The presentation, management and outcome of patients with ductal carcinoma in situ (DCIS) with microinvasion (invasion ≤1 mm in size)-results from the UK Sloane Project.

BACKGROUND: The diagnosis, management and prognosis of microinvasive breast carcinoma remain controversial. METHODS: We analysed the outcomes of patients with DCIS with and without microinvasion diagnosed between 2003 and 2012 within the Sloane project. RESULTS: Microinvasion was recorded in 521 of 11,285 patients (4.6%), with considerable variation in reported incidence among screening units (0-25%). Microinvasion was associated with high-grade DCIS, larger DCIS size, comedo necrosis and solid, cribriform architecture (all P < 0.001). Microinvasion was more frequent in patients who underwent mastectomy compared with breast-conserving surgery (BCS) (6.9% vs 3.6%, P < 0.001), and in those undergoing axillary nodal surgery (60.4% vs 30.3%, P < 0.001) including the subset undergoing BCS (43.4% vs 8.5%, P < 0.001). Nodal metastasis rate was low and not statistically significant difference from the DCIS only group (P = 0.68). Following median follow-up of 110 months, 3% of patients had recurrent ipsilateral high-grade DCIS, and 4.2% developed invasive carcinoma. The subsequent ipsilateral invasion was of Grade 3 in 71.4% of patients with microinvasion vs 30.4% in DCIS without microinvasion (P = 0.02). Distant metastasis and breast cancer mortality were higher with microinvasion compared with DCIS only (1.2% vs 0.3%, P = 0.01 and 2.1% vs 0.8%; P = 0.005). CONCLUSIONS: The higher breast cancer mortality with microinvasion indicates a more aggressive disease.

Management of Abemaciclib-Associated Adverse Events in Patients with Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Safety Analysis of MONARCH 2 and MONARCH 3.

BACKGROUND: Abemaciclib demonstrated efficacy in hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. Here we provide a comprehensive summary of the most common adverse events (AEs), their management, and whether AEs or dose reductions influenced progression-free survival (PFS), in the MONARCH 2 and 3 trials. MATERIALS AND METHODS: Incidence of the most clinically relevant AEs, management, and outcomes were summarized. Time-dependent covariate analyses examined the impact of dose reductions on PFS. PFS was estimated for patients with and without early onset of diarrhea or neutropenia. RESULTS: The most frequently reported AE was diarrhea, with clinically significant diarrhea (grade ≥2) reported for 42.8% of patients taking abemaciclib. Median time to onset was 1 week, and duration ranged from 6 to 12 days, depending on grade and study. Diarrhea was adequately managed by antidiarrheal medication (72.8%), dose omissions (17.3%), and reductions (16.7%). The highest rates of grade ≥2 diarrhea were observed in the first cycles and decreased in subsequent cycles. Neutropenia (grade ≥3) occurred in 25.4% of abemaciclib-treated patients. Neutropenia resolved with dose omissions (16.8%) and/or dose reductions (11.2%). Incidence of febrile neutropenia (0.7%) or other relevant grade ≥3 hematological events (<9%) was low. Venous thromboembolic events (5.3%) were primarily treated with anticoagulants. Interstitial lung disease/pneumonitis (3.4%) was treated with corticosteroids and/or antibiotics. PFS benefit of abemaciclib was not impacted by dose reductions or early onset of toxicities. CONCLUSION: Abemaciclib was generally well tolerated. The most common AEs were effectively managed by supportive medications, and/or dose adjustments, with no detriment to PFS. IMPLICATIONS FOR PRACTICE: Treatment with abemaciclib plus fulvestrant or nonsteroidal aromatase inhibitors is generally well tolerated in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. In MONARCH 2 and MONARCH 3, any-grade diarrhea and grade ≥3 neutropenia were effectively managed with supportive medication and/or dose adjustment. Venous thromboembolic events were treated with anticoagulants and did not often require treatment discontinuation. Interstitial lung disease/pneumonitis was infrequent and treated with corticosteroids and/or antibiotics. Clinicians should be aware of and implement management strategies, including dose adjustments according to local labels, for commonly occurring and serious adverse events to ensure continued treatment and optimize clinical benefit/risk ratio.

Parent-to-Parent Advice on Considering Spinal Fusion in Children with Neuromuscular Scoliosis.

OBJECTIVES: To convey advice from families whose children recently underwent spinal fusion to families whose children are under consideration for initial spinal fusion for neuromuscular scoliosis and to providers who counsel families on this decision. STUDY DESIGN: We interviewed 18 families of children who underwent spinal fusion between August 2017 and January 2019 at a freestanding children's hospital. We conducted phone interviews a median of 65 (IQR 51-77) days after surgery. We audio recorded, transcribed, and coded (line-by-line) interviews using grounded theory by 2 independent reviewers, and discussed among investigators to induce themes associated with surgical decision making and preparation. RESULTS: Six themes emerged about decision making and preparation for spinal fusion: (1) simplify risks and benefits; it is easy to get lost in the details; (2) families prolonging the decision whether or not to pursue spinal fusion surgery may not benefit the child; (3) anticipate anxiety and fear when making a decision about spinal fusion; (4) realize that your child might experience a large amount of pain; (5) anticipate a long recovery and healing process after spinal fusion; and (6) be engaged and advocate for your child throughout the perioperative spinal fusion process. CONCLUSIONS: Parents of children who had recently undergone spinal fusion had strong perceptions about what information to convey to families considering surgery, which may improve communication between future parents and physicians. Further investigation is needed to assess how best to incorporate the wisdom and experiences of parent peers into shared decision making and preparation for spinal fusion in children with neuromuscular scoliosis.

Well-Child Visits of Medicaid-Insured Children with Medical Complexity.

OBJECTIVE: Well-child visits (WCVs) help optimize children's health. We measured annual WCVs for children with medical complexity (CMC) and correlated WCVs with hospitalizations. STUDY DESIGN: This was a retrospective analysis of 93 121 CMC aged 1-18 years continuously enrolled in 10 state Medicaid programs in the Truven MarketScan Database between 2010 and 2014. CMC had a complex chronic condition or 3 or more chronic conditions of any complexity identified from International Classification of Diseases, Ninth Revision codes, and the use of 1 or more chronic medications. We measured the number of years with 1 or more WCVs. The χ2 test and logistic regression were used to assess the relationships of WCV-years with the children's characteristics and hospitalization. RESULTS: Over 5 years, 13.4% of CMC had 0 WCVs; 17.3% had WCVs in 1 year, 40.8% had WCVs in 2-3 years, and 28.5% had WCVs in 4-5 years. Fewer children received WCVs in 4-5 years when enrolled in Medicaid fee-for-service compared with managed care (20.9% vs 31.5%; P < .001) and when enrolled due to a disability compared with another reason (18.2% vs 32.2%; P < .001). The percentage of CMC hospitalized decreased as the number of years receiving WCV increased (21.5% at 0 years vs 16.9% at 5 years; P < .001). The adjusted odds of hospitalization were higher in CMC with WCVs in 0-4 years compared with CMC with WCVs in all 5 years (OR range across years, 1.1 [95% CI, 1.0-1.2] to 1.3 [95% CI, 1.3-1.4]). CONCLUSIONS: Most Medicaid-insured CMC do not receive annual WCVs consistently over time. Children with fewer annual WCVs have a higher likelihood of hospitalization. Further investigation is needed to improve the use of WCVs in CMC.

Distinct physiological and behavioural functions for parental alleles of imprinted Grb10.

Imprinted genes, defined by their preferential expression of a single parental allele, represent a subset of the mammalian genome and often have key roles in embryonic development, but also postnatal functions including energy homeostasis and behaviour. When the two parental alleles are unequally represented within a social group (when there is sex bias in dispersal and/or variance in reproductive success), imprinted genes may evolve to modulate social behaviour, although so far no such instance is known. Predominantly expressed from the maternal allele during embryogenesis, Grb10 encodes an intracellular adaptor protein that can interact with several receptor tyrosine kinases and downstream signalling molecules. Here we demonstrate that within the brain Grb10 is expressed from the paternal allele from fetal life into adulthood and that ablation of this expression engenders increased social dominance specifically among other aspects of social behaviour, a finding supported by the observed increase in allogrooming by paternal Grb10-deficient animals. Grb10 is, therefore, the first example of an imprinted gene that regulates social behaviour. It is also currently alone in exhibiting imprinted expression from each of the parental alleles in a tissue-specific manner, as loss of the peripherally expressed maternal allele leads to significant fetal and placental overgrowth. Thus Grb10 is, so far, a unique imprinted gene, able to influence distinct physiological processes, fetal growth and adult behaviour, owing to actions of the two parental alleles in different tissues.

Barriers to HPV immunization among blacks and latinos: a qualitative analysis of caregivers, adolescents, and providers.

BACKGROUND: Despite recommendations that 11-12-year-olds receive the full three-shot Human papillomavirus (HPV) vaccine series, national HPV immunization coverage rates remain low. Disparities exist, with Blacks and Latinos being less likely than Whites to complete the series. We aimed to identify and compare barriers to HPV immunization perceived by healthcare providers, Black and Latino adolescents, and their caregivers to inform a clinic-based intervention to improve immunization rates. METHODS: We conducted semi-structured interviews between March and July 2014 with Black and Latino adolescents (n = 24), their caregivers (n = 24), and nurses (n = 18), and 2 focus groups with 18 physicians recruited from two pediatric primary care clinics. Qualitative protocol topics included: general perceptions and attitudes towards vaccines; HPV knowledge; and perceived individual and systems-level barriers affecting vaccine initiation and completion. RESULTS: Themes were identified and organized by individual and systems-level barriers to HPV immunization. Adolescents and their caregivers, particularly Blacks, expressed concerns about HPV being an untested, "newer" vaccine. All families felt they needed more information on HPV and found it difficult to return for multiple visits to complete the vaccine series. Providers focused on challenges related to administering multiple vaccines simultaneously, and perceptions of parental reluctance to discuss sexually transmitted infections. CONCLUSIONS: Optimizing HPV immunization rates may benefit from a multi-pronged approach to holistically address provider, structural, and individual barriers to care. Further research should examine strategies for providing multiple modalities of support for providers, including a routinized system of vaccine promotion and delivery, and for addressing families' concerns about vaccine safety and efficacy.

Social Work Services Utilization by Children with Medical Complexity.

OBJECTIVES: Children with medical complexity (CMC) are a growing population in pediatric primary care practices, and families caring for these children face increased medical, developmental, education and social needs. The objective of this study was to quantify hospital-wide social work services utilization by CMC compared to non-medically-complex children (non-CMC) to inform the development of family-centered care models that support these vulnerable patients and families. METHODS: Social work department records from a tertiary children's hospital were used to compare CMC aged 0-17 (n = 564) with age- and sex-matched non-CMC (n = 1128) over a 16-month retrospective period. The main outcomes measures were the proportion of patients who used social work services and mean number of hours of services provided per patient, both by social work providers in the primary care setting and throughout the hospital. RESULTS: A greater percentage of CMC used social work services than non-CMC (60.3 vs. 18.9%), and CMC used more hours per child (5.50 h/child vs. 0.69). In multivariate analysis, medical complexity was associated with 6.23-fold greater odds of using social work services (95% CI 4.94-7.85) and with 8.07 times more hours of services per child (95% CI 6.30-10.34), independent of primary health insurance, age, or sex. CONCLUSION: This study confirms that CMC use significantly more social work services in the medical setting. This must be considered when designing proactive medical home models to provide high quality family-centered care for this population, and further research is needed to elucidate the factors that drive this utilization.

What can psychiatrists do to better support victims of family violence?

OBJECTIVE: This article aims to draw psychiatrists' attention to the problem of family violence and offer pragmatic guidance to detect and manage family violence in the psychiatric context. METHODS: Selective narrative review. RESULTS: Family violence involves complex interactions between societal, cultural, family and individual factors. Awareness and understanding of family violence is important for psychiatrists as engagement can result in enhanced opportunities for early intervention and harm reduction. CONCLUSIONS: There are barriers facing psychiatrists regarding successful family violence intervention outcomes. Concerted action is required to improve services and support to victims and perpetrators.

Identifying and testing candidate genetic polymorphisms in the irritable bowel syndrome (IBS): association with TNFSF15 and TNFα.

OBJECTIVES: The postinfectious irritable bowel syndrome (PI-IBS) suggests that impaired resolution of inflammation could cause IBS symptoms. The authors hypothesised that polymorphisms in genes whose expression were altered by gastroenteritis might be linked to IBS with diarrhoea (IBS-D) which closely resembles PI-IBS. DESIGN: Part 1: 25 healthy volunteers (HVs), 21 patients 6 months after Campylobacter jejuni infection, 37 IBS-D and 19 IBS with constipation (IBS-C) underwent rectal biopsy for gene expression analysis and peripheral blood mononuclear cell cytokine production assessment. Part 2: Polymorphisms in genes whose expression was altered in Part 1 were assessed in 179 HV, 179 IBS-D, 122 IBS-C and 41 PI-IBS. RESULTS: Part 1: Mucosal expression of seven genes was altered in IBS: CCL11, CCL13, Calpain 8 and TNFSF15 increased while NR1D1, GPR161 and GABRE decreased with similar patterns after infection with C jejuni. Part 2: The authors assessed 21 known single nucleotide polymorphisms (SNPs) in these seven genes and one SNP in each of the TNFα and IL-10 genes. Three out of five TNFSF15 SNPs (rs6478108, rs6478109 and rs7848647) showed reduced minor allele frequency (MAF) (0.28, 0.27 and 0.27) in subjects with IBS-D compared with HV (0.38, 0.36 and 0.37; p=0.007, 0.015 and 0.007, respectively) confirming others recent findings. The authors also replicated the previously reported association of the TNFα SNP rs1800629 with PI-IBS which showed an increase in the MAF at 0.30 versus 0.19 for HV (p=0.04). CONCLUSION: IBS-D and PI-IBS patients are associated with TNFSF15 and TNFα genetic polymorphisms which also predispose to Crohn's disease suggesting possible common underlying pathogenesis.

Saliva-derived secondary DNA transfer on fabric: The impact of varying conditions.

This study explored secondary DNA transfer involving saliva, a body fluid often encountered in forensic investigations. Various factors were examined to investigate their potential impact on the transfer of DNA from saliva stains deposited onto common types of fabric (cotton, nylon, and towel). We examined varying types of saliva moisture (wet, dry, and rehydrated) and different types of contact (controlled pressure and active/friction pressure) to quantitatively evaluate how such variables could impact transfer and possible conclusions surrounding saliva-derived DNA deposits. The transfer of DNA was generally least pronounced with more absorbent primary fabrics (cotton and towel materials) while a less absorbent primary fabric (nylon) exhibited a greater propensity for DNA transfer. There were significantly higher amounts of transferred DNA (p < 0.05) observed in wet saliva samples compared to dry and rehydrated saliva samples. Further, the use of active pressure (friction) appeared to result in more DNA transfer overall as compared to controlled pressure contact. Experiments conducted with wet saliva and active pressure (friction) demonstrated the highest likelihood of transfer, with the primary nylon and secondary towel fabric combination demonstrating the greatest average transfer percentage of 94.74 %. The variables explored in this study presented multiple combinations wherein a sufficient amount of DNA (≥ 240 pg total) was transferred to the secondary fabric, making it potentially suitable for STR-PCR amplification in our laboratory. The findings from this study indicate that the type of primary fabric receiving the saliva deposit, the type of saliva moisture, the type of secondary fabric and its moisture type, and the type of contact all have the potential to affect the quantity of DNA transferred and recovered. This study provides empirical data on the ease, and to what extent, DNA from saliva transfers between fabrics and aids DNA activity level evaluations. The significance of this research lies in its contribution to expanding our current understanding of DNA transfer involving saliva within forensic science and criminal investigations.

Reducing the Risk of Delayed Colorectal Cancer Diagnoses Through an Ambulatory Safety Net Collaborative.

BACKGROUND: An estimated 12 million adults in the United States experience delayed diagnoses and other diagnostic errors annually. Ambulatory safety nets (ASNs) are an intervention to reduce delayed diagnoses by identifying patients with abnormal results overdue for follow-up using registries, workflow redesign, and patient navigation. The authors sought to co-design a collaborative and implement colorectal cancer (CRC) ASNs across various health care settings. METHODS: A working group was convened to co-design implementation guidance, measures, and the collaborative model. Collaborative sites were recruited through a medical professional liability insurance program and chose to begin with developing an ASN for positive at-home CRC screening or overdue surveillance colonoscopy. The 18-month Breakthrough Series Collaborative ran from January 2022 to July 2023, with sites continuing to collect data while sustaining their ASNs. Data were collected from sites monthly on patients in the ASN, including the proportion that was successfully contacted, scheduled, and completed a follow-up colonoscopy. RESULTS: Six sites participated; four had an operational ASN at the end of the Breakthrough Series, with the remaining sites launching three months later. From October 2022 through February 2024, the Collaborative ASNs collectively identified 5,165 patients from the registry as needing outreach. Among patients needing outreach, 3,555 (68.8%) were successfully contacted, 2,060 (39.9%) were scheduled for a colonoscopy, and 1,504 (29.1%) completed their colonoscopy. CONCLUSION: The Collaborative successfully identified patients with previously abnormal CRC screening and facilitated completion of follow-up testing. The CRC ASN Implementation Guide offers a comprehensive road map for health care leaders interested in implementing CRC ASNs.

Evaluation of raising adolescent families together program: a medical home for adolescent mothers and their children.

OBJECTIVES: This study described a medical home model for adolescent mothers and their children, and their 1- and 2-year preventive care, repeat pregnancy, and psychosocial outcomes. METHODS: In this prospective, single cohort demonstration project, adolescent mothers (14-18 years old) and their children received care in a medical home. Demographic, medical and social processes, and outcomes data were collected at enrollment through 24 months. Change over time and predictors of repeat pregnancy were analyzed. RESULTS: A total of 181 adolescents enrolled, with 79.6% participating for 2 years. At 2 years, 90.2% of children were completely immunized. Children and adolescent mothers met standards for health care visits, and adolescent condom use improved. Rates of cumulative repeat pregnancy were 14.7% and 24.6%, school attendance 77.6% and 68.7%, and employment 21.2% and 32.3% at 1 and 2 years, respectively. CONCLUSIONS: A medical home model with comprehensive and integrated medical care and social services can effectively address the complex needs of adolescent parents and their children.

Adolescent childbearing: consequences and interventions.

PURPOSE OF REVIEW: Adolescent childbearing in the United States continues to occur at high rates compared with other industrialized nations, despite a recent decline. Adolescent mothers and their offspring are at risk for negative outcomes. Recent literature exploring the consequences of teenage childbearing and interventions to ameliorate these consequences are presented. RECENT FINDINGS: Negative consequences of adolescent childbearing can impact mothers and their offspring throughout the lifespan. These consequences are likely attributable to social and environmental factors rather than solely to maternal age. Increasing educational attainment, preventing repeat pregnancy and improving mother-child interactions can improve outcomes for mothers and their children. Home, community, school and clinic-based programs are all viable models of service delivery to this population. SUMMARY: Connecting teen mothers with comprehensive services to meet their social, economic, health and educational needs can potentially improve long-term outcomes for both mothers and their offspring. Programs that deliver care to this population in culturally sensitive, developmentally appropriate ways have demonstrated success. Future investigation of parenting interventions with larger sample sizes and that assess multiple outcomes will allow comparison among programs. Explorations of the role of the father and coparenting are also directions for future research.

Teen pregnancy prevention: current perspectives.

PURPOSE OF REVIEW: Teen pregnancy has been subject of public concern for many years. In the United States, despite nearly 2 decades of declining teen pregnancy and birth rates, the problem persists, with significant disparities present across racial groups and in state-specific rates. This review examines recent trends, pregnancy prevention initiatives and family planning policies that address the special needs of vulnerable youth. RECENT FINDINGS: Unintended teen pregnancies impose potentially serious social and health burdens on teen parents and their children, as well as costs to society. Trends in teen pregnancy and birth rates show continued decline, but state and racial disparities have widened. Demographic factors and policy changes have contributed to these disparities. Research supports comprehensive pregnancy prevention initiatives that are multifaceted and promote consistent and correct use of effective methods of contraception for youth at risk of becoming pregnant. SUMMARY: There is strong consensus that effective teen pregnancy prevention strategies should be multifaceted, focusing on delay of sexual activity especially in younger teens while promoting consistent and correct use of effective methods of contraception for those youth who are or plan to be sexually active. There is a need for further research to identify effective interventions for vulnerable populations.

Longitudinal study of depressive symptoms and social support in adolescent mothers.

Previous studies have suggested that adolescent mothers with higher social support have lower depressive symptoms. This is a longitudinal study of adolescent mothers to examine the association of social support and depressive symptoms over one year postpartum. This was a prospective study of adolescent mothers (N at baseline = 120, N at 1 year = 89; age < 19 years) enrolled in a teen tot program. Participants completed the Center for Epidemiological Studies Depression Scale for children (CES-DC) and the Duke-UNC Functional Social Support Questionnaire at baseline, 12 weeks, and 1 year. A score of ≥ 16 on the CES-DC was suggestive of major depression. The mean CES-DC scores of the adolescent mothers were ≥ 16 points at all three time points (baseline: mean = 18.7 ± 10.3; 53% ≥ 16; 12 weeks: mean = 18.4 ± 11.4, 57% ≥ 16; one year: mean = 20.0 ± 11.4; 57% ≥ 16). Social support had a significant, inverse association with depressive symptoms for all participants from baseline to 12 weeks with a stronger association for those with more depressive symptoms (score ≥ 16) at baseline (beta = -0.030 ± 0.007; P < 0.001) than for those with fewer depressive symptoms (score < 16) at baseline (beta = -0.013 ± 0.006; P = 0.021). From 12 weeks to one year, increased social support was only significantly associated with decreased depressive symptoms for those with a higher baseline level of depressive symptoms (beta = - 0.039 ± 0.009; P < 0.001). Depressive symptoms were prevalent among adolescent mothers. For more depressed adolescent mothers, higher levels of social support were associated with less depressive symptoms over the 1 year follow-up. Effective long-term interventions are needed to lessen depression and enhance social support.

The Role of Social Determinants of Health in the Use of Telemedicine for Asthma in Children.

Asthma is the most common chronic health condition among children in the United States. The adverse impacts of social determinants of health often manifest in unmet health-related social needs, potentially contributing to worse asthma outcomes. With the onset and rapid spread of coronavirus disease 2019 (COVID-19) and the identification of asthma as a potential risk factor for more severe disease, our asthma program quickly pivoted to a remote-access telemedicine asthma population management platform to best meet the needs of our most at-risk patients. Our practice provides care to a large proportion of Black and Latino/a/e children in urban areas insured by the State Medicaid Program and impacted by unmet social needs. As we pivoted to telemedicine, we consistently reached a greater number of patients and families than prepandemic and observed decreased emergency department visits and hospitalizations. About 1 in 5 families received resource touch points spanning categories of transportation, food and supplies, clothing, utilities, and rent. Overall, families reported positive experiences with telemedicine, including the ability to connect remotely with our social work and resource teams. Telemedicine may be an effective strategy for addressing both the medical and the social needs of children with asthma at risk for worse outcomes.

Improving HPV Vaccination Rates in a Racially and Ethnically Diverse Pediatric Population.

BACKGROUND AND OBJECTIVES: Nationally, 54.2% of youth are fully vaccinated for human papilloma virus (HPV) with persistent gender and racial/ethnic disparities. We used a quality improvement approach to improve completion of the HPV vaccine series by age 13 years. As a secondary aim, we examined racial/ethnic and gender differences in vaccine uptake. METHODS: The study setting included 2 pediatric, academic, primary care practices in Massachusetts. We designed a multilevel patient-, provider-, and systems-level intervention addressing parental hesitancy, provider communication, and clinical operations. Rates of HPV series completion by age 13 were monitored using a control p chart. Bivariate and multivariate analyses evaluated vaccine completion differences on the basis of clinic size, gender, and race/ethnicity. RESULTS: Between July 1, 2014, and September 30, 2021, control p charts showed special cause variation with HPV vaccine initiation by age 9 years, increasing from 1% to 52%, and vaccine completion by 13 years, increasing from 37% to 77%. Compared with White and Black children, Hispanic children were more likely to initiate the HPV vaccine at age 9 (adjusted odds ratio [95% confidence interval] = (1.4-2.6)] and complete the series by age 13 (adjusted odds ratio [95% confidence interval] = 2.3 (1.7-3.0). CONCLUSIONS: A multilevel intervention was associated with sustained HPV vaccine series completion by age 13 years. Hispanic children were more likely to be vaccinated. Qualitative family input was critical to intervention design. Provider communication training addressed vaccine hesitancy. Initiation of the vaccine at age 9 and clinicwide vaccine protocols were key to sustaining improvements.

Unresected screen-detected ductal carcinoma in situ: Outcomes of 311 women in the Forget-Me-Not 2 study.

BACKGROUND AND AIM: The natural history of ductal carcinoma in situ (DCIS) is poorly understood. The aim of this cohort study was to determine the outcomes of women who had no surgery for screen-detected DCIS in the 6 months following diagnosis. METHODS: English breast screening databases were retrospectively searched for women diagnosed with DCIS without invasive cancer at screening and who had no record of surgery within 6 months of diagnosis. These were cross-referenced with cancer registry data. Details of the potentially eligible women were sent to the relevant breast screening units for verification and for completion of data forms detailing clinical, radiological and pathological findings, non-surgical treatment and subsequent clinical course. RESULTS: Data for 311 eligible women (median age 62 years) were available. 60 women developed invasive cancer, 56 ipsilateral and 4 contralateral. Ipsilateral invasion risk increased approximately linearly with time for at least 10 years. The 10-year cumulative risk of ipsilateral invasion was 9% (95% CI 4-21%), 39% (24-58%) and 36% (24-50%) for low, intermediate and high grade DCIS respectively and was higher in younger women, in those with larger DCIS lesions and in those with microinvasion. Most invasive cancers that developed were grade 2 or 3. CONCLUSION: The findings suggest that active surveillance may be a reasonable alternative to surgery in patients with low grade DCIS but that women with intermediate or high grade disease should continue to be offered surgery. This highlights the importance of reproducible grading of DCIS to ensure patients receive appropriate treatment.