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.

Bending the cost curve: a unique collaboration between radiation oncologists and Blue Cross Blue Shield of Massachusetts to optimize the use of advanced technology.

PURPOSE: Intensity-modulated radiation therapy (IMRT) limits the dose of radiation to critical normal tissue structures and can be applied to the management of most cancers treated with radiation therapy. Because of increased treatment planning time and quality assurance, IMRT is costly. Blue Cross Blue Shield of Massachusetts (BCBSMA) and the Massachusetts Radiation Oncology Physicians Advisory Council (PAC) developed a strategy to develop standards for the appropriate use of IMRT. METHODS: Normal tissue volume guidelines were established in multiple oncology disease areas and body site regions. Guidelines were activated in September 2011, and the use of IMRT per case was tracked quarterly by BCBSMA staff. RESULTS: During the first year of activation of the volume-based guidelines, use of IMRT decreased by 17% in Massachusetts, in contrast to a 20% increase during the previous year. CONCLUSIONS: The normal tissue-based guidelines have decreased the use of IMRT in Massachusetts; increased the use of 3D treatment; continued communication between treating radiation oncologists and an insurance organization responsible for cost and quality in medicine; increased cost savings; enabled an efficient appeal process; and provided optimal, cost-effective patient care. This may prove to be an effective model for other disciplines and other developing and maturing radiation technologies.

Estimating chlamydia re-infection rates: an empirical example.

OBJECTIVE: Chlamydia re-infection data are used to inform and evaluate chlamydia control programmes. We quantitatively investigated the effect of denominator selection on estimating re-infection rates and trends. METHODS: Using data on women aged 15-44 years enrolled in Group Health Cooperative (GH), a Pacific Northwest health plan, annual chlamydia re-infection rates from 1998 to 2006 were calculated. Three different denominators were compared using person-years contributed by: (1) all women; (2) women with a prior documented chlamydial infection regardless of whether they were retested; and (3) women with a prior chlamydial infection who were retested within 14 months. RESULTS: From 1998 to 2006, among all women 15-44 years enrolled in GH, re-infection rates increased from 64 to 149 cases per 100 000 person-years. Among women with a prior infection, rates decreased from 10 857 to 8782 cases per 100 000 person-years. Among women with a prior infection who were retested, rates increased from 29 374 to 42 475 cases per 100 000 person-years. CONCLUSIONS: Using the same dataset, we demonstrate that it is possible to tell three different stories about the magnitude of rates and trends in chlamydia re-infection among women by using different denominators. All of these strategies have limitations, but restricting the denominator to women with a prior infection who are retested may best represent the population at-risk for re-infection. Still, rates do not account for additional factors influencing the number of re-infections diagnosed, including screening coverage and changes in test technology. Caution is needed in examining and comparing re-infection data.

Factors related to increasing prevalence of resistance to ciprofloxacin and other antimicrobial drugs in Neisseria gonorrhoeae, United States.

Using data from the Gonococcal Isolate Surveillance Project, we studied changes in ciprofloxacin resistance in Neisseria gonorrhoeae isolates in the United States during 2002-2007. Compared with prevalence in heterosexual men, prevalence of ciprofloxacin-resistant N. gonorrhoeae infections showed a more pronounced increase in men who have sex with men (MSM), particularly through an increase in prevalence of strains also resistant to tetracycline and penicillin. Moreover, that multidrug resistance profile among MSM was negatively associated with recent travel. Across the surveillance project sites, first appearance of ciprofloxacin resistance in heterosexual men was positively correlated with such resistance for MSM. The increase in prevalence of ciprofloxacin resistance may have been facilitated by use of fluoroquinolones for treating gonorrhea and other conditions. The prominence of multidrug resistance suggests that using other classes of antimicrobial drugs for purposes other than treating gonorrhea helped increase the prevalence of ciprofloxacin-resistant strains that are also resistant to those drugs.

Chlamydia trachomatis infections among women attending prenatal clinics: United States, 2004-2009.

BACKGROUND: Chlamydia screening practices, positivity, and trends from 2004 to 2009 in publicly funded prenatal clinics have not been described. METHODS: A phone-based survey assessing chlamydia screening practices was conducted among a random sample of clinics providing prenatal services (prenatal, family planning, and integrated clinics: "prenatal clinics") that reported data to the Infertility Prevention Project (IPP) in 2008. Using existing IPP data, chlamydia positivity and trends were assessed among women aged 15 to 24 years seeking care in any prenatal clinic reporting ≥3 years of data to IPP from 2004 to 2009. Linear trends of the effect of year (a continuous variable) on positivity were evaluated using a correlated modeling approach with a random intercept where the unit of analysis was the individual clinic performing chlamydia tests (clinic-based analysis). Covariates included race, age, test technology, and geography. RESULTS: Of 210 sampled clinics, 166 (79%) completed the survey. Of these, 163 (98.2%) had documented chlamydia screening criteria. Most clinics screened all women during their first trimester and reported 100% screening coverage. From 2004 to 2009, 267,416 tests among women aged 15 to 24 years were reported to IPP from eligible prenatal clinics. Overall chlamydia positivity was 8.3%. Controlling for all covariates, positivity decreased from 2004 to 2009 (odds ratio: 0.93 per year, 95% confidence interval: 0.92, 0.95, 35% decrease overall). CONCLUSIONS: The substantial burden of chlamydia among young women tested in prenatal clinics reporting data to IPP suggests the continued need for routine screening. Decreasing trends from 2004 to 2009 in the IPP prenatal population correspond to findings of overall decreasing chlamydia prevalence in the United States.

Patterns of care for non-small-cell lung cancer at an academic institution affiliated with a national cancer institute-designated cancer center.

PURPOSE: Evidence-based treatment guidelines for non-small-cell lung cancer (NSCLC) exist to improve the quality of care for patients with this disease. However, how often evidence-based decisions are used for care of NSCLC is poorly understood. PATIENTS AND METHODS: We examined patterns of care and rate of adherence to evidence-based guidelines for 185 new NSCLC patients seen between 2007 and 2009. Evidence-based care status was determined for 150 patients. RESULTS: Eighty-one percent of the patients were white, the mean age was 66 years, 49% were women, 11% were never smokers, 83% had Eastern Cooperative Oncology Group performance status 0 to 1, 49.7% of tumors were adenocarcinomas, 57.1% of never smokers had tumors genotyped (EGFR, ALK, KRAS), and 13.3% participated in clinical trials. The rate of evidence-based treatment adherence was 94.1% (16 of 17), 100% (21 of 21) and 100% (36 of 36) in patients with stages I, II, and III NSCLC, respectively. Stage IV disease, with adherence of 76.3% (58 of 76), was correlated with a higher rate of nonadherence when compared with stages I-III (odds ratio 16.33; 95% CI, 1.94 to 137.73). In patients with stage IV disease, the rate of evidence-based adherence was 95% (72 of 76) for first-line therapy, 95.2% (40 of 42) for second-line therapy, and only 33.3% (6 of 18) for third-line therapy (P < .001). There was no significant correlation between evidence-based adherence status and the patient's age, sex, performance status, smoking history, ethnicity, or the treating physician. CONCLUSION: These data point toward the need for improved evidence-based use of resources in the third-line setting of stage IV NSCLC.

Effects of screening and partner notification on Chlamydia positivity in the United States: a modeling study.

OBJECTIVES: Model impact of increasing screening and partner notification (PN) on chlamydia positivity. METHODS: We used a stochastic simulation model describing pair formation and dissolution in an age-structured heterosexual population. The model accounts for steady, casual, and concurrent partnerships and a highly sexually active core group. The model used existing sexual behavior data from the United States and was validated using chlamydia positivity data from Region X (Alaska, Idaho, Oregon, Washington). A screening program with a coverage rate of 20% was implemented among women aged 15 to 24 years. After 10 years, we increased screening coverage to 35%, 50%, and 65% and partner treatment rates from 20% to 40% and 55%. Finally, we included male screening (aged 15-24, screening coverage: 20% and 35%, partner treatment: 25% and 40%). We analyzed the effects on chlamydia positivity in women and the frequency of reinfection 6 months after treatment. RESULTS: The model described the decline in positivity observed from 1988 to 1997 in Region X, given screening coverage of 20% and a 25% partner treatment rate. Increasing screening coverage from 35% to 65% resulted in incremental decreases in positivity as did increasing the PN rate; a 23% reduction in positivity was achieved by either increasing screening by 3-fold or PN by 2-fold. Adding male screening to the program had less impact than increasing screening coverage or PN among women. Increased PN and treatment reduced reinfection rates considerably. CONCLUSIONS: Increasing efforts in PN may contribute at least as much to control of chlamydia infection as increasing screening coverage rates.

Sexually transmitted infections in newly arrived refugees: is routine screening for Neisseria gonorrheae and Chlamydia trachomatis infection indicated?

More than 340 million cases of bacterial and protozoal sexually transmitted infections (STIs) occur annually. Approximately 70,000 refugees arrive in the United States on a yearly basis. Refugees are a particularly disenfranchised and vulnerable population. The prevalence of Chlamydia and gonorrhea in refugee populations has not been described, and the utility of routine screening is unknown. We performed a descriptive evaluation of 25,779 refugees who completed a screening medical examination in Minnesota during 2003-2010. A total of 18,516 (72%) refugees were tested for at least one STI: 183 (1.1%) of 17,235 were seropositive for syphilis, 15 (0.6%) of 2,512 were positive for Chlamydia, 5 (0.2%) of 2,403 were positive for gonorrhea, 136 (2.0%) of 6,765 were positive for human immunodeficiency virus, and 6 (0.1%) of 5,873 were positive for multiple STIs. Overall prevalence of Chlamydia (0.6%) and gonorrhea (0.2%) infection was low, which indicated that routine screening may not be indicated. However, further research on this subject is encouraged.

Long-term trends in Chlamydia trachomatis infections and related outcomes in a U.S. managed care population.

BACKGROUND: Given recent increasing case rates of Chlamydia trachomatis infection, we evaluated trends in chlamydia rates and related health outcomes in women and men aged 15 to 44 years who were enrolled in a Pacific Northwest health plan. METHODS: We identified chlamydia, pelvic inflammatory disease (PID), ectopic pregnancy, and male urethritis cases occurring annually during 1997-2007 using computerized health plan databases, calculating rates per 100,000 person-years (py) by gender and 5-year age groups. We also calculated annual chlamydia testing rates. RESULTS: In women, chlamydia testing rates increased by approximately 23% (220 tests per 1000 py in 1997 to 270 tests per 1000 in 2007). Chlamydia diagnosis rates rose from 449 cases/100,000 py in 1997 to 806/100,000 in 2007, a 79% increase (P = 0.01). Increases were greatest during 2005-2007, also the period of major conversion to nucleic acid amplification test. PID rates in this interval declined steadily from 823 cases/100,000 py to 473/100,000 (P < 0.01). Ectopic pregnancy rates remained unchanged. In men, chlamydia testing rates increased nearly 3.5-fold, from 12 to 42 tests per 1000 py. Chlamydia rates for men also rose significantly throughout the study interval (from 91 cases/100,000 py to 218/100,000; P < 0.01) as did urethritis diagnosis rates (P < 0.01). CONCLUSION: Between 1997 and 2007, annual health plan chlamydia rates increased significantly for both women and men. These trends may be due in part to increased testing rates and increased use of more sensitive tests, but they likely do not explain the increased urethritis rates. During this same interval, we observed steady declines in PID rates, consistent with other national data sources.

Chlamydia trachomatis trends in the United States among persons 14 to 39 years of age, 1999-2008.

BACKGROUND: We report the first population-based assessment of national trends in chlamydia prevalence in the United States. METHODS: We investigated trends in chlamydia prevalence in representative samples of the U.S. population aged 14 to 39 years using data from five 2-year survey cycles of the National Health and Nutrition Examination Survey from 1999 to 2008. Prevalence estimates and 95% confidence intervals (CI) are reported stratified by age, gender, and race/ethnicity. Percent change in prevalence over this time period was estimated from regression models. RESULTS: In the 2007-2008 cycle, chlamydia prevalence among participants aged 14 to 39 years was 1.6% (95% CI: 1.1%-2.4%). Prevalence was higher among females (2.2%, 95% CI: 1.4%-3.4%) than males (1.1%, 95% CI: 0.7%-1.7%). Prevalence among non-Hispanic black persons was 6.7% (95% CI: 4.6%-9.9%) and was 2.5% (95% CI: 1.6%-3.8%) among adolescents aged 14 to 19 years. Over the five 2-year cycles, there was an estimated 40% reduction (95% CI: 8%-61%) in prevalence among participants aged 14 to 39 years. Decreases in prevalence were notable in men (53% reduction, 95% CI: 19%-72%), adolescents aged 14 to 19 years (48% reduction, 95% CI: 11%-70%), and adolescent non-Hispanic black persons (45%, reduction, 95% CI: 4%-70%). There was no change in prevalence among females aged 14 to 25 years, the population targeted for routine annual screening. CONCLUSIONS: On the basis of population estimates of chlamydia prevalence, the overall chlamydia burden in the United States decreased from 1999 to 2008. However, there remains a need to reduce prevalence in populations most at risk and to reduce racial disparities.

Detection of pelvic inflammatory disease: development of an automated case-finding algorithm using administrative data.

ICD-9 codes are conventionally used to identify pelvic inflammatory disease (PID) from administrative data for surveillance purposes. This approach may include non-PID cases. To refine PID case identification among women with ICD-9 codes suggestive of PID, a case-finding algorithm was developed using additional variables. Potential PID cases were identified among women aged 15-44 years at Group Health (GH) and Kaiser Permanente Colorado (KPCO) and verified by medical record review. A classification and regression tree analysis was used to develop the algorithm at GH; validation occurred at KPCO. The positive predictive value (PPV) for using ICD-9 codes alone to identify clinical PID cases was 79%. The algorithm identified PID appropriate treatment and age 15-25 years as predictors. Algorithm sensitivity (GH = 96.4%; KPCO = 90.3%) and PPV (GH = 86.9%; KPCO = 84.5%) were high, but specificity was poor (GH = 45.9%; KPCO = 37.0%). In GH, the algorithm offered a practical alternative to medical record review to further improve PID case identification.

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.

Lives Saved Tool supplement detection and treatment of syphilis in pregnancy to reduce syphilis related stillbirths and neonatal mortality.

BACKGROUND: Globally syphilis is an important yet preventable cause of stillbirth, neonatal mortality and morbidity. OBJECTIVES: This review sought to estimate the effect of detection and treatment of active syphilis in pregnancy with at least 2.4 MU benzathine penicillin (or equivalent) on syphilis-related stillbirths and neonatal mortality. METHODS: We conducted a systematic literature review of multiple databases to identify relevant studies. Data were abstracted into standardised tables and the quality of evidence was assessed using adapted GRADE criteria. Where appropriate, meta-analyses were undertaken. RESULTS: Moderate quality evidence (3 studies) supports a reduction in the incidence of clinical congenital syphilis of 97% (95% c.i 93 - 98%) with detection and treatment of women with active syphilis in pregnancy with at least 2.4 MU penicillin. The results of meta-analyses suggest that treatment with penicillin is associated with an 82% reduction in stillbirth (95% c.i. 67 - 90%) (8 studies), a 64% reduction in preterm delivery (95% c.i. 53 - 73%) (7 studies) and an 80% reduction in neonatal deaths (95% c.i. 68 - 87%) (5 studies). Although these effect estimates were large and remarkably consistent across studies, few of the studies adjusted for potential confounding factors and thus the overall quality of the evidence was considered low. However, given these large observed effects and a clear biological mechanism for effectiveness the GRADE recommendation is strong. CONCLUSION: Detection and appropriate, timely penicillin treatment is a highly effective intervention to reduce adverse syphilis-related pregnancy outcomes. More research is required to identify the most cost-effective strategies for achieving maximum coverage of screening for all pregnant women, and access to treatment if required.

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.

Gonorrhoea positivity among women aged 15-24 years in the USA, 2005-2007.

OBJECTIVE: To examine the epidemiology of young women screened for gonorrhoea in the USA. METHODS: Data on tests for gonorrhoea among women aged 15-24 years attending family planning clinics from 2005 to 2007 were obtained through the infertility prevention project. Clinics testing 90% or more of women for gonorrhoea and sending 50 or more gonorrhoea tests per year were included. Gonorrhoea positivity on a state and county level was calculated and compared by age and race/ethnicity. RESULTS: A total of 1,119,394 tests from 948 clinics was eligible for inclusion. Median state-specific gonorrhoea positivity was 1.3% (IQR 0.7-2.0%). Positivity was higher among women aged 15-19 years (1.4%, IQR 0.9-2.6%) than among those aged 20-24 years (1.1%, IQR 0.6-1.4%, p=0.03) and among non-Hispanic black women (3.8%, IQR 3.2-4.6%) than non-Hispanic white women (0.6%, IQR 0.4-0.8%, p<0.0001). Half of all gonorrhoea cases in these women originated from 57 of 753 counties. Among non-Hispanic white women, positivity was 2.0% or greater in 4% of counties, while 83% of counties had gonorrhoea positivity of less than 1.0%. Gonorrhoea positivity among non-Hispanic black women was 2.0% or greater in 58% of counties, and less than 1.0% in only one-third of counties. These disparities were present diffusely across the geographical areas included in this analysis. CONCLUSIONS: Gonorrhea positivity was consistently high for young non-Hispanic black women attending family planning clinics across multiple geographical regions. A large proportion of gonorrhoea morbidity was concentrated in a relatively small number of counties in the USA among this population of young women.

Evaluation of Syracuse Healthy Start's program for abnormal flora management to reduce preterm birth among pregnant women.

UNLABELLED: Randomized trials of bacterial vaginosis (BV) treatment among pregnant women to reduce preterm birth have had mixed results. Among non-pregnant women, BV recurs frequently after treatment. Randomized trials of early BV treatment for pregnant women in which recurrence was retreated have shown promise in reducing preterm birth. Syracuse's Healthy Start (SHS) program began in 1997; in 1998 prenatal care providers for pregnant women living in high infant mortality zip codes were encouraged to screen for abnormal vaginal flora at the first prenatal visit. Vaginal swabs were sent to a referral hospital laboratory for Gram staining and interpretation. SHS encouraged providers to treat and rescreen women with bacterial vaginosis or abnormal flora (BV). We abstracted prenatal and hospital charts of live births between January 2000 and March 2002 for maternal conditions and treatments. We merged abstracted data with local electronic data. We evaluated the effect of BV screening before 22 weeks gestation, treatment, and rescreening using a retrospective cohort study design. Among 838 women first screened before 22 weeks, 346 (41%) had normal flora and 492 (59%) women had BV at a mean of 13 weeks gestation; 202 (24%) did not have treatment documented and 290 (35%) received treatment at a mean of 15 weeks gestation; 267 (92%) of those treated were re-screened. Among pregnant women with early BV, 42 (21%) untreated women and 28 (10%) treated women delivered preterm (Odds Ratio [OR] 0.4, 95% confidence interval [CI] 0.2-0.7)). After adjustment for age, race, prior preterm birth and other possible confounders, treatment remained associated with a reduced risk of preterm birth compared to no treatment (aOR = 0.5, 95% CI 0.3-0.9); the aOR for women with normal flora was not significantly different. CONCLUSION: Screening, treatment, and rescreening for BV/abnormal flora between the first prenatal visit and 22 weeks gestation showed promise in reducing preterm births and deserves further study.

Sexually transmitted diseases treatment guidelines, 2010.

These guidelines for the treatment of persons who have or are at risk for sexually transmitted diseases (STDs) were updated by CDC after consultation with a group of professionals knowledgeable in the field of STDs who met in Atlanta on April 18-30, 2009. The information in this report updates the 2006 Guidelines for Treatment of Sexually Transmitted Diseases (MMWR 2006;55[No. RR-11]). Included in these updated guidelines is new information regarding 1) the expanded diagnostic evaluation for cervicitis and trichomoniasis; 2) new treatment recommendations for bacterial vaginosis and genital warts; 3) the clinical efficacy of azithromycin for chlamydial infections in pregnancy; 4) the role of Mycoplasma genitalium and trichomoniasis in urethritis/cervicitis and treatment-related implications; 5) lymphogranuloma venereum proctocolitis among men who have sex with men; 6) the criteria for spinal fluid examination to evaluate for neurosyphilis; 7) the emergence of azithromycin-resistant Treponema pallidum; 8) the increasing prevalence of antimicrobial-resistant Neisseria gonorrhoeae; 9) the sexual transmission of hepatitis C; 10) diagnostic evaluation after sexual assault; and 11) STD prevention approaches.