The clinical and molecular diversity of mast cell leukemia with or without associated hematologic neoplasm.

Mast cell leukemia is a rare variant of advanced systemic mastocytosis characterized by at least 20% of mast cells in a bone marrow smear. We evaluated clinical and molecular characteristics of 28 patients with (n=20, 71%) or without an associated hematologic neoplasm. De novo mast cell leukemia was diagnosed in 16 of 28 (57%) patients and secondary mast cell leukemia evolving from other advanced systemic mastocytosis subtypes in 12 of 28 (43%) patients, of which 7 patients progressed while on cytoreductive treatment. Median bone marrow mast cell infiltration was 65% and median serum tryptase was 520 µg/L. C-findings were identified in 26 of 28 (93%) patients. Mutations in KIT (D816V, n=19; D816H/Y, n=5; F522C, n=1) were detected in 25 of 28 (89%) patients and prognostically relevant additional mutations in SRSF2, ASXL1 or RUNX1 (S/A/Rpos) in 13 of 25 (52%) patients. Overall response rate in 18 treatment-naïve patients was 5 of 12 (42%) on midostaurin and 1 of 6 (17%) on cladribine, and after switch 1 of 4 (25%) on midostaurin and 0 of 3 on cladribine, respectively. S/A/Rpos adversely affected response to treatment and progression to secondary mast cell leukemia (n=6) or acute myeloid leukemia (n=3) while on treatment (P<0.05). The median overall survival from mast cell leukemia diagnosis was 17 months as compared to 44 months in a control group of 124 patients with advanced systemic mastocytosis but without mast cell leukemia (P=0.03). In multivariate analyses, S/A/Rpos remained the only independent poor prognostic variable predicting overall survival (P=0.007). In conclusion, the molecular signature should be determined in all patients with mast cell leukemia because of its significant clinical and prognostic relevance.

A Pilot Study to Assess the Feasibility of Group Exercise and Animal-Assisted Therapy in Older Adults.

This pilot study assessed the feasibility of incorporating animal-assisted therapy teams (ATT) into a 6-week group exercise program for older adults (77 ± 6 years). Fifteen participants were randomly assigned to an exercise with ATT (E+ATT; n = 8) or exercise only (E; n = 7) group. Groups exercised 3x/week for 45 min. Feasibility was assessed by three objectives: (1) ATT will not need extensive preparation beyond their original therapy training; (2) the study will require minimal cost; and (3) ATT must not impair the effectiveness of the exercise program. By the study conclusion, all objectives were met. Time and cost were minimal for ATT, and adherence was 93% and 90% for E+ATT and E, respectively. There were significant improvements in both groups (p ≤ .05) for arm curls, get-up and go, and 6-min walk. The results of this pilot study suggest that it is feasible to incorporate ATT into group exercise programming for older adults.

Reinfections during the Florida syphilis epidemic, 2000-2008.

BACKGROUND: The last 3 syphilis epidemics in the United States peaked after 5 to 6 years, but rates have now increased for 8 years. We questioned whether persons with multiple syphilis diagnoses (repeaters) are fueling the epidemic. METHODS: The Florida Department of Health database of all syphilis cases reported between 2000 and 2008 was used to examine demographics and disease presentation of repeaters and nonrepeaters using bivariate and multivariate analyses. RESULTS: Of 26,070 persons diagnosed with syphilis, 643 (2.5%) were repeaters (range, 2-5 diagnoses): 82 women, 444 men who have sex with men (MSM), and 117 men identified as either heterosexual (n = 43) or unknown sexual orientation (n = 74). The mean time between first and second diagnosis was approximately 3 years. Median titer increase among those with a second diagnosis of early latent was 32-fold. In multivariate analysis, compared with nonrepeaters, repeaters were more likely to be MSM (odds ratio [OR], 5.3), human immunodeficiency virus (HIV)-infected (OR, 2.0), white (OR, 1.5), ages 35 to 39 (OR, 1.8), and to live in Miami-Dade or Broward Counties (OR, 1.7). Overall, the stage at diagnosis was similar for repeaters, whether it was their initial or subsequent diagnosis. However, HIV-infected MSM were more likely to be diagnosed with early latent at second diagnosis compared with initial diagnosis (P ≤ 0.01). CONCLUSIONS: Most syphilis diagnosed in the current Florida epidemic is among persons infected for the first time. Repeaters are mainly MSM who present with symptoms or large increases in titers. HIV-infected MSM may have higher rates of early asymptomatic disease because of more frequent screening. These are likely to be true new infections.

Infectious syphilis among adolescent and young adult men: implications for human immunodeficiency virus transmission and public health interventions.

BACKGROUND: In 2008, an increase in syphilis among young black men was noted in New York City (NYC), Miami-Fort Lauderdale, and Philadelphia. To explore this trend, we examined infectious syphilis cases from 2000 to 2008 among adolescent and young adult men in these areas. METHODS: Descriptive analysis of male infectious syphilis cases reported to public health authorities in NYC, FL, and Philadelphia. RESULTS: From 2000 to 2008, infectious syphilis cases among males increased in NYC (107-1027 cases), Miami-Fort Lauderdale (109-374), and Philadelphia (41-142). This increase was largely attributable to cases among men who have sex with men. Rates among black adolescent males (15-19 years) increased in NYC ([2.6-43.0]/100,000), Miami-Fort Lauderdale ([5.5-48.1]/100,000), and Philadelphia (]8.3-40.3]/100,000). Among males with infectious syphilis in 2008 in NYC, 9.1% of blacks and 6.6% of Hispanics were adolescents compared with 1.6% of whites (P < 0.001). In Miami-Fort Lauderdale, 12.2% of black males were adolescents compared to 2.0% of whites (P < 0.01) and 2.7% of Hispanics (P < 0.01). Black males dominated all age groups in Philadelphia, but were more likely to be <25 years of age than whites (P = 0.02). Human immunodeficiency virus coinfection rates were 14.8% among adolescent males in NYC, 15.4% in Philadelphia, and 25.0% in Miami-Fort Lauderdale. CONCLUSIONS: Very young black males have emerged as a risk group for syphilis in these 3 areas, as have young Hispanic males in NYC. Many are men who have sex with men and some are already human immunodeficiency virus-infected. Targeted risk reduction interventions for these populations are critical.

Whole-body Vibration Training in Frail, Skilled Nursing Home Residents.

Frailty is a geriatric syndrome characterized by diminished muscle strength, endurance, and weakened physical function. Physical frailty is often unaddressed clinically as it tends to manifest among chronic illnesses and sarcopenia, and consensus criteria for frailty diagnosis remains elusive. Whole-body vibration training (WBVT) has been used to improve deficits in lower body muscular strength and functional performance in healthy and high functioning older adults; therefore, the purpose of this study was to determine the effects of WBVT on physical frailty in skilled nursing home residents. This study compared the effects of 12 wks (2x/wk) of WBVT (n = 10) to standard care, which served as the control (CON: n = 10), on isometric knee extension strength (KE), body composition, and functional performance in 20 (16 female) pre-frail and frail skilled nursing home residents (82 ± 5 yrs). Frailty was assessed using the FRAIL scale and function was measured using the short physical performance battery (SPPB). WBVT consisted of 4 lower body exercises (partial squat, narrow squat, wide squat, calf raise) during vertical vibration (25 - 40 Hz). Data were analyzed using two-way ANOVA (group × time) and post-hoc paired and independent t-tests. Significance was set at p ≤ 0.05. There were significant group-by-time interactions for KE and SPPB. Post-hoc paired t-tests revealed that WBVT improved KE (22.3 ± 4.0 to 29.0 ± 4.5 kg) and improvement in SPPB performance approached significance (4.5 ± 2.3 to 5.2 ± 2.1 units, p = 0.089). WBVT was well tolerated and occurred without adverse health complications. WBVT can be used to counteract losses in leg strength without adverse health complications in skilled nursing home residents.

Use of a Business Approach to Improve Disease Surveillance Data Management Systems and Information Technology Process in Florida's Bureau of STD Prevention and Control.

The business of sexually transmitted disease (STD) prevention and control demands technology that is capable of supporting a wide array of program activities-from the processing of laboratory test results to the complex and confidential process involved in contact investigation. The need for a tool that enables public health officials to successfully manage the complex operations encountered in an STD prevention and control program, and the need to operate in an increasingly poor resource environment, led the Florida Bureau of STD to develop the Patient Reporting Investigation Surveillance Manager. Its unique approach, technical architecture, and sociotechnical philosophy have made this business application successful in real-time monitoring of disease burden for local communities, identification of emerging outbreaks, monitoring and assurance of appropriate treatments, improving access to laboratory data, and improving the quality of data for epidemiologic analysis. Additionally, the effort attempted to create and release a product that promoted the Centers for Disease Control and Prevention's ideas for integration of programs and processes.

[(Pan-)cytopenia as first manifestation of kryptic telomeropathies in adults]. / Selten sofort erkannt: Zytopenien als Erstmanifestation einer Telomeropathie im Erwachsenenalter.

Telomere syndromes (syn. Telomeropathies) are inherited disorders hallmarked by accelerated telomere shortening based on a molecular defect within the telomerase/telomere complex. The rare, but well-defined model disorder Dyskeratosis congenita (DKC) characterized by typical skin manifestations and bone marrow failure represents the classical manifestation of telomere syndromes in childhood and adolescence. However, cryptic variants of DKC, clinically manifest through appearance of atypical bone marrow failure, lung fibrosis or liver cirrhosis - especially in adults up to the fifth decade of age - are frequently underdiagnosed. Clinical awareness is of utmost importance for this group of patients considering the fundamental implications of this diagnosis for treatment decisions and surveillance. Here, we review the importance of screening, correct diagnosis and therapeutic implications of telomeropathies in adult patients with mostly cryptic DKC with particular focus on (pan-)cytopenia as first and most frequent clinical manifestation.

A model of tailoring effects: A randomized controlled trial examining the mechanisms of tailoring in a web-based STD screening intervention.

OBJECTIVE: This study explores the mechanisms of tailoring within the context of RU@Risk a brief Web-based intervention designed to promote sexually transmitted disease (STD) testing among young adults. This is one of a few studies to empirically examine theorized message processing mechanisms of tailoring and persuasion outcomes in a single model. METHOD: Sexually active college students (N = 1065) completed a pretest, were randomly assigned to explore a tailored or nontailored website, completed a posttest, and were offered the opportunity to order a free at-home STD test kit. As intervention effects were hypothesized to work via increases in perceived risk, change in perceived risk from pretest to posttest by condition was examined. Hypothesized mechanisms of tailoring (perceived personal relevance, attention, and elaboration) were examined using structural equation modeling (SEM). All analyses controlled for demographic variables and sexual history. RESULTS: As predicted, perceived risk of STDs increased from pretest to posttest, but only in the tailored condition. Results revealed that exposure to the tailored (vs. nontailored) website increased perceived personal relevance, attention to, and elaboration of the message. These effects in turn were associated with greater perceived risk of STDs and intentions to get tested. Additionally, participants in the tailored condition were more likely to order a test kit. CONCLUSIONS: Findings provide insight into the mechanisms of tailoring with important implications for optimizing message design. (PsycINFO Database Record

Risk for HIV following a diagnosis of syphilis, gonorrhoea or chlamydia: 328,456 women in Florida, 2000-2011.

Several effective interventions are available for preventing HIV in women. Targeting interventions requires understanding their risk of acquiring HIV. We used surveillance data to estimate risks of HIV acquisition for 13-59-year-old women following a diagnosis of syphilis, gonorrhoea or chlamydia in Florida during 2000-2009. We excluded women reported with HIV before their STI, and measured HIV reported subsequent to STI (through 2011). Rates were compared to women with no reported STI. A total of 328,456 women had: syphilis (3325), gonorrhoea (67,784) or chlamydia (257,347). During 2,221,944 person-years of follow-up, 2118 of them were diagnosed with HIV. For women with no STI reported, during 64,763,832 person-years, 19,531 were reported with HIV. The crude rate of subsequent HIV diagnosis (per 100,000 person-years) was higher for women diagnosed with syphilis (597.9), gonorrhoea (171.3) or chlamydia (66.3) than women with no STI (30.2). Annual rates of HIV decreased over-all by 61.8% between 2001 and 2011. Women with syphilis or gonorrhoea were at highest risk for HIV and therefore might benefit from intensive counselling. However, they represented only a small fraction of the women who acquired HIV. Most cases of HIV infection among women occurred among the large group of women who were not at highest risk.

Dissecting Genomic Aberrations in Myeloproliferative Neoplasms by Multiplex-PCR and Next Generation Sequencing.

In order to assess the feasibility of amplicon-based parallel next generation sequencing (NGS) for the diagnosis of myeloproliferative neoplasms (MPN), we investigated multiplex-PCR of 212 amplicons covering genomic mutational hotspots in 48 cancer-related genes. Samples from 64 patients with MPN and five controls as well as seven (myeloid) cell lines were analyzed. Healthy donor and reactive erythrocytosis samples showed several frequent single-nucleotide polymorphisms (SNPs) but no known pathogenic mutation. Sequencing of the cell lines confirmed the presence of the known mutations. In the patient samples, JAK2 V617F was present in all PV, 4 of 10 ET, and 16 of 19 MF patients. The JAK2 V617F allele burden was different in the three groups (ET, 33+/-22%; PV 48+/-28% and MF 68+/- 29%). Further analysis detected both previously described and undescribed mutations (i.e., G12V NRAS, IDH1 R132H, E255G ABL, and V125G IDH1 mutations). One patient with lymphoid BC/Ph+ ALL who harbored a T315I ABL mutation and was treated with ponatinib was found to have developed a newly acquired V216M TP53 mutation (12% of transcripts) when becoming resistant to ponatinib. Ponatinib led to a decrease of ABL T315I positive transcripts from 47% before ponatinib treatment to 16% at the time of ponatinib resistance in this patient, suggesting that both TP53 and ABL mutations were present in the same clone and that the newly acquired TP53 mutation might have caused ponatinib resistance in this patient. In conclusion, amplicon-sequencing-based NGS allows simultaneous analysis of multiple MPN associated genes for diagnosis and during treatment and measurement of the mutant allele burden.

The impact of laws on HIV and STD prevention.

HIV and sexually transmitted diseases (STDs) are major public health problems in the United States. Since the start of the epidemic, nearly 800,000 persons have been reported with AIDS, and approximately 900,000 Americans are currently living with HIV infection. Each year, 15 million people in the United States become infected with one or more STDs. The direct and indirect costs of the major STDs--not including HIV infection--and their complications are estimated to total at least $10 billion annually. This article underscores the importance of law and other structural factors in the prevention and treatment of HIV and STDs. It describes state-level laws on STD screening, name-based reporting of STDs, name-based reporting of HIV and HIV partner notification implementation, and the impact of laws on STD and HIV risk behaviors and prevention services. More broadly, the article focuses on how the law influences the vulnerability or resilience of persons facing the risk of STDs, HIV infection, or AIDS.

Cumulative risk of chlamydial infection among young women in Florida, 2000-2011.

PURPOSE: Chlamydia trachomatis is a very common infection among young women in the United States; information on cumulative risk of infection is limited. We sought to estimate the cumulative risk of chlamydial infection for young women. METHODS: We measured cumulative risk of reported chlamydial infection for 14- to 34-year-old women in Florida between 2000 and 2011 using surveillance records and census estimates. We calculated reported infections per woman, analyzed first infections to get cumulative risk, and calculated risk of repeat infection over the 12-year period. RESULTS: There were 457,595 infections reported among 15- to 34-year-old women. Reports increased annually from 25,390 to 51,536. Nineteen-year-olds were at highest risk with 5.1 infections reported per 100 women in 2011. There were 341,671 different women infected. Among women aged 14-17 years in 2000, over 20% had at least one infection reported within 12 years, and among blacks, this risk was over 36%, and that underestimates risk because 18% of cases were missing race/ethnicity information. Repeat infections were common. Among 53,109 with chlamydia at the age of 15-20 years during 2000-2003, 36.7% had additional infections reported by 2011. CONCLUSIONS: More than one out of five women in Florida was reported as having chlamydia during her young-adult years; risk was highest for black women. True infection risks were likely much higher because many infections were not diagnosed or reported. Young women who had chlamydia were very likely to get reinfected. Rates of infection remain high despite years of screening. More information is needed on how to prevent chlamydial infection.

High risk for HIV following syphilis diagnosis among men in Florida, 2000-2011.

OBJECTIVE: Multiple interventions have been shown to reduce the risk of HIV acquisition, including preexposure prophylaxis with antiretroviral medications, but high costs require targeting interventions to people at the highest risk. We identified the risk of HIV following a syphilis diagnosis for men in Florida. METHODS: We analyzed surveillance records of 13- to 59-year-old men in Florida who were reported as having syphilis from January 1, 2000, to December 31, 2009. We excluded men who had HIV infection reported before their syphilis diagnosis (and within 60 days after), then searched the database to see if the remaining men were reported as having HIV infection by December 31, 2011. RESULTS: Of the 9,512 men with syphilis we followed, 1,323 were subsequently diagnosed as having HIV infection 60-3,753 days after their syphilis diagnosis. The risk of a subsequent diagnosis of HIV infection was 3.6% in the first year after syphilis was diagnosed and reached 17.5% 10 years after a syphilis diagnosis. The risk of HIV was higher for non-Hispanic white men (3.4% per year) than for non-Hispanic black men (1.8% per year). The likelihood of developing HIV was slightly lower for men diagnosed with syphilis in 2000 and 2001 compared with subsequent years. Of men diagnosed with syphilis in 2003, 21.5% were reported as having a new HIV diagnosis by December 31, 2011. CONCLUSION: Men who acquire syphilis are at very high risk of HIV infection.

Evaluating the impact of human papillomavirus vaccines.

While two prophylactic HPV vaccines have been proven notably efficacious in clinical trials, the effectiveness of these vaccines at the population level remains to be evaluated. To lay the foundation for understanding the strengths and limitations of different endpoints for future effectiveness research, we present a comprehensive review of HPV-related clinical outcomes, including: (i) HPV type-specific positivity and persistence, (ii) Pap diagnoses (ASC-US, LSIL, and HSIL), (iii) histologic cervical cancer precursor lesions (i.e., CIN1, CIN2, and CIN3), (iv) invasive cervical cancer (ICC), (v) anogenital warts, (vi) recurrent respiratory papillomatosis (RRP), and (vii) other HPV-associated cancers (vulvar, vaginal, anal, penile, and oropharyngeal). While research on the vaccines' effects on these HPV clinical outcomes in the general population is presently limited, numerous large trials will soon be completed, making a priori discussion of these potential outcomes especially urgent. Furthermore, population level systems to track HPV-associated clinical outcomes may need to be developed for HPV vaccine effectiveness evaluation.

Brief strengths-based case management promotes entry into HIV medical care: results of the antiretroviral treatment access study-II.

OBJECTIVE: The Antiretroviral Treatment Access Study-II (ARTAS-II) evaluated a brief case management intervention delivered in health departments and community-based organizations (CBOs) to link recently diagnosed HIV-infected persons to medical care rapidly. METHODS: Recently diagnosed HIV-infected persons were recruited from 10 study sites across the United States during 2005 to 2006. The intervention consisted of up to 5 sessions with an ARTAS linkage case manager over a 90-day period. The outcome measure was whether or not the participant had seen an HIV medical care provider at least once within 6 months of enrollment. Multivariate logistic regression was used to identify significant predictors of receiving HIV medical care. RESULTS: Seventy-nine percent (497 of 626) of participants visited an HIV clinician at least once within the first 6 months. Participants who were older than 25 years of age, Hispanic, and stably housed; had not recently used noninjection drugs; had attended 2 or more sessions with the case manager; and were recruited at a study site that had HIV medical care colocated on its premises were all significantly more likely to have received HIV care. CONCLUSIONS: The ARTAS linkage case management intervention provides a model that health departments and CBOs can use to ensure that recently diagnosed HIV-infected persons attend an initial HIV care encounter.

Florida's multifaceted response for increases in syphilis among MSM: the Miami-Ft. Lauderdale initiative.

After many years of declining rates, it became apparent in 1999 that syphilis cases were on the rise in Florida. Data analysis identified that the outbreak was predominately contained in Miami and Ft. Lauderdale and among men who have sex with men. An in-depth investigation was undertaken to identify the risk factors, the best way to attack the outbreak, and how to build sustainability into implemented strategies. After thorough review of the data and extensive dialogue with local public health and community participants, the Bureau of STD Prevention & Control developed initiatives that focused public awareness through print, radio, and television media resources; expanded access to men's health services; and enhanced education/training for public and private health care providers, STD program field staff, and community representatives. This initiative has resulted in unprecedented community involvement in syphilis control efforts.