Complete pathologic response to short-course neoadjuvant alectinib in mediastinal node positive (N2) ALK rearranged lung cancer.

OBJECTIVES: Neoadjuvant therapy prior to surgical resection for locally advanced lung cancer has evolved to incorporate systemic cytotoxic chemotherapy +/- immunotherapy +/- radiotherapy. The role of neoadjuvant precision therapies remains understudied. MATERIALS AND METHODS: We report cases with major and complete pathologic responses to off-label neoadjuvant alectinib. RESULTS: A case with stage IIIA (cT1b cN2 cM0) EML4-ALK variant 3a/b lung adenocarcinoma received 6 weeks of alectinib followed by R0 left upper lobectomy with complete pathological response (ypT0 ypN0). Another case with stage IIIA (cT3 cN2 cM0) EML4-ALK variant 2 received 12 weeks of alectinib followed by R0 right middle lobectomy with a major pathologic response (ypT1a ypN0) but systemic recurrence 12 months post-operatively. CONCLUSION: Ongoing clinical trials are evaluating the role of both neoadjuvant and adjuvant ALK-directed therapy. Our cases support the completion of ongoing trials (ALINA: NCT03456076 and ALNEO: NCT05015010), and highlight the ability of second generation ALK inhibitors to induce major and complete pathologic responses in the neoadjuvant setting plus the likely role of long-term adjuvant kinase inhibitor therapy to prevent radiographic/clinical recurrence.

Sexually transmitted diseases program performance measures: how are they performing?

BACKGROUND: Performance measures were developed in order to improve the performance of sexually transmitted disease (STD) prevention programs. METHODS: A consultant worked with persons from STD programs and Centers for Disease Control and Prevention to identify possible measures. Measures were pilot tested for feasibility and relevance in several programs, then implemented nationwide in 2004. Data were collated and shared with programs and presented at national meetings. Site visits, webinars, and technical assistance focused on program improvement related to the measures. Reported data were analyzed to see if national performance improved on the activities measured. RESULTS: Some measures were dropped or revised, and quality of reported data improved over time. There was little evidence that overall program performance improved. CONCLUSIONS: Performance measures are one way to monitor performance, and might contribute to program improvement, but additional efforts are needed to improve performance.

A prospective study of the psychosocial impact of a positive Chlamydia trachomatis laboratory test.

BACKGROUND: Few data exist on potential harms of chlamydia screening. We assessed the psychosocial impact of receiving a positive Chlamydia trachomatis test result. METHODS: We prospectively studied women ≥16 years of age undergoing chlamydia testing in 2 Midwestern family planning clinics. We surveyed women at baseline and about 1 month after receiving test results, using 9 validated psychosocial scales/subscales and chlamydia-specific questions. Changes in scale scores were calculated for each woman. Mean percent changes in scores for chlamydia-positive and -negative women were compared using a t test. RESULTS: We enrolled 1807 women (response rate, 84%). Of the 1688 women with test results, 149 (8.8%) tested positive. At follow-up, chlamydia-positive women (n = 71) had a 75% increase in anxiety about sexual aspects of their life on the Multidimensional Sexual Self-Concept Questionnaire (P < 0.001), significantly greater than the 26% increase among 280 randomly selected chlamydia-negative women (P = 0.02). There were no differences for the other 8 scales/subscales, including general measures of anxiety, depression, and self-esteem. Chlamydia-positive women were more likely than chlamydia-negative women to be "concerned about chlamydia" (80% vs. 40%, P < 0.001) and to report breaking up with a main partner (33% vs. 11%, P < 0.001) at follow-up. Women testing positive reported a range of chlamydia-specific concerns. CONCLUSIONS: Chlamydia-positive women had significant increases in anxiety about sex and concern about chlamydia, but did not have marked changes in more general measures of psychosocial well-being about 1 month after diagnosis. Chlamydia diagnoses were associated with some disruption of relationships with main partners. Chlamydia-specific concerns may guide counseling messages to minimize psychosocial impact.

Screening and treatment to prevent sequelae in women with Chlamydia trachomatis genital infection: how much do we know?

BACKGROUND: An important question for chlamydia control programs is the extent to which finding and treating prevalent, asymptomatic Chlamydia trachomatis genital infection reduces reproductive sequelae in infected women. METHODS: We reviewed the literature to critically evaluate evidence on the effect of chlamydia screening on development of sequelae in infected women. RESULTS: Two randomized controlled trials of 1-time screening for chlamydial infection-in a Seattle-area health maintenance organization and a Danish school district-revealed that screening was associated with an approximately 50% reduction in the incidence of pelvic inflammatory disease over the following year. However, both of these trials had methodological issues that may have affected the magnitude of observed screening benefits and might limit generalizability to other populations. A large, nonrandomized cohort of chlamydia screening among US Army recruits, although limited by lack of outpatient data, did not find a benefit of similar magnitude to the randomized trials. Methodological limitations restrict valid conclusions about individual benefits of screening using data from historical cohorts and ecological studies. We identified no trials directly evaluating the effect of chlamydia screening on subclinical tubal inflammation or damage, ectopic pregnancy, or tubal factor infertility and no studies addressing the effects of >1 round of screening, the optimal frequency of screening, or the benefits of screening for repeat infections. CONCLUSIONS: Additional studies of the effectiveness of chlamydia screening would be valuable; feasible study designs may depend on the degree to which screening programs are already established. In addition, better natural history data on the timing of tubal inflammation and damage after C. trachomatis infection and development of more accurate, noninvasive tools to assess chlamydial sequelae are essential to informing chlamydia control efforts.

Dilemmas in the management of syphilis: a survey of infectious diseases experts.

We surveyed infectious diseases consultants to determine how they manage syphilis when there are insufficient data to guide management or when guidelines cannot be followed because of a lack of available definitive diagnostic tests. Most providers did not have access to dark-field microscopy. We found variation in management of syphilis, especially for patients with human immunodeficiency virus infection.

Screening male prisoners for Chlamydia trachomatis: impact on test positivity among women from their neighborhoods who were tested in family planning clinics.

BACKGROUND: Chlamydia trachomatis screening test positivity among women in the United States has remained high, leading researchers to suggest that programs should also screen men. Men have been screened in Philadelphia prisons since 2002. Philadelphia prisons are similar to jails in other jurisdictions; in 2003 the median duration of incarceration was 17 days. We studied whether screening and treating men in prison influenced C. trachomatis infection among women living in their communities. METHODS: We divided the city into 2 areas: "high-treatment" (high percentage of men were treated for C. trachomatis detected in prison) and "low-treatment" (low percentage of men were treated for C. trachomatis detected in prison). We compared changes in test positivity among women from those areas, who were tested in family planning clinics during the 2 years before versus the 3 years after the male prison screening program began. RESULTS: In 2002 to 2004, prison screening led to treatment of 1054 infections among 23,203 men aged 20 to 24 years living in high-treatment areas and 98 infections among 21,057 men aged 20 to 24 years in low-treatment areas. Test positivity declined among 20- to 24-year-old women in both areas. In high-treatment areas, positivity decreased 9.1% per year from 1999 to 2001 and 4.9% per year from 2001 to 2004. In low-treatment areas, positivity decreased 13.2% per year from 1999 to 2001 and 7.5% per year from 2001 to 2004. CONCLUSION: C. trachomatis test positivity among 20- to 24-year-old women tested in family planning clinics continued to decrease after men were treated for C. trachomatis; however, we found no evidence that the continued decrease was due to the new prison screening program.

Emerging antimicrobial resistance in Neisseria gonorrhoeae: urgent need to strengthen prevention strategies.

Prevention and control of gonorrhea is an important public health concern due to the high burden of disease, the recent increase in reported infection rates, and the reproductive and economic consequences of infection. Effective antibiotic treatment is one essential component of an integrated approach to gonorrhea control. Over the past 60 years, however, development of resistance in Neisseria gonorrhoeae to multiple antimicrobial classes challenges this component of gonorrhea control. An integrated, comprehensive prevention strategy should include enhancement of national and international surveillance systems to monitor antimicrobial resistance and new strategies to maximize the benefit and prolong the utility of antimicrobials, including combination regimens, implementation of screening recommendations for individuals at high risk for infection, and the assurance of prompt and effective treatment for infected persons and their sexual partners. Progress in controlling the epidemic and avoiding a resurgence as treatment options wane will require careful attention to all components of a comprehensive prevention strategy.

Organ deformation and dose coverage in robotic respiratory-tracking radiotherapy.

PURPOSE: Respiratory motion presents a significant challenge in stereotactic body radiosurgery. Respiratory tracking that follows the translational movement of the internal fiducials minimizes the uncertainties in dose delivery. However, the effect of deformation, defined as any changes in the body and organs relative to the center of fiducials, remains unanswered. This study investigated this problem and a possible solution. METHODS AND MATERIALS: Dose delivery using a robotic respiratory-tracking system was studied with clinical data. Each treatment plan was designed with the computed tomography scan in the end-expiration phase. The planned beams were applied to the computed tomography scan in end-inspiration following the shift of the fiducials. The dose coverage was compared with the initial plan, and the uncertainty due to the deformation was estimated. A necessary margin from the clinical target volume to the planning target volume was determined to account for this and other sources of uncertainty. RESULTS: We studied 12 lung and 5 upper abdomen lesions. Our results demonstrated that for lung patients with properly implanted fiducials a 3-mm margin is required to compensate for the deformation and a 5-mm margin is required to compensate for all uncertainties. Our results for the upper abdomen tumors were still preliminary but indicated a similar result, although a larger margin might be required. CONCLUSION: The effect of body deformation was studied. We found that adequate dose coverage for lung tumors can be ensured with proper fiducial placement and a 5-mm planning target volume margin. This approach is more practical and effective than a recent proposal to combine four-dimensional planning with respiratory tracking.

Epidemiology of STD disparities in African American communities.

This article reviews the epidemiology of sexually transmitted disease (STD) disparities for African American communities in the United States. Data are reviewed from a variety of sources such as national case reporting and population-based studies. Data clearly show a disproportionately higher burden of STDs in African American communities compared with white communities. Although disparities exist for both viral and bacterial STDs, disparities are greatest for bacterial STDs such as gonorrhea, chlamydia, and syphilis. Gonorrhea rates among African Americans are highest for adolescents and young adults, and disparities are greatest for adolescent men. Although disparities for men who have sex with men (MSM) are not as great as for heterosexual populations, STD rates for both white and African American MSM populations are high, so efforts to address disparities must also include African American MSM. Individual risk behavior and sociodemographic characteristics of African Americans do not seem to account fully for increased STD rates for African Americans. Population-level determinants such as sexual networks seem to play an important role in STD disparities. An understanding of the epidemiology of STD disparities is critical for identifying appropriate strategies and tailoring strategies for African American communities. Active efforts are needed to reduce not only the physical consequences of STDs, such as infertility, ectopic pregnancy, chronic pelvic pain, newborn disease, and increased risk of HIV infection, but also the social consequences of STDs such as economic burden, shame, and stigma.

Sexually transmitted diseases treatment guidelines, 2006.

These guidelines for the treatment of persons who have sexually transmitted diseases (STDs) were developed by CDC after consultation with a group of professionals knowledgeable in the field of STDs who met in Atlanta, Georgia, during April 19-21, 2005. The information in this report updates the Sexually Transmitted Diseases Treatment Guidelines, 2002 (MMWR 2002;51[No. RR-6]). Included in these updated guidelines are an expanded diagnostic evaluation for cervicitis and trichomoniasis; new antimicrobial recommendations for trichomoniasis; additional data on the clinical efficacy of azithromycin for chlamydial infections in pregnancy; discussion of the role of Mycoplasma genitalium and trichomoniasis in urethritis/cervicitis and treatment-related implications; emergence of lymphogranuloma venereum protocolitis among men who have sex with men (MSM); expanded discussion of the criteria for spinal fluid examination to evaluate for neurosyphilis; the emergence of azithromycin- resistant Treponema pallidum; increasing prevalence of quinolone-resistant Neisseria gonorrhoeae in MSM; revised discussion concerning the sexual transmission of hepatitis C; postexposure prophylaxis after sexual assault; and an expanded discussion of STD prevention approaches.

Electromagnetic navigation bronchoscopy-guided fiducial placement for robotic stereotactic radiosurgery of lung tumors: a feasibility study.

BACKGROUND: Stereotactic radiosurgery (Cyberknife; Accuray Incorporated; Sunnyvale, CA) is a treatment option for patients who are medically unfit to undergo lung tumor resection. For precise tumor ablation, the Cyberknife requires fiducial marker placement in or near the target tumor. Fiducial placement under transthoracic CT guidance is associated with a high risk of iatrogenic pneumothorax. Electromagnetic navigation bronchoscopy (ENB) may offer a less morbid alternative to accurately deploy fiducials to bronchoscopically invisible peripheral lung lesions. OBJECTIVE: Open-label, feasibility study to assess fiducial placement in peripheral lung tumors by ENB. METHOD: Consecutive patients with peripheral lung tumors and who were evaluated to be nonsurgical candidates underwent fiducial placement under ENB. This procedure was considered successful if fiducials were placed in or near the tumors and remained in place without migration for radiosurgery to proceed. The need for alternative or additional intrathoracic fiducial placement was documented as procedure failure. RESULTS: A total of 39 fiducials markers were successfully deployed in eight of nine patients (89%). Of these eight successful cases, seven had fiducials placed directly within the tumor (88%). At Cyberknife planning, 7 to 10 days after fiducial placement, 35 of 39 fiducial markers (90%) were still in place and were adequate to allow radiosurgery to proceed. No immediate bronchoscopic complications were observed. One patient had a COPD exacerbation. Another patient returned within 1 day with transient, self-limiting fever. CONCLUSIONS: ENB can be used to deploy fiducial markers for Cyberknife radiosurgery of lung tumors safely and accurately without the complications associated with transthoracic placement.

Seroprevalence of herpes simplex virus types 1 and 2 in pregnant women in the United States.

OBJECTIVE: The purpose of this study was to determine seroprevalence of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in a national cross-sectional sample of pregnant women. STUDY DESIGN: Pregnancy tests (urine and serum) were performed for female patients 12-59 years of age who participated in the National Health and Nutrition Examination Survey from 1999-2002. Immunodot assays were used to detect antibodies to HSV-1 and HSV-2. RESULTS: The mean age of the 626 pregnant women was 27 years, and the median number of lifetime sex partners was 4. Overall, HSV-1 seroprevalence was 63%; HSV-2 seroprevalence was 22%; infection with both HSV-1 and HSV-2 was 13%, and HSV seronegativity was 28%. HSV seroprevalence differed by race/ethnicity, with nonHispanic white patients more likely to be seronegative compared with other racial/ethnic groups (40% vs 11%; P < .001). The number of lifetime sex partners was also associated with serostatus. On the basis of serostatus-specific rates of neonatal herpes from a published study, the rate of neonatal herpes is projected to be 33/100,000 live births and is 40% higher in nonHispanic white women than in other racial/ethnic groups. CONCLUSION: The seroprevalence of HSV-1 and HSV-2 varied by race/ethnicity; babies born to nonHispanic white mothers, whose HSV seroprevalence was the lowest, appear to be at greater risk for neonatal herpes.

Trends in primary and secondary syphilis among men who have sex with men in the United States.

OBJECTIVES: We assessed the epidemiology of primary and secondary syphilis in the United States and estimated the percentages of cases occurring among men who have sex with men (MSM). METHODS: We reviewed US syphilis surveillance data from 1990 through 2003. We estimated the number of cases occurring among MSM by modeling changes in the ratio of syphilis cases among men to cases among women. RESULTS: During 1990 through 2000, the rate of primary and secondary syphilis decreased 90% overall, declining 90% among men and 89% among women. The overall rate increased 19% between 2000 and 2003, reflecting a 62% increase among men and a 53% decrease among women. In 2003, an estimated 62% of reported cases occurred among MSM. CONCLUSIONS: Increasing syphilis cases among MSM account for most of the recent overall increase in rates and may be a harbinger of increasing rates of HIV infection among MSM. National efforts are under way to improve monitoring of syphilis trends, better understand factors associated with the observed increases, and improve efforts to prevent syphilis transmission.

Trends in herpes simplex virus type 1 and type 2 seroprevalence in the United States.

CONTEXT: Herpes simplex virus type 1 (HSV-1) and type 2 are common infections worldwide. Herpes simplex virus type 2 (HSV-2) is the cause of most genital herpes and is almost always sexually transmitted. In contrast, HSV-1 is usually transmitted during childhood via nonsexual contacts. Preexisting HSV-1 antibodies can alleviate clinical manifestations of subsequently acquired HSV-2. Furthermore, HSV-1 has become an important cause of genital herpes in some developed countries. OBJECTIVE: To examine trends in HSV-1 and HSV-2 seroprevalence in the United States in 1999-2004 compared with 1988-1994. DESIGN, SETTINGS, AND PARTICIPANTS: Cross-sectional, nationally representative surveys (US National Health and Nutrition Examination Surveys [NHANES]), were used to compare national seroprevalence estimates from 1999-2004 with those from 1988-1994, and changes in HSV-1 and HSV-2 seroprevalence since 1976-1980 were reviewed. Persons aged 14 to 49 years were included in these analyses. MAIN OUTCOME MEASURES: Seroprevalence of HSV-1 and HSV-2 antibodies based on results from type-specific immunodot assays; diagnosis of genital herpes. RESULTS: The overall age-adjusted HSV-2 seroprevalence was 17.0% (95% confidence interval [CI], 15.8%-18.3%) in 1999-2004 and 21.0% (95% CI, 19.1%-23.1%) in 1988-1994, a relative decrease of 19.0% between the 2 surveys (95% CI, -28.6% to -9.5%; P<.001). Decreases in HSV-2 seroprevalence were especially concentrated in persons aged 14 to 19 years between 1988 and 2004. In adolescents aged 17 to 19 years and young adults, the decreases in HSV-2 seroprevalence were significant even after adjusting for changes in sexual behaviors. Among those infected with HSV-2, the percentage who reported having been diagnosed with genital herpes was statistically different (14.3% in 1999-2004 and 9.9% in 1988-1994; P = .02). Seroprevalence of HSV-1 decreased from 62.0% (95% CI, 59.6%-64.6%) in 1988-1994 to 57.7% (95% CI, 55.9%-59.5%) in 1999-2004, a relative decrease of 6.9% between the 2 surveys (95% CI, -11.6% to -2.3%; P = .006). Among persons infected with HSV-1 but not with HSV-2, a higher percentage reported having been diagnosed with genital herpes in 1999-2004 compared with 1988-1994 (1.8% vs 0.4%, respectively; P<.001). CONCLUSIONS: These data show declines in HSV-2 seroprevalence, suggesting that the trajectory of increasing HSV-2 seroprevalence in the United States has been reversed. Seroprevalence of HSV-1 decreased but the incidence of genital herpes caused by HSV-1 may be increasing.

Induction docetaxel and carboplatin followed by weekly docetaxel and carboplatin with concurrent radiotherapy, then surgery in stage III non-small cell lung cancer: a Phase I study.

PURPOSE: To determine the maximum-tolerated dose of docetaxel (DOC) in combination with carboplatin (CAR) and thoracic radiotherapy (RT), in the setting of trimodality treatment of patients with stage III non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Thirty-two patients with biopsy-proven stage IIIA (n = 20) or IIIB (n = 12) NSCLC were given two initial cycles of CAR (area under the curve = 6) and DOC (75 mg/m(2)), subsequent RT (54 Gy) with concurrent weekly CAR (area under the curve = 2), and DOC at six dose levels from 10 to 40 mg/m(2), then surgery if the patient's disease was resectable. RESULTS: Three patients did not complete induction computed tomography (CT). Twenty-nine patients received concurrent CT/RT. Fifteen patients were eligible for surgery. Dose-limiting toxicities occurred in 2 patients, at dose levels two (atrial fibrillation) and three (transaminitis). The maximum-tolerated dose, as defined by the protocol, was not reached, although grade 3 and 4 toxicities were encountered at all dose levels. The most common more than or equal to grades 3 toxicities were neutropenia, nausea, vomiting, and fatigue. Four patients (13.3%) responded to induction CT. Ten patients (38.5%) responded to CT/RT. Eight surgical patients (57.1%) were downstaged, including 3 pathologic complete responses. Median relapse free and overall survivals are 8.5 and 12 months. One-year and estimated 2-year survival rates are 56.3 and 34.3%. CONCLUSION: This new regimen for stage III NSCLC of induction CAR/DOC, then weekly CAR/DOC with concurrent RT followed by surgery, can be safely administered and offers encouraging results. DOC at 30 mg/m(2) in combination with CAR and RT is recommended for Phase II study.

Ciprofloxacin for the treatment of uncomplicated gonorrhea infection in adolescents: does the benefit outweigh the risk?

The highest rates of reported gonorrhea infections occur among adolescent females aged 15-19 years. Among the Centers for Disease Control and Prevention (CDC)-recommended single-dose gonorrhea treatment regimens, ciprofloxacin, a fluoroquinolone antibiotic, is approximately half the cost of other CDC-recommended oral treatment regimens. Fluoroquinolone use in patients aged <18 years has been limited because of irreversible articular cartilage damage demonstrated in large, weight-bearing joints of young animals. We reviewed the medical literature to assess whether the risks of a single 500-mg dose of ciprofloxacin to treat uncomplicated gonorrhea infection in adolescents appears to outweigh the benefits. We found no reports of irreversible cartilage toxicity or age-associated adverse events in 5236 human children and adolescents (aged 5 days-24 years) treated with a total of 5486 courses of fluoroquinolones.