Mohs Surgery for SEER Registry-Captured Melanoma In Situ and Rare Cutaneous Tumors: Comparing National Utilization Patterns Before and After Implementation of the Affordable Care Act (2010) and Appropriate Use Criteria (2012).

Dermatol Surg. 2020 08;46(8):1021-1029

Authors: Garland K, Condon S, Xiong DD, Crowe D, Knackstedt TJ

Abstract
BACKGROUND: The Affordable Care Act (ACA) and the appropriate use criteria (AUC) for Mohs micrographic surgery (MMS) had the potential to increase utilization rates of MMS for indicated skin cancers, but it is unknown whether this has occurred.
OBJECTIVE: To determine whether rates of MMS utilization for head and neck melanoma in situ (MIS) and rare cutaneous tumors (RCTs) increased after the implementation of the ACA and AUC publication.
MATERIALS AND METHODS: Retrospective review using data from the SEER database. Melanoma in situ and RCT tumor cases from before and after the ACA and AUC publication were compared.
RESULTS: Twenty-four thousand six hundred seventy-eight cases were analyzed. Mohs micrographic surgery utilization for MIS decreased from 13.9% before the ACA to 12.3% after the ACA (odds ratio 0.87; p = .012). There was no significant change in MMS utilization for MIS after publication of the AUC. There was also no significant change in MMS utilization for treatment of RCT after the ACA or AUC publication. Stratification of patients into age groups younger or older than 65 years did not change utilization rates.
CONCLUSION: Rates of MMS for treatment of MIS and RCT have not increased since the advent of the ACA or AUC. This finding highlights the need for continued efforts to improve access to MMS and to increase education of its utility in treating skin cancer.

PMID: 31929340 [PubMed - indexed for MEDLINE]

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 2021/01/05

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 2021/01/05

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.

Zhonghua Er Ke Za Zhi. 2021 Jan 2;59(1):56-58. doi: 10.3760/cma.j.cn112140-20200722-00742.

NO ABSTRACT

PMID:33397006 | DOI:10.3760/cma.j.cn112140-20200722-00742

Successful use of hyperbaric oxygen therapy for limb salvage of acute limb ischemia as a complication of acute carbon monoxide poisoning.

Undersea Hyperb Med. 2020 Second Quarter;47(2):235-240

Authors: Kim YS, Youn YJ, Cha YS

Abstract
Acute limb ischemia (ALI) as a complication of acute carbon monoxide (CO) poisoning is rare. Several reports have utilized hyperbaric oxygen therapy (HBO2) as an adjunctive therapy for peripheral arterial diseases. However, no study has yet described the use of HBO2 for ALI precipitated by CO poisoning. Herein we report successful limb salvage achieved with adjunctive HBO2 and conventional therapies in a patient with CO-induced ALI. A 69-year-old man was admitted with acute CO poisoning; ALI of both lower extremities occurred on hospitalization day 3. Pre-existing risk factors for ALI other than CO were not definite. After conventional treatments including catheter-directed thrombolysis and endovascular thrombectomy, the right-side lesion remained and a left-side lesion was newly developed. In addition to prior therapies, 47 sessions of serial HBO2 were administered as adjunctive therapy, resulting in limb salvage. Acute CO poisoning can cause ALI as a rare complication. HBO2 may be utilized as an adjunctive treatment in ALI.

PMID: 32574440 [PubMed - in process]

Commentary on rare dyslipidaemia paper.

Atherosclerosis. 2020 02;295:54-58

Authors: Stock JK

PMID: 31952820 [PubMed - in process]

[What entertainment television can do to convey medical knowledge to students and laypeople-raising awareness of rare diseases].

Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2020 Dec 09;:

Authors: Schaefer JR, von Hirschhausen E

Abstract
People with complex and rare diseases often have a difficult time in our health system. It can take years to reach a diagnosis and there is often no suitable therapy. Rare diseases are anything but rare among patients: around 4 million people are affected in Germany alone. Nevertheless, rare diseases can often only be diagnosed when they are well enough known and the population is made aware of their existence-this applies to both laypeople and medical professionals. The rather unusual form of imparting knowledge via entertainment television can make an important contribution to disseminate medical knowledge and to raise awareness of medical topics. In specific cases, entertainment television can help to diagnose rare diseases or encourage laypeople to take lifesaving measures, which we try to illustrate in this paper.Series and quiz shows reach more viewers than traditional health programs. They have also proven to be exceptionally effective in student teaching. Since the narrative form focuses on cheering and guessing, instead of simply conveying facts, the medical topics become more emotionally anchored memories and easier to recall. Entertainment television thus offers an innovative approach to increase the health literacy of the population-a potential that could be used more intensively in Germany.

PMID: 33296003 [PubMed - as supplied by publisher]

Phenotype-genotype comorbidity analysis of patients with rare disorders provides insight into their pathological and molecular bases.

PLoS Genet. 2020 10;16(10):e1009054

Authors: Díaz-Santiago E, Jabato FM, Rojano E, Seoane P, Pazos F, Perkins JR, Ranea JAG

Abstract
Genetic and molecular analysis of rare disease is made difficult by the small numbers of affected patients. Phenotypic comorbidity analysis can help rectify this by combining information from individuals with similar phenotypes and looking for overlap in terms of shared genes and underlying functional systems. However, few studies have combined comorbidity analysis with genomic data. We present a computational approach that connects patient phenotypes based on phenotypic co-occurence and uses genomic information related to the patient mutations to assign genes to the phenotypes, which are used to detect enriched functional systems. These phenotypes are clustered using network analysis to obtain functionally coherent phenotype clusters. We applied the approach to the DECIPHER database, containing phenotypic and genomic information for thousands of patients with heterogeneous rare disorders and copy number variants. Validity was demonstrated through overlap with known diseases, co-mention within the biomedical literature, semantic similarity measures, and patient cluster membership. These connected pairs formed multiple phenotype clusters, showing functional coherence, and mapped to genes and systems involved in similar pathological processes. Examples include claudin genes from the 22q11 genomic region associated with a cluster of phenotypes related to DiGeorge syndrome and genes related to the GO term anterior/posterior pattern specification associated with abnormal development. The clusters generated can help with the diagnosis of rare diseases, by suggesting additional phenotypes for a given patient and potential underlying functional systems. Other tools to find causal genes based on phenotype were also investigated. The approach has been implemented as a workflow, named PhenCo, which can be adapted to any set of patients for which phenomic and genomic data is available. Full details of the analysis, including the clusters formed, their constituent functional systems and underlying genes are given. Code to implement the workflow is available from GitHub.

PMID: 33001999 [PubMed - in process]

[Orphan drugs and drug pirates].

Ned Tijdschr Geneeskd. 2020 06 18;164:

Authors: Bannenberg WJ, 't Hoen EFM

Abstract
The European Orphan Medicines Regulation, which came into effect in 2000, stimulates the development of medicines for rare diseases. The number of registered orphan medicines has increased from eight in 2000 to 169 in 2019; 38% of these are available in the Netherlands. The costs for orphan medicines in the Netherlands are increasing by 9% every year, and now amount to €272 million annually. There is, however, still no effective medication for thousands of rare diseases. The Orphan Regulation was intended for new orphan medicines, but some companies also use it for 'repurposing' of old agents, for which they also get 10 years exclusive market rights in the EU. The improper use of legislation has led to concern among patients, doctors, and medical insurance companies. The Netherlands Council for Public Health and Society and MPs in the lower house of the Netherlands parliament have proposed measures for tackling the high prices of medicines and Mr. Bruins, the former Minister of Health, wanted to propose legislative change in the EU. The EU 'pharmaceutical incentive review' offers the possibility to revise the current rules.

PMID: 32749801 [PubMed - in process]

Patent landscape of novel technologies for combating category-A Arenavirus infections.

Expert Opin Ther Pat. 2020 Jul;30(7):557-565

Authors: Sudhakar H, Bhate J, Patra AK

Abstract
INTRODUCTION: Arenavirus are unique category-A pathogens that are also classified as Orphan diseases. Very few options exist currently for treating Viral Hemorrhagic Fever (VHF) caused by viruses belonging to the Arenaviridae family [1]. The current review provides detailed patent landscape and a description of selected technologies developed for combating category-A Arenavirus. Currently, Arenavirus infections are epidemic [2] but could cause widespread pandemics due to ease of dissemination and lack of immunity against these viruses.
AREAS COVERED: The key strings for selected Arenavirus VHF were run separately in MCPaIRS®, PatSeer, and Questel database. The search was limited to Title, Abstract and Claim fields; one member per patent family was considered for analysis.
EXPERT OPINION: Synthetic molecules dominate the patent landscape, while natural products have not been extensively claimed for the treatment of Arenavirus infection. The broad-spectrum activity has been highly desired for Arenavirus treatment, but few reports have experimentally tested it. With each year, a constant increase in number of patents published is seen, while the maximum number of applications was filed in 2017. The research in VHF is driven by public funds; the maximum numbers of patents were filed by publicly funded organizations.

PMID: 32274944 [PubMed - in process]

BMJ Case Rep. 2020 Dec 31;13(12):e237208. doi: 10.1136/bcr-2020-237208.

ABSTRACT

Nocardiosis is a rare infection in patients with myasthenia gravis (MG). We identified three cases of MG admitted with nocardiosis in our unit. We performed systematic literature search of previous publications and identified 18 patients. This paper presents three patients and reviews the clinical characteristics of 21 patients. The first case was a 69-year-old woman with thymomatous MG who presented with pustules and left lower limb pain. Evaluation showed osteomyelitis of the pubic ramus and ileopsoas abscess. The second case was a 54-year-old man who presented in myasthenic crisis due to pulmonary nocardiosis. The third case was a 48-year-old man with thymomatous MG who presented with lung abscess. All of them recovered completely after treatment with co-trimoxazole. Analysis of the 21 patients identified four risk factors for nocardiosis in MG: elderly men; thymoma; immunosuppressant medication, mainly steroid therapy; and pre-existing lung disease. Lungs was the most common site of infection. Suppurative disease was common manifestation regardless of organ involved. Clinical course is not unfavourable.

PMID:33384345 | PMC:PMC7780555 | DOI:10.1136/bcr-2020-237208

BMJ Case Rep. 2020 Dec 31;13(12):e237061. doi: 10.1136/bcr-2020-237061.

ABSTRACT

Hafnia alvei is a rare, poorly understood commensal bacterium which has, on occasion, been shown to infect humans. We present two cases. The first patient presented with a 1-week history of dyspnoea, pleurisy and a productive cough, and the second with a prodrome of fatigue and night sweats. The former had a history of severe chronic obstructive pulmonary disease and the latter had a history of Crohn's disease. Both patients had underlying comorbidities and immunosuppression, but differed in presentation, radiological findings and recovery. This case series aims to remind readers of the broad differential of pathogens that can lead to disease in the immunocompromised and that one should not dismiss atypical cultured bacteria as commensal too hastily.

PMID:33384344 | PMC:PMC7780556 | DOI:10.1136/bcr-2020-237061

ACCELERATE: A Patient-Powered Natural History Study Design Enabling Clinical and Therapeutic Discoveries in a Rare Disorder.

Cell Rep Med. 2020 Dec 22;1(9):100158

Authors: Pierson SK, Khor JS, Ziglar J, Liu A, Floess K, NaPier E, Gorzewski AM, Tamakloe MA, Powers V, Akhter F, Haljasmaa E, Jayanthan R, Rubenstein A, Repasky M, Elenitoba-Johnson K, Ruth J, Jacobs B, Streetly M, Angenendt L, Patier JL, Ferrero S, Zinzani PL, Terriou L, Casper C, Jaffe E, Hoffmann C, Oksenhendler E, Fosså A, Srkalovic G, Chadburn A, Uldrick TS, Lim M, van Rhee F, Fajgenbaum DC

Abstract
Geographically dispersed patients, inconsistent treatment tracking, and limited infrastructure slow research for many orphan diseases. We assess the feasibility of a patient-powered study design to overcome these challenges for Castleman disease, a rare hematologic disorder. Here, we report initial results from the ACCELERATE natural history registry. ACCELERATE includes a traditional physician-reported arm and a patient-powered arm, which enables patients to directly contribute medical data and biospecimens. This study design enables successful enrollment, with the 5-year minimum enrollment goal being met in 2 years. A median of 683 clinical, laboratory, and imaging data elements are captured per patient in the patient-powered arm compared with 37 in the physician-reported arm. These data reveal subgrouping characteristics, identify off-label treatments, support treatment guidelines, and are used in 17 clinical and translational studies. This feasibility study demonstrates that the direct-to-patient design is effective for collecting natural history data and biospecimens, tracking therapies, and providing critical research infrastructure.

PMID: 33377129 [PubMed]

[Rare dermatological diseases: The role of social workers regarding adult patients. The example of epidermal necrolysis].

Ann Dermatol Venereol. 2020 Apr;147(4):318-321

Authors: Bourgeois A, Colin A, Redlich J, de Prost N, Ingen-Housz-Oro S

PMID: 32087980 [PubMed - indexed for MEDLINE]

PLoS One. 2020 Dec 31;15(12):e0243562. doi: 10.1371/journal.pone.0243562. eCollection 2020.

ABSTRACT

BACKGROUND: Recruitment of individuals with rare diseases for studies of real-world patient-reported outcomes is limited by small base populations. Myeloproliferative neoplasms (MPNs) are a group of rare, chronic, hematologic malignancies. In this study, recruitment strategies and geographic representativeness from the Living with MPNs survey are reported.

METHODS: The Living with MPNs online cross-sectional survey was conducted between April and November 2016. Individuals 18 to 70 years of age living in the United States and diagnosed with an MPN were eligible to participate. Recruitment approaches included direct contact via emails and postcards; posts on MPN-focused social media and patient advocacy websites; postcard mailings to doctors' offices; and advertisements on medical websites, Google, and Facebook. Geographic representativeness was assessed based on the number of survey respondents living in each state or the District of Columbia and by the number of survey respondents per 10 million residents.

RESULTS: A total of 904 respondents with MPNs completed the survey. The recruitment method yielding the greatest number of respondents was advertisements on MPN-focused social media (47.6% of respondents), followed by emails (35.1%) and postcards (13.9%) sent through MPN advocacy groups. Home state information was provided by 775 respondents from 46 states (range of respondents per state, 1-89). The number of respondents per 10 million residents in the 46 states with respondents ranged from 12.1 to 52.7.

CONCLUSIONS: Recruitment using social media and communications through patient groups and advocacy organizations are effective in obtaining geographically representative samples of individuals with MPNs in the United States. These approaches may also be effective in other rare diseases.

PMID:33382745 | PMC:PMC7774910 | DOI:10.1371/journal.pone.0243562

Int J Environ Res Public Health. 2020 Dec 28;18(1):139. doi: 10.3390/ijerph18010139.

ABSTRACT

Fifteen percent of the 5000 to 8000 rare diseases (RDs) can manifest in the oral and maxillofacial region. Little attention has been paid to the care situation of people with RDs in dentistry. Hence, the aim of this study was to assess the level of knowledge about RDs among dentists at a university hospital (DUs) compared to dentists with different professional backgrounds and among general dentists, specialist dentists and DUs in the chamber district of Westfalen-Lippe. Moreover, self-assessment of the level of knowledge was evaluated. A questionnaire was designed, which was made available digitally via a link. A random sample of 1500 dentists, specialist dentists, and oral- and craniomaxillofacial surgeons from the membership of the Dental Association of Westfalen-Lippe, and all dentists, specialist dentists, and oral- and craniomaxillofacial surgeons working at the University Dental Hospitals Münster and Witten/Herdecke, were invited to participate to our study. Differences in the level of knowledge between DUs and non-DUs and differences between DUs, general dentists, and specialist dentists were tested via two-sided Fischer's exact tests. Differences between the three groups of self-assessment of the level of knowledge and the self-assessment of how sufficient their own knowledge about RDs is were tested via two-sided Kruskal-Wallis tests. The global level of significance was controlled by the Bonferroni method. A total of 267 questionnaires were completed, of which 64.0% were answered by general dentists, 25.5% by specialist dentists and 10.5% by DUs. DUs had a significant higher level of knowledge about RDs (adjusted p = 0.012) compared to non-DUs and achieved higher scores (median = 16.5 points) than general (median = 13 points) and specialist dentists (median = 13 points) (p = 0.001). In the self-assessments, the differences were not significant (p > 0.05). In conclusion, most participants showed no or little knowledge about RDs, and DUs had a significant higher level of knowledge than non-university dentists.

PMID:33379144 | PMC:PMC7796213 | DOI:10.3390/ijerph18010139

14 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 2020/12/29

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.

BMJ Case Rep. 2020 Dec 21;13(12):e234888. doi: 10.1136/bcr-2020-234888.

NO ABSTRACT

PMID:33370937 | PMC:PMC7754646 | DOI:10.1136/bcr-2020-234888

SPEG binds with desmin and its deficiency causes defects in triad and focal adhesion proteins.

Hum Mol Genet. 2020 Dec 23;:

Authors: Luo S, Li Q, Lin J, Murphy Q, Marty I, Zhang Y, Kazerounian S, Agrawal PB

Abstract
SPEG, a member of the myosin light chain kinase family, is localized at the level of triad surrounding myofibrils in skeletal muscles. In humans, SPEG mutations are associated with centronuclear myopathy and cardiomyopathy. Using a striated muscle specific Speg-knockout (KO) mouse model, we have previously shown that SPEG is critical for triad maintenance and calcium handling. Here we further examined the molecular function of SPEG and characterized the effects of SPEG deficiency on triad and focal adhesion proteins. We used yeast two-hybrid assay, and identified desmin, an intermediate filament protein, to interact with SPEG and confirmed this interaction by co-immunoprecipitation. Using domain-mapping assay, we defined that Ig-like and fibronectin III domains of SPEG interact with rod domain of desmin. In skeletal muscles, SPEG depletion leads to desmin aggregates in vivo and a shift in desmin equilibrium from soluble to insoluble fraction. We also profiled the expression and localization of triadic proteins in Speg-KO mice using western blot and immunofluorescence. The amounts of RyR1 and triadin were markedly reduced, whereas DHPRα1, SERCA1, and triadin were abnormally accumulated in discrete areas of Speg-KO myofibers. In addition, Speg-KO muscles exhibited internalized vinculin and β1 integrin, both of which are critical components of the focal adhesion complex. Further, β1 integrin was abnormally accumulated in early endosomes of Speg-KO myofibers. These results demonstrate that SPEG-deficient skeletal muscles exhibit several pathological features similar to those seen in MTM1 deficiency. Defects of shared cellular pathways may underlie these structural and functional abnormalities in both types of diseases.

PMID: 33355670 [PubMed - as supplied by publisher]

Proc Natl Acad Sci U S A. 2021 Jan 12;118(2):e2008861118. doi: 10.1073/pnas.2008861118.

ABSTRACT

The paucity of knowledge about cardiomyocyte maturation is a major bottleneck in cardiac regenerative medicine. In development, cardiomyocyte maturation is characterized by orchestrated structural, transcriptional, and functional specializations that occur mainly at the perinatal stage. Sarcomeres are the key cytoskeletal structures that regulate the ultrastructural maturation of other organelles, but whether sarcomeres modulate the signal transduction pathways that are essential for cardiomyocyte maturation remains unclear. To address this question, here we generated mice with cardiomyocyte-specific, mosaic, and hypomorphic mutations of α-actinin-2 (Actn2) to study the cell-autonomous roles of sarcomeres in postnatal cardiomyocyte maturation. Actn2 mutation resulted in defective structural maturation of transverse-tubules and mitochondria. In addition, Actn2 mutation triggered transcriptional dysregulation, including abnormal expression of key sarcomeric and mitochondrial genes, and profound impairment of the normal progression of maturational gene expression. Mechanistically, the transcriptional changes in Actn2 mutant cardiomyocytes strongly correlated with those in cardiomyocytes deleted of serum response factor (SRF), a critical transcription factor that regulates cardiomyocyte maturation. Actn2 mutation increased the monomeric form of cardiac α-actin, which interacted with the SRF cofactor MRTFA and perturbed its nuclear localization. Overexpression of a dominant-negative MRTFA mutant was sufficient to recapitulate the morphological and transcriptional defects in Actn2 and Srf mutant cardiomyocytes. Together, these data indicate that Actn2-based sarcomere organization regulates structural and transcriptional maturation of cardiomyocytes through MRTF-SRF signaling.

PMID:33361330 | PMC:PMC7812832 | DOI:10.1073/pnas.2008861118