Western Connecticut Health Network

BACKGROUND: The growing advances in DNA sequencing tools have made analyzing the human genome cheaper and faster. While such analyses are intended to identify complex variants, related to disease susceptibility and efficacy of drug responses, they have blurred the definitions of mutation and polymorphism. DISCUSSION: In the era of personal genomics, it is critical to establish clear guidelines regarding the use of a reference genome. Nowadays DNA variants are called as differences in comparison to a reference. In a sequencing project Single Nucleotide Polymorphisms (SNPs) and DNA mutations are defined as DNA variants detectable in >1 % or <1 % of the population, respectively. The alternative use of the two terms mutation or polymorphism for the same event (a difference as compared with a reference) can lead to problems of classification. These problems can impact the accuracy of the interpretation and the functional relationship between a disease state and a genomic sequence. We propose to solve this nomenclature dilemma by defining mutations as DNA variants obtained in a paired sequencing project including the germline DNA of the same individual as a reference. Moreover, the term mutation should be accompanied by a qualifying prefix indicating whether the mutation occurs only in somatic cells (somatic mutation) or also in the germline (germline mutation). We believe this distinction in definition will help avoid confusion among researchers and support the practice of sequencing the germline and somatic tissues in parallel to classify the DNA variants thus defined as mutations.

OBJECTIVE: To examine changes that occur in infant and parent salivary oxytocin (OT) and salivary cortisol (SC) levels during skin-to-skin contact (SSC) and whether SSC alleviates parental stress and anxiety while also supporting mother-father-infant relationships. METHODS: This randomized crossover study was conducted in the neonatal intensive care unit (NICU) with a sample of 28 stable preterm infants and their parents. Saliva samples were collected from infants, mothers, and fathers on Days 1 and 2 (1/parent) for OT and cortisol measurement pre-SSC, during a 60-min SSC session, and a 45-min post-SSC. Parental anxiety was measured at the same time points. Parent-infant interaction was examined prior to discharge on Day 3 via video for synchrony and responsiveness using Dyadic Mutuality Coding. RESULTS: Salivary OT levels increased significantly during SSC for mothers ( p < .001), fathers ( p < .002), and infants ( p < .002). Infant SC levels decreased significantly ( p < .001) during SSC as compared to before and after SSC. Parent anxiety scores were significantly related to parent OT and SC levels. Parents with higher OT levels exhibited more synchrony and responsiveness ( p < .001) in their infant interactions. CONCLUSION: This study addresses a gap in understanding the mechanisms linking parent-infant contact to biobehavioral responses. SSC activated OT release and decreased infant SC levels. Facilitation of SSC may be an effective intervention to reduce parent and infant stress in the NICU. Findings advance the exploration of OT as a potential moderator for improving responsiveness and synchrony in parent-infant interactions.

INTRODUCTION: Intravenous medication errors persist despite the use of smart pumps. This suggests the need for a standardised methodology for measuring errors and highlights the importance of identifying issues around smart pump medication administration in order to improve patient safety. OBJECTIVES: We conducted a multisite study to investigate the types and frequency of intravenous medication errors associated with smart pumps in the USA. METHODS: 10 hospitals of various sizes using smart pumps from a range of vendors participated. Data were collected using a prospective point prevalence approach to capture errors associated with medications administered via smart pumps and evaluate their potential for harm. RESULTS: A total of 478 patients and 1164 medication administrations were assessed. Of the observed infusions, 699 (60%) had one or more errors associated with their administration. Identified errors such as labelling errors and bypassing the smart pump and the drug library were predominantly associated with violations of hospital policy. These types of errors can result in medication errors. Errors were classified according to the National Coordinating Council for Medication Error Reporting and Prevention (NCC MERP). 1 error of category E (0.1%), 4 of category D (0.3%) and 492 of category C (excluding deviations of hospital policy) (42%) were identified. Of these, unauthorised medication, bypassing the smart pump and wrong rate were the most frequent errors. CONCLUSION: We identified a high rate of error in the administration of intravenous medications despite the use of smart pumps. However, relatively few errors were potentially harmful. The results of this study will be useful in developing interventions to eliminate errors in the intravenous medication administration process.

BACKGROUND: Endometrial cancer is the most common gynecologic malignancy, and its incidence and associated mortality are increasing. Despite the immediate need to detect these cancers at an earlier stage, there is no effective screening methodology or protocol for endometrial cancer. The comprehensive, genomics-based analysis of endometrial cancer by The Cancer Genome Atlas (TCGA) revealed many of the molecular defects that define this cancer. Based on these cancer genome results, and in a prospective study, we hypothesized that the use of ultra-deep, targeted gene sequencing could detect somatic mutations in uterine lavage fluid obtained from women undergoing hysteroscopy as a means of molecular screening and diagnosis. METHODS AND FINDINGS: Uterine lavage and paired blood samples were collected and analyzed from 107 consecutive patients who were undergoing hysteroscopy and curettage for diagnostic evaluation from this single-institution study. The lavage fluid was separated into cellular and acellular fractions by centrifugation. Cellular and cell-free DNA (cfDNA) were isolated from each lavage. Two targeted next-generation sequencing (NGS) gene panels, one composed of 56 genes and the other of 12 genes, were used for ultra-deep sequencing. To rule out potential NGS-based errors, orthogonal mutation validation was performed using digital PCR and Sanger sequencing. Seven patients were diagnosed with endometrial cancer based on classic histopathologic analysis. Six of these patients had stage IA cancer, and one of these cancers was only detectable as a microscopic focus within a polyp. All seven patients were found to have significant cancer-associated gene mutations in both cell pellet and cfDNA fractions. In the four patients in whom adequate tumor sample was available, all tumor mutations above a specific allele fraction were present in the uterine lavage DNA samples. Mutations originally only detected in lavage fluid fractions were later confirmed to be present in tumor but at allele fractions significantly less than 1%. Of the remaining 95 patients diagnosed with benign or non-cancer pathology, 44 had no significant cancer mutations detected. Intriguingly, 51 patients without histopathologic evidence of cancer had relatively high allele fraction (1.0%-30.4%), cancer-associated mutations. Participants with detected driver and potential driver mutations were significantly older (mean age mutated = 57.96, 95% confidence interval [CI]: 3.30-∞, mean age no mutations = 50.35; p-value = 0.002; Benjamini-Hochberg [BH] adjusted p-value = 0.015) and more likely to be post-menopausal (p-value = 0.004; BH-adjusted p-value = 0.015) than those without these mutations. No associations were detected between mutation status and race/ethnicity, body mass index, diabetes, parity, and smoking status. Long-term follow-up was not presently available in this prospective study for those women without histopathologic evidence of cancer. CONCLUSIONS: Using ultra-deep NGS, we identified somatic mutations in DNA extracted both from cell pellets and a never previously reported cfDNA fraction from the uterine lavage. Using our targeted sequencing approach, endometrial driver mutations were identified in all seven women who received a cancer diagnosis based on classic histopathology of tissue curettage obtained at the time of hysteroscopy. In addition, relatively high allele fraction driver mutations were identified in the lavage fluid of approximately half of the women without a cancer diagnosis. Increasing age and post-menopausal status were associated with the presence of these cancer-associated mutations, suggesting the prevalent existence of a premalignant landscape in women without clinical evidence of cancer. Given that a uterine lavage can be easily and quickly performed even outside of the operating room and in a physician's office-based setting, our findings suggest the future possibility of this approach for screening women for the earliest stages of endometrial cancer. However, our findings suggest that further insight into development of cancer or its interruption are needed before translation to the clinic.

There is a paucity of data to support evidence-based practices in the provision of patient/family education in the context of a new childhood cancer diagnosis. Since the majority of children with cancer are treated on pediatric oncology clinical trials, lack of effective patient/family education has the potential to negatively affect both patient and clinical trial outcomes. The Children's Oncology Group Nursing Discipline convened an interprofessional expert panel from within and beyond pediatric oncology to review available and emerging evidence and develop expert consensus recommendations regarding harmonization of patient/family education practices for newly diagnosed pediatric oncology patients across institutions. Five broad principles, with associated recommendations, were identified by the panel, including recognition that (1) in pediatric oncology, patient/family education is family-centered; (2) a diagnosis of childhood cancer is overwhelming and the family needs time to process the diagnosis and develop a plan for managing ongoing life demands before they can successfully learn to care for the child; (3) patient/family education should be an interprofessional endeavor with 3 key areas of focus: (a) diagnosis/treatment, (b) psychosocial coping, and (c) care of the child; (4) patient/family education should occur across the continuum of care; and (5) a supportive environment is necessary to optimize learning. Dissemination and implementation of these recommendations will set the stage for future studies that aim to develop evidence to inform best practices, and ultimately to establish the standard of care for effective patient/family education in pediatric oncology.

Abstract Purpose: The high fatality-to-case ratio of ovarian cancer is directly related to platinum resistance. Exportin-1 (XPO1) is a nuclear exporter that mediates nuclear export of multiple tumor suppressors. We investigated possible clinicopathologic correlations of XPO1 expression levels and evaluated the efficacy of XPO1 inhibition as a therapeutic strategy in platinum-sensitive and -resistant ovarian cancer. Experimental Design: XPO1 expression levels were analyzed to define clinicopathologic correlates using both TCGA/GEO datasets and tissue microarrays (TMA). The effect of XPO1 inhibition, using the small-molecule inhibitors KPT-185 and KPT-330 (selinexor) alone or in combination with a platinum agent on cell viability, apoptosis, and the transcriptome was tested in immortalized and patient-derived ovarian cancer cell lines (PDCL) and platinum-resistant mice (PDX). Seven patients with late-stage, recurrent, and heavily pretreated ovarian cancer were treated with an oral XPO1 inhibitor. Results: XPO1 RNA overexpression and protein nuclear localization were correlated with decreased survival and platinum resistance in ovarian cancer. Targeted XPO1 inhibition decreased cell viability and synergistically restored platinum sensitivity in both immortalized ovarian cancer cells and PDCL. The XPO1 inhibitor–mediated apoptosis occurred through both p53-dependent and p53-independent signaling pathways. Selinexor treatment, alone and in combination with platinum, markedly decreased tumor growth and prolonged survival in platinum-resistant PDX and mice. In selinexor-treated patients, tumor growth was halted in 3 of 5 patients, including one with a partial response, and was safely tolerated by all. Conclusions: Taken together, these results provide evidence that XPO1 inhibition represents a new therapeutic strategy for overcoming platinum resistance in women with ovarian cancer. Clin Cancer Res; 23(6); 1552–63. ©2016 AACR.

BACKGROUND: Prostate-specific membrane antigen (PSMA) is a well-characterized target that is overexpressed selectively on prostate cancer cells. PSMA antibody-drug conjugate (ADC) is a fully human IgG1 monoclonal antibody conjugated to the microtubule disrupting agent monomethyl auristatin E (MMAE), which is designed to specifically bind PSMA-positive cells, internalize, and then release its cytotoxic payload into the cells. PSMA ADC has demonstrated potent and selective antitumor activity in preclinical models of advanced prostate cancer. A Phase 1 study was conducted to assess the safety, pharmacokinetics, and preliminary antitumor effects of PSMA ADC in subjects with treatment-refractory prostate cancer. METHODS: In this first-in-man dose-escalation study, PSMA ADC was administered by intravenous infusion every three weeks to subjects with progressive metastatic castration-resistant prostate cancer (mCRPC) who were previously treated with docetaxel chemotherapy. The primary endpoint was to establish a maximum tolerated dose (MTD). The study also examined the pharmacokinetics of the study drug, total antibody, and free MMAE. Antitumor effects were assessed by measuring changes in serum prostate-specific antigen (PSA), circulating tumor cells (CTCs), and radiologic imaging. RESULTS: Fifty-two subjects were administered doses ranging from 0.4 to 2.8 mg/kg. Subjects had a median of two prior chemotherapy regimens and prior treatment with abiraterone and/or enzalutamide. Neutropenia and peripheral neuropathy were identified as important first-cycle and late dose-limiting toxicities, respectively. The dose of 2.5 mg/kg was determined to be the MTD. Pharmacokinetics were approximately dose-proportional with minimal drug accumulation. Reductions in PSA and CTCs in subjects treated with doses of ≥1.8 mg/kg were durable and often concurrent. CONCLUSIONS: In an extensively pretreated mCRPC population, PSMA ADC demonstrated acceptable toxicity. Antitumor activity was observed over dose ranges up to and including 2.5 mg/kg. The observed anti-tumor activity supported further evaluation of this novel agent for the treatment of advanced metastatic prostate cancer.

OBJECTIVE: As healthcare systems and providers move toward meaningful use of electronic health records, longitudinal care plans (LCPs) may provide a means to improve communication and coordination as patients transition across settings. The objective of this study was to determine the current state of communication of LCPs across settings and levels of care. MATERIALS AND METHODS: We conducted surveys and interviews with professionals from emergency departments, acute care hospitals, skilled nursing facilities, and home health agency settings in six regions in the USA. We coded the transcripts according to the Agency for Healthcare Research and Quality (AHRQ) 'Broad Approaches' to care coordination to understand the degree to which current practice meets the definition of an LCP. RESULTS: Participants (n=22) from all settings reported that LCPs do not exist in their current state. We found LCPs in practice, and none of these were shared or reconciled across settings. Moreover, we found wide variation in the types and formats of care plan information that was communicated as patients transitioned. The most common formats, even when care plan information was communicated within the same healthcare system, were paper and fax. DISCUSSION: These findings have implications for data reuse, interoperability, and achieving widespread adoption of LCPs. CONCLUSIONS: The use of LCPs to support care transitions is suboptimal. Strategies are needed to transform the LCP from vision to reality.

OBJECTIVE: Clinical outcomes of 500 high-intensity focused ultrasound (HIFU)-treated uterine fibroids and adenomyosis are analyzed and presented. MATERIALS AND METHODS: This is a retrospective cross-sectional analysis from a single tertiary medical center. From April 2015 to October 2018, 546 cases were enrolled for the study. After excluding 46 patients with less than 3 months of follow-up period, there were 404 fibroids, 149 adenomyosis and 53 mixed conditions entered for analysis. The patients' uterine fibroids and adenomyosis were treated by HIFU according to Chongqing Haifu protocol, with 12 cm diameter transducer of focal length 10-16 cm at 0.8 or 1.6 MHz T2-weight MRI imaging was rendered prior to and 3 month post treatment to assess lesion volume change using non-perfusion volume, which was the primary outcome. Secondary outcomes including quality of life, subjective satisfaction, adverse events and pregnancy rate were determined using self-reported questionnaires. The mean follow up period ranged from 3 to 38 months with an average of 21 months. RESULTS: Three months after HIFU-treated uterine fibroids and adenomyosis, the lesion size reduced 40.2% and 46.3%, respectively. Symptoms all improved with better quality of life for the fibroid group, while those with adenomyosis or combined diseases benefit the most from pain control. Serum CA125 decreased significantly for all studied groups, and LDH only showed improvement for fibroids group. Number of adverse events is comparable to Chongqing data (approximately 10.2%), with mostly mild and self-resolving conditions. No permanent sequelae or death was documented. Twelve pregnancies are reported in this cohort. CONCLUSION: HIFU is safe and effective in treating uterine fibroids and adenomyosis. The results are reproducible if standardized treatment schedules are followed. It is a promising treatment alternative with the advantages of precision, non-invasiveness, rapid recovery and readiness for pregnancy.

BACKGROUND: Uterine leiomyosarcoma (uLMS) responds poorly to conventional chemotherapeutic agents, and personalized therapies have yet to be systematically explored. Comprehensive genomic profiling (CGP) can identify therapeutic targets and provide insight into the biology of this highly aggressive tumor. We report a case of uLMS treated with the CGP-matched therapy palbociclib, a CDK4/6 inhibitor, with sustained clinical benefit in this rare and deadly malignancy. MATERIALS AND METHODS: This study analyzed 279 clinically advanced/recurrent uLMS samples. Median patient age was 54 years (range, 23-83 years). DNA was extracted from 40 µm of formalin-fixed, paraffin-embedded sections, and CGP was performed on hybridization-captured, adaptor ligation-based libraries for up to 405 cancer-related genes plus introns from up to 31 genes frequently rearranged in cancer. Sequencing data were analyzed for base pair substitutions, insertions/deletions, copy number alterations, and rearrangements. RESULTS: mutation, resulting in disease stabilization and significant symptom reduction. CONCLUSION: Comprehensive genomic profiling (CGP) of individuals with uterine leiomyosarcoma (uLMS) indicates that nearly 20% of patients may harbor a mutation affecting the cyclin-dependent kinase (CDK) pathway. The case presented demonstrates that a CDK inhibitory drug may provide clinical benefit to such individuals. Given the lack of curative therapies for uLMS, CGP could be performed on all cases of advanced uLMS and a CDK inhibitor could be recommended (preferably as part of a clinical trial) for individuals harboring a mutation in the CDK pathway.

Handbook of Healthcare Delivery Systems Yeuhwern Yih 2011, CRC Press 812 pages, hardcover

The landscape of HPV infection in racial/ethnic subgroups of head and neck cancer (HNC) patients has not been evaluated carefully. In this study, a meta-analysis examined the prevalence of HPV in HNC patients of African ancestry. Additionally, a pooled analysis of subject-level data was also performed to investigate HPV prevalence and patterns of p16 (CDNK2A) expression amongst different racial groups. Eighteen publications (N = 798 Black HNC patients) were examined in the meta-analysis, and the pooled analysis included 29 datasets comprised of 3,129 HNC patients of diverse racial/ethnic background. The meta-analysis revealed that the prevalence of HPV16 was higher among Blacks with oropharyngeal cancer than Blacks with non-oropharyngeal cancer. However, there was great heterogeneity observed among studies (Q test P<0.0001). In the pooled analysis, after adjusting for each study, year of diagnosis, age, gender and smoking status, the prevalence of HPV16/18 in oropharyngeal cancer patients was highest in Whites (61.1%), followed by 58.0% in Blacks and 25.2% in Asians (P<0.0001). There was no statistically significant difference in HPV16/18 prevalence in non-oropharyngeal cancer by race (P=0.682). With regard to the pattern of HPV16/18 status and p16 expression, White patients had the highest proportion of HPV16/18+/p16+ oropharyngeal cancer (52.3%), while Asians and Blacks had significantly lower proportions (23.0% and 22.6%, respectively) [P <0.0001]. Our findings suggest that the pattern of HPV16/18 status and p16 expression in oropharyngeal cancer appears to differ by race and this may contribute to survival disparities.

PURPOSE: To evaluate spectral-domain optical coherence tomography (SD-OCT) as a strategy for identifying occult macular disease preoperatively in patients scheduled for cataract surgery with implantation of an advanced-technology intraocular lens (IOL). SETTING: Private practice, Danbury, Connecticut, USA. DESIGN: Retrospective consecutive case series. METHODS: Macular SD-OCT scans were performed on all patients scheduled for cataract surgery and Restor multifocal or toric IOL implantation over a 6-month period. All scans were reviewed for abnormalities of the retina, retinal pigment epithelium, or vitreomacular interface. For subgroup analysis, the following health information was collected: age, sex, smoking history, hypertension, heart disease, hyperlipidemia or hypercholesterolemia, and diabetes. RESULTS: Two hundred sixty-five consecutive scans from 149 patients were obtained. Macular pathology was found in 35 eyes (13.2%). The most common condition was age-related macular degeneration in 15 eyes (5.66%) followed by idiopathic epiretinal membrane in 11 eyes (4.15%). Ischemic atrophy from previously undiagnosed retinal vascular pathology was found in 5 eyes (1.89%) and edema in 3 eyes (1.13%). A subgroup analysis found a higher incidence of macular pathology in patients with a history of heart disease (30.6%, P < .001) or smoking (20.2%, P < .05), and in men (23.9%, P < .01). Media opacities precluded interpretation of 17 scans (6.42%). CONCLUSION: Preoperative macular SD-OCT scanning was effective in identifying patients at risk for compromised visual outcomes after advanced-technology IOL surgery. FINANCIAL DISCLOSURE: None of the authors has a financial or proprietary interest in any material or method mentioned.

5502 Background: Surgery is the primary treatment modality for early cervical cancer. Compared to open (ORH), a robotic (RRH) or laparoscopic (LRH) approach to radical hysterectomy may have decreased morbidity, but the influence of surgical approach on survival, specific perioperative complications, and costs is unknown. Methods: The 2010-2013 National Cancer Database (NCDB) was used to evaluate the 5-year survival (5YS) of women with stage IB1 cervical squamous cell carcinoma or adenocarcinoma after radical hysterectomy performed open or by minimally invasive surgery (MIS). Survival times were estimated with the Kaplan-Meier method. Multivariable Cox proportional-hazards model (CPH) was used to adjust for measured confounders. The 2010-2015 Premier Healthcare Database was used to compare complications, length of stay (LOS), readmission rates, and hospitalization costs between ORH, RRH, and LRH. All p-values are two-sided. Results: From the NCDB, 982 and 910 women underwent ORH versus MIS radical hysterectomy, respectively. Women with a tumor size ≥ 2 cm who underwent MIS radical hysterectomy had decreased survival compared to women who underwent ORH (5YS (95% CI): 81.3% (75.6%-87.3%) versus 90.8% (87.7%-93.9%); hazard ratio (95% CI) 2.14 (1.36-3.38), P < 0.001). From Premier, 2830 women had radical hysterectomy: 45.1% (1277) ORH, 48.9% (1384) RRH, and 6% (169) LRH. ORH was associated with longer LOS compared to RRH or LRH (days, median (IQR): ORH 3 (3-5); RRH 1 (0-2); LRH 0 (0-2), P < 0.001). ORH also had a higher composite complication rate than RRH or LRH (ORH 44.9%; RRH 13.9%; LRH; 12.4%, P < 0.001), with increased bowel injuries, infections, electrolyte or fluid disorders, transfusions, and ileus (all P ≤ 0.001) associated with ORH. Thirty-day readmission rates were similar (ORH 2.3%; RRH 1.4%; LRH 1.8%, P = 0.17). Total surgical hospitalization costs favored MIS (P < 0.001 between groups) with median (IQR) values: ORH $12080 (8957-16052); RRH $11562 (8636-14600); LRH $9649 (7478- 13010). Conclusions: MIS is associated with decreased morbidity and costs. However, among women with ≥ 2 cm stage IB1 cervical cancer, MIS was associated with significantly decreased survival.

OBJECTIVES: To evaluate the validity of serum CA-125, Human Epididymis protein 4 (HE4) and Risk of Malignancy Algorithm (ROMA) at standard and optimal cut-offs, in preoperative prediction of epithelial ovarian carcinoma (EOC) in Vietnam. SUBJECTS AND METHODS: Cross-sectional, descriptive study on 277 patients with ovarian masses hospitalized at the OBGYN Departments, Hue University Hospital and Hue Central Hospital, Vietnam, from 01/2016 to 11/2017. All patients had measurements of serum CA-125 by Elecsys 2010 system and HE4 by immunoassay ARCHITECT® HE4 kits; ROMA calculated, and preoperative malignancy risk estimated. Matching these values to postoperative histopathology resulted in the preoperative prediction values. RESULTS: There were 30 (10.8%) cases of EOC. Median values of CA 125, HE4, and ROMA of EOC and benign tumors were 214.20 U/ml, 18.91 U/ml; 90.00 pmol/l, 39.80 pmol/l; and 55.20%, 4.80%, respectively. The sensitivities and specificity of CA125, HE4, and ROMA to distinguish between malignant and benign tumors at standard cut-offs were 83.3% and 78.5%; 50% and 98.38%; 80.0% and 84,6%, and those at optimal cut-offs were 83.3% and 86.6%; 80.0% and 91.5%, 86.7% and 88.7%, respectively. AUCs of CA-125, HE4, and ROMA were 0.872, 0.894, 0.912; and those for the post-menopausal group were 0.900, 0.894 and 0.924, respectively. CONCLUSION: Serum CA 125 and HE4 levels and ROMA have good validity in the diagnosis of EOC, of which ROMA gives the best result. The ROMA index should be applied in clinical practice to help in the assessment and management of patients with suspected ovarian cancer.

Platinum therapy represents first line of treatment in many malignancies but its high systemic toxicity limits the therapeutic dosage. Herein, we report the synthesis of carboplatin-like complexes with azide and alkyne functional groups and the formation of a platinum (II) - nuclear localization sequence peptide (Pt-NLS) hybrid to improve the import of platinum (II) complexes directly into the cell's nucleus. The Pt-NLS hybrid successfully enters cells and their nuclei, forming Pt-induced nuclear lesions. The in vitro efficacy of Pt-NLS is high, superior to native carboplatin at the same concentration. The methodology used is simple and cost-effective and most importantly can easily be extended to load the Pt (II) onto other supports, opening new possibilities for enhanced delivery of Pt (II) therapy.

BACKGROUND: Annual lung cancer screening using low-dose computed tomography (LDCT) scans is associated with a survival benefit, but it is also associated with potential harm. Unlike descriptive probability formats, experienced tasks have been shown to decrease perceptions of rare events. The objective of this study was to compare descriptive versus experienced probability formats on patients' knowledge, beliefs, endorsement of screening for heavy smokers, and preference (choice predisposition) to undergo screening. METHODS: A total of 276 patients attending an outpatient pulmonary practice were randomized to learn about screening using 1 of 3 formats: numbers only, numbers + icon arrays, numbers + a set of slides illustrating LDCT scans of 250 people in random order that displayed the number of normal scans, false-positive lung nodules, cancers found leading to a life saved, and cancers found leading to death despite treatment. RESULTS: Knowledge differed between the 3 formats (P= 0.001), with participants randomized to the numbers + icon array format having the highest knowledge score. Beliefs were more favorable among participants randomized to the numbers + experienced format compared with the numbers + icon array format (difference between means [95% confidence interval]= 1.6 [0.4-2.8]). Differences in participants' endorsement of screening (P= 0.4) and choice predisposition (P= 0.6) across probability format mirrored those of beliefs but were not statistically significant. DISCUSSION: Contrary to what we expected, the experienced format increased propensity toward screening compared with the numbers + icon array format, as indicated by more favorable beliefs and nonsignificant trends toward stronger choice predisposition and endorsement. Experienced risk formats may not be a practical approach to improve risk communication for patients deciding whether or not to undergo annual lung cancer screening.

OBJECTIVE: The purpose of this trial was to evaluate the effect of krill oil supplementation, a source of ω-3 fatty acids, on cardiovascular disease risk factors and blood glucose control among participants with type 2 diabetes. RESEARCH DESIGN AND METHODS: A randomized, double-blind controlled cross-over trial was employed. Outcomes assessed were: endothelial function, blood lipids, glucose, glycated hemoglobin, serum antioxidant level, C peptide, and calculated Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) scores. Participants were randomized to either krill oil or olive oil supplementation for 4 weeks, underwent a 2-week washout period, and then crossed to the other supplementation for 4 weeks. All participants were then offered an additional 17 weeks of krill supplementation. Testing occurred at 3 time points: baseline, after first supplementation, and after second supplementation. Testing also occurred after an optional 17 weeks of krill oil supplementation. Difference scores were calculated for each participant in both sequences (ie, differences in outcome measures in the first and second period of the sequence). The mean and SD of the scores in the 2 sequence groups were used to test for differences between treatment effects at a significance level of p<0.05. RESULTS: A total of 47 participants were included in the initial cross-over study. Participants who received krill oil for 4 weeks had an improvement in their endothelial function and a reduction in blood C peptide levels and HOMA scores as compared with the olive oil. A total of 34 participants completed the additional 17-week supplementation period. When compared with their respective baseline measures, these participants had a statistically significant improvement in endothelial function and blood high-density lipoprotein (HDL). CONCLUSIONS: Krill oil may lead to moderate improvement of cardiovascular risks, specifically endothelial dysfunction and HDL in patients with type 2 diabetes. TRIAL REGISTRATION NUMBER: Registered with ClinicalTrials.gov: NCT02091193.

Nintedanib has been approved for the treatment of idiopathic pulmonary fibrosis (IPF) in more than 60 countries, including the USA [1]. In the two phase III INPULSIS trials, nintedanib reduced disease progression by reducing decline in forced vital capacity [2]. Most patients were able to manage the side-effects of nintedanib, with 19.3% of patients treated with nintedanib versus 13.0% treated with placebo permanently discontinuing the study medication due to adverse events. The most frequent adverse events were gastrointestinal, particularly diarrhoea. The proportion of patients who had one or more serious adverse events was similar between nintedanib and placebo (30.4% versus 30.0%). The safety and tolerability profile of nintedanib in patients with IPF in the clinical setting is consistent with the product label <http://ow.ly/Nulb30jPAld> The authors would like to acknowledge the contribution of Alexandar Allinger, Boehringer Ingelheim Pharma GmbH & Co. KG (Ingelheim am Rhein, Germany) to the acquisition and analysis of the data. Medical writing assistance was provided by Julie Fleming and Wendy Morris of FleishmanHillard Fishburn (London, UK), which was contracted and funded by Boehringer Ingelheim Pharmaceuticals, Inc. All authors were involved in the interpretation of the data and writing of this letter and have approved the final version.

WHAT IS KNOWN AND OBJECTIVE: Breast cancer (BCa) and prostate cancer (PCa), both hormone-dependent cancers, are the second leading cause of death in both women and men, respectively. Calcium channel blockers (CCBs) have been thought to increase the risk of cancer by inhibiting calcium signal-mediated apoptosis, but the evidence for this association remains inconclusive. We have reviewed pertinent literature and pooled data to establish a consensus on the relationship of CCB use and the incidence of these two cancers. METHODS: PubMed was used to conduct a search for English articles from inception to April 2016. Relevant data including study design, number of total participants and CCB users, total cases of BCa and PCa, age (mean and/or range), follow-up period and statistical outcomes were retrieved. Quality assessment was carried out using Newcastle Ottawa system, with the selection of high-quality studies. Summary effects were obtained using random- and mixed-effects models, followed by sensitivity analysis, and testing for publication bias. RESULTS AND DISCUSSION: This meta-analysis includes 11 relevant studies for BCa and 6 for PCa. The odds ratio (OR) association between BCa and CCB use was 1.14 (95%CI: 1.02, 1.27, P = .02). The OR association between PCa and CCB use was 1.12 (95%CI .94-1.35, P = .21). WHAT IS NEW AND CONCLUSION: Although a statistically significant association between CCB use and incidence of BCa does exist, the limitations of the individual studies restrict the clinical application of this relationship. Our meta-regression model does newly identify a 9-year latency period of CCB use and a significantly increased risk of BCa. No significant association exists between CCB use and the incidence of PCa. Our meta-regression shows CCB may have a protective effect upon PCa incidence among older populations.