Risk of acute myeloid leukemia and myelodysplastic syndrome among older women receiving anthracycline-based adjuvant chemotherapy for breast cancer on Modern Cooperative Group Trials (Alliance A151511).

PURPOSE: We examined acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) events among 9679 women treated for breast cancer on four adjuvant Alliance for Clinical Trials in Oncology trials with >90 months of follow-up in order to better characterize the risk for AML/MDS in older patients receiving anthracyclines. METHODS: We used multivariable Cox regression to examine factors associated with AML/MDS, adjusting for age (≥65 vs. <65 years; separately for ≥70 vs. <70 years), race/ethnicity, insurance, performance status, and anthracycline receipt. We also examined the effect of cyclophosphamide, the interaction of anthracycline and age, and outcomes for those developing AML/MDS. RESULTS: On Cancer and Leukemia Group B (CALGB) 40101, 49907, 9344, and 9741, 7290 received anthracyclines; 15% were in the age ≥65 and 7% were ≥70. Overall, 47 patients developed AML/MDS (30 AML [0.3%], 17 MDS [0.2%]); 83% of events occurred within 5 years of study registration. Among those age ≥65 and ≥70, 0.8 and 1.0% developed AML/MDS (vs. 0.4% for age <65), respectively. In adjusted analyses, older age and anthracycline receipt were significantly associated with AML/MDS (adjusted hazard ratio [HR] for age ≥65 [vs. <65] = 3.13, 95% confidence interval [CI] 1.18-8.33; HR for anthracycline receipt [vs. no anthracycline] = 5.16, 95% CI 1.47-18.19). There was no interaction between age and anthracycline use. Deaths occurred in 70% of those developing AML/MDS. CONCLUSIONS: We observed an increased risk for AML/MDS for older patients and those receiving anthracyclines, though these events were rare. Our results help inform discussions surrounding anticipated toxicities of adjuvant chemotherapy in older patients.

Contraception for the perimenopausal woman.

Perimenopause, or the menopause transition, is a time in a woman's life that bridges her reproductive years through to the non-surgical cessation of ovulation, or menopause. For many women this time is one of changes: changes in gynecological issues, onset of symptoms not experienced in her youth and increasing risks for adverse medical conditions. Despite the clear changes that occur for many women during this time, one critical issue is frequently ignored, namely, that, until the onset of menopause, she is exposed to pregnancy if sexually active, and pregnancy for older reproductive women is fraught with considerable increases in morbidity and mortality compared to younger women. This paper will present a review of the reproductive issues of the perimenopause and interventions geared to preventing pregnancy and relieving menopause-related symptoms. As counseling remains a critical aspect in empowering women to make informed choices about their health care, this paper will present current evidence that will help clinicians provide accurate reproductive counseling to women in the menopause transition.

Tracking intervention delivery in the 'Tobacco-Free Teachers/Tobacco-Free Society' program, Bihar, India.

In health education and behavior change interventions, process tracking monitors the delivery of an intervention and its receipt to the intended audience. A randomized controlled trial in the state of Bihar, India was conducted to help school teachers become tobacco free through appropriately designed intervention program and delivery system. We describe the results from process tracking of this intervention delivery. The intervention program was centred on six topics delivered in each school through 12 sessions over 6 successive months. The program deliverers recorded the process measures as total number of sessions and program-components implemented (fidelity); time spent conducting sessions (dose) and proportion of teachers attending at least one session (reach). The outcome measures (teachers' exposure to intervention messages and tobacco policy adoption) were assessed post-intervention. All 12 sessions were delivered in 33 out of 36 schools. Thirty-one schools implemented all six program components. In 18 schools, ≥95% of the teachers participated in one or more sessions. Thirty-three schools received 12 or more hours of dose. In 29 schools, 100% teachers reported exposure to all program messages. Tobacco policy was adopted by all schools. Thus, the intervention was generally delivered as planned and it had a positive impact on teachers and schools.

Polygenic inheritance of paclitaxel-induced sensory peripheral neuropathy driven by axon outgrowth gene sets in CALGB 40101 (Alliance).

Peripheral neuropathy is a common dose-limiting toxicity for patients treated with paclitaxel. For most individuals, there are no known risk factors that predispose patients to the adverse event, and pathogenesis for paclitaxel-induced peripheral neuropathy is unknown. Determining whether there is a heritable component to paclitaxel-induced peripheral neuropathy would be valuable in guiding clinical decisions and may provide insight into treatment of and mechanisms for the toxicity. Using genotype and patient information from the paclitaxel arm of CALGB 40101 (Alliance), a phase III clinical trial evaluating adjuvant therapies for breast cancer in women, we estimated the variance in maximum grade and dose at first instance of sensory peripheral neuropathy. Our results suggest that paclitaxel-induced neuropathy has a heritable component, driven in part by genes involved in axon outgrowth. Disruption of axon outgrowth may be one of the mechanisms by which paclitaxel treatment results in sensory peripheral neuropathy in susceptible patients.

Caring for patients with surgically resectable cancers: experience from a specialised centre in rural Rwanda.

SETTING: Butaro Cancer Centre of Excellence (BCCOE), Burera District, Rwanda. OBJECTIVES: To describe characteristics, management and 6-month outcome of adult patients presenting with potentially surgically resectable cancers. DESIGN: Retrospective cohort study of patients presenting between 1 July and 31 December 2012. RESULTS: Of 278 patients, 76.6% were female, 51.4% were aged 50-74 years and 75% were referred from other district or tertiary hospitals in Rwanda. For the 250 patients with treatment details, 115 (46%) underwent surgery, with or without chemotherapy/radiotherapy. Median time from admission to surgery was 21 days (IQR 2-91). Breast cancer was the most common type of cancer treated at BCCOE, while other forms of cancer (cervical, colorectal and head and neck) were mainly operated on in tertiary facilities. Ninety-nine patients had no treatment; 52% of these were referred out within 6 months, primarily for palliative care. At 6 months, 6.8% had died or were lost to follow-up. CONCLUSION: Surgical care was provided for many cancer patients referred to BCCOE. However, challenges such as inadequate surgical infrastructure and skills, and patients presenting late with advanced and unresectable disease can limit the ability to manage all cases. This study highlights opportunities and challenges in cancer care relevant to other hospitals in rural settings.

Contexte : Centre anticancéreux d'excellence de Butaro (BCCOE), District de Butera, Rwanda.Objectifs : Décrire les caractéristiques, la prise en charge et les résultats à 6 mois de patients adultes se présentant avec des cancers potentiellement extirpables par chirurgie.Schema : Etude rétrospective de cohorte des patients admis entre le 1er juillet et le 31 décembre 2012.Resultats : Sur 278 patients, 76,6% étaient des femmes, 51,4% étaient âgés entre 50 et 74 ans et 75% étaient référés d'un autre district ou d'un hôpital tertiaire du Rwanda. Parmi les 250 patients dont les traitements étaient connus, 115 (46%) ont bénéficié d'une intervention chirurgicale avec ou sans chimiothérapie/radiothérapie. Le temps médian écoulé entre l'admission et la chirurgie était de 21 jours (IQR 2 à 91). Le cancer du sein était le plus fréquent des cancers traités au BCCOE, tandis que les autres cancers (col utérin, colorectal et tumeur cérébrale ou cervicale) étaient généralement opérés dans des hôpitaux tertiaires. Quatre-vingt-dix-neuf patients n'ont eu aucun traitement ; 52% ont été référés à l'extérieur dans les 6 mois, généralement pour un traitement palliatif. A 6 mois, 6,8% étaient décédés ou perdus de vue.Conclusion : De nombreux patients référés au BCCOE pour cancer ont bénéficié d'une intervention chirurgicale. Cependant la prise en charge de tous les cas est confrontée à la limite de capacité chirurgicale et au problème des patients admis tardivement avec un cancer avancé et non extirpable. Cette étude met en lumière les opportunités et les défis de la prise en charge des cancers pour les hôpitaux situés en zone rurale.

Marco de Referencia: El Centro Butaro de Excelencia en Cáncer (BCCOE) del distrito de Burera, en Ruanda.Objetivos: Describir las características, el manejo y el desenlace clínico a los 6 meses de pacientes adultos que se presentaron con cánceres cuyo tratamiento quirúrgico podía ser viable.Métodos: Fue este un estudio retrospectivo de cohortes de los pacientes que acudieron al centro entre el 1° de julio y el 31 de diciembre del 2012.Resultados: Se incluyeron en el estudio 278 pacientes, de los cuales 76,6% eran de sexo femenino, 51,4% tenían entre 50 y 74 años de edad y 75% habían sido remitidos de otro hospital distrital o de centros de atención terciaria de Ruanda. De los 250 expedientes que contaban con detalles sobre el tratamiento, en 115 casos (46%) los pacientes recibieron tratamiento quirúrgico con o sin quimioterapia o radioterapia. La mediana del lapso entre la hospitalización y la cirugía fue 21 días (intervalo intercuartil de 2 a 91). El cáncer de mama fue el tipo más frecuente de cáncer que se trató en el BCCOE y la cirugía de otras formas de cáncer (cuello uterino, colorrectal y de cara y cuello) se realizó principalmente en centros de atención terciaria. Noventa y nueve pacientes no recibieron tratamiento; el 52% de estos se remitió a otras instituciones en los primeros 6 meses, esencialmente con el propósito de recibir tratamiento paliativo. A los 6 meses, el 6,8% de los pacientes había fallecido o se habían perdido durante el seguimiento.Conclusión: Muchos de los pacientes remitidos recibieron tratamiento quirúrgico en el BCCOE. Sin embargo, la posibilidad de tratar todos los casos se ve limitada por obstáculos como una capacidad quirúrgica inadecuada y el hecho de que los pacientes acuden tarde, en una fase avanzada de la enfermedad, con un cáncer inoperable. El presente estudio pone de relieve oportunidades y dificultades en el tratamiento del cáncer que son pertinentes para otros centros hospitalarios en un entorno rural.

Biopsy case mix and diagnostic yield at a Malawian central hospital.

Cancer is a major disease burden worldwide resulting in high morbidity and mortality. It is the leading cause of mortality in developed countries and is one of the three leading causes of death for adults in developing countries. Pathological examination of tissue biopsies with histological confirmation of a correct cancer diagnosis is central to cancer care. Without an accurate and specific pathologic diagnosis, effective treatment cannot be planned or delivered. In addition, there are marked geographical variations in incidence of cancer overall, and of the specific cancers seen. Much of the published literature on cancer incidence in developing countries reflects gross estimates and may not reflect reality. Performing baseline studies to understand these distributions lays the groundwork for further research in this area of cancer epidemiology. Our current study surveys and ranks cancer diagnoses by individual anatomical site at Queen Elizabeth Central Hospital (QECH) which is the largest teaching and referral hospital in Malawi. A retrospective study was conducted reviewing available pathology reports over a period of one full year from January 2010 to December 2010 for biopsies from patients suspected clinically of having cancer. There were 544 biopsies of suspected cancer, taken from 96 anatomical sites. The oesophagus was the most common biopsied site followed by breast, bladder, bone, prostate, bowel, and cervical lymph node. Malignancies were found in biopsies of the oesophagus biopsies (squamous cell carcinoma, 65.1%; adenocarcinoma, 11.6%), breast (57.5%), bladder (squamous cell carcinoma, 53.1%) and stomach (37.6%). Our study demonstrates that the yield of biopsy for clinically suspected malignancy was greater than 50% for the 11 most common sites and provides a current survey of cancer types by site present in the population reporting to our hospital.

Difficulties in implementing an organized screening program for breast cancer in Brazil with emphasis on diagnostic methods.

INTRODUCTION: Breast cancer is the most common type of cancer among women, and the leading cause of cancer deaths worldwide. Among early detection methods, screening by mammography has been used in most developed countries as gold standard. The goal of this study was to evaluate the difficulties and opportunities in implementing breast cancer screening in Brazil, with an emphasis on the diagnostic methods used according to stage distribution. METHODS: Between 2007 and 2009, 248 women were diagnosed with breast cancer in the Barretos region. Most of these were interviewed in their homes using a questionnaire with sociodemographic and preventive breast cancer screening questions. All other data were obtained from Barretos Cancer Hospital (BCH) medical records. RESULTS: The screening program conducted by BCH was responsible for 46.1% of diagnosed cases, with 30.1% of these referred from the private system and 23.8% from the public system. Among asymptomatic women screened by the BCH Screening Program 70.8% had clinical stage 0-I disease, compared with 58.1% in the private and 50% in the public systems. Monthly breast self-examination was reported by 48.5% of the women. Clinical breast examinations were regularly performed by 88.9% of gynecologists in the private and 40.7% in the public health systems. Only 5.6% of the women reported difficulty in accessing mammography and this was most frequently due to fear of the disease or lack of knowledge about mammography in asymptomatic women. CONCLUSION: This breast cancer screening program resulted in a substantial number of patients presenting with clinical stage (CS) 0-I disease. The success of this program was due to intensive community interventions, free mammography, and the availability of health care and mammography close to patients' homes.

Androgens and menopause.

The cessation of ovarian sex steroidigenesis, either as result as surgical extirpation, certain medical therapies or the gradual cessation of ovarian function, leads to menopause with all its associated physiological, physical and lifestyle changes. The changing hormonal milieu of menopause is most commonly associated with declining levels of estrogens. However, ovarian senescence also results in declining levels of androgens. Indeed, it is the loss of physiological levels of estrogens and androgens that result in the varied signs and symptoms of menopause including vasomotor symptoms, bone mineral density loss, reduced interest in sex, alterations in mood and energy and hair loss, among others. This paper will provide a review of the role of androgens in the menopause and assess the potential of androgen therapies in the management of the menopause.

Unraveling the puzzle of human anellovirus infections by comparison with avian infections with the chicken anemia virus.

Current clinical studies on human annelloviruses infections are directed towards finding an associated disease. In this review we have emphasized the many similarities between human anellovirus and avian circoviruses and the cell and tissue types infected by these pathogens. We have done this in order to explore whether knowledge acquired from natural and experimental avian infections could reflect and be extrapolated to the less well-characterized human annellovirus infections. The knowledge gained from the avian system may provide suggestions for decoding the enigmatic human anellovirus infections, and finding the specific disease or diseases caused by these human anellovirus infections. Each additional parallelism between chicken anemia virus (CAV) and Torque teno virus (TTV) further strengthens this premise. As we have seen information from human infections can also be used to better understand avian infections as well. Increased attention must be focused on the "hidden" or unrecognized, seemingly asymptomatic effects of circovirus and anellovirus infections. Understanding the facilitating effect of these infections on disease progression caused by other pathogens may help to explain differences in outcome of complicated poultry and human diseases. The final course of a pathogenic infection is determined by variations in the state of health of the host before, during and after contact with a pathogen, in addition to the phenotype of the pathogen and host. The health burden of circoviridae and anellovirus infections may be underestimated, due to lack of awareness of the need to search past the predominant clinical effect of identified pathogens and look for modulation of cellular-based immunity caused by co-infecting circoviruses, and by analogy, human anneloviruses.

Mutant p53 protein in serum could be used as a molecular marker in human breast cancer.

p53 wild-type is a tumor suppressor gene involved in DNA gene transcription or DNA repair mechanisms. When damage to DNA is unrepairable, p53 induces programmed cell death (apoptosis). The mutant p53 gene is the most frequent molecular alteration in human cancer, including breast cancer. Here, we analyzed the genetic alterations in p53 oncogene expression in 55 patients with breast cancer at different stages and in 8 normal women. We measured by ELISA assay the serum levels of p53 mutant protein and p53 antibodies. Immunohistochemistry and RT-PCR using specific p53 primers as well as mutation detection by DNA sequencing were also evaluated in breast tumor tissue. Serological p53 antibody analysis detected 0/8 (0%), 0/4 (0%) and 9/55 (16.36%) positive cases in normal women, in patients with benign breast disease and in breast carcinoma, respectively. We found positive p53 mutant in the sera of 0/8 (0.0%) normal women, 0/4 (0%) with benign breast disease and 29/55 (52.72%) with breast carcinoma. Immunohistochemistry evaluation was positive in 29/55 (52.73%) with mammary carcinoma and 0/4 (0%) with benign breast disease. A very good correlation between p53 mutant protein detected in serum and p53 accumulation by immunohistochemistry (83.3% positive in both assays) was found in this study. These data suggest that detection of mutated p53 could be a useful serological marker for diagnostic purposes.

Late first-trimester invasive prenatal diagnosis: results of an international randomized trial.

OBJECTIVE: To assess, in a randomized trial, the safety and accuracy of amniocentesis and transabdominal chorionic villus sampling (CVS) performed at 11-14 weeks of gestation, given that this time frame is increasingly relevant to early trisomy screening. METHODS: We compared amniocentesis with CVS from 77 to 104 days of gestation in a randomized trial in a predominantly advanced maternal age population. Before randomization, the feasibility of both procedures was confirmed by ultrasonography, and experienced operators performed sampling under ultrasound guidance; conventional cytogenetic analysis was employed. The primary outcome measure was a composite of fetal loss plus preterm delivery before 28 weeks of gestation in cytogenetically normal pregnancies. RESULTS: We randomized 3,775 women into 2 groups (1,914 to CVS; 1,861 to amniocentesis), which were comparable at baseline. More than 99.6% had the assigned procedure, and 99.9% were followed through delivery. In contrast to previous thinking, in the cytogenetically normal cohort (n = 3,698), no difference in primary study outcome was observed: 2.1% (95% confidence interval 1.5, 2.8) for CVS and 2.3% (95% confidence interval, 1.7, 3.1) for amniocentesis. However, spontaneous losses before 20 weeks and procedure-related, indicated terminations combined were increased in the amniocentesis group (P =.07, relative risk 1.74). We found a 4-fold increase in the rate of talipes equinovarus after amniocentesis (P =.02) overall and in week 13 (P =.03, relative risk = 4.65), but data were insufficient to determine this risk in week 14. CONCLUSION: Amniocentesis at 13 weeks carries a significantly increased risk of talipes equinovarus compared with CVS and also suggests an increase in early, unintended pregnancy loss. LEVEL OF EVIDENCE: I

Primary systemic treatment of advanced Hodgkin's disease with EVA (etoposide, vinblastine, doxorubicin): 10-year follow-up.

BACKGROUND: The most commonly used regimen for the treatment of advanced Hodgkin's disease (HD) is ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine). Two of these components, bleomycin and dacarbazine, have defined toxicities such as pulmonary fibrosis and nausea/vomiting, and also uncertain single-drug activity. The EVA regimen (etoposide, vinblastine, doxorubicin) is an attempt to substitute a known active agent, etoposide, for bleomycin and dacarbazine. PATIENTS AND METHODS: A series of 51 patients with advanced HD without prior systemic therapy were treated. The series included 12 stage II patients with bulky (>10 cm) mediastinal tumors, 10 of whom received complementary radiation therapy. The remaining patients received EVA only. Response, duration of response, survival, toxicity and the efficacy of salvage therapy were evaluated in all patients. The median follow-up time was 111 months and permitted an assessment of the long-term effects of treatment and natural history of a cohort of treated patients. RESULTS: EVA achieved a complete response (or clinical complete response) in 48/51 patients (94%). Of these 48 responders, 16 relapsed in a median of 11 months (range 3-48 months). In follow-up, 32/51 patients had no evidence of relapsed HD, although three died from other causes (two from vascular events and one from large cell lymphoma), resulting in progression-free survival for the entire group of 57% at 111 months. Eight of the 16 were alive and free from disease at follow-up at 111 months. In the entire series, only seven patients (14%) died of HD. 37 patients (73%) continued free from disease. There was no pulmonary toxicity. CONCLUSIONS: The EVA regimen appears to have an overall survival (OS) outcome comparable to ABVD, but without the lung toxicity. The high salvage rate of second-line therapy, in most instances at conventional dosage, suggests an absence of cross-resistance to alkylating agents in patients treated with EVA.

Localized thigh swelling mimicking a neoplastic process: involvement of coxsackie virus type A21.

UNLABELLED: A 4-y-old girl was admitted because of a left leg limp with an isolated swollen upper thigh and normal muscle enzymes. A radioisotope scan showed increased uptake especially in the bone and soft tissue of the left thigh, while magnetic resonance imaging of that region demonstrated widespread oedema in striated muscle. On muscle biopsy perivascular infiltrates were demonstrated but muscle fibres were not shown to be affected. Sequence analysis of reverse transcription-polymerase chain reaction amplified fragments from the 5'-non-coding region of human enteroviruses identified a local strain of coxsackie virus A21 in the muscle. Clinical symptomatology subsided with oral steroids. CONCLUSION: Local swelling mimicking a neoplasm may be related to infestation of coxsackie virus in muscle tissue.

Phase I trial of intraperitoneal injection of the E1B-55-kd-gene-deleted adenovirus ONYX-015 (dl1520) given on days 1 through 5 every 3 weeks in patients with recurrent/refractory epithelial ovarian cancer.

PURPOSE: Resistance to chemotherapy in ovarian cancer is frequently associated with mutations in the p53 gene. The adenovirus dl1520 (ONYX-015) with the E1B 55-kd gene deleted, allowing selective replication in and lysis of p53-deficient tumor cells, has shown preclinical efficacy against p53-deficient nude mouse-human ovarian carcinomatosis xenografts. PATIENTS AND METHODS: We undertook a phase I trial of intraperitoneal dl1520 in patients with recurrent ovarian cancer. Sixteen women with recurrent/refractory ovarian cancer received 35 cycles (median, two cycles) of dl1520 delivered on days 1 through 5 in four dose cohorts: 1 x 10(9) plaque forming units (pfu), 1 x 10(10) pfu, 3 x 10(10) pfu, and 1 x 10(11) pfu. RESULTS: The most common significant toxicities related to virus administration were flu-like symptoms, emesis, and abdominal pain. One patient receiving 1 x 10(10) pfu developed common toxicity criteria grade 3 abdominal pain and diarrhea, which was dose-limiting. The maximum-tolerated dose was not reached at 10(11) pfu, and at this dose level patients did not experience significant toxicity. There was no clear-cut evidence of clinical or radiologic response in any patient. Blood samples were taken for adenovirus DNA and neutralizing antibodies. Polymerase chain reaction data indicating presence of virus up to 10 days after the final (day 5) infusion of dl1520 are suggestive of continuing viral replication. CONCLUSION: This article therefore describes the first clinical experience with the intraperitoneal delivery of any replication-competent/-selective virus in cancer patients.

Retrospective radiographic analysis of sinus graft and implant placement procedures from the Academy of Osseointegration Consensus Conference on Sinus Grafts.

A retrospective quantitative radiographic analysis determined the effect of graft material and smoking status on the maintenance of graft height over 3 years. Analysis of variance models with planned comparison were constructed to compare mean graft change by (1) graft material and (2) smoking status. Maintenance of bone height was significantly greater in intraoral autogenous grafts versus allografts (P < .05). The effect of smoking on implant loss revealed a significant difference in implant survival (P < .05). Autogenous bone generally resulted in a more favorable outcome over a 3-year period. Smoking adversely impacted implant survival in sinus grafts.

What is the ideal duration of adjuvant therapy for primary breast cancer: are four cycles of cyclophosphamide and doxorubicin enough?

For 25 years we have known that adjuvant chemotherapy improves both disease-free and overall survival for many of our patients with primary breast cancer. We also know that these therapies have significant toxicities and are not always effective. We have therefore focused a great deal of effort into maximizing the effectiveness of adjuvant chemotherapy and defining just how much chemotherapy, with respect to both dose and duration, is necessary to achieve this maximum benefit. In our attempt to define these parameters through clinical trials, we have been faced with many options, and we may not yet have defined an optimal regimen of chemotherapy, or an optimal duration. Although many physicians in the United States consider four cycles of cyclophosphamide and doxorubicin as "standard of care" for patients with primary breast cancer, many feel that both choice of regimen and duration of treatment remain controversial. The reasons for this uncertainty and lack of clarity are complex, and they are addressed in this review.

CMV reactivation induced BK virus-associated late onset hemorrhagic cystitis after peripheral blood stem cell transplantation.

Hemorrhagic cystitis (HC) is a known complication of stem cell transplantation. In contrast to early-onset HC that is usually attributed to cyclophosphamide and occurs within a few days of infusion, late onset HC is associated with viral infection. In recent years BK virus has emerged as an important causative agent. We describe two patients who developed late onset HC (38 and 92 days post transplant) associated with BK viruria concomitant with CMV reactivation and suggest a possible role of CMV in the process of BK virus DNA replication.

Controlled trial with a monthly combination injectable contraceptive in the USA.

A monthly injectable contraceptive combining estradiol cypionate and medroxyprogesterone acetate was found to be well tolerated and effective in a phase III prospective, multicenter trial conducted in the United States. In this open-label comparison with an oral contraceptive, there were no pregnancies in the group receiving the monthly combination injectable contraceptive versus one pregnancy in those receiving the oral contraceptive. The rates of discontinuation for adverse events in the two treatment groups over the 60-week trial did not differ significantly. The majority of patients in both groups reported satisfaction with the method of contraception which they were receiving.

Cystic fibrosis.

Although mutation detection rates have not universally reached the 95% detection level recommended by the American Society of Human Genetics and are not likely to exceed 90% for many populations in the foreseeable future, CF carrier screening will probably be offered routinely in the near future. Although CF carrier information will be of benefit to some individuals and couples, the inability of conventional prenatal diagnosis to provide definitive diagnostic outcomes to some couples, specifically those couples in which only one partner has a detectable mutation, will make for considerable anguish and concern for some. Because genetic screening and counseling is meant to provide information and alleviate concerns and fears, the potential for CF screening to result in such a contradictory effect is of a continuing concern to those who provide obstetric and genetic services. In a National Institute of Health-sponsored workshop, Menutti and colleagues recommended that those populations to which carrier screening should be offered might include individuals and couples in high-risk groups (e.g., Ashkenazi Jews, central or northern Europeans, one partner with CF, and individuals with a family history of CF) who seek preconception counseling, infertility care, or prenatal care. The workshop participants concluded, however, that before screening can be offered systematically to these individuals or couples, practice guidelines, educational materials for providers and patients, informed-consent protocols, and laboratory standards for testing must be developed. Further advances in DNA and protein analytic capabilities, such as microchip analytic systems and protein truncation assays, may make CF screening and diagnosis more accurate and less likely to result in equivocal outcomes. In addition, it is hoped that continuing improvements in CF therapies will increase the life expectancy and improve the quality of life for individuals affected with CF. Expanding our current knowledge of genotype-phenotype correlations will not only allow us better to predict clinical outcomes but also may improve our treatments for individuals with CF because more targeted therapies may be developed for CF caused by specific mutations. Nonetheless, educational and counseling issues will, for the foreseeable future, remain of critical importance to ensure appropriate clinical care to low- and high-risk individuals.