BNPC. Data were analyzed for incidence trends, demographic, and tumor characteristics, as well as potential outcome prognosticators.
RESULTS: White male patients between the ages of 40 to 79 years were most commonly affected. The incidence was measured at 0.06 per 100 thousand people. The majority of tumors were considered high grade (grade III/IV; 92.2%). At presentation, patients were most commonly advanced stage (American Joint Committee on Cancer [AJCC] stage IV) at 29.3%, followed by AJCC stages II and III (20.7%, respectively). T2 tumors were most common at 28.8%. Cervical node involvement and distant metastasis were measured at 53.7% and 10.4%, respectively. One-year, 5-year, and 10-year disease-specific survival was 87.7%, 60.7%, and 29.8%, respectively. No prognostic factors were identified in this study.
CONCLUSION: Basaloid squamous cell carcinoma represents a histologic subtype of nasopharyngeal carcinoma with excellent short-term outcomes but poor survival at 10 years when compared to conventional squamous cell carcinomas.
LEVEL OF EVIDENCE: NA Laryngoscope, 129:2727-2732, 2019.

PMID: 30632158 [PubMed - indexed for MEDLINE]

Implementation of a genomic medicine multi-disciplinary team approach for rare disease in the clinical setting: a prospective exome sequencing case series.

Genome Med. 2019 07 25;11(1):46

Authors: Taylor J, Craft J, Blair E, Wordsworth S, Beeson D, Chandratre S, Cossins J, Lester T, Németh AH, Ormondroyd E, Patel SY, Pagnamenta AT, Taylor JC, Thomson KL, Watkins H, Wilkie AOM, Knight JC

Abstract
BACKGROUND: A multi-disciplinary approach to promote engagement, inform decision-making and support clinicians and patients is increasingly advocated to realise the potential of genome-scale sequencing in the clinic for patient benefit. Here we describe the results of establishing a genomic medicine multi-disciplinary team (GM-MDT) for case selection, processing, interpretation and return of results.
METHODS: We report a consecutive case series of 132 patients (involving 10 medical specialties with 43.2% cases having a neurological disorder) undergoing exome sequencing over a 10-month period following the establishment of the GM-MDT in a UK NHS tertiary referral hospital. The costs of running the MDT are also reported.
RESULTS: In total 76 cases underwent exome sequencing following triage by the GM-MDT with a clinically reportable molecular diagnosis in 24 (31.6%). GM-MDT composition, operation and rationale for whether to proceed to sequencing are described, together with the health economics (cost per case for the GM-MDT was £399.61), the utility and informativeness of exome sequencing for molecular diagnosis in a range of traits, the impact of choice of sequencing strategy on molecular diagnostic rates and challenge of defining pathogenic variants. In 5 cases (6.6%), an alternative clinical diagnosis was indicated by sequencing results. Examples were also found where findings from initial genetic testing were reconsidered in the light of exome sequencing including TP63 and PRKAG2 (detection of a partial exon deletion and a mosaic missense pathogenic variant respectively); together with tissue-specific mosaicism involving a cytogenetic abnormality following a normal prenatal array comparative genomic hybridization.
CONCLUSIONS: This consecutive case series describes the results and experience of a multidisciplinary team format that was found to promote engagement across specialties and facilitate return of results to the responsible clinicians.

PMID: 31345272 [PubMed - indexed for MEDLINE]

Antisynthetase Syndrome and Autoantibodies: A Literature Review and Report of 4 Cases.

Am J Case Rep. 2019 Jul 25;20:1094-1103

Authors: Marin FL, Sampaio HP

Abstract
BACKGROUND With the advent and advancement of autoantibodies, there has been progress in the diagnosis, prognosis, and treatment of rheumatologic diseases. Antisynthetase syndrome (ASS) is a great example of a disease that initially was described as arthritis, myositis, interstitial lung disease, mechanic's hands, Raynaud's phenomenon, and fever in the presence of the anti-JO-1 antibody, but nowadays it presents with a different spectrum related to new antibodies. CASE REPORT We describe 4 patients with antisynthetase syndrome who were diagnosed with antibodies specific for myositis associated with different clinical findings. All patients responded to immunosuppressive therapy, and rituximab was the most used. CONCLUSIONS It is necessary to search for specific autoantibodies related to the syndrome in suspected clinical cases and in other rheumatological diseases refractory to the usual treatment.

PMID: 31344020 [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 2020/01/29

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.

10 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 2020/01/28

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.