Disease-modifying drug initiation patterns in commercially insured multiple sclerosis patients: a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>The goal of this research was to compare the demographics, clinical characteristics and treatment patterns for newly diagnosed multiple sclerosis (MS) patients in a commercial managed care population who received disease-modifying drug (DMD) therapy versus those not receiving DMD therapy.</p> <p>Methods</p> <p>A retrospective cohort study using US administrative healthcare claims identified individuals newly diagnosed with MS (no prior MS diagnosis 12 months prior using ICD-9-CM 340) and ≥ 18 years old during 2001-2007 to characterize them based on demographics, clinical characteristics, and pharmacologic therapy for one year prior to and a minimum of one year post-index. The index date was the first MS diagnosis occurring in the study period. Follow-up of subjects was done by ICD-9-CM code identification and not by actual chart review. Multivariate analyses were conducted to adjust for confounding variables.</p> <p>Results</p> <p>Patients were followed for an average of 35.7 ± 17.5 months after their index diagnosis. Forty-three percent (n = 4,462) of incident patients received treatment with at least one of the DMDs during the post-index period. Treated patients were primarily in the younger age categories of 18-44 years of age, with DMD therapy initiated an average of 5.3 ± 9.1 months after the index diagnosis. Once treatment was initiated, 27.7% discontinued DMD therapy after an average of 17.6 ± 14.6 months, and 16.5% had treatment gaps in excess of 60 days.</p> <p>Conclusions</p> <p>Nearly 60% of newly-diagnosed MS patients in this commercial managed care population remained untreated while over a quarter of treated patients stopped therapy and one-sixth experienced treatment gaps despite the risk of disease progression or a return of pre-treatment disease activity.</p

Distribution characteristics of air-bone gaps : evidence of bias in manual audiometry

OBJECTIVES : Five databases were mined to examine distributions of airbone gaps obtained by automated and manual audiometry. Differences in distribution characteristics were examined for evidence of influences unrelated to the audibility of test signals. DESIGN : The databases provided air- and bone-conduction thresholds that permitted examination of air-bone gap distributions that were free of ceiling and floor effects. Cases with conductive hearing loss were eliminated based on air-bone gaps, tympanometry, and otoscopy, when available. The analysis is based on 2,378,921 threshold determinations from 721,831 subjects from five databases. RESULTS : Automated audiometry produced air-bone gaps that were normally distributed suggesting that air- and bone-conduction thresholds are normally distributed. Manual audiometry produced air-bone gaps that were not normally distributed and show evidence of biasing effects of assumptions of expected results. In one database, the form of the distributions showed evidence of inclusion of conductive hearing losses. CONCLUSIONS : Thresholds obtained by manual audiometry show tester bias effects from assumptions of the patient’s hearing loss characteristics. Tester bias artificially reduces the variance of bone-conduction thresholds and the resulting air-bone gaps. Because the automated method is free of bias from assumptions of expected results, these distributions are hypothesized to reflect the true variability of air- and boneconduction thresholds and the resulting air-bone gaps.Portions of this work were supported by Grant RC3DC010986 from the National Institute of Deafness and Other Communication Disorders and by contract No. VA118-12-C-0029 from the US Department of Veterans Affairs. The Rehabilitation Research and Development Service of the US Department of Veterans Affairs supported this work through the Auditory and Vestibular Dysfunction Research Enhancement Award Program (REAP) and a Senior Research Career Scientist award to the second author.http://journals.lww.com/ear-hearing2017-03-31hb2016Speech-Language Pathology and Audiolog

Distribution characteristics of normal pure-tone thresholds

OBJECTIVE : This study examined the statistical properties of normal air-conduction thresholds obtained with automated and manual audiometry to test the hypothesis that thresholds are normally distributed and to examine the distributions for evidence of bias in manual testing. DESIGN : Four databases were mined for normal thresholds. One contained audiograms obtained with an automated method. The other three were obtained with manual audiometry. Frequency distributions were examined for four test frequencies (250, 500, 1000, and 2000 Hz). STUDY SAMPLE : The analysis is based on 317 569 threshold determinations of 80 547 subjects from four clinical databases. RESULTS : Frequency distributions of thresholds obtained with automated audiometry are normal in form. Corrected for age, the mean thresholds are within 1.5 dB of reference equivalent threshold sound pressure levels. Frequency distributions of thresholds obtained by manual audiometry are shifted toward higher thresholds. Two of the three datasets obtained by manual audiometry are positively skewed. CONCLUSIONS : The positive shift and skew of the manual audiometry data may result from tester bias. The striking scarcity of thresholds below 0 dB HL suggests that audiologists place less importance on identifying low thresholds than they do for higher-level thresholds. We refer to this as the Good enough bias and suggest that it may be responsible for differences in distributions of thresholds obtained by automated and manual audiometry.By grant RC3DC010986 from the National Institutes of Deafness and Other Communication Disorders. The Rehabilitation Research and Development Service of the U.S. Department of Veterans Affairs supported this work through the Auditory and Vestibular Dysfunction Research Enhancement Award Program (REAP) and a Senior Research Career Scientist.http://www.tandfonline.com/loi/iija202016-05-31hb2016Speech-Language Pathology and Audiolog

False air-bone gaps at 4 kHz in listeners with normal hearing and sensorineural hearing loss

OBJECTIVE : This report presents data from four studies to examine standard bone-conduction reference equivalent threshold force levels (RETFL), especially at 4 kHz where anomalous air-bone gaps are common. DESIGN : Data were mined from studies that obtained air- and bone-conduction thresholds from normal-hearing and sensorineural hearing loss (SNHL) participants, using commercial audiometers and standard audiometric transducers. STUDY SAMPLE : There were 249 normal-hearing and 188 SNHL participants. RESULTS : (1) Normal-hearing participants had small air-bone gaps at 0.5, 1.0, and 2.0 kHz (-1.7 to 0.3 dB) and larger air-bone gaps at 4 kHz (10.6 dB). (2) SNHL participants had small air-bone gaps at 0.5, 1.0, and 2.0 kHz (-0.7 to 1.7 dB) and a larger air-bone gap at 4 kHz (14.1 dB). (3) The 4-kHz air-bone gap grew with air-conduction threshold from 10.1 dB when the air-conduction threshold was 5-10 dB HL to 21.1 dB when the air-conduction threshold was greater than 60 dB. (4) With the 4-kHz RETFL corrected by the average SNHL air-bone gap, the relationship between RETFL and frequency is linear with a slope of - 12 dB per octave. CONCLUSIONS : The 4-kHz air-bone gaps for listeners with SNHL could be avoided by adjusting the 4-kHz RETFL by - 14.1 dB.Portions of this work were supported by grants R41DC05110 and RC3DC010986 from the National Institutes of Deafness and Other Communication Disorders.http://www.tandfonline.com/loi/iija20hb2016Speech-Language Pathology and Audiolog

Association of HIV neutralizing antibody with lower viral load after treatment interruption in a prospective trial (A5170)

We investigated the impact of neutralizing antibodies (NAbs) on CD4 T-cell count and viral load in a cohort of HAART recipients who underwent extended structured treatment interruption

MRI-targeted or standard biopsy for prostate-cancer diagnosis

Background Multiparametric magnetic resonance imaging (MRI), with or without targeted biopsy, is an alternative to standard transrectal ultrasonography-guided biopsy for prostate-cancer detection in men with a raised prostate-specific antigen level who have not undergone biopsy. However, comparative evidence is limited. Methods In a multicenter, randomized, noninferiority trial, we assigned men with a clinical suspicion of prostate cancer who had not undergone biopsy previously to undergo MRI, with or without targeted biopsy, or standard transrectal ultrasonography-guided biopsy. Men in the MRI-targeted biopsy group underwent a targeted biopsy (without standard biopsy cores) if the MRI was suggestive of prostate cancer; men whose MRI results were not suggestive of prostate cancer were not offered biopsy. Standard biopsy was a 10-to-12-core, transrectal ultrasonography-guided biopsy. The primary outcome was the proportion of men who received a diagnosis of clinically significant cancer. Secondary outcomes included the proportion of men who received a diagnosis of clinically insignificant cancer. Results A total of 500 men underwent randomization. In the MRI-targeted biopsy group, 71 of 252 men (28%) had MRI results that were not suggestive of prostate cancer, so they did not undergo biopsy. Clinically significant cancer was detected in 95 men (38%) in the MRI-targeted biopsy group, as compared with 64 of 248 (26%) in the standard-biopsy group (adjusted difference, 12 percentage points; 95% confidence interval [CI], 4 to 20; P=0.005). MRI, with or without targeted biopsy, was noninferior to standard biopsy, and the 95% confidence interval indicated the superiority of this strategy over standard biopsy. Fewer men in the MRI-targeted biopsy group than in the standard-biopsy group received a diagnosis of clinically insignificant cancer (adjusted difference, -13 percentage points; 95% CI, -19 to -7; P&lt;0.001). Conclusions The use of risk assessment with MRI before biopsy and MRI-targeted biopsy was superior to standard transrectal ultrasonography-guided biopsy in men at clinical risk for prostate cancer who had not undergone biopsy previously. (Funded by the National Institute for Health Research and the European Association of Urology Research Foundation; PRECISION ClinicalTrials.gov number, NCT02380027 .)

Trends in Incidence of Hospitalized Acute Myocardial Infarction in the Cardiovascular Research Network (CVRN)

Monitoring trends in cardiovascular events can provide key insights into the effectiveness of prevention efforts. Leveraging data from electronic health records provides a unique opportunity to examine contemporary, community-based trends in acute myocardial infarction hospitalizations

Care-Related Risk Factors for Hospital-Acquired Pressure Ulcers in Elderly Adults with Hip Fracture

To identify care-related factors associated with increased incidence of hospital-acquired pressure ulcers (HAPU

Unrecognized Non-Q-Wave Myocardial Infarction: Prevalence and Prognostic Significance in Patients with Suspected Coronary Disease

Using delayed-enhancement cardiovascular magnetic resonance, Han Kim and colleagues show that in patients with suspected coronary disease the prevalence of unrecognized myocardial infarction without Q-waves is more than 3-fold higher than that with Q-waves and predicts subsequent mortality

Diversity and Complexity of the Large Surface Protein Family in the Compacted Genomes of Multiple Pneumocystis Species

Pneumocystis, a major opportunistic pathogen in patients with a broad range of immunodeficiencies, contains abundant surface proteins encoded by a multicopy gene family, termed the major surface glycoprotein (Msg) gene superfamily. This superfamily has been identified in all Pneumocystis species characterized to date, highlighting its important role in Pneumocystis biology. In this report, through a comprehensive and in-depth characterization of 459 msg genes from 7 Pneurnocystis species, we demonstrate, for the first time, the phylogeny and evolution of conserved domains in Msg proteins and provide a detailed description of the classification, unique characteristics, and phylogenetic relatedness of five Msg families. We further describe, for the first time, the relative expression levels of individual msg families in two rodent Pneumocystis species, the substantial variability of the msg repertoires in P. coda from laboratory and wild rats, and the distinct features of the expression site for the classic msg genes in Pneumocystis from 8 mammalian host species. Our analysis suggests multiple functions for this superfamily rather than just conferring antigenic variation to allow immune evasion as previously believed. This study provides a rich source of information that lays the foundation for the continued experimental exploration of the functions of the Msg superfamily in Pneumocystis biology. IMPORTANCE Pneumocystis continues to be a major cause of disease in humans with immunodeficiency, especially those with HIV/AIDS and organ transplants, and is being seen with increasing frequency worldwide in patients treated with immunode-pleting monoclonal antibodies. Annual health care associated with Pneumocystis pneumonia costs similar to$475 million dollars in the United States alone. In addition to causing overt disease in immunodeficient individuals, Pneumocystis can cause subclinical infection or colonization in healthy individuals, which may play an important role in species preservation and disease transmission. Our work sheds new light on the diversity and complexity of the msg superfamily and strongly suggests that the versatility of this superfamily reflects multiple functions, including antigenic variation to allow immune evasion and optimal adaptation to host environmental conditions to promote efficient infection and transmission. These findings are essential to consider in developing new diagnostic and therapeutic strategies.Peer reviewe