Factors Associated With Hospital Admission in the Last Month: A Retrospective Single Center Analysis.

CONTEXT: Driven by concerns about care quality, patient experience, and national metrics, health systems are increasingly focusing on identifying risk factors for patients who are hospitalized in the last month of life. OBJECTIVE: To evaluate patient factors associated with hospital admission in the last month (30 days). METHODS: We analyzed a retrospective cohort of 8488 patients with a primary care visit in a tertiary health system in the last year of life using a linked electronic health record and decedent dataset. We examined healthcare utilization (primary care, emergency, hospital, intensive care unit encounters) and end-of-life related outcomes (palliative care consultation, do-not-resuscitate orders, advance care planning documentation, hospice at hospital discharge, death in health system). Multivariable logistic regressions identified patient factors associated with admission in the last month. RESULTS: About 2202 (25.9%) patients had a hospital admission in the last month. Among the 1282 (15.1%) who died in a health system facility, most (1103/1282, 86.0%) were admitted to the hospital in the last month. Among patients with a hospital admission and discharged in the last month, 60.9% (686/1126) were discharged on hospice. Compared to those without these diseases, metastatic cancer, liver disease, or heart failure had the highest odds of admission in the last month (adjusted OR 2.36 95%CI 2.05-2.72; 2.28, 95%CI 1.98-2.62; and 2.17 95%CI 1.93-2.45 respectively). CONCLUSIONS: As patients with heart or liver disease or metastatic cancer had the highest odds of admission in the last month, collaborative interventions between primary, palliative, and specialty care may improve quality of care at the end of life.

Using Design Thinking to Promote Goals of Care Conversations With Seriously Ill Patients.

BACKGROUND: Goals of care (GOC) conversations can improve serious illness outcomes such as pain and symptom management and patient satisfaction. PROBLEM: However, we recognized that very few Duke Health patients who died had a GOC conversation documented in the designated electronic health record (EHR) tab. Therefore, in 2020, we set a target that all Duke Health patients who died should have had a GOC conversation documented in a designated EHR tab in the last 6 months of life. INTERVENTION: In developing a strategy to promote GOC conversations, we used two interwoven approaches. The first was RE-AIM, a model for designing, reporting and evaluating health behavior research. The second was less of a model than a way of approaching problems, known as "design thinking." OUTCOMES: We employed both of these approaches in a system-wide effort that achieved a 50% prevalence of GOC conversations in the last 6 months of life. KEY MESSAGE: In combination, simple interventions can have a significant impact on behavior change in an academic health system. LESSONS LEARNED: We found that design thinking techniques offered a useful bridge between RE-AIM strategy and clinical.

Clinician Perspectives on Managing Chronic Pain After Curative-Intent Cancer Treatment.

PURPOSE: Among cancer survivors who have completed curative-intent treatment, the high prevalence and adverse consequences of chronic pain are well documented. Yet, research on clinicians' experiences with and perspectives on managing chronic pain among cancer survivors is critically lacking. METHODS: We conducted semistructured interviews with 17 clinicians (six oncology, three palliative care, and eight primary care) affiliated with an academic medical center. Interview questions addressed clinicians' experiences with and perspectives on managing chronic pain (with or without opioid therapy) during the transition from active treatment to survivorship. A multidisciplinary team conducted content analysis of interview transcripts to identify and refine themes related to current practices and challenges in managing chronic pain in this context. RESULTS: Overall, clinicians perceived chronic pain to be relatively uncommon among cancer survivors. Identified challenges included a lack of clarity about which clinician (or clinicians) are best positioned to manage chronic pain among cancer survivors, and (relatedly) complexities introduced by long-term opioid management, with many clinicians describing this practice as outside their skill set. Additionally, although most clinicians recognized chronic pain as a biopsychosocial phenomenon, they described challenges with effectively managing psychosocial stressors, including difficulty accessing mental or behavioral health services for cancer survivors. CONCLUSION: Discovered challenges highlight unmet needs related to cancer survivor-clinician communication about chronic pain and the absence of a chronic pain management home for cancer survivors, including those requiring long-term opioid therapy. Research evaluating routine pain monitoring and accessible, tailored models of multimodal pain care in survivorship may help to address these challenges.

Top Ten Tips Palliative Care Clinicians Should Know About Caring for Chinese American Patients.

The Chinese American population is one of the fastest-growing communities in the United States, composed of ∼5.4 million people, and represents ∼5.5% of overseas Chinese populations. With an expected exponential population rise, Chinese American patients who experience serious illness or approach end-of-life (EOL) may find their cultural values influencing the medical care they receive. Palliative care clinicians must recognize diverse cultural beliefs and preferences of Chinese American patients and their families. In this study, we provide 10 cultural pearls to guide the provision of palliative and EOL care for Chinese American patients, including discussions of Chinese traditions, communication strategies for Chinese patients and families, advance care planning, and EOL care beliefs.

Trajectories of Palliative Care Needs in the ICU and Long-Term Psychological Distress Symptoms.

OBJECTIVES: While palliative care needs are assumed to improve during ICU care, few empiric data exist on need trajectories or their impact on long-term outcomes. We aimed to describe trajectories of palliative care needs during ICU care and to determine if changes in needs over 1 week was associated with similar changes in psychological distress symptoms at 3 months. DESIGN: Prospective cohort study. SETTING: Six adult medical and surgical ICUs. PARTICIPANTS: Patients receiving mechanical ventilation for greater than or equal to 2 days and their family members. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the 13-item Needs at the End-of-Life Screening Tool (NEST; total score range 0-130) completed by family members at baseline, 3, and 7 days. The Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and Post-Traumatic Stress Scale (PTSS) were completed at baseline and 3 months. General linear models were used to estimate differences in distress symptoms by change in need (NEST improvement ≥ 10 points or not). One-hundred fifty-nine family members participated (median age, 54.0 yr [interquartile range (IQR), 44.0-63.0 yr], 125 [78.6%] female, 54 [34.0%] African American). At 7 days, 53 (33%) a serious level of overall need and 35 (22%) ranked greater than or equal to 1 individual need at the highest severity level. NEST scores improved greater than or equal to 10 points in only 47 (30%). Median NEST scores were 22 (IQR, 12-40) at baseline and 19 (IQR, 9-37) at 7 days (change, -2.0; IQR, -11.0 to 5.0; p = 0.12). There were no differences in PHQ-9, GAD-7, or PTSS change scores by change in NEST score (all p > 0.15). CONCLUSIONS: Serious palliative care needs were common and persistent among families during ICU care. Improvement in needs was not associated with less psychological distress at 3 months. Serious needs may be commonly underrecognized in current practice.

Postnatal eye size in mice is controlled by SREBP2-mediated transcriptional repression of Lrp2 and Bmp2.

Eye size is a key parameter of visual function, but the precise mechanisms of eye size control remain poorly understood. Here, we discovered that the lipogenic transcription factor sterol regulatory element-binding protein 2 (SREBP2) has an unanticipated function in the retinal pigment epithelium (RPE) to promote eye size in postnatal mice. SREBP2 transcriptionally represses low density lipoprotein receptor-related protein 2 (Lrp2), which has been shown to restrict eye overgrowth. Bone morphogenetic protein 2 (BMP2) is the downstream effector of Srebp2 and Lrp2, and Bmp2 is suppressed by SREBP2 transcriptionally but activated by Lrp2. During postnatal development, SREBP2 protein expression in the RPE decreases whereas that of Lrp2 and Bmp2 increases as the eye growth rate reduces. Bmp2 is the key determinant of eye size such that its level in mouse RPE inversely correlates with eye size. Notably, RPE-specific Bmp2 overexpression by adeno-associated virus effectively prevents the phenotypes caused by Lrp2 knock out. Together, our study shows that rapid postnatal eye size increase is governed by an RPE-derived signaling pathway, which consists of both positive and negative regulators of eye growth.

FOXO3-dependent suppression of PD-L1 promotes anticancer immune responses via activation of natural killer cells.

Boosting anticancer immunity by blocking immune checkpoints such as the programmed death-1 (PD-1) or its ligand (PD-L1) is a breakthrough anticancer therapy. However, many cancer patients do not respond well to immune checkpoint blockades (ICBs) alone. Here we show that low-dose pharmacological immunoactivators (e.g., SN38, topotecan, sorafenib, etc.) notably downregulate PD-L1 and upregulate FOXO3 expression in various human and murine cancer cell lines. In a mouse tumor model, low-dose SN38 treatment markedly suppresses tumor growth, reduces PD-L1 expression, and enhances FOXO3 expression in primary tumor specimens. SN38 therapy engages the tumor-infiltrating mouse NK1.1/CD49b/NKG2D-positive natural killer (NK) cells to attack tumor cells by inducing mouse IFN-γ and granzyme-B secretion in the tumor microenvironment (TME) in vivo. SN38 treatment also promotes tumor cell apoptosis in the TME. SN38 treatment significantly decreases STAT3-pY705 and IL-6 protein levels; FOXO3 is essential for SN38-mediated PD-L1 downregulation. Collectively, these findings may contribute to future translational or clinical investigations tackling difficult-to-treat cancers with immune-activating medicines or combined with ICB immunotherapy.

Promoting timely goals of care conversations between gynecologic cancer patients at high-risk of death and their providers.

OBJECTIVE: We designed a multi-faceted intervention to increase the rate of outpatient goals of care (GOC) conversations in women with gynecologic cancers who are at high-risk of death. METHODS AND MATERIALS: A multidisciplinary team developed an educational program around GOC conversations at end-of-life and chose criteria to prospectively identify patients at high-risk of death who might benefit from timely GOC conversations: recurrent or metastatic endometrial, cervical or vulvar cancer or platinum-resistant ovarian cancer. Gynecologic oncology provider consensus was built regarding the need to improve the quality and timing of GOC conversations. Eligible outpatients were prospectively identified and providers alerted pre-encounter; timely GOC documentation within 3 visits of high-risk identification was tracked. Our institution concurrently and subsequently tracked GOC documentation during the last 6 months of life among all established oncology patients. RESULTS: Of 220 pilot period high-risk patients (96 pre- and 124 during pilot period 2017-2018), timely GOC discussion documentation increased from 30.2% to 88.7% (p < 0.001) and this increase was sustained over time. In the post-pilot period (2019-2020), among patients seen by oncologists during last 6 months of life, compared to other cancer types, gynecologic cancer patients had a higher rate of GOC documentation (81% versus 9%; p < 0.001), a lower rate of receiving chemotherapy during the last 14 days of life (2% vs 5%; p = 0.051), and no difference in end-of-life admissions (29% vs 31%; p = NS). CONCLUSIONS: Implementation of systematic outpatient identification of high-risk gynecologic oncology patients is feasible, sustainable, and increases the timely conduct of GOC conversations.

Early Palliative Care Consultation in the Medical ICU: A Cluster Randomized Crossover Trial.

OBJECTIVES: To assess the impact of early triggered palliative care consultation on the outcomes of high-risk ICU patients. DESIGN: Single-center cluster randomized crossover trial. SETTING: Two medical ICUs at Barnes Jewish Hospital. PATIENTS: Patients (n = 199) admitted to the medical ICUs from August 2017 to May 2018 with a positive palliative care screen indicating high risk for morbidity or mortality. INTERVENTIONS: The medical ICUs were randomized to intervention or usual care followed by washout and crossover, with independent assignment of patients to each ICU at admission. Intervention arm patients received a palliative care consultation from an interprofessional team led by board-certified palliative care providers within 48 hours of ICU admission. MEASUREMENTS AND MAIN RESULTS: Ninety-seven patients (48.7%) were assigned to the intervention and 102 (51.3%) to usual care. Transition to do-not-resuscitate/do-not-intubate occurred earlier and significantly more often in the intervention group than the control group (50.5% vs 23.4%; p < 0.0001). The intervention group had significantly more transfers to hospice care (18.6% vs 4.9%; p < 0.01) with fewer ventilator days (median 4 vs 6 d; p < 0.05), tracheostomies performed (1% vs 7.8%; p < 0.05), and postdischarge emergency department visits and/or readmissions (17.3% vs 38.9%; p < 0.01). Although total operating cost was not significantly different, medical ICU (p < 0.01) and pharmacy (p < 0.05) operating costs were significantly lower in the intervention group. There was no significant difference in ICU length of stay (median 5 vs 5.5 d), hospital length of stay (median 10 vs 11 d), in-hospital mortality (22.6% vs 29.4%), or 30-day mortality between groups (35.1% vs 36.3%) (p > 0.05). CONCLUSIONS: Early triggered palliative care consultation was associated with greater transition to do-not-resuscitate/do-not-intubate and to hospice care, as well as decreased ICU and post-ICU healthcare resource utilization. Our study suggests that routine palliative care consultation may positively impact the care of high risk, critically ill patients.

Development of a Novel Quinoline Derivative as a P-Glycoprotein Inhibitor to Reverse Multidrug Resistance in Cancer Cells.

Multidrug resistance (MDR) is one of conventional cancer chemotherapy's limitations. Our group previously synthesized a series of quinoline-based compounds in an attempt to identify novel anticancer agents. With a molecular docking analysis, the novel compound 160a was predicted to target p-glycoprotein, an MDR candidate. The purpose of this study is to evaluate 160a's MDR reversal effect and investigate the underlying mechanism at the molecular level. To investigate 160a's inhibitory effect, we used a series of parental cancer cell lines (A549, LCC6, KYSE150, and MCF-7), the corresponding doxorubicin-resistant cell lines, an MTS cytotoxicity assay, an intracellular doxorubicin accumulation test, and multidrug resistance assays. The Compusyn program confirmed, with a combination index (CI) value greater than 1, that 160a combined with doxorubicin exerts a synergistic effect. Intracellular doxorubicin accumulation and transported calcein acetoxymethyl (AM) (a substrate for p-glycoprotein) were both increased when cancer cells with MDR were treated with compound 160a. We also showed that compound 160a's MDR reversal effect can persist for at least 1 h. Taken together, these results suggest that the quinoline compound 160a possesses high potential to reverse MDR by inhibiting p-glycoprotein-mediated drug efflux in cancer cells with MDR.

Targeting DNA Binding for NF-κB as an Anticancer Approach in Hepatocellular Carcinoma.

Quinoline core has been shown to possess a promising role in the development of anticancer agents. However, the correlation between its broad spectrum of bioactivity and the underlying mechanism of actions is poorly understood. The present study, with the use of bioinformatics approaches, reported a series of designed molecules which integrated quinoline core and sulfonyl moiety, with the objective of evaluating the substituent and linker effects on anticancer activities and associated mechanistic targets. We identified potent compounds (1h, 2h, 5 and 8) exhibiting significant anticancer effects towards liver cancer cells (Hep3B) with the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) relative values of cytotoxicity below 0.40, a value in the range of doxorubicin positive control with the value of 0.12. Bulky substituents and the presence of bromine atom, as well as the presence of sulfonamide linkage, are likely the favorable structural components for molecules exerting a strong anticancer effect. To the best of our knowledge, our findings obtained from chemical synthesis, in vitro cytotoxicity, bioinformatics-based molecular docking analysis (similarity ensemble approach, SEA),and electrophoretic mobility shift assay provided the first evidence in correlation to the anticancer activities of the selected compound 5 with the modulation on the binding of transcription factor NF-κB to its target DNA. Accordingly, compound 5 represented a lead structure for the development of quinoline-based NF-κB inhibitors and this work added novel information on the understanding of the mechanism of action for bioactive sulfonyl-containing quinoline compounds against hepatocellular carcinoma.

Pharmacological activation of FOXO3 suppresses triple-negative breast cancer in vitro and in vivo.

Triple-negative breast cancer (TNBC) is the most lethal form of breast cancer. Lacking effective therapeutic options hinders treatment of TNBC. Here, we show that bepridil (BPD) and trifluoperazine (TFP), which are FDA-approved drugs for treatment of schizophrenia and angina respectively, inhibit Akt-pS473 phosphorylation and promote FOXO3 nuclear localization and activation in TNBC cells. BPD and TFP inhibit survival and proliferation in TNBC cells and suppress the growth of TNBC tumors, whereas silencing FOXO3 reduces the BPD- and TFP-mediated suppression of survival in TNBC cells. While BPD and TFP decrease the expression of oncogenic c-Myc, KLF5, and dopamine receptor DRD2 in TNBC cells, silencing FOXO3 diminishes BPD- and TFP-mediated repression of the expression of these proteins in TNBC cells. Since c-Myc, KLF5, and DRD2 have been suggested to increase cancer stem cell-like populations in various tumors, reducing these proteins in response to BPD and TFP suggests a novel FOXO3-dependent mechanism underlying BPD- and TFP-induced apoptosis in TNBC cells.

Clinical Implications of Noncaseating Granulomas on Histology in Patients with Ileal Pouches.

BACKGROUND: Granulomas are occasionally detected on biopsy specimen of the ileal pouch and their clinical implications are not clear. The aim of this study was to evaluate clinical implications of noncaseating granuloma on histology in patients with ileal pouches. METHODS: All eligible patients with confirmed noncaseating granulomas on histology of the biopsy specimens of the pouch body, afferent limb, or cuff in our prospectively maintained Pouch Registry between 2002 and 2014 were evaluated. Demographic and clinical factors were analyzed. The disease course of those patients was evaluated. RESULTS: Of 1564 patients in the Registry, 42 met the criteria and were included. The median duration from the pouch construction to the last visit was 9 years (range, 2-28 yr). Twenty-eight patients (66.7%) developed clinical Crohn's disease (CD) of the pouch, whereas 14 (33.3%) were classified as having histologic CD of the pouch. Six patients (21.4%) in the clinical CD of the pouch group and 4 (28.6%) in the histologic CD of the pouch group had granulomas on more than 1 endoscopy. Postoperative biological therapy was administered more in the clinical CD group than in the histologic CD group (39.3% versus 0%, P = 0.007). Pouch-related fistulae and presacral sinus were verified more in clinical CD group than the histologic CD group. However, Kaplan-Meier plot showed comparable pouch survival between clinical CD and histologic CD groups. CONCLUSIONS: In our current study, one-third of the patients with noncaseating pouch granulomas did not develop clinical CD of the pouch. With proper medical therapy, long-term pouch outcomes appeared to be similar in those patients with clinical CD or histologic CD of the pouch.

Prediction of need for surgery after endoscopic balloon dilation of ileocolic anastomotic stricture in patients with Crohn's disease.

BACKGROUND: Endoscopic balloon dilation is used to treat ileocolic anastomotic stricture attributed to recurrent Crohn's disease. OBJECTIVE: The purpose of this work was to investigate long-term outcomes after dilation of ileocolic anastomotic stricture and to identify risk factors associated with the need for subsequent surgical intervention. DESIGN: This was a retrospective study based on chart review of an electronic medical chart system. SETTINGS: The study was conducted at a tertiary care center. PATIENTS: All of the eligible patients with ileocolic anastomotic stricture attributed to recurrent Crohn's disease treated with endoscopic dilation between December 1998 and May 2013 were evaluated. Patients with concurrent enterocutaneous fistula or abdominal or pelvic abscess were excluded. MAIN OUTCOME MEASURES: The main outcome measure was the need for subsequent salvage surgery because of stricture-related symptoms. RESULTS: A total of 185 patients with Crohn's disease (45.9% women; mean age, 43.1 years; symptomatic strictures in 80%) underwent 462 endoscopic dilations of ileocolic anastomosis (median per-patient dilations, 2; range, 1-3). During a mean follow-up of 3.9 years, 27 patients (14.6%) required hospitalization without surgery for stricture-related symptoms, and 66 patients (35.7%) required subsequent salvage surgery. Specific medical management, type of anastomosis, and endoscopic intralesional steroid injection had no impact on the risk of needing surgery. Significant factors associated with the need for surgery on multivariable analysis were symptomatic disease (HR, 3.54 [95% CI, 1.41-8.93]), longer time interval from last surgery (HR, 1.05 [95% CI, 1.01-1.10]), and radiographic proximal bowel dilation (HR, 2.36 [95% CI, 1.38-4.03]). A nomogram estimating the need for surgery was created with a concordance index of 0.67. LIMITATIONS: The study was limited by its retrospective design. CONCLUSIONS: Although endoscopic dilation is a valid option for ileocolic anastomotic stricture attributed to recurrent Crohn's disease, the need for surgery is common. The nomogram can identify patients who might benefit from upfront surgery.

Successful endoscopic treatment of fecalith blocking sinus in a patient with ileal pouch-anal anastomosis / Tratamento endoscópico bem-sucedido de fecálito bloqueando seio em paciente com anastomose bolsa ileal-anal

Background: Ulcerative colitis patients who underwent restorative proctocolectomy with ileal pouch-anal anastomosis can develop various mechanical complications. Among them is presacral sinus resulting from chronic anastomotic leak. Methods: We present a symptomatic patient with a large fecalith blocking the sinus which was successfully treated with Doppler ultrasound guided endoscopic needle knife sinusotomy along with fecalith extraction. Results: A 67-year-old female presented with a 4-month history of perianal pain and urgency. Pouchocopy showed a 3-cm deep wide-mouthed anastomotic sinus, the orifice of which was blocked by a large hard fecalith. Removal of the fecalith using RothNet, Tripod, or Basket were made but failed. Then needle knife was applied to cut the orifice to enlarge the opening of the sinus. One month later, the patient returned and the fecalith was successfully removed with two Baskets and two Rothnets. Six months after fecalith extraction, pouchoscopy showed a compartalized distal pouch sinus with two cavities, which was treated by two sessions of Doppler ultrasound guided endoscopic needle knife sinusotomy. Six months following the treatment, the sinus was completed healed. The patient tolerated all procedures well without any complication. Conclusion: Fecalith blocking pouch anastomotic sinus is a rare complication in patients with restorative proctocolectomy. In our case, this surgical complication was successfully treated with a carefully planned, stepwise endoscopy approach. (AU)

Experiênria: Pacientes com colite ulcerativa tratados por proctocolectomia restauradora com anastomose bolsa ileal-anal podem ser acometidos por diversas complicações mecânicas. Entre elas, cita-se o seio pré-sacral resultante de vazamento crônico pela anastomose. Métodos: Apresentamos uma paciente sintomática com um grande fecálito bloqueando o seio, com tratamento bem-sucedido com sinusotomia por bisturi-agulha guiado por ultrassom, juntamente com a extração do fecálito. Resultados: Mulher, 67 anos, apresentou-se com história de 4 meses de dor perianal e urgência. A avaliação endoscópica da bolsa ileal revelou um seio anastomótico com grande abertura situada a 3 cm de profundidade, cujo orifício estava bloqueado por um grande fecálito endurecido. Foi tentada sem sucesso a remoção do fecálito com a ajuda de Roth-Net, Tripod, ou cestos recuperadores. Depois dessas tentativas, aplicamos um bisturi-agulha com o objetivo de seccionar o orifício com vistas à ampliação da abertura do seio. Um mês depois, a paciente retornou, e o fecálito foi removido com sucesso com dois cestos recuperadores e dois RothNets. Transcorridos seis meses após a remoção do fecálito, uma avaliação endoscópica da bolsa ileal revelou um seio distal compartimentado com duas cavidades, tratado por duas sessões de sinusotomia endoscópica por bisturi-agulha guiado por ultrassom. Seis meses depois do tratamento, o seio estava completamente curado. A paciente tolerou satisfatoriamente todos os procedimentos, sem qualquer complicação. Conclusão: A presença de um fecálito bloqueando o seio anastomótico de bolsa ileal é complicação rara em pacientes submetidos a uma proctocolectomia restauradora. Em nosso caso, essa complicação cirúrgica foi tratada com sucesso com uma abordagem endoscópica em etapas, cuidadosamente planejada. (AU)

Reprogramming ovarian and breast cancer cells into non-cancerous cells by low-dose metformin or SN-38 through FOXO3 activation.

Cancer is a leading cause of death worldwide. Because the cytotoxic effects of conventional chemotherapies often harm normal tissue cells along with cancer cells, conventional chemotherapies cause many unwanted or intolerable side effects. Thus, there is an unmet medical need to establish a paradigm of chemotherapy-induced differentiation of cancer cells with tolerable side effects. Here we show that low-dose metformin or SN-38 inhibits cell growth or survival in ovarian and breast cancer cells and suppresses their tumor growth in vivo. Low-dose metformin or SN-38 increases FOXO3 nuclear localization as well as the amount of DNA damage markers and downregulates the expression of a cancer-stemness marker CD44 and other stemness markers, including Nanog, Oct-4, and c-Myc, in these cancer cells. This treatment also inhibits spheroid body-formation in 3-dimensional culture. In contrast, silencing FOXO3 diminishes all these cellular events when ovarian/breast cancer cells are treated with the mentioned drugs. These results suggest that low-dose metformin or SN-38 may reprogram these cancer cells into non-cancerous cells in a FOXO3-dependent manner, and may allow patients to overcome these cancers with minimal side effects.

Birth cohort screening for chronic hepatitis during colonoscopy appointments.

OBJECTIVES: More than 70% of infections with hepatitis C viruses (HCV) occur among people born between 1945 and 1965 (baby boomers). The US Centers for Disease Control estimate that 70% of people with chronic hepatitis are not aware that they are infected with a virus. We performed a prospective trial to determine whether people born during this time period would accept testing for chronic viral infection (hepatitis B virus (HBV) and HCV) during routine colonoscopies. We also evaluated acceptance and efficacy of screening for immunity to hepatitis A (HAV) and B viruses. METHODS: During a 3-month period, 500 people, 50-65 years old, who received a colonoscopy were offered a test for viral hepatitis. Patients answered questions about vaccination, exposure, diagnoses, and risk factors related to viral hepatitis, and blood samples were collected. Patients who tested positive for antibodies to HCV or hepatitis B surface antigen (HBsAg) were contacted for further testing and possible therapy. Patients without immunity to HAV or HBV were offered vaccinations. RESULTS: Three hundred and seventy-six people (158 men) agreed to be tested. Four were found to have antibodies against HCV and one had detectable virus. None of the patients tested positive for HBsAg; 136 (36%) had at least one risk factor for chronic hepatitis and 31 (8%) had multiple risk factors. Three hundred and fifteen patients (84%) were not immune to HAV, HBV, or both viruses. CONCLUSIONS: It is possible to screen patients for viral hepatitis during visits for routine colonoscopy. This approach can identify individuals with undiagnosed chronic HBV and HCV infections who could benefit from education, vaccination, or therapy.

The use of lipid-lowering therapy for secondary prevention in patients undergoing percutaneous coronary intervention.

BACKGROUND: Recent literature suggests that lipid-lowering therapy may have an early beneficial effect among patients undergoing percutaneous coronary intervention (PCI) because the therapy decreases cardiac mortality, morbidity and possibly restenosis. OBJECTIVE: The primary objective of the present study was to determine the proportion of PCI patients receiving lipid-lowering therapy at a large, tertiary-care referral centre. METHODS: Patients undergoing a first PCI between August 2000 and August 2002 with corresponding inpatient medication information were included in the study. Patient demographics, procedural variables, and lipid-lowering and other evidence-based cardiac medication data were collected. A multiple logistical regression model was constructed to evaluate the factors associated with the use of lipid-lowering therapy. RESULTS: Of the 3254 cases included in the analyses, 52% were elective, 44% were urgent or salvage, and 4% were emergent. The mean patient age was 63 years, and 73% of patients were male. Over 76% of patients were receiving lipid-lowering therapy at the time of PCI. Patient use of other medications was as follows: acetylsalicylic acid in 96%, beta-blocker in 80% and angiotensin-converting enzyme inhibitor in 59%. In the multiple regression analysis, variables significantly associated with lipid-lowering therapy use included hypercholesterolemia, beta-blocker use, angiotensin-converting enzyme inhibitor use, case urgency, prior coronary artery bypass graft surgery, age and sex. CONCLUSION: Lipid-lowering therapy use rates exceeded those previously reported in the literature. Women and patients undergoing elective procedures appear to be treated less often with lipid-lowering therapy. There remains an opportunity to further optimize use in this high-risk cohort at time of PCI.