Page C. Moore

The Efficacy and Safety of Gentamicin Plus Azithromycin and Gemifloxacin Plus Azithromycin as Treatment of Uncomplicated Gonorrhea

BACKGROUND Ceftriaxone is the foundation of currently recommended gonorrhea treatment. There is an urgent need for backup treatment options for patients with cephalosporin allergy or infections due to suspected cephalosporin-resistant Neisseria gonorrhoeae. We evaluated the efficacy and tolerability of 2 combinations of existing noncephalosporin antimicrobials for treatment of patients with urogenital gonorrhea. METHODS We conducted a randomized, multisite, open-label, noncomparative trial in 5 outpatient sexually transmitted disease clinic sites in Alabama, California, Maryland, and Pennsylvania. Patients aged 15-60 years diagnosed with uncomplicated urogenital gonorrhea were randomly assigned to either gentamicin 240 mg intramuscularly plus azithromycin 2 g orally, or gemifloxacin 320 mg orally plus azithromycin 2 g orally. The primary outcome was microbiological cure of urogenital infections (negative follow-up culture) at 10-17 days after treatment among 401 participants in the per protocol population. RESULTS Microbiological cure was achieved by 100% (lower 1-sided exact 95% confidence interval [CI] bound, 98.5%) of 202 evaluable participants receiving gentamicin/azithromycin, and 99.5% (lower 1-sided exact 95% CI bound, 97.6%) of 199 evaluable participants receiving gemifloxacin/azithromycin. Gentamicin/azithromycin cured 10 of 10 pharyngeal infections and 1 of 1 rectal infection; gemifloxacin/azithromycin cured 15 of 15 pharyngeal and 5 of 5 rectal infections. Gastrointestinal adverse events were common in both arms. CONCLUSIONS Gentamicin/azithromycin and gemifloxacin/azithromycin were highly effective for treatment of urogenital gonorrhea. Gastrointestinal adverse events may limit routine use. These non-cephalosporin-based regimens may be useful alternative options for patients who cannot be treated with cephalosporin antimicrobials. Additional treatment options for gonorrhea are needed. Clinical Trials Registration. NCT00926796.

Socioeconomic Disparities in Community-Based Treatment of Tobacco Dependence

OBJECTIVES We examined socioeconomic disparities in a community-based tobacco dependence treatment program. METHODS We provided cognitive-behavioral treatment and nicotine patches to 2739 smokers. We examined treatment use, clinical and environmental, and treatment outcome differences by socioeconomic status (SES). We used logistic regressions to model end-of-treatment and 3- and 6-month treatment outcomes. RESULTS The probability of abstinence 3 months after treatment was 55% greater for the highest-SES than for the lowest-SES (adjusted odds ratio [AOR] = 1.55; 95% confidence interval [CI] = 1.03, 2.33) smokers and increased to 2.5 times greater for the highest-SES than for the lowest-SES smokers 6 months after treatment (AOR = 2.47; 95% CI = 1.62, 3.77). Lower-SES participants received less treatment content and had fewer resources and environmental supports to manage a greater number of clinical and environmental challenges to abstinence. CONCLUSIONS Targets for enhancing therapeutic approaches for lower socioeconomic groups should include efforts to ensure that lower-SES groups receive more treatment content, strategies to address specific clinical and environmental challenges associated with treatment outcomes for lower-SES smokers (i.e., higher dependence and stress levels and exposure to other smokers), and strategies to provide longer-term support.

Association between natural killer cells and regression in melanocytic lesions

Mortality from melanoma, the deadliest of skin cancers, continues to increase in all age groups. A small number of melanomas spontaneously regress. In vitro studies suggest a role for the natural killer cell in effecting regression. In this study, the goal was to determine if natural killer cells are preferentially involved in the cytotoxic response in regressing lesions. Forty-two cases were selected: nevi with regression, nonregressing melanoma with brisk inflammation, and regressing melanoma. Sections were stained with hematoxylin and eosin and immunostained for CD8, CD56, and T-cell intracytoplasmic antigen 1. Numbers of total lymphocytes, CD8-positive lymphocytes, and T-cell intracytoplasmic antigen 1-positive lymphocytes did not differ among the 3 populations or based on location. CD56 positivity was significantly different among the 3 populations. Regressing melanomas showed the greatest CD56 activity, followed by regressing nevi, whereas inflamed, nonregressing melanomas showed the least. CD56(+) lymphocytes were mostly counted in areas of early regression. The natural killer cell could plausibly play a role in the occurrence of regression as a cytotoxic effector cell or as a mediator of the cytotoxic mechanism.

Geographic variability in human papillomavirus vaccination among U.S. young women

BACKGROUND Little information is available on geographic disparity of human papillomavirus (HPV) vaccination among women aged 18-26 years in the U.S. Genital HPV is the most common sexually transmitted infection in the U.S. Persistent HPV infection with oncogenic types can cause cervical cancer. PURPOSE This study utilized data collected from the 2010 National Health Interview Survey (NHIS). It identified geographic variability and other factors contributing to the disparities in HPV vaccine series initiation in a nationally representative sample of women aged 18-26 years. METHODS The study utilized data collected from 1867 women who participated in the Cancer Control Module Supplement of the 2012 NHIS. A multivariable logistic regression model was used to assess characteristics associated with initiation of the HPV series. Analyses were performed in 2012. RESULTS After adjusting for other characteristics, women living in the West and North Central/Midwest had 54% and 20% greater odds of initiating the HPV series, respectively, compared with those living in the Northeast. Other factors associated with HPV series initiation were younger age, Hispanic background, being single/never married, childlessness, a history of HPV, and current alcohol use. Factors correlated with failure to initiate the HPV series were: not having insurance, living below the 200% poverty level, not being a high school graduate, not currently using hormone-based birth control, most recent Pap >1 year ago, no regular provider, last clinic visit ≥12 months ago, and never having received the hepatitis B vaccine. CONCLUSIONS Results demonstrate disparity in HPV vaccine uptake by region of residence in the U.S. among young women. Further research is needed to understand the factors contributing to this geographic disparity. Evaluation of vaccination policies and practices associated with higher coverage regions might help characterize effective methods to improve HPV vaccination among women aged 18-26 years.

Outcomes of Cartilage Tympanoplasty in the Pediatric Population

Objective To justify the successful use of a patient selection algorithm based on age for primary cartilage tympanoplasty. Study Design Case series with chart review. Setting Tertiary care pediatric hospital. Subjects and Methods We performed a retrospective chart review of patients between ages 4 and 13 years who underwent cartilage tympanoplasty for tympanic membrane perforations from August 2005 to November 2011. Demographics, complication data, and auditory outcomes were collected. Results Patients were subdivided into 3 age groups. Group 1 consisted of patients younger than 7 years (n = 43); group 2, ages 7 to 10 years (n = 40); and group 3, ages 10 to 13 years (n = 36). Mean follow-up was 595 days (range, 48-1742). Complication rates respective to the 3 groups were as follows: remnant perforation (6.97%, 5.00%, 2.78%), revision tympanoplasty (2.33%, 2.50%, 0%), and need for tympanostomy tubes (4.65%, 2.50%, 0%). Logistic regression models were used to evaluate complication rates between groups. No significant differences were found (remnant perforation, P = .710; repeat tympanoplasty, P = .998; tympanostomy tubes, P = .875). No significance was found among audiological outcomes between the 3 groups. Conclusion These data suggest cartilage tympanoplasty can be performed effectively in young children when appropriate conditions exist.

Potential Years of Life Lost Due to Urogenital Cancer in the United States: Trends From 1972 to 2006 Based on Data From the SEER Database

PURPOSE Urogenital cancer is a major health problem in the United States. We assessed potential years of life lost secondary to genitourinary cancer in the United States from 1972 to 2006 using the SEER (Surveillance, Epidemiology and End Results) database. We report trends in potential years of life lost during the same period. MATERIALS AND METHODS Potential years of life lost were calculated to assess premature mortality trends for ureter, bladder, kidney and renal pelvis, penis, testis and prostate cancers. Calculations were based on SEER cancer mortality data. Potential years of life lost up to and including age 75 years were calculated by and across genders in 5-year increments between 1972 and 2006. RESULTS A total of 7,733,235 potential years of life were lost in men and women. In each gender the greatest potential loss was for kidney and renal pelvis cancer related mortality. In each gender no improvement in the potential loss due to ureteral and bladder cancer related mortality was observed during 3 decades. In males the greatest decrease in potential years of life lost was for testicular cancer, followed by prostate cancer. CONCLUSIONS There has been an increasing trend in potential years of life lost related to urogenital cancer during the last 35 years for males and females. This trend is mainly due to an increase in kidney cancer. The continued increase in potential years of life lost due to renal cancer and the lack of a decrease in the loss in those with bladder cancer should alert urologists and health care policy makers to deficient areas that most need to be addressed.

Cochlear implant failure, revision, and reimplantation.

Objective To evaluate the long-term adverse cochlear implant (CI) outcomes resulting in revision surgery including CI reimplantation (CIR). Patients Pediatric and adult patients requiring revision procedures after CI placement. Intervention(s) Revision surgery on cochlear implant patients. Main Outcome Measures Device type, length of total device follow-up, time to device failure, cause for failure, peak pre-CIR and post-CIR audiometric performance, rate of surgical site complications, and operative findings. Results A total of 317 patients, receiving 439 CIs between January 2000 and April 2012, met inclusion criteria for this series. For the patients implanted at our institution, the revision surgery rate was 4.1%, with a CIR rate of 3.0%. The CIR rates among the pediatric and adult populations were 5.0% and 1.3%, respectively (p = 0.0336). The rate of revision procedures because of failed fixation or device extrusion was 0.9%. Device failure was experienced in 8 patients in our series, with 75% occurring with the CI24R (CS) device. Conclusion All reimplanted patients with available data had good audiometric outcomes, with the exception of those reimplanted for soft failure who had poor immediate auditory function. Using the manufacturers’ recommended surgical technique, including drilling a bony recess with suture fixation, very low surgical revision rates were achieved. Pediatric patients experienced significantly higher complications requiring CIR. All hard failures in this series occurred in the pediatric group and in a single device. Continued follow-up will be needed to determine if additional devices will succumb to this mode of failure.

Patterns of failure in canal wall down mastoidectomy cavity instability.

Objective To evaluate patterns of failure for canal wall down mastoid cavities requiring surgical revision. Study Design Retrospective review. Setting Academic tertiary referral center Patients Adults and children that underwent revision of an unstable open mastoid cavity from 1995 to 2010. Intervention(s) Review of demographic data, tympanomastoid pathology, and plausible risk factors for an unstable cavity. Available computed tomography (CT) scans were reviewed for indicators of suboptimal cavity shape. Spearman’s correlation analysis was undertaken. Findings were classified as Type 1 (primary tympanomastoid pathology), Type 2 (cavity shape/size), or Type 3 (negative host environment). Main Outcome Measure(s) Frequency of risk factors and correlation. Results Approximately 130 cases were reviewed. Stapes erosion (49.2%), absent malleus (26.2%), cholesteatoma (44.6%), tympanic membrane perforation (34.6%), and fibrotic middle ear mucosa (20.8%) were common. CT scans often demonstrated an intact open mastoid tip (87.5%) and a high facial ridge (54.2%). Notable correlations were discovered between the facial ridge height proximally and the height distally (r = 0.46437, p = 0.0256) and tympanic membrane perforation and absent malleus (r = −0.17944, p = 0.0419). Approximately 68% of the subjects had at least 1 Class 1 risk factor present among cholesteatoma, tympanic membrane perforation/atelectasis, and extruded prosthesis. All CT scans reviewed demonstrated at least 1 Class 2 factor. Conclusion Although primary tympanomastoid pathology is quite common, some aspect of suboptimal mastoid cavity size and shape is pervasive. Correlation analysis suggests that surgeons tend to either lower the facial ridge completely or not at all and that an absent malleus seems to be associated with a tympanic membrane perforation.

Outcome of patients with relapsed/refractory acquired immune deficiency syndrome-related lymphoma diagnosed 1999–2008 and treated with curative intent in the AIDS Malignancy Consortium

Abstract No comparative studies exist for relapsed/refractory (rel/rfr) acquired immune deficiency syndrome (AIDS)-related lymphoma (ARL). To determine practices over the last decade and to assess the outcomes of salvage chemotherapy with curative intent and autologous stem cell transplant (ASCT), we retrospectively evaluated treatment outcomes in patients with rel/rfr ARL who were treated in 13 national AIDS Malignancy Consortium (AMC) sites between 1999 and 2008 (n = 88). The most commonly used second-line therapies were ICE (ifosfamide/carboplatin/etoposide, n = 34), dose adjusted EPOCH (etoposide/prednisone/vincristine/cyclophosphamide/doxorubicin, n = 17) and ESHAP (etoposide/methylprednisolone/cytarabine/cisplatin, n = 11). The odds of achieving a response were lower for those with non-Hodgkin lymphoma (NHL) than for those with HL and for those with primary refractory disease than for those with relapse. Overall survival (OS) was significantly longer for those with relapsed disease compared to those with refractory disease and for those with non-Burkitt NHL compared to those with Burkitt. OS was longer in patients who underwent ASCT compared to those who did not (1-year OS: 63.2% vs. 37.2%). However, among 32 patients (36%) who achieved a complete or partial reponse (CR/PR) after second-line therapy, 1-year OS was not different between the two groups (87.5% for ASCT vs. 81.8% for non-ASCT). Long-term survival in some patients with rel/rfr ARL may be possible without transplant, although transplant remains the standard of care for chemotherapy sensitive disease.

A phase 1/pharmacokinetic study of sunitinib in combination with highly active antiretroviral therapy in human immunodeficiency virus‐positive patients with cancer: AIDS Malignancy Consortium trial AMC 061

The treatment of non–acquired immunodeficiency syndrome‐defining cancers may be complicated by drug interactions between highly active antiretroviral therapy (HAART) and chemotherapy. This trial is the first by the AIDS Malignancy Consortium to assess targeted therapies and HAART in human immunodeficiency virus‐positive patients (ClinicalTrials.gov identifier: NCT00890747).