Cutaneous leukocytoclastic vasculitis due to amoxicillin hypersensitivity.

Ann Allergy Asthma Immunol. 2016 Aug 30;

Authors: Sáenz de Santa María García M, Morales-Cabeza C, Noguerado-Mellado B, Rojas-Pérez-Ezquerra P, Zubeldia JM

PMID: 27590637 [PubMed - as supplied by publisher]

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

("orphan disease" OR "rare disease" OR "orphan diseases" OR "rare diseases")

These pubmed results were generated on 2016/09/03

PubMed comprises more than 24 million 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.

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

("orphan disease" OR "rare disease" OR "orphan diseases" OR "rare diseases")

These pubmed results were generated on 2016/09/02

PubMed comprises more than 24 million 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.

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

("orphan disease" OR "rare disease" OR "orphan diseases" OR "rare diseases")

These pubmed results were generated on 2016/09/01

PubMed comprises more than 24 million 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.

Treatment of Inoperable Vulvar Cancer: Where We Come From and Where Are We Going.

Int J Gynecol Cancer. 2016 Aug 29;

Authors: Martinez-Castro P, Poveda A, Guinot JL, Minig L

Abstract
Vulvar cancer is a rare disease affecting elderly women that is commonly treated with surgery, radiation, and chemotherapy. When tumors compromise the urethra and the anus, or when it is in the groin lymph nodes, radiotherapy, chemotherapy, or both are necessary after surgery.The treatment of locally advanced vulvar cancer has suffered significant changes though the recent decades. So far, the best sequence of treatment is not known: surgery, chemotherapy, or radiotherapy. The radical surgeries usually need a long recovery term both in the region of the vulva and in the area of the groin lymph nodes. When it is performed, convalescence can delay other treatments, such as radiotherapy and chemotherapy. On the other hand, the use of radiotherapy and chemotherapy as a first step treatment can result in a complete elimination of the disease in at least 30% of the cases or substantial reduction of its size, allowing less extensive surgery. Therefore, the historical evolution of locally advanced vulvar cancer is reviewed.

PMID: 27575631 [PubMed - as supplied by publisher]

Evaluation of Specialty Drug Price Trends Using Data from Retrospective Pharmacy Sales Transactions.

J Manag Care Spec Pharm. 2016 Sep;22(9):1010-1017

Authors: Penington R, Stubbings JA

Abstract
BACKGROUND: The past 25 years have seen a substantial increase in the effect of specialty drugs on patient care. These agents were initially not considered financially viable because they often served a comparatively small market of patients. However, the extended monopoly afforded to manufacturers of these drugs by the Orphan Drug Act of 1983 has made treatment of rare diseases, which specialty drugs often target, a more viable option. As a result, pharmaceutical companies began to increase research and development expenditures in this area, and the pipeline of specialty drugs began to grow in the late 1980s.
OBJECTIVE: To analyze the annual change in wholesale acquisition cost (WAC) pricing of specialty drugs sold over a period of 11 years.
METHODS: Pharmacy claims data, including date and WAC, were collected for each specialty drug transaction that occurred from 2002 through 2013 at the University of Illinois at Chicago Ambulatory Care Pharmacy Department. The data were organized to create a chronological sequence of WAC values from the initial to final sales of each available drug. Those values were then used to calculate annual percentage of change in WAC. These results were grouped into subsets and graphed in order to illustrate the effects that various factors had on the annual changes in price.
RESULTS: The price of the specialty drugs studied has generally shown a greater rate of increase since experiencing a trough rate increase in 2009 of 4.08%. The economic crisis of 2008 created a short pause in this overall trend, but increases in the rate of price growth have since rebounded. WACs increased at a rate of 7.03% or greater from 2010 through the end of the study period. There was a clear increase over the last few years of the study in the number of drugs with more than 10% annual increases in WAC, which has also shown a rebound after the economic crisis at the end of the last decade.
CONCLUSIONS: Specialty drugs are getting more expensive at a faster rate over time. The period from 2010 to 2013, the final year of this study, has also seen biologic agents take a more prominent role in driving these annual increases in WAC.
DISCLOSURES: No funding was provided for the commission of this study. The source data was provided by the University of Illinois at Chicago Ambulatory Care Pharmacy Department and described de-identified data from customer transactions from 2002 through 2013. The authors report no conflicts of interest. Study concept and design and data interpretation were contributed by Stubbings and Penington. The manuscript was written primarily by Penington with assistance from Stubbings.

PMID: 27574742 [PubMed - as supplied by publisher]

The changing epidemiology of Ebstein's anomaly and its relationship with maternal mental health conditions: a European registry-based study.

Cardiol Young. 2016 Aug 30;:1-9

Authors: Boyle B, Garne E, Loane M, Addor MC, Arriola L, Cavero-Carbonell C, Gatt M, Lelong N, Lynch C, Nelen V, Neville AJ, O'Mahony M, Pierini A, Rissmann A, Tucker D, Zymak-Zakutnia N, Dolk H

Abstract
OBJECTIVES: The aim of this study was to describe the epidemiology of Ebstein's anomaly in Europe and its association with maternal health and medication exposure during pregnancy.
DESIGN: We carried out a descriptive epidemiological analysis of population-based data.
SETTING: We included data from 15 European Surveillance of Congenital Anomalies Congenital Anomaly Registries in 12 European countries, with a population of 5.6 million births during 1982-2011. Participants Cases included live births, fetal deaths from 20 weeks gestation, and terminations of pregnancy for fetal anomaly. Main outcome measures We estimated total prevalence per 10,000 births. Odds ratios for exposure to maternal illnesses/medications in the first trimester of pregnancy were calculated by comparing Ebstein's anomaly cases with cardiac and non-cardiac malformed controls, excluding cases with genetic syndromes and adjusting for time period and country.
RESULTS: In total, 264 Ebstein's anomaly cases were recorded; 81% were live births, 2% of which were diagnosed after the 1st year of life; 54% of cases with Ebstein's anomaly or a co-existing congenital anomaly were prenatally diagnosed. Total prevalence rose over time from 0.29 (95% confidence interval (CI) 0.20-0.41) to 0.48 (95% CI 0.40-0.57) (p<0.01). In all, nine cases were exposed to maternal mental health conditions/medications (adjusted odds ratio (adjOR) 2.64, 95% CI 1.33-5.21) compared with cardiac controls. Cases were more likely to be exposed to maternal β-thalassemia (adjOR 10.5, 95% CI 3.13-35.3, n=3) and haemorrhage in early pregnancy (adjOR 1.77, 95% CI 0.93-3.38, n=11) compared with cardiac controls.
CONCLUSIONS: The increasing prevalence of Ebstein's anomaly may be related to better and earlier diagnosis. Our data suggest that Ebstein's anomaly is associated with maternal mental health problems generally rather than lithium or benzodiazepines specifically; therefore, changing or stopping medications may not be preventative. We found new associations requiring confirmation.

PMID: 27572669 [PubMed - as supplied by publisher]

Off-label use of tumour necrosis factor-alpha inhibitors and anakinra at an Australian tertiary hospital.

Intern Med J. 2016 Aug 30;

Authors: Linger MW, van Driel ML, Hollingworth SA, Martin JH

Abstract
BACKGROUND: Tumour necrosis factor-alpha inhibitors (anti-TNFα) and anakinra are monoclonal antibodies against pro-inflammatory cytokines overexpressed in many systemic inflammatory diseases. In Australia they are registered for the treatment of several rheumatological, gastroenterological and dermatological indications. Despite increasing observational evidence for their use in off-label indications, there is a paucity of outcome research from the Australian hospital sector.
AIMS: To describe the off-label use of anti-TNFα and anakinra at a tertiary referral hospital in Queensland, Australia and consideration of a drug register to inform future clinical decision-making.
METHODS: We performed an in-depth retrospective chart audit of off-label treatment with anti-TNFα or anakinra at the Royal Brisbane and Women's Hospital from mid-2010 to mid-2014, linking demographic, phenotypic, pathology and outcome data with these drugs.
RESULTS: Off-label use was identified in 10 patients. The most frequent indications were sarcoidosis and dermatological conditions. Three patients required sequential therapy with a second anti-TNFα (total responses = 13). Complete response occurred in 46%, partial response in 38% and primary non-response in 8%. Response was unable to be determined in 8%. We recorded 14 adverse events (infections most common).
CONCLUSION: This study suggests anti-TNFα may be beneficial for some off-label indications (e.g. sarcoidosis). However, the observational design of this study (and pre-existing research) limits the ability to infer causality and generalise results. We propose the creation of a mandatory drug register to monitor off-label use. Whilst comparative efficacy cannot be established without a matched placebo arm, a register would enable some reporting on effectiveness in rare diseases and identify infrequent but serious adverse events.

PMID: 27572659 [PubMed - as supplied by publisher]

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

("orphan disease" OR "rare disease" OR "orphan diseases" OR "rare diseases")

These pubmed results were generated on 2016/08/30

PubMed comprises more than 24 million 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.

[Radiotherapy for retroperitoneal sarcomas].

Cancer Radiother. 2016 Aug 24;

Authors: Sargos P, Stoeckle E, Henriques de Figueiredo B, Antoine M, Delannes M, Mervoyer A, Kantor G

Abstract
The management of retroperitoneal sarcoma can be very challenging, and the quality of initial treatment strategy appears to be a crucial prognostic factor. En bloc surgery is currently the standard of care for these rare tumours and perioperative treatments such as chemotherapy or radiotherapy have not been validated yet. However, local-regional relapse constitutes the most common disease course. While adjuvant radiotherapy is less and less common due to gastrointestinal toxicities, preoperative radiation therapy offers numerous advantages and is being evaluated as part of a national multicentre phase II study (TOMOREP trial) and is the subject of a European randomized phase III study (STRASS trial). The objective of this article is to present data on preoperative irradiation in terms of dose, volumes and optimal radiotherapy techniques for the treatment of this rare disease.

PMID: 27568294 [PubMed - as supplied by publisher]

Explorations to improve the completeness of exome sequencing.

BMC Med Genomics. 2016;9(1):56

Authors: Du C, Pusey BN, Adams CJ, Lau CC, Bone WP, Gahl WA, Markello TC, Adams DR

Abstract
BACKGROUND: Exome sequencing has advanced to clinical practice and proven useful for obtaining molecular diagnoses in rare diseases. In approximately 75 % of cases, however, a clinical exome study does not produce a definitive molecular diagnosis. These residual cases comprise a new diagnostic challenge for the genetics community. The Undiagnosed Diseases Program of the National Institutes of Health routinely utilizes exome sequencing for refractory clinical cases. Our preliminary data suggest that disease-causing variants may be missed by current standard-of-care clinical exome analysis. Such false negatives reflect limitations in experimental design, technical performance, and data analysis.
RESULTS: We present examples from our datasets to quantify the analytical performance associated with current practices, and explore strategies to improve the completeness of data analysis. In particular, we focus on patient ascertainment, exome capture, inclusion of intronic variants, and evaluation of medium-sized structural variants.
CONCLUSIONS: The strategies we present may recover previously-missed, disease causing variants in second-pass exome analysis. Understanding the limitations of the current clinical exome search space provides a rational basis to improve methods for disease variant detection using genome-scale sequencing techniques.

PMID: 27568008 [PubMed - as supplied by publisher]

New insights into central nervous system involvement in FOP: Case report and review of the literature.

Am J Med Genet A. 2015 Nov;167A(11):2817-21

Authors: Bertamino M, Severino M, Schiaffino MC, Garrè ML, Bocciardi R, Ravazzolo R, Rossi A, Di Rocco M

Abstract
Fibrodyspasia ossificans progressiva is an autosomal dominant disease due to activating mutations in activin receptor type IA and characterized by progressive heterotopic ossification. Recently, the same non-synonymous heterozygous somatic mutations of ACVR1 have been identified in brain biopsies or autopsy of 24-27% of patients with a rare cerebral tumor, the diffuse intrinsic pontine glioma. We report the first case of a patient with FOP with incidental findings of an abnormal soft tissue mass surrounding the brainstem and causing obstructive hydrocephalus, associated with bilateral dentate lesions. Clinico-radiological course during 10 years of follow-up was consistent with a benign lesion, excluding an oncogenic role of ACVR1 mutations.

PMID: 26239063 [PubMed - indexed for MEDLINE]

A novel 2q37 microdeletion containing human neural progenitors genes including STK25 results in severe developmental delay, epilepsy, and microcephaly.

Am J Med Genet A. 2015 Nov;167A(11):2808-16

Authors: Imitola J, Khurana DS, Teplyuk NM, Zucker M, Jethva R, Legido A, Krichevsky AM, Frangieh M, Walsh CA, Carvalho KS

Abstract
2q37 microdeletion syndrome is a rare syndrome characterized by neurodevelopmental delay, bone, cardiovascular, and neurological alterations. This syndrome is typically associated with loss of genetic material of approximately 100 genes in the 2q37 band. However, the genes associated with neurodevelopmental phenotype in this syndrome are still unknown. We identified a deleted region of 496 kb by whole genome array CGH in a patient who fulfilled criteria for 2q37 microdeletion syndrome with developmental delay, microcephaly, hypoplasia of the corpus callosum, hand wringing, toe walking, and seizures. The deleted segment contains genes that are highly expressed in the developing human cortical plate and the subventricular zone (SVZ) in vivo and human neural progenitors in vitro, including SEPT2, THAP4, ATG4B, PPP1R7, and STK25. Network analysis revealed that STK25 was the most interacting gene associated with neural development in this deletion. Our report narrows the likely causative genomic region for microcephaly and neurodevelopmental delay in 2q37 microdeletion syndrome to a small genomic region enriched with neural progenitor genes that may represent an important locus for the development of the human cortex and corpus callosum.

PMID: 26238961 [PubMed - indexed for MEDLINE]

Response to long-term growth hormone therapy in patients affected by RASopathies and growth hormone deficiency: Patterns of growth, puberty and final height data.

Am J Med Genet A. 2015 Nov;167A(11):2786-94

Authors: Tamburrino F, Gibertoni D, Rossi C, Scarano E, Perri A, Montanari F, Fantini MP, Pession A, Tartaglia M, Mazzanti L

Abstract
RASopathies are developmental disorders caused by heterozygous germline mutations in genes encoding proteins in the RAS-MAPK signaling pathway. Reduced growth is a common feature. Several studies generated data on growth, final height (FH), and height velocity (HV) after growth hormone (GH) treatment in patients with these disorders, particularly in Noonan syndrome, the most common RASopathy. These studies, however, refer to heterogeneous cohorts in terms of molecular information, GH status, age at start and length of therapy, and GH dosage. This work reports growth data in 88 patients affected by RASopathies with molecularly confirmed diagnosis, together with statistics on body proportions, pubertal pattern, and FH in 33, including 16 treated with GH therapy for proven GH deficiency. Thirty-three patients showed GH deficiency after pharmacological tests, and were GH-treated for an average period of 6.8 ± 4.8 years. Before starting therapy, HV was -2.6 ± 1.3 SDS, and mean basal IGF1 levels were -2.0 ± 1.1 SDS. Long-term GH therapy, starting early during childhood, resulted in a positive height response compared with untreated patients (1.3 SDS in terms of height-gain), normalizing FH for Ranke standards but not for general population and Target Height. Pubertal timing negatively affected pubertal growth spurt and FH, with IGF1 standardized score increased from -2.43 to -0.27 SDS. During GH treatment, no significant change in bone age velocity, body proportions, or cardiovascular function was observed.

PMID: 26227443 [PubMed - indexed for MEDLINE]

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

("orphan disease" OR "rare disease" OR "orphan diseases" OR "rare diseases")

These pubmed results were generated on 2016/08/28

PubMed comprises more than 24 million 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.

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

("orphan disease" OR "rare disease" OR "orphan diseases" OR "rare diseases")

These pubmed results were generated on 2016/08/27

PubMed comprises more than 24 million 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:

("orphan disease" OR "rare disease" OR "orphan diseases" OR "rare diseases")

These pubmed results were generated on 2016/08/26

PubMed comprises more than 24 million 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.

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

("orphan disease" OR "rare disease" OR "orphan diseases" OR "rare diseases")

These pubmed results were generated on 2016/08/25

PubMed comprises more than 24 million 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.

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

("orphan disease" OR "rare disease" OR "orphan diseases" OR "rare diseases")

These pubmed results were generated on 2016/08/24

PubMed comprises more than 24 million 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.

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

("orphan disease" OR "rare disease" OR "orphan diseases" OR "rare diseases")

These pubmed results were generated on 2016/08/23

PubMed comprises more than 24 million 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.