Nonfulfillment of desired postpartum permanent contraception and resultant maternal and pregnancy health outcomes.

BACKGROUND: Up to half of the patients requesting postpartum permanent contraception do not undergo the desired procedure. Although nonfulfillment of desired postpartum permanent contraception is associated with increased risk of pregnancy within 12 months of delivery, its long-term reproductive and maternal health outcomes are less clear. OBJECTIVE: This study aimed to determine the association of fulfillment of postpartum permanent contraception with number and timing of subsequent pregnancies and maternal health outcomes. STUDY DESIGN: This was a retrospective single-center cohort chart review study of health outcomes in the 4 years following delivery (2016-2018) for 1331 patients with a documented contraceptive plan of female permanent contraception at time of postpartum discharge from 2012 to 2014. Rates of permanent contraception fulfillment within 90 days of delivery and clinical and demographic characteristics associated with permanent contraception were calculated. We determined number of and time to subsequent pregnancies, and diagnoses of medical comorbidities (hypertension, diabetes mellitus, depression, anxiety, asthma, anemia), sexually transmitted infection, and pregnancy comorbidities (preterm birth, gestational diabetes mellitus, gestational hypertension, preeclampsia, postpartum hemorrhage, low birthweight, intrauterine fetal demise) in the 4 years following delivery. RESULTS: Of the 1331 patients desiring permanent contraception postpartum, 588 (44.1%) had their requests fulfilled within 90 days of delivery and 743 (55.8%) did not. Patients who achieved permanent contraception fulfillment tended to have attended more outpatient prenatal visits, delivered via cesarean delivery, and were older, married, college-educated, and privately insured. Patients who received their desired postpartum permanent contraception were less likely to have subsequent intrauterine pregnancies (P<.001). In those who did not achieve permanent contraception, 22 (9.0%) subsequent pregnancies occurred within 6 months of previous deliveries, and 223 (91.0%) occurred after short interpregnancy intervals (within 18 months). Of 178 continued pregnancies, 26 (14.6%) were delivered preterm. There were no differences between the 2 groups in terms of ever attending an outpatient, preventive, or emergency room visit, or in most nonreproductive health outcomes investigated. CONCLUSION: Nonfulfillment of desired postpartum permanent contraception is associated with subsequent maternal reproductive and nonreproductive health ramifications. Given the barriers to permanent contraception, alternative plans for contraception should be discussed proactively if permanent contraception is not provided.

Abortion as Essential Health Care and the Critical Role Your Practice Can Play in Protecting Abortion Access.

Few obstetrician-gynecologists (ob-gyns) provide abortion care, resulting in abortion being separated from other reproductive health care. This segregation of services disrupts the ob-gyn patient-clinician relationship, generates needless costs, delays access to abortion care, and contributes to stigma. General ob-gyns have both the skills and the knowledge to incorporate abortion into their clinical practices. In this way, they can actively contribute to the protection of abortion access now with the loss of federal protection for abortion under Roe v Wade . For those who live where abortion remains legal, now is the time to start providing abortions and enhancing your abortion-referral process. For all, regardless of state legislation, ob-gyns must be leaders in advocacy by facilitating abortion care-across state lines, using telehealth, or with self-managed abortion-and avoiding any contribution to the criminalization of those who seek or obtain essential abortion care. Our patients deserve a specialty-wide concerted effort to deliver comprehensive reproductive health care to the fullest extent.

Falling insulin requirement in late pregnancy: association with obstetric and neonatal outcomes.

OBJECTIVE: To investigate whether diminishing insulin requirement in the third trimester is associated with placental dysfunction. STUDY DESIGN: Two-year retrospective cohort study at one tertiary care center of women with pregestational or gestational diabetes, their insulin requirements, and complications associated with placental dysfunction. RESULTS: Of 157 women, 21 (13%) experienced declining insulin requirement, with average decline of 28% at 34 weeks. They were more likely to have pregestational diabetes (71.4% vs. 42.6%; p < 0.01) and delivered earlier (median 36w4d vs. 37w4d; p < 0.01). There was no difference in placental dysfunction related complications (33% vs. 24%; p = 0.37). There was an increased rate of polyhydramnios (42.9% vs. 8.8%; p < 0.01). NICU admission (62% vs. 33%; p < 0.01) and neonatal respiratory distress (52% vs. 24%; p < 0.01) was higher in cases of declining insulin requirement independent of gestational age. CONCLUSIONS: A decline in insulin requirement should raise concern for increased risk of NICU admission and neonatal respiratory distress.

Association of race and ethnicity with postpartum contraceptive method choice, receipt, and subsequent pregnancy.

BACKGROUND: We sought to assess racial/ethnic differences in choice of postpartum contraceptive method after accounting for clinical and demographic correlates of contraceptive use. METHODS: This is a secondary analysis of a single-center retrospective cohort study examining postpartum women from 2012 to 2014. We determined the association between self-identified race/ethnicity and desired postpartum contraception, receipt, time to receipt, postpartum visit attendance, and subsequent pregnancy within 365 days of delivery. RESULTS: Of the 8649 deliveries in this study, 46% were by Black women, 36% White women, 12% Hispanic, and 6% by women of other races. Compared with White women, Black and Hispanic women were more likely to have a postpartum contraception plan for all methods. After multivariable analysis, Hispanic women (relative to White women) were less likely to receive their chosen method (odds ratio [OR] 0.74, 95% confidence interval [CI] 0.64-0.87). Women of races other than Black or Hispanic were less likely to experience a delay in receipt of their desired highly-effective method compared to White women (hazard ratio [HR] = 0.70, 95% CI 0.52-0.94). There were no differences between racial/ethnic groups in terms of postpartum visit adherence. Black women were more likely to be diagnosed with a subsequent pregnancy compared to White women (OR 1.17, 95% CI 1.04-1.32). CONCLUSION: Racial/ethnic variation in postpartum contraceptive outcomes persists after accounting for clinical and demographic differences. While intrinsic patient-level differences in contraceptive preferences should be better understood and respected, clinicians should take steps to ensure that the observed differences in postpartum contraceptive plan methods between racial/ethnic groups are not due to biased counseling.

Underlying dimensions of the EORTC QLQ-C30 in a Cuban population of patients with advanced non-small cell lung cancer.

BACKGROUND: Quality of Life Core Questionnaire of the European Organization for the Research and Treatment of Cancer (EORTC QLQ-C30) is one of the most used quality of life questionnaires in cancer studies. It provides scores for five functional scales, nine symptom scales, and two single items which assess overall health status and quality of life. However, high correlations among QLQ-C30 items suggest a reduced dimensionality for the scale. OBJECTIVE: To assess the dimensionality of the EORTC QLQ-C30 using item response theory (IRT) in a training sample and confirmatory factor analysis (CFA) in a test sample. METHODS: We analyzed responses to QLQ-C30 from 1,107 patients with advanced lung cancer who were included in five clinical trials of immunotherapy. We used non-parametric and parametric IRT models (Mokken, and Samejima's graded response) in a random training set (n = 332) for initial assessment of dimensions and item characteristics of the QLQ-C30. Finally, we used CFA in the test set (n = 775) to confirm the measurement domains. RESULTS: Mokken model showed that QLQ-C30 fits a unidimensional scale, whereas Samejima model showed that most QLQ-C30 items present adequate difficulty and discrimination. All items showed adequate scalability indexes with an overall scalability of 0.47 (medium scale). The QLQ-C30-reduced dimensionality was confirmed by CFA (comparative fit index = 0.98, root mean square error of approximation = 0.055) with all items presenting factorial loadings > 0.40. CONCLUSIONS: The EORTC QLQ-C30 fits a unidimensional latent construct identified with perceived quality of life in advanced lung cancer patients. TRIAL REGISTRATION: RPCEC00000161, RPCEC00000181 and RPCEC00000205.

Association between neighborhood disadvantage and fulfillment of desired postpartum sterilization.

BACKGROUND: Adequacy of prenatal care is associated with fulfillment of postpartum sterilization requests, though it is unclear whether this relationship is indicative of broader social and structural determinants of health or reflects the mandatory Medicaid waiting period required before sterilization can occur. We evaluated the relationship between neighborhood disadvantage (operationalized by the Area Deprivation Index; ADI) and the likelihood of undergoing postpartum sterilization. METHODS: Secondary analysis of a single-center retrospective cohort study examining 8654 postpartum patients from 2012 to 2014, of whom 1332 (15.4%) desired postpartum sterilization (as abstracted from the medical record at time of delivery hospitalization discharge) and for whom ADI could be calculated via geocoding their home address. We determined the association between ADI and sterilization completion, postpartum visit attendance, and subsequent pregnancy within 365 days of delivery via logistic regression and time to sterilization via Cox proportional hazards regression. RESULTS: Of the 1332 patients included in the analysis, patients living in more disadvantaged neighborhoods were more likely to be younger, more parous, delivered vaginally, Black, unmarried, not college educated, and insured via Medicaid. Compared to patients living in less disadvantaged areas, patients living in more disadvantaged areas were less likely to obtain sterilization (44.8% vs. 53.5%, OR 0.84, 95% CI 0.75-0.93), experienced greater delays in the time to sterilization (HR 1.23, 95% CI 1.06-1.44), were less likely to attend postpartum care (58.9% vs 68.9%, OR 0.86, CI 0.79-0.93), and were more likely to have a subsequent pregnancy within a year of delivery (15.1% vs 10.4%, OR 1.56, 95% CI 1.10-1.94). In insurance-stratified analysis, for patients with Medicaid, but not private insurance, as neighborhood disadvantage increased, the rate of postpartum sterilization decreased. The rate of subsequent pregnancy was positively associated with neighborhood disadvantage for both Medicaid as well as privately insured patients. CONCLUSION: Living in an area with increased neighborhood disadvantage is associated with worse outcomes in terms of desired postpartum sterilization, especially for patients with Medicaid insurance. While revising the Medicaid sterilization policy is important, addressing social determinants of health may also play a powerful role in reducing inequities in fulfillment of postpartum sterilization.

Variation in effectiveness of planned postpartum contraception at two time points from prenatal to postpartum care.

OBJECTIVE: To identify characteristics of women who have consistent plans in terms of contraceptive effectiveness from antepartum to postpartum care. STUDY DESIGN: This is a secondary analysis of a retrospective chart review of women who delivered at a single tertiary care center from 2012 to 2014. Preferred postpartum contraceptive plan was abstracted at three time points (prenatal care, hospital discharge, and outpatient postpartum care) and categorized into three tiers of effectiveness. We then examined consistency between the first two time points for the effectiveness in postpartum contraceptive method planned. RESULTS: Of the 8,394 women in the study cohort, 2,642 (31.5%) had a consistent postpartum contraceptive plan. Women who had a consistent plan were more likely to have higher parity (aOR 2.36, 95% CI 2.06-2.70 for parity 2+), choose highly effective methods of contraception (p < 0.001), achieve their contraception plan (adjusted odds ratio [aOR] 2.16, 95% confidence interval [95% CI] 1.85-2.52), but not more likely to have a subsequent pregnancy within 365 days of delivery (aOR 0.92, 95% CI 0.81-1.05). CONCLUSION: Better understanding contraceptive decision-making as a journey and removing external barriers during that process is a necessary component of pregnancy care. IMPLICATIONS: Counseling and documentation of contraceptive preferences throughout antepartum and postpartum care can help improve contraceptive outcomes.

Desired Sterilization Procedure at the Time of Cesarean Delivery According to Insurance Status.

OBJECTIVE: To evaluate whether women with Medicaid are less likely than their privately insured counterparts to receive a desired sterilization procedure at the time of cesarean delivery. METHODS: This is a secondary analysis of a single-center retrospective cohort examining 8,654 postpartum women from 2012 to 2014, of whom 2,205 (25.5%) underwent cesarean delivery. Insurance was analyzed as Medicaid compared with private insurance. The primary outcome was sterilization at the time of cesarean delivery. Reason for sterilization noncompletion and Medicaid sterilization consent form validity were recorded. Secondary outcomes included postpartum visit attendance, outpatient postpartum sterilization, and subsequent pregnancy within 365 days of delivery. RESULTS: Of the 481 women included in this analysis, 78 of 86 (90.7%) women with private insurance and 306 of 395 (77.4%) women with Medicaid desiring sterilization obtained sterilization at the time of cesarean delivery (relative risk 0.85, 95% CI 0.78-0.94). After multivariable logistic regression, gestational age at delivery (1.02 [1.00-1.03]), adequacy of prenatal care (1.30 [1.18-1.43]), and marital status (1.09 [1.01-1.19]) were associated with achievement of sterilization at the time of cesarean delivery. Sixty-four (66.0%) women who desired but did not receive sterilization at the time of cesarean delivery did not have valid, signed Medicaid sterilization forms, and 10 (10.3%) sterilizations were not able to be completed at the time of surgery owing to adhesions. Sterilization during cesarean delivery was not associated with less frequent postpartum visit attendance for either the Medicaid or privately insured population. Rates of outpatient postpartum sterilization were similar among those with Medicaid compared with private insurance. Among patients who did not receive sterilization at the time of delivery, 15 patients (each with Medicaid) had a subsequent pregnancy within the study period. CONCLUSION: Women with Medicaid insurance received sterilization at the time of cesarean delivery less frequently than privately insured counterparts, most commonly due to the absence of a valid Medicaid sterilization consent form as well as adhesive disease. The constraints surrounding the Medicaid form serve as a significant barrier to achieving desired sterilization.

The Association of Public Insurance with Postpartum Contraception Preference and Provision.

BACKGROUND: Prior studies have noted that public insurance status is associated with increased uptake of postpartum contraception whereas others have pointed to public insurance as a barrier to accessing highly effective forms of contraception. OBJECTIVE: To assess differences in planned method and provision of postpartum contraception according to insurance type. STUDY DESIGN: This is a secondary analysis of a retrospective cohort study examining postpartum women delivered at a single hospital in Cleveland, Ohio from 2012-2014. Contraceptive methods were analyzed according to Tier-based effectiveness as defined by the Centers for Disease Control and Prevention. The primary outcome was postpartum contraception method preference. Additional outcomes included method provision, postpartum visit attendance, and subsequent pregnancy within 365 days of delivery. RESULTS: Of the 8281 patients in the study cohort, 1372 (16.6%) were privately and 6990 (83.4%) were publicly insured. After adjusting for the potentially confounding clinical and demographic factors through propensity score analysis, public insurance was not associated with preference for a Tier 1 versus Tier 2 postpartum contraceptive method (matched adjusted odds ratio [maOR] 0.89, 95% CI 0.69-1.15), but was associated with a preference for Tier 1/2 vs Tier 3/None (maOR 1.41, 95% CI 1.17-1.69). There was no difference between women with private or public insurance in terms of method provision by 90 days after delivery (maOR 0.94, 95% CI 0.75-1.17). Public insurance status was also associated with decreased postpartum visit attendance (maOR 0.54, 95% CI 0.43-0.68) and increased rates of subsequent pregnancy within 365 days of delivery (maOR 1.29, 95% CI 1.05-1.59). CONCLUSION: Public insurance status does not serve as a barrier to either the preference or provision of effective postpartum contraception. Women desiring highly- or moderately effective methods of contraception should have these methods provided prior to hospital discharge to minimize barriers to method provision.

Medicaid and receipt of interval postpartum long-acting reversible contraception.

OBJECTIVE: We sought to evaluate the impact of insurance type on receipt of an interval postpartum LARC, controlling for demographic and clinical factors. STUDY DESIGN: This is a retrospective cohort study of 1072 women with a documented plan of LARC for contraception at time of postpartum discharge. This is a secondary analysis of 8654 women who delivered at 20 weeks or beyond from January 1, 2012, through December 31, 2014, at an urban teaching hospital in Ohio. LARC receipt within 90 days of delivery, time to receipt, and rate of subsequent pregnancy after non-receipt were compared between women with Medicaid and women with private insurance. Postplacental LARC was not available at the time of study completion. RESULTS: One hundred eighty-seven of 822 Medicaid-insured and 43 of 131 privately insured women received a LARC postpartum (22.7% vs 32.8%, P=.02). In multivariable analysis, private insurance status was not significantly associated with LARC receipt (OR 1.29, 95% C.I. 0.83-1.99) though adequate prenatal care was (OR 2.33, 95% C.I. 1.42-4.00). Of women who wanted but did not receive a LARC, 208 of 635 (32.8%) Medicaid patients and 19 of 88 (21.6%) privately insured patients became pregnant within 1 year (P=.02). CONCLUSION: Differences in receipt of interval postpartum LARC were not significant between women with Medicaid insurance versus private insurance after adjusting for clinical and demographic factors. Adequate prenatal care was associated with LARC receipt. Medicaid patients who did not receive a LARC were more likely to become pregnant within one year of delivery than those with private insurance. IMPLICATIONS: While insurance-related barriers have been reduced given recent policy changes, access to care remains an important determinant of postpartum LARC provision and subsequent unintended pregnancy.

Role of Bridge Contraception in Postpartum Long-Acting Reversible Contraception and Sterilization Fulfillment Rates.

OBJECTIVE: To estimate the association of bridge contraception with interval long-acting reversible contraception (LARC) and sterilization fulfillment rates. METHODS: This is a secondary analysis of a retrospective single-center cohort chart review study examining 1,851 postpartum women who requested LARC or sterilization after discharge. Bridge contraception was requested by 597 of these women. Primary outcomes included LARC or sterilization fulfillment, time to fulfillment, postpartum visit attendance, and pregnancy within 365 days of delivery. RESULTS: The rate of LARC or sterilization fulfillment within 90 days of delivery was 147 of 597 (24.6%) women using bridge contraception and 287 of 1,254 (22.9%) women not using bridge contraception (P=.41). After adjusting for maternal age, parity, gestational age, mode of delivery, adequacy of prenatal care, race-ethnicity, and education level, the use of bridge contraception was associated with LARC or sterilization fulfillment (adjusted odds ratio [OR] 1.30, 95% CI 1.02-1.67). Adequacy of prenatal care and black race was associated with fulfillment. The use of bridge contraception was not associated with time to fulfillment (adjusted hazard ratio 1.17, 95% CI 0.95-1.44) or postpartum visit attendance (adjusted OR 0.97, 95% CI 0.77-1.23). The use of bridge contraception was not associated with increased pregnancy within 365 days of delivery (OR 1.00, 95% CI 0.95-1.05; adjusted OR 0.96, 95% CI 0.73-1.26). CONCLUSION: Bridge contraception is associated with increased LARC and sterilization fulfillment after postpartum discharge. Long-acting reversible contraception or sterilization fulfillment after discharge occurred in less than one in four women. Strategies to improve provision of LARC or sterilization before hospital discharge are necessary.

Medicaid and fulfillment of desired postpartum sterilization.

OBJECTIVE: We sought to assess fulfillment of sterilization requests while accounting for the complex interplay between insurance, clinical and social factors in a contemporary context that included both inpatient and outpatient postpartum sterilization procedures. STUDY DESIGN: This is a retrospective single-center cohort chart review study of 1331 women with a documented contraceptive plan at time of postpartum discharge of sterilization. We compared sterilization fulfillment within 90days of delivery, time to sterilization and rate of subsequent pregnancy after nonfulfillment between women with Medicaid and women with private insurance. RESULTS: A total of 475 of 1030 Medicaid-insured and 100 of 154 privately insured women received postpartum sterilization (46.1% vs. 64.9%, p<.001). Women with Medicaid had a longer time from delivery to completion of the sterilization request (p<.001). After adjusting for age, parity, gestational age, mode of delivery, adequacy of prenatal care, race/ethnicity, marital status and education level, private insurance status was not associated with either sterilization fulfillment [odds ratio 0.94, 95% confidence interval (CI) 0.54-1.64] or time to sterilization (hazard ratio 1.03, 95% C.I. 0.73-1.34). Of the 555 Medicaid-insured women who did not receive a postpartum sterilization, 267 (48.1%) had valid Title XIX sterilization consent forms at time of delivery. Of women who did not receive sterilization, 132 of 555 Medicaid patients and 5 of 54 privately insured patients became pregnant within 1 year (23.8% vs. 9.3%, p=.023). CONCLUSION: Differences in fulfillment rates of postpartum sterilization and time to sterilization between women with Medicaid versus private insurance are similar after adjusting for relevant clinical and demographic factors. Women with Medicaid are more likely than women with private insurance to have a short interval repeat pregnancy after an unfulfilled sterilization request. IMPLICATIONS: Efforts are needed to ensure that Medicaid recipients who desire sterilization receive timely services.

Safety and Immunogenicity of a Human Epidermal Growth Factor Receptor 1 (HER1)-Based Vaccine in Prostate Castration-Resistant Carcinoma Patients: A Dose-Escalation Phase I Study Trial.

Metastatic castration-resistant prostate cancer (CRPC) remains incurable due to the lack of effective therapies. Activation of the human epidermal growth factor receptor 1 (HER1) in prostate cancer contributes to metastatic progression as well as to disease relapse. Here, we determined the toxicity and immunogenicity of a HER1-based cancer vaccine in CRPC patients included in a phase I clinical trial. CRPC patients (n = 24) were intramuscularly vaccinated with HER1 vaccine consisting of the extracellular domain of HER1 molecule (ECD) and very small size proteoliposome from Neisseria meningitidis (VSSP) and Montanide ISA-51 VG as adjuvants. Patients were included in five groups according to the vaccine dose (100, 200, 400, 600, and 800 µg). The primary endpoints were safety and immunogenicity. The anti-HER1 antibodies were measured by an ELISA, the recognition of an HER1 positive tumor cell line and the inhibition of HER1 phosphorylation by sera were determined by flow cytometry and western blot analysis, respectively. The HER1-specific T cell response was assessed by determination of IFN-γ-producing T cells using ELISpot assay. The vaccine was well tolerated. No grade III or IV adverse events were reported. High titers of anti-HER1 antibodies were observed in most of the evaluated patients. There were no significant differences regarding the geometric means of the anti-HER1 titers among the dose groups except the group of 100 µg in which antibody titers were significantly lower. A Th1-type IgG subclasses pattern was predominant in most patients. Only patients receiving the higher doses of vaccine showed significant tumor cell recognition and HER1 phosphorylation inhibition by hyperimmune sera. Forty two percent of the patients showed a specific T cell response against HER1 peptides pool in post-treatment samples. There was a trend toward survival benefit in those patients showing high anti-HER1 specific antibody titers and a significant association between cellular immune response and clinical outcome.

A Systematic Review on Confidentiality, Disclosure, and Stigma in the United States: Lessons for HIV Care in Pregnancy From Reproductive Genetics.

The fields of HIV care in pregnancy and reproductive genetics have always been 'exceptional' in that patients are highly concerned about the potential for stigma and the corresponding need for privacy and confidentiality. However, the two fields have diverged in how they have addressed these concerns. The systematic review analyzed 61 manuscripts for similarities and differences between the fields of HIV care in pregnancy and reproductive genetics in the United States, with respect to privacy, confidentiality, disclosure, and stigma. The systematic review revealed that the field of HIV care in pregnancy has insufficiently addressed patient concerns about privacy, confidentiality, and stigma compared to the field of reproductive genetics. Failure to adequately protect confidentiality of HIV-positive patients, and failure to reduce stigma associated with HIV testing and treatment are deficiencies in the delivery of care to HIV-positive pregnant woman and barriers to reducing vertical transmission of HIV. Improvements in care and policy should mirror the field of reproductive genetics.

Nimotuzumab plus radiotherapy for unresectable squamous-cell carcinoma of the head and neck.

The prognosis of patients with advanced head and neck cancer remain dismal. For this tumor type, elevated levels of EGFR are associated with a shorter disease free survival and time to treatment failure, reflecting a more aggressive phenotype. Nimotuzumab is a humanized monoclonal antibody that recognizes domain III of the extracellular region of the EGFR, within an area that overlaps with both the surface patch recognized by cetuximab and the binding site for EGF. In order to assess the efficacy of nimotuzumab in combination with radiotherapy, a controlled, double blind, randomized clinical trial was conducted in 106 advanced squamous cell carcinoma of the head and neck patients, mostly, unfit for chemoradiotherapy. Control patients received a placebo and radiotherapy. Treatment was safe and the most frequent adverse events consisted on grade I or II asthenia, fever, headache and chills. No skin rash was detected. A significant complete response rate improvement was found in the group of patients treated with nimotuzumab as compared to the placebo. In the intent to treat analysis, a trend towards survival benefit for nimotuzumab treated subjects was found. The survival benefit became significant when applying the Harrington-Fleming test, a weighted log-rank that underscores the detection of differences deferred on time. In addition, a preliminary biomarker investigation showed a significant survival improvement for nimotuzumab treated patients as compared to controls for subjects with EGFR positive tumors. All patients showed a quality of life improvement and a reduction of the general and specific symptoms of the disease.

Combining an EGF-based cancer vaccine with chemotherapy in advanced nonsmall cell lung cancer.

An epidermal growth factor (EGF) vaccine was given before and after standard first line chemotherapy to patients with advanced nonsmall cell lung cancer (NSCLC), to investigate the immunologic and clinical results in a phase 1 study. Twenty patients diagnosed with advanced NSCLC were recruited. Two vaccinations were given before the first line of chemotherapy treatment, with subsequent monthly vaccination after concluding chemotherapy. The EGF vaccination dose was increased compared with previous trials; the primary end points were immunogenicity and safety. Anti-EGF antibody titers were more than 20 times higher than those previously obtained, without any increase in adverse events, serum EGF concentration decreased to undetectable levels in all patients. Ninety-two percent of the evaluated patients (n=13) showed an immunodominant antibody response against the central region on the EGF molecule. High percentages of EGF/EGF receptor binding inhibition were observed, which significantly positively correlated with the increased antibody response against the EGF immunodominant region. Survival of the patients in this study correlates positively with antibody titers. This study has shown that combination of EGF vaccination at high dose, with chemotherapy is feasible and well tolerated higher anti-EGF antibody titers and reduction of serum EGF concentration seen; do not entail an increase in severe adverse events. The correlation of survival with antibody titers observed is being confirmed confirmation in a wider and randomized trial currently ongoing.

Active immunotherapy with 1E10 anti-idiotype vaccine in patients with small cell lung cancer: report of a phase I trial.

1E10 is an anti-idiotype murine monoclonal antibody (Ab2 MAb) specific to an Ab1 MAb which reacts with NeuGc-containing gangliosides, sulfatides and with antigens expressed in some human tumors. Preparations containing this Ab2 were capable to induce a strong anti-metastatic effect in tumor-bearing mice. We conducted a Phase I clinical trial to evaluate the toxicity and humoral immune response elicited by 1E10 vaccine in patients with small cell lung cancer (SCLC). Eligible patients were those who after received chemotherapy and/or radiotherapy had partial or complete response to treatment. Patients received four biweekly injections with 2 mg of aluminum hydroxide-precipitated 1E10 MAb, then other six doses at 28-day intervals, and later the patients who maintained a good performance status were reimmunized. Six patients with limited-stage disease and three with extensive-stage disease were enrolled in the study. Most of the patients who received at least four doses of 1E10 vaccine developed strong specific antibody responses against 1E10 MAb and NeuGc-GM3 ganglioside. Antibodies able to react with lung carcinoma tissue sections were detected in sera from vaccinated patients. A prolonged survival was observed in several patients treated with the anti-idiotype vaccine. No evidence of serious adverse effects was found.

Defining urticarial dermatitis: a subset of dermal hypersensitivity reaction pattern.

BACKGROUND: Urticarial dermatitis may represent a useful term for a subset of a reaction pattern designated most commonly as dermal hypersensitivity by pathologists. The term is not commonly used, and requires definition to determine whether it is clinically relevant. OBJECTIVES: To define urticarial dermatitis and distinguish it from other urticarial reaction patterns and to review the frequency with which dermatologists can recognize clinical settings that match the biopsy findings of urticarial dermatitis. DESIGN: Retrospective analysis of clinical and/or histological diagnosis of urticarial dermatitis, applying strict histological criteria in a center using urticarial dermatitis as a diagnostic term in 190 archived reports. SETTING: Tertiary referral dermatopathology service reporting for dermatological practices in Sydney, Australia. MAIN OUTCOME MEASURES: The correlation between clinical and histological diagnoses of urticarial dermatitis and alternate diagnoses was analyzed. The frequency of positive immunofluorescence findings for bullous pemphigoid was determined in a subset of patients with urticarial dermatitis in whom this test was ordered to exclude prodromal bullous pemphigoid. RESULTS: Urticarial dermatitis was the histological diagnosis in at least 1 biopsy result in 148 patients, and matched the provisional clinical diagnosis in 49 (33.1%) patients. Urticarial dermatitis was the only diagnosis provided in 21 patients. The main alternate clinical diagnoses provided were early bullous pemphigoid or dermatitis herpetiformis (47 patients [31.8%]), dermatitis (39 patients [26.4%]), drug reaction (35 patients [23.6%]), urticarial vasculitis (24 patients [16.2%]), and urticaria (12 patients [8.1%]). In 91 patients with a clinical diagnosis of urticarial dermatitis, the histological diagnosis in at least 1 biopsy result was matched in 49 patients (53.8%); other histological diagnoses included dermatitis (21 patients [23.1%]), papular urticaria (12 patients [13.2%]), drug reaction (6 patients [6.6%]), and urticaria (3 patients [3.3%]). Review of 38 direct immunofluorescent results for prodromal bullous pemphigoid and a biopsy finding of urticarial dermatitis revealed only 3 positive results (7.9%). CONCLUSIONS: Urticarial dermatitis seems to be a useful histological and clinical term for a subset of the dermal hypersensitivity reaction pattern. Although the clinical presentation is not restricted to a specific entity, eczema and drug reactions seem to be the most frequent clinical associations; and in a subset of patients, urticarial dermatitis remains as a recognizable reaction pattern. Urticarial dermatitis without eosinophilic spongiosis is not a reliable indicator for bullous pemphigoid, because the findings of immunofluorescence are often negative.