pinecone/core-2020-05-10-deduplication huggingface dataset:
Health, Wealth, and the 21st Century Cures Act

Americans are increasingly apprehensive about our future, so it is inspiring when Congress produces legislation intended to both enhance our health and expand our economy. The 21st Century Cures Act,1 recently passed by the House with an impressive bipartisan majority vote of 344 to 77, intends to accelerate the many-step process of drug discovery and development, from basic scientific research to clinical development to delivery, distribution, and ongoing monitoring. Among other things, the legislation boosts National Institute of Health funding, dramatically speeds up the US Food and Drug Administration (FDA) approval process, and aims to make use of new information technology to better monitor the performance of medical products after they reach the market. This landmark bill now awaits a comparable piece of legislation being developed by the Senate Health Education, Labor, and Pensions Committee. Together, they will transform the biomedical ecosystem and provide the foundation for the next several decades of innovative life-saving and health-enhancing solutions for our nation and the world
Assessment of overall survival, quality of life, and safety benefits associated with new cancer medicines

Importance: There is a dearth of evidence examining the impact of newly licensed cancer medicines on therapy. This information could otherwise support clinical practice, and promote value-based decision-making in the cancer drug market. Objective: To evaluate the comparative therapeutic value of all new cancer medicines approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) between 2003 and 2013. Design, Setting, and Participants: We used a narrative synthesis approach to systematically synthesize and analyze English, French, and Australian health technology assessments (HTAs) of all new cancer medicines licensed in the United States and Europe between 2003 and 2013. Interventions: Sixty-two new molecular entities with a primary oncology indication. Main Outcomes and Measures: Overall survival (OS), quality of life (QoL), and safety. Results:  Of the 62 new active cancer molecules approved by the FDA and EMA between 2003 and 2013, 53 were appraised by English, French, or Australian HTA agencies through May 2015. Of these 53 drugs, 23 (43%) increased OS by 3 months or longer, 6 (11%) by less than 3 months, and 8 (15%) by an unknown magnitude; there was no evidence to suggest that the remaining 16 (30%) increased OS over best alternative treatments. Where overall survival gains could be quantified, all new cancer drugs were associated with a mean (SE) total increase in OS of 3.43 (0.63) months over the treatments that were available in 2003. Drug-related improvements in OS were, however, widely distributed across therapeutic targets—ranging between 0 (thyroid, ascites) and 8.48 months (breast cancers)—and were sometimes based on modeled data, indirect or nonactive comparisons, or nonvalidated evidence. Although 22 (42%) of 53 new medicines were associated with an increase in QoL, 24 (45%) were also associated with reduced patient safety. Of the 53 new cancer drugs, 42 (79%) were associated with at least some improvement in OS, QoL, or safety. Conclusions and Relevance: Although innovation in the oncology drug market has contributed to improvements in therapy, the magnitude and dimension of clinical benefits vary widely, and there may be reasons to doubt that claims of efficacy reflect real-world effectiveness exactly. These findings raise important questions for clinical decision-making and value-based policy
Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases

IMPORTANCE: The causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. OBJECTIVE: To conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases. DATA SOURCES: Genomewide association studies (GWAS) published up to January 15, 2015. STUDY SELECTION: GWAS of noncommunicable diseases that assayed germline genetic variation and did not select cohort or control participants on the basis of preexisting diseases. Of 163 GWAS of noncommunicable diseases identified, summary data from 103 were available. DATA EXTRACTION AND SYNTHESIS: Summary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population. MAIN OUTCOMES AND MEASURES: Odds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation. RESULTS: Summary data were available for 35 cancers and 48 non-neoplastic diseases, corresponding to 420 081 cases (median cases, 2526 per disease) and 1 093 105 controls (median, 6789 per disease). Increased telomere length due to germline genetic variation was generally associated with increased risk for site-specific cancers. The strongest associations (ORs [95% CIs] per 1-SD change in genetically increased telomere length) were observed for glioma, 5.27 (3.15-8.81); serous low-malignant-potential ovarian cancer, 4.35 (2.39-7.94); lung adenocarcinoma, 3.19 (2.40-4.22); neuroblastoma, 2.98 (1.92-4.62); bladder cancer, 2.19 (1.32-3.66); melanoma, 1.87 (1.55-2.26); testicular cancer, 1.76 (1.02-3.04); kidney cancer, 1.55 (1.08-2.23); and endometrial cancer, 1.31 (1.07-1.61). Associations were stronger for rarer cancers and at tissue sites with lower rates of stem cell division. There was generally little evidence of association between genetically increased telomere length and risk of psychiatric, autoimmune, inflammatory, diabetic, and other non-neoplastic diseases, except for coronary heart disease (OR, 0.78 [95% CI, 0.67-0.90]), abdominal aortic aneurysm (OR, 0.63 [95% CI, 0.49-0.81]), celiac disease (OR, 0.42 [95% CI, 0.28-0.61]) and interstitial lung disease (OR, 0.09 [95% CI, 0.05-0.15]). CONCLUSIONS AND RELEVANCE: It is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases. Copyright 2017 American Medical Association. All rights reserved
Effect of Intravitreous Anti–Vascular Endothelial Growth Factor Therapy on Choroidal Thickness in Neovascular Age-Related Macular Degeneration Using Spectral-Domain Optical Coherence Tomography

A critical method of monitoring patients with neovascular age-related macular degeneration (AMD) being treated with anti–vascular endothelial growth factor (anti-VEGF) is optical coherence tomography (OCT), which uses low-coherence interferometry of light to examine the retina in vivo on a micrometer scale.National Institutes of Health (U.S.) (Grant R01-EY11289-25)National Institutes of Health (U.S.) (Grant R01-EY13178-10)National Institutes of Health (U.S.) (Grant R01-EY013516-07)National Institutes of Health (U.S.) (Grant R01-EY019029-02)United States. Air Force Office of Scientific Research (Grant FA9550-10-1-0551)United States. Air Force Office of Scientific Research (Grant FA9550-10-1-0063)Massachusetts Lions Club
Clinical aspects of usher syndrome and the USH2A gene in a cohort of 433 patients

IMPORTANCE A new statistical approach is needed to describe the clinical differences
between type I and type II Usher syndrome and between the 2 most frequent mutations in
the USH2A gene.
OBJECTIVES To describe the primary phenotypic characteristics and differences between
type I and type II Usher syndrome and to establish a phenotype-genotype correlation for the
2 most frequent mutations in the USH2A gene.
DESIGN, SETTING, AND PARTICIPANTS Cross-sectional study at a genetics department, in
which clinical evaluations were performed for 433 patients (297 unrelated families) who were
classified as having type I, II, III, atypical, or unclassified Usher syndrome according to their
clinical history, pedigree data, results from ophthalmological studies, and audiological,
neurophysiological, and vestibular test results. Molecular studies were performed for 304
patients (256 unrelated families). The Mann-Whitney U test or the χ2 test was used for
calculating the differences between mean values for the analyzed parameters.
MAIN OUTCOMES AND MEASURES Age at diagnosis; age at onset of night blindness, visual field
loss, visual acuity loss, and cataracts; and severity and age at diagnosis of hearing loss.
RESULTS The comparison between patients with type I Usher syndrome and those with type
II Usher syndrome revealed P < .001 for most items analyzed. The most frequent mutations in
the USH2A gene were the p.Glu767Serfs*21 and p.Cys759Phe mutations, with an allelic
frequency of 23.2%(63 of 272 alleles) and 8.1% (22 of 272 alleles), respectively. The
phenotypic analysis for patients carrying p.Cys759Phe showed P < .001 for most items
analyzed when compared with patients carrying p.Glu767Serfs*21 and when compared with
patients carrying other mutations in the USH2A gene. None of the p.Cys759Phe patients
exhibited a severe hearing loss phenotype, and more than 60%had only mild hearing loss.
Most patients carrying the p.Glu767Serfs*21 mutation (72.1%) were moderately deaf.
CONCLUSIONS AND RELEVANCE Our study presents the clinical differences between type I and
type II Usher syndrome and between the 2 most frequent mutations in the USH2A gene.
Detailed genotype-phenotype correlations, as presented in our study, allow for a better
correlation of clinical signs with a known genotype and can improve the clinical management,
genetic counseling, and risk assessment of patients with Usher syndrome because an
estimated prognosis of their disease can be madeThis work was supported by
grant PI13/00226 (to Servicio de Genética, Instituto
de Investigación–Fundación Jiménez Díaz, Madrid,
Spain), by grant PI13/00638 (to Unidad de
Genética y Diagnóstico Prenatal, Hospital
Universitario y Politécnico La Fe, Valencia, Spain),
and by grant 06/07/0036 (to Centro de
Investigación Biomédica en Red de Enfermedades
Raras, Madrid, Spain) from Fundaluce and
Organización Nacional de Ciegos Españole
Treatment strategies in primary vitreoretinal lymphoma: a 17-center European collaborative study.

IMPORTANCE: The best treatment option for primary vitreoretinal lymphoma (PVRL) without signs of central nervous system lymphoma (CNSL) involvement determined on magnetic resonance imaging or in cerebrospinal fluid is unknown.
OBJECTIVE: To evaluate the outcomes of treatment regimens used for PVRL in the prevention of subsequent CNSL.
DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study was conducted at 17 referral ophthalmologic centers in Europe. We reviewed clinical, laboratory, and imaging data on 78 patients with PVRL who did not have CNSL on presentation between January 1, 1991, and December 31, 2012, with a focus on the incidence of CNS manifestations during the follow-up period.
INTERVENTIONS: The term extensive treatment was used for various combinations of systemic and intrathecal chemotherapy, whole-brain radiotherapy, and peripheral blood stem cell transplantation. Therapy to prevent CNSL included ocular radiotherapy and/or ocular chemotherapy (group A, 31 patients), extensive systemic treatment (group B, 21 patients), and a combination of ocular and extensive treatment (group C, 23 patients); 3 patients did not receive treatment. A total of 40 patients received systemic chemotherapy.
MAIN OUTCOMES AND MEASURES: Development of CNSL following the diagnosis of PVRL relative to the use or nonuse of systemic chemotherapy and other treatment regimens.
RESULTS: Overall, CNSL developed in 28 of 78 patients (36%) at a median follow-up of 49 months. Specifically, CNSL developed in 10 of 31 (32%) in group A, 9 of 21 (43%) in group B, and 9 of 23 (39%) in group C. The 5-year cumulative survival rate was lower in patients with CNSL (35% [95% CI, 50% to 86%]) than in patients without CNSL (68% [95% CI, 19% to 51%]; P = .003) and was similar among all treatment groups (P = .10). Adverse systemic effects occurred in 9 of 40 (23%) patients receiving systemic chemotherapy; the most common of these effects was acute renal failure.
CONCLUSIONS AND RELEVANCE: In the present series of patients with isolated PVRL, the use of systemic chemotherapy was not proven to prevent CNSL and was associated with more severe adverse effects compared with local treatment
A Proposed Minimum Standard Set of Outcome Measures for Cataract Surgery

This article made available in accordance with the publisher's policy.Importance  Aligning outcome measures for cataract surgery, one of the most frequently performed procedures globally, may facilitate international comparisons that can drive improvements in the outcomes most meaningful to patients.\ud
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Objective  To propose a minimum standard set of outcome measures for cataract surgery that enables global comparisons.\ud
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Design, Setting, and Participants  A working group of international experts in cataract outcomes and registries was convened, along with a patient advocate, to agree on a consensus of outcome measures for cataract surgery. In a modified Delphi process, the group met regularly between November 10, 2012, and November 21, 2013, to discuss which outcomes to include in a standard set. Included factors were based on extant literature, existing registries, and the experience of group members. Similarly, a series of consensus discussions were held to determine a set of risk factors to be gathered for each patient. The final shortlist was compiled into a standard set. Analysis was performed from November 22, 2013, to April 5, 2014.\ud
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Main Outcomes and Measures  Development of a recommended standard set encompassing preoperative metrics including patient risk factors, intraoperative factors including surgical complications, and postoperative cataract surgery outcomes.\ud
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Results  The recommended standard set encompasses all patients treated for cataracts by 1 of 4 surgical approaches (phacoemulsification, sutured manual extracapsular cataract extraction, sutureless manual extracapsular cataract extraction, or intracapsular cataract extraction). The recommended metrics to be recorded preoperatively include demographics, ocular history and comorbidities, preoperative visual acuity, and patient-reported visual function. The recommended outcomes were split into intraoperative and postoperative metrics. Intraoperative outcomes include capsule-related problems, dislocation of lens nucleus fragments into the vitreous, and other complications. Postoperative outcomes include visual acuity, refractive error, patient-reported visual function, and early and late complications of surgery. The suggested follow-up for collection of postoperative outcomes is up to 3 months.\ud
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Conclusions and Relevance  A minimum standard set of outcome measures for cataract surgery is important for meaningful comparison across contexts. The proposed data set is a compromise between all useful data and the practicalities of data collection
Clinical validation of a smartphone-based adapter for optic disc imaging in Kenya

Visualization and interpretation of the optic nerve and retina are essential parts of most physical examinations. To design and validate a smartphone-based retinal adapter enabling image capture and remote grading of the retina. This validation study compared the grading of optic nerves from smartphone images with those of a digital retinal camera. Both image sets were independently graded at Moorfields Eye Hospital Reading Centre. Nested within the 6-year follow-up (January 7, 2013, to March 12, 2014) of the Nakuru Eye Disease Cohort in Kenya, 1460 adults (2920 eyes) 55 years and older were recruited consecutively from the study. A subset of 100 optic disc images from both methods were further used to validate a grading app for the optic nerves. Data analysis was performed April 7 to April 12, 2015. Vertical cup-disc ratio for each testwas compared in terms of agreement (Bland-Altman and weighted κ) and test-retest variability. A total of 2152 optic nerve images were available from both methods (also 371 from the reference camera but not the smartphone, 170 from the smartphone but not the reference camera, and 227 from neither the reference camera nor the smartphone). Bland-Altman analysis revealed a mean difference of 0.02 (95%CI, −0.21 to 0.17) and a weighted κ coefficient of 0.69 (excellent agreement). The grades of an experienced retinal photographer were compared with those of a lay photographer (no health care experience before the study), and no observable difference in image acquisition quality was found. Nonclinical photographers using the low-cost smartphone adapter were able to acquire optic nerve images at a standard that enabled independent remote grading of the images comparable to those acquired using a desktop retinal camera operated by an ophthalmic assistant. The potential for task shifting and the detection of avoidable causes of blindness in the most at-risk communities makes this an attractive public health intervention
Rare Genetic Variants Associated With Development of Age-Related Macular Degeneration

Contains fulltext :
                  162147pub.pdf (publisher's version ) (Open Access)IMPORTANCE: Rare variants in the complement genes CFH, CFI, C9, and C3 have been found to be highly associated with age-related macular degeneration (AMD); however, the effect on clinical characteristics and familial segregation by these variants is lacking. OBJECTIVES: To determine the contribution of rare CFH Arg1210Cys, CFI Gly119Arg, C9 Pro167Ser, and C3 Lys155Gln variants in the development of AMD in 22 multiplex families and to describe clinical differences in carriers vs noncarriers in these families and a large case-control cohort. DESIGN, SETTING, AND PARTICIPANTS: This retrospective case-control study included 114 affected and 60 unaffected members of 22 multiplex families with AMD as well as 1589 unrelated patients with AMD and 1386 unrelated control individuals enrolled in the European Genetic Database (EUGENDA). Patients were recruited from March 29, 2006, to April 26, 2013, and data were collected from April 20, 2012, to May 7, 2014. All participants underwent an extensive ophthalmic examination and completed a questionnaire. Venous blood samples were obtained from all participants for genetic analysis, including whole-exome sequencing and measurements of complement activation. Data were analyzed from September 23, 2014, to November 4, 2015. MAIN OUTCOMES AND MEASURES: Differences between carriers and noncarriers of rare variants in age at onset of symptoms, the family history of AMD, complement activation levels (C3d:C3 ratio), the presence of reticular pseudodrusen, and AMD phenotype. RESULTS: Among the 114 affected and 60 unaffected members of 22 multiplex families with AMD and the 1598 unrelated patients with AMD and 1386 controls in the EUGENDA cohort who underwent analysis, the presence of the CFI Gly119Arg, C9 Pro167Ser, or C3 Lys155Gln variant was confirmed in 18 individuals in 5 families but did not completely segregate with the disease. In the case-control cohort, the 91 affected carriers of these variants were younger at symptom onset (mean [SD] age, 67.4 [8.5] vs 71.3 [8.9] years; P = .01) and more often reported a positive family history (35 of 79 [44.3%] vs 367 of 1201 [30.6%]; P = .008) compared with the 1498 noncarriers. Patients with advanced atrophic AMD carried these rare variants more frequently than patients with neovascular AMD (11 of 93 [11.8%] vs 40 of 835 [4.8%]; P = .04). CONCLUSIONS AND RELEVANCE: Previously reported rare variants do not completely segregate within families with AMD. However, patients carrying these rare variants differ clinically from noncarriers by an earlier age at symptom onset, higher prevalence of a positive family history, and AMD phenotype. These results suggest that genetic tests for AMD might be designed to detect common and rare genetic variants, especially in families, because rare variants contribute to the age at onset and progression of the disease
Clinical Outcomes and Cataract Formation Rates in Eyes 10 Years After Posterior Phakic Lens Implantation for Myopia.

Intraocular collamer lenses (ICLs) are posterior chamber phakic lenses that provide a refractive surgery option for those with high myopia or astigmatism. The short-term and midterm results indicate good refraction stability, efficacy, and safety. Cataract has been suggested to be an important long-term complication of ICL implantation.
To report the rates of cataract development and refractive outcomes 10 years after ICL implantation.
The study included 133 eyes of 78 patients undergoing consecutive V4 model ICL implantations, which took place from January 1, 1998, through December 31, 2004, at Jules-Gonin Eye Hospital, Lausanne, Switzerland. Data analysis was performed from January 1, 2014, to May 31, 2014. The lenses implanted were as follows: 53 V4 model ICLs of -15.5 D or greater, 73 V4 model ICLs of less than -15.5 diopter (D), and 7 V4 model toric ICLs for myopia.
Rate of cataract surgery, lens opacity, ocular hypertension, refractive safety, predictability, and stability.
A total of 133 eyes of 78 patients (34 men and 44 women, with a mean [SD] age of 38.8 [9.2] years at enrollment) met the inclusion criteria. The rate of lens opacity development was 40.9% (95% CI, 32.7%-48.8%) and 54.8% (95% CI, 44.7%-63.0%) at 5 and 10 years, respectively. Phacoemulsification was performed in 5 eyes (4.9%; 95% CI, 1.0%-8.7%) and 18 eyes (18.3%; 95% CI, 10.1%-25.8%) at 5 and 10 years after ICL implantation, respectively. The vault height (distance between the posterior ICL surface and anterior lens surface) measured a mean (SD) of 426 (344) μm immediately postoperatively, decreasing to 213 (169) μm at 10 years. A smaller vault height was associated with the development of lens opacity and phacoemulsification (P = .005 and .008, respectively). The intraocular pressure was 15 mm Hg postoperatively, and there was no significant increase in intraocular pressure observed until the 10-year follow-up (16 mm Hg, P = .02). At 10 years, 12 eyes (12.9%; 95% CI, 5.6%-19.6%) had developed ocular hypertension that required topical medication. At 10 years, the mean (SD) safety index was 1.25 (0.57), with a manifest spherical equivalent of -0.5 D at 1-year postoperatively vs -0.7 D at 10 years postoperatively in eyes aimed at emmetropia.
This retrospective single center study indicates that ICL implantation provides good long-term safety and stability of refraction in patients with high myopia compared with similar short-term studies. However, the rates of cataract formation and ocular hypertension at 10 years have important clinical implications, and as such this information should be part of the available patient information before ICL implantation