Avoiding the needle: A quality improvement program introducing apixaban for extended thromboprophylaxis after major gynecologic cancer surgery.

OBJECTIVE: Patients undergoing gynecologic cancer surgery at our centre are recommended up to 28 days of enoxaparin for extended post-operative thromboprophylaxis (EP). Baseline survey revealed 92% patient adherence, but highlighted negative effects on patient experience due to the injectable route of administration. We aimed to improve patient experience by reducing pain and bruising by 50%, increasing adherence by 5%, and reducing out-of-pocket cost after introducing apixaban as an oral alternative for EP. METHODS: In this interrupted time series quality improvement study, gynecologic cancer patients were offered a choice between apixaban (2.5 mg orally twice daily) or enoxaparin (40 mg subcutaneously once daily) at time of discharge. A multidisciplinary team informed project design, implementation, and evaluation. Process interventions included standardized orders, patient and care team education programs. Telephone survey at 1 and 6 weeks and chart audit informed outcome, process, and balancing measures. RESULTS: From August to October 2022, 127 consecutive patients were included. Apixaban was chosen by 84%. Survey response rate was 74%. Patients who chose apixaban reported significantly reduced pain, bruising, increased confidence with administration, and less negative impact of the medication (p < 0.0001 for all). Adherence was unchanged (92%). The proportion of patients paying less than $125 (apixaban cost threshold) increased from 45% to 91%. There was no difference in bleeding and no VTE events. CONCLUSIONS: Introduction of apixaban for EP was associated with significant improvement in patient-reported quality measures and reduced financial toxicity with no effect on adherence or balancing measures. Apixaban is the preferred anticoagulant for EP at our centre.

Evaluating equity of access and predictors of minimally invasive hysterectomy for endometrial and cervical cancer from 2000 to 2017 in Ontario, Canada: A population-based cohort study.

INTRODUCTION: We sought to assess the uptake of minimally invasive hysterectomy among patients with endometrial and cervical cancer in Ontario, Canada, and assess the equity of access to minimally invasive surgery (MIS) by evaluating associations with patient, disease, institutional, and provider factors. METHODS: This is a retrospective population-based cohort study of hysterectomy for endometrial and cervical cancer in Ontario (2000-2017). Surgical approach, clinicopathologic, sociodemographic, institutional, and provider factors were identified through administrative databases. Fisher's exact, χ2 , Wilcoxon rank sum, logistic regression, and Cox proportional hazards modeling were used to explore factors associated with MIS. RESULTS: A total of 27 652 patients were included. In total, 6199/24 264 (26%) endometrial and 842/3388 (25%) cervical cancer patients received MIS. The proportion of MIS to open surgeries increased from <0.1% in 2000 to over 55% in 2017 (odds ratio [OR] = 1.31, confidence interval [CI] = 1.28-1.34). Low-income quintile, rurality, low hospital volume, nonacademic hospital, nongynecologic oncology surgeon, and earlier year of surgeon graduation were associated with reduced odds of MIS (OR < 1). CONCLUSIONS: The uptake of MIS hysterectomy increased steadily over the time period. Receipt of MIS is dependent upon multiple social determinants, provider variables, and systems factors. These disparities raise concern for health equity in Ontario and have significant implications for health systems planning and resource allocation.

A double-blinded, randomized trial comparing surgeon-administered transversus abdominis plane block with placebo after midline laparotomy in gynecologic oncology surgery.

BACKGROUND: Surgeon-administered transversus abdominis plane block is a contemporary approach to providing postoperative analgesia, and this approach is performed by transperitoneally administering local anesthetic in the plane between the internal oblique and transversus abdominis muscles to target the sensory nerves of the anterolateral abdominal wall. Although this technique is used in many centers, it has not been studied prospectively in patients undergoing a midline laparotomy. OBJECTIVE: This study aimed to evaluate whether surgeon-administered transversus abdominis plane block reduces postoperative opioid requirements and improves clinical outcomes. STUDY DESIGN: In this double-blind, randomized, placebo-controlled trial, patients with a suspected or proven gynecologic malignancy undergoing surgery through a midline laparotomy at 1 Canadian tertiary academic center were randomized to either the bupivacaine group (surgeon-administered transversus abdominis plane blocks with 40 mL of 0.25% bupivacaine) or the placebo group (surgeon-administered transversus abdominis plane blocks with 40 mL of normal saline solution) before fascial closure. The primary outcome was the total dose of opioids (in morphine milligram equivalents) received in the first 24 hours after surgery. The secondary outcomes included opioid doses between 24 and 48 hours, pain scores, postoperative nausea and vomiting, incidence of clinical ileus, time to flatus, and hospital length of stay. The exclusion criteria included contraindications to study medication, history of chronic opioid use, significant adhesions on the anterior abdominal wall preventing access to the injection site, concurrent nonabdominal surgical procedure, and the planned use of neuraxial anesthesia or analgesia. To detect a 20% decrease in opioid requirements with a 2-sided type 1 error of 5% and power of 80%, a sample size of 36 patients per group was calculated. RESULTS: From October 2020 to November 2021, 38 patients were randomized to the bupivacaine arm, and 41 patients were randomized to the placebo arm. The mean age was 60 years, and the mean body mass index was 29.3. A supraumbilical incision was used in 30 of 79 cases (38.0%), and bowel resection was performed in 10 of 79 cases (12.7%). Patient and surgical characteristics were evenly distributed. The patients in the bupivacaine group required 98.0±59.2 morphine milligram equivalents in the first 24 hours after surgery, whereas the patients in the placebo group required 100.8±44.0 morphine milligram equivalents (P=.85). The mean pain score at 4 hours after surgery was 3.1±2.4 (0-10 scale) in the intervention group vs 3.1±2.0 in the placebo group (P=.93). Clinically significant nausea or vomiting was reported in 1 of 38 patients (2.6%) in the intervention group vs 1 of 41 patients (2.4%) in the placebo group (P=.95). Time to first flatus, rates of clinical ileus, and length of stay were similar between groups. Subgroup analysis of patients with a body mass index of <25 and patients who received an infraumbilical incision showed similarly comparable outcomes. CONCLUSION: Surgeon-administered transversus abdominis plane block with bupivacaine was not found to be superior to the placebo intervention in reducing postoperative opioid requirements or improving other postoperative outcomes for patients undergoing a midline laparotomy. These results differed from previous reports evaluating the ultrasound-guided transversus abdominis plane block approach. Surgeon-administered transversus abdominis plane block should not be considered standard of care in postoperative multimodal analgesia.

Evaluating compliance of extended venous thromboembolism prophylaxis following abdominopelvic surgery for cancer: A multidisciplinary quality improvement project.

BACKGROUND AND OBJECTIVES: Despite quality evidence supporting postoperative extended venous thromboembolism prophylaxis (eVTEp) following abdominopelvic cancer surgery, baseline use of eVTEp at our institution was 3%. Our project aim was to improve the proportion of patients prescribed eVTEp following surgery for gynecologic, hepatobiliary, and colorectal cancers by a 30% absolute increase. METHODS: We performed an interrupted time series study using quality improvement methodology. Postoperative order sets, pre-printed prescriptions, process checklists, and multimodal education were introduced. Process and outcome data were collected and analyzed on statistical process control charts. RESULTS: We included 324 patients with gynecologic and hepatobiliary cancers. Despite efforts to include them, the colorectal team did not participate. The monthly mean order set-use was 58% (SD = 14%), by specialty: gynecology 79%, hepatobiliary 47%. The proportion of patients prescribed eVTEp increased from 3% to 70% (SD = 14%). The target goal was surpassed and sustained by both cohorts. Patient compliance was 73% (n = 117/160, SD = 16%). Of those who stopped eVTEp early, 45% (n = 14/31) objected because of the injectable nature. Bleeding events were infrequent (0.6%, n = 2/324). CONCLUSIONS: Three process changes and multimodal education resulted in a significant increase in eVTEp use. Failure to identify improvement champions limited project expansion to colorectal patients. Patient compliance was largely limited by the injectable nature of the medication.

The Use of Patient-Reported Outcome Measures in Phase I Oncology Clinical Trials.

OBJECTIVE: To investigate patient-reported outcome (PRO) usage in phase I oncology clinical trials, including types of PRO measures and changes over time. METHODS: We analyzed ClinicalTrials.gov records of phase I oncology clinical trials completed by December 2019. RESULTS: Of all eligible trials, 2.3% (129/5,515) reported ≥1 PRO, totaling 181 instances of PRO usage. PRO usage increased over time, from 0.6% (trials initiated before 2000) to 3.4% (trials starting between 2015 and 2019). The most common PRO measures were unspecified (29%), tumor-specific (24%), and generic cancer (19%). CONCLUSION: Although uncommon in phase I oncology clinical trials, PRO usage is increasing over time. PRO measures were often unspecified on ClinicalTrials.gov, suggesting that more precise reporting and standardization are needed.

A pneumococcal pneumonia and influenza vaccination quality improvement program for women receiving chemotherapy for gynecologic cancers at a major tertiary cancer Centre.

OBJECTIVE: International guidelines recommend pneumococcal pneumonia and influenza vaccination for all patients with solid organ malignancies prior to initiating chemotherapy. Baseline vaccination rates (March 2019) for pneumococcal pneumonia and influenza at our tertiary cancer centre were 8% and 40%, respectively. The aim of this study was to increase the number of gynecologic chemotherapy patients receiving pneumococcal and influenza vaccinations to 80% by March 2020. METHODS: We performed an interrupted time series study using structured quality improvement methodology. Three interventions were introduced to address vaccination barriers: an in-house vaccination program, a staff education campaign, and a patient care bundle (pre-printed prescription, information brochure, vaccine record booklet). Process and outcome data were collected by patient survey and pharmacy audit and analyzed on statistical process control charts. RESULTS: We identified 195 eligible patients. Pneumococcal and influenza vaccination rates rose significantly from 5% to a monthly mean of 61% and from 36% to a monthly mean of 67%, respectively. The 80% target was reached for both vaccines during one or more months of study. The in-house vaccination and staff education programs were major contributors to the improvement, whereas the information brochure and record booklet were minor contributors. CONCLUSIONS: Three interventions to promote pneumococcal and influenza vaccination among chemotherapy patients resulted in significantly improved vaccination rates. Lessons learned about promoting vaccine uptake may be generalizable to different populations and vaccine types. In response to the global COVID-19 pandemic, initiatives to expand the program to all chemotherapy patients at our centre are underway.

Race and ethnicity representation in clinical trials: findings from a literature review of Phase I oncology trials.

Aim: To provide an assessment of published literature on the demographic representation in Phase I trials of biopharmaceutical oncology agents. Materials & methods: We conducted a rapid evidence assessment to identify demographic representation reported in Phase I clinical trials for biopharmaceutical oncology agents published in 2019. Results: Globally, the population was predominantly White/Caucasian (62.2%). In the USA, the distribution was heavily skewed toward White/Caucasian (84.2%), with minimal representation of Blacks/African-Americans (7.3%), Asians (3.4%), Hispanics/Latinos (2.8%) or other race/ethnicity groups. Conclusion: Our data highlight that Phase I oncology trials do not reflect the population at large, which may perpetuate health disparities. Further research is needed to understand and address barriers to participation, particularly among under-represented groups.

Lay abstract A plain language version of this article is available and is published alongside the paper online: www.futuremedicine.com/doi/suppl/10.2217/fon-2020-1262.

Thirty-day outcomes after gynecologic oncology surgery: A single-center experience of enhanced recovery after surgery pathways.

INTRODUCTION: The purpose of the study is to evaluate the impact of an enhanced recovery after surgery (ERAS) program implemented in a Gynecologic Oncology population undergoing a laparotomy at a Canadian tertiary care center. MATERIAL AND METHODS: Prospectively collected data, using the American College of Surgeons' National Surgical Quality Improvement Program dataset (ACS NSQIP), was used to compare 30-day postoperative outcomes of gynecologic oncology patients undergoing a laparotomy before and after the 2018 implementation of an ERAS program in a Canadian regional cancer center. Patient demographics, surgical variables and postoperative outcomes of 187 patients undergoing surgery in 2019 were compared with those of 441 patients undergoing surgery between January 2016 and December 2017. Student's t, Mann-Whitney U and Chi-square tests, as well as multivariate linear and logistic regressions were used to evaluate baseline characteristics and 30-day postoperative complications. RESULTS: Length of stay was significantly shortened in the study population after introducing the ERAS protocol, from a mean of 4.7 (SD = 3.8) days to a mean of 3.8 (SD = 3.2) days (P = .0001). The overall complication rate decreased from 24.3% to 16% (P = .02). Significant decreases in the rates of postoperative infections (adjusted odds ratio [OR] 0.56, 95% confidence interval [CI] 0.31-0.99) and cardiovascular complications (adjusted OR 0.27, 95% CI 0.09-0.79) were noted, without a significant increase in readmission rate (adjusted OR 0.50, 95% CI 0.21-1.07). CONCLUSIONS: Introducing an ERAS program for gynecologic oncology patients undergoing laparotomy was effective in shortening length of stay and the overall complication rate without a significant increase in readmission. Advocacy for broader implementation of ERAS among gynecologic oncology services and ongoing discussion on challenges and opportunities in the implementation process are warranted to improve patient outcomes and experiences.

Well-Differentiated Papillary Mesothelioma With Two Synchronous Serous Gynaecologic Carcinomas in a 62-Year-Old Woman: Lessons Learned for the Gynaecologic Surgeon.

BACKGROUND: Well-differentiated papillary mesothelioma (WDPM) is a rare tumor of unknown malignant potential. It is typically diagnosed incidentally during benign gynaecologic surgery. We report the first published case of WDPM in a woman with synchronous serous carcinomas of the gynaecologic tract and highlight lessons learned for general gynaecologists and gynaecologic oncologists alike. CASE: A 62-year-old woman was referred for assessment and management of a pelvic mass. Intraoperatively, metastatic high-grade carcinoma was identified and the patient underwent a successful debulking procedure that identified 3 synchronous tumors: ovarian high-grade serous carcinoma, endometrial serous carcinoma, and 2 foci of pelvic WDPM. CONCLUSION: This case of WDPM with 2 synchronous serous gynaecologic tumors is a novel addition to the reported literature and offers many learning points about the disease. Gynaecologic surgeons should be familiar with WDPM, as it is predominantly found in reproductive-aged women undergoing benign gynaecologic surgery, may be linked with endometriosis, and has an unclear malignant potential. Multidisciplinary care is essential for accurate diagnosis. Further research is needed to clarify the optimal management and surveillance of WDPM.

Internal Iliac Artery Balloon Tamponade in Placenta Accreta: Outcomes From the Largest Tertiary Accreta Referral Centre in British Columbia.

OBJECTIVE: Placenta accreta syndromes are well-recognized risk factors for severe postpartum hemorrhage and are associated with significant maternal morbidity. Internal iliac artery balloon tamponade is an adjunctive procedure used to reduce blood loss at the time of Caesarean hysterectomy with variable results in the reported literature. This study investigated the outcomes of preoperative balloon tamponade at the largest tertiary referral centre for placenta accreta in British Columbia. METHODS: Women treated with Caesarean hysterectomy for histologically confirmed placenta accreta from 2003 to 2015 were identified through medical records. A retrospective cohort study was performed after categorizing patients by receipt of internal iliac artery balloon tamponade. Statistically significant differences in clinical variables were assessed using Fisher exact and Mann-Whitney tests. RESULTS: The study population included 24 women. There was no significant difference in the primary outcomes of estimated blood loss or number of units of blood products transfused. Among emergency cases (n = 16), there was a significant reduction in the total number of blood products transfused (3.5 units vs. 15 units, P = 0.04). Operative (P = 0.003) and anaesthetic (P = 0.0001) times were longer among those women undergoing balloon tamponade. There were no differences in intensive care unit admission, length of stay, disseminated intravascular coagulation, or operative morbidity. CONCLUSION: Internal iliac artery balloon tamponade decreases blood transfusion requirements among women requiring emergency Caesarean hysterectomy for placenta accreta. Balloon insertion in the operating room may be an important factor in ensuring efficacy of this procedure. Further studies are required to clarify the potential benefits of balloon tamponade in the elective setting.

Treatment of patients waitlisted for liver transplant with all-oral direct-acting antivirals is a cost-effective treatment strategy in the United States.

All-oral direct acting antivirals (DAAs) have been shown to have high safety and efficacy in treating patients with hepatitis C virus (HCV) awaiting liver transplant (LT). However, there is limited empirical evidence comparing the health and economic outcomes associated with treating patients pre-LT versus post-LT. The objective of this study was to analyze the cost-effectiveness of pre-LT versus post-LT treatment with an all-oral DAA regimen among HCV patients with hepatocellular carcinoma (HCC) or decompensated cirrhosis (DCC). We constructed decision-analytic Markov models of the natural disease progression of HCV in HCC patients and DCC patients waitlisted for LT. The model followed hypothetical cohorts of 1,000 patients with a mean age of 50 over a 30-year time horizon from a third-party US payer perspective and estimated their health and cost outcomes based on pre-LT versus post-LT treatment with an all-oral DAA regimen. Transition probabilities and utilities were based on the literature and hepatologist consensus. Sustained virological response rates were sourced from ASTRAL-4, SOLAR-1, and SOLAR-2. Costs were sourced from RedBook, Medicare fee schedules, and published literature. In the HCC analysis, the pre-LT treatment strategy resulted in 11.48 per-patient quality-adjusted life years and $365,948 per patient lifetime costs versus 10.39 and $283,696, respectively, in the post-LT arm. In the DCC analysis, the pre-LT treatment strategy resulted in 9.27 per-patient quality-adjusted life years and $304,800 per patient lifetime costs versus 8.7 and $283,789, respectively, in the post-LT arm. As such, the pre-LT treatment strategy was found to be the most cost-effective in both populations with an incremental cost-effectiveness ratio of $74,255 (HCC) and $36,583 (DCC). Sensitivity and scenario analyses showed that results were most sensitive to the utility of patients post-LT, treatment sustained virological response rates, LT costs, and baseline Model for End-Stage Liver Disease score (DCC analysis only). CONCLUSION: The timing of initiation of antiviral treatment for HCV patients with HCC or DCC relative to LT is an important area of clinical and policy research; our results indicate that pre-LT treatment with a highly effective, all-oral DAA regimen provides the best health outcomes and is the most cost-effective strategy for the treatment of HCV patients with HCC or DCC waitlisted for LT. (Hepatology 2017;66:46-56).

Comparative treatment effectiveness of direct acting antiviral regimens for hepatitis C: Data from the Veterans administration.

BACKGROUND AND AIMS: Data addressing real world effectiveness of direct acting antiviral agents in hepatitis C infected patients are now emerging. This study compared the sustained virologic response rates achieved 12 weeks post-treatment in patients treated with three such agents by the Veterans Health Administration. METHODS: A retrospective cohort study was conducted using patients who terminated treatment by July 1, 2015. Data were retrieved from the Veterans Health Administration electronic medical records system. Patients were included if sufficient viral load laboratory data were available to determine sustained virologic response. Applying an intention to treat approach and logistic regression analysis, the sustained virologic response rates achieved were compared across drug regimens. RESULTS: A total of 11 464 patients met study selection criteria. Without controlling for other risk factors, sustained virologic response at least 12 weeks post treatment was achieved in 92% of ledipasvir/ sofosbuvir, 86% of ombitasvir/paritaprevir/ritonavir/dasabuvir, and 83% of simeprevir/sofosbuvir patients. After adjusting for patient characteristics, simeprevir/sofosbuvir (93.3%) and ledipasvir/sofosbuvir (96.2%) patients were statistically more likely than ombitasvir/paritaprevir/ritonavir/dasabuvir (91.8%) patients to demonstrate sustained virologic response. Human immunodeficiency virus, hepatitis B infection, diabetes, obesity, previous treatment history and augmentation therapy using ribavirin did not impact sustained virologic response rates. Sustained virologic response rates were lower for patients under age 65, with cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, indications of fibrosis, or a non-genotype 1 infection. Women and Caucasian patients were more likely to achieve a sustained virologic response. CONCLUSIONS: All three direct acting antiviral regimens appear highly effective in achieving sustained virologic response.

Evidence for increased Chlamydia case finding after the introduction of rectal screening among women attending 2 Canadian sexually transmitted infection clinics.

BACKGROUND: Chlamydia trachomatis is the most common notifiable disease in Canada, and extragenital sites are believed to serve as hidden reservoirs for ongoing transmission of infection. There are no specific Canadian screening guidelines for asymptomatic individuals from extragenital sites. We sought to determine the prevalence and factors associated with rectal C. trachomatis among female sexually transmitted infection (STI) clinic attendees in Alberta, Canada. METHODS: Between 20 July and 31 December 2012, all female attendees at 2 Provincial STI clinics receiving a pelvic examination, regardless of a history of anal intercourse, were screened for rectal C. trachomatis using the Gen-Probe Aptima COMBO 2 Assay. Demographic and behavior variables were compared between rectal-only chlamydia cases and genitourinary cases using χ(2) or Fisher exact test, Mann-Whitney test, and logistic regression. RESULTS: A total of 3055 women were screened for rectal chlamydia. The prevalence of rectal chlamydia ranged from 11.7% to 13.5%. There were 133 rectal-only cases, increasing case detection by 44.3% from 300 genitourinary cases to 433 total cases, ranging from 21.7% to 88.2% by clinic. Women who were a contact to an STI were less likely to have rectal-only chlamydia for both clinics (P ≤ .001). CONCLUSIONS: Our findings add to the growing body of evidence supporting universal rectal screening in high-risk women such as those undergoing pelvic exams at STI clinics.

Estimated Human and Economic Burden of Four Major Adult Vaccine-Preventable Diseases in the United States, 2013.

Low uptake of routinely recommended adult immunizations is a public health concern. Using data from the peer-reviewed literature, government disease-surveillance programs, and the US Census, we developed a customizable model to estimate human and economic burden caused by four major adult vaccine-preventable diseases (VPD) in 2013 in the United States, and for each US state individually. To estimate the number of cases for each adult VPD for a given population, we multiplied age-specific incidence rates obtained from the literature by age-specific 2013 Census population data. We then multiplied the estimated number of cases for a given population by age-specific, estimated medical and indirect (non-medical) costs per case. Adult VPDs examined were: (1) influenza, (2) pneumococcal disease (both invasive disease and pneumonia), (3) herpes zoster (shingles), and (4) pertussis (whooping cough). Sensitivity analyses simulated the impact of various epidemiological scenarios on the total estimated economic burden. Estimated US annual cost for the four adult VPDs was $26.5 billion (B) among adults aged 50 years and older, $15.3B (58 %) of which was attributable to those 65 and older. Among adults 50 and older, influenza, pneumococcal disease, herpes zoster, and pertussis made up $16.0B (60 %), $5.1B (19 %), $5.0B (19 %), and $0.4B (2 %) of the cost, respectively. Among those 65 and older, they made up $8.3B (54 %), $3.8B (25 %), $3.0B (20 %), and 0.2B (1 %) of the cost, respectively. Most (80-85 %) pneumococcal costs stemmed from nonbacteremic pneumococcal pneumonia (NPP). Cost attributable to adult VPD in the United States is substantial. Broadening adult immunization efforts beyond influenza only may help reduce the economic burden of adult VPD, and a pneumococcal vaccination effort, primarily focused on reducing NPP, may constitute a logical starting place. Sensitivity analyses revealed that a pandemic influenza season or change in size of the US elderly population could increase these costs dramatically.

Prevalence and characteristics of rectal chlamydia and gonorrhea cases among men who have sex with men after the introduction of nucleic acid amplification test screening at 2 Canadian sexually transmitted infection clinics.

We sought to determine the prevalence of rectal chlamydia and gonorrhea after the introduction of nucleic acid amplification tests for screening in men reporting receptive anal intercourse. The rectal chlamydia prevalence was 14.1% (95% confidence interval, 11.9-16.3), and the gonorrhea prevalence was 5.9% (95% confidence interval, 4.4-7.3). Most cases were positive only from the rectum.

Pseudomyxoma peritonei arising from mature ovarian teratoma, a rare entity: Report of six cases and review of current literature.

Background: Pseudomyxoma peritonei (PMP) is a clinical syndrome characterised by intraperitoneal accumulation of mucus due to mucinous neoplasia. It is a rare condition affecting 1-2 per million individuals per year. The majority of PMP arises from a ruptured mucinous appendiceal tumour, with infrequent occurrences from other primary gastrointestinal tumours and mucinous ovarian tumours. PMP arising from a mature ovarian teratoma is a rare entity, with limited case reports in the literature. Given the infrequent and sporadic occurrences of these tumours, little is known about the tumour behaviour and prognosis. Case series and literature review: Herein, we report six cases of PMP arising from a mature ovarian teratoma who were treated with primary cytoreductive surgery (CRS), with one case of recurrence. Literature review identified 21 cases from 12 manuscripts. Nineteen patients were treated with CRS alone, with two patients receiving adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC). Follow up data were variably reported, with no recurrence in 20 patients during their follow up of 5-54 months. One patient reported to have died of disease at 49 months. Conclusion: Despite the lack of high-quality evidence and limitations of small case series, our review indicates that close surveillance after CRS could be considered as the preferred treatment over more morbid CRS and HIPEC, with HIPEC reserved for patients who recur or progress after CRS.

Interdisciplinary Approach to an Unusual Case of Myocarditis in Pregnancy.

We present a case of myocarditis in a 26-year-old pregnant woman at 29 weeks gestation. Despite optimal medical therapy, she experienced a cardiac arrest 10 days postadmission. An interdisciplinary team facilitated emergency delivery of her baby by perimortem (ie, during maternal cardiac arrest) Caesarean section and initiation of emergency mechanical circulatory support. A cardiac biopsy revealed a mixed eosinophilic and histiocytic infiltrate. After a course of steroid therapy, she experienced full recovery. Both the patient and the infant are alive and well. The case highlights the success of modern interdisciplinary care, as well as ongoing gaps in our knowledge of myocarditis.

Nous présentons un cas de myocardite chez une femme de 26 ans enceinte de 29 semaines, qui a subi un arrêt cardiaque 10 jours après son admission. Une équipe interdisciplinaire a favorisé l'accouchement d'urgence par césarienne perimortem (c.-à-d. durant l'arrêt cardiaque de la mère), et la mise en place en urgence d'une assistance mécanique. Une biopsie cardiaque a révélé un infiltrat mixte d'éosinophiles et d'histiocytes. Il y a eu récupération complète de la fonction ventriculaire après un traitement aux stéroïdes. La patiente et l'enfant sont en vie et se portent bien. Le cas témoigne de la réussite de la pratique moderne des soins interdisciplinaires, et met en lumière les lacunes actuelles de nos connaissances sur la myocardite.

The Impact of Delayed Hepatitis C Viral Load Suppression on Patient Risk: Historical Evidence from the Veterans Administration.

BACKGROUND: The high cost of new hepatitis C (HCV) treatments has resulted in "watchful waiting" strategies being developed to safely delay treatment, which will in turn delay viral load suppression (VLS). OBJECTIVE: To document if delayed VLS adversely impacted patient risk for adverse events and death. METHODS: 187,860 patients were selected from the Veterans Administration's (VA) clinical registry (CCR), a longitudinal compilation of electronic medical records (EMR) data for 1999-2010. Inclusion criteria required at least 6 months of CCR/EMR data prior to their HCV diagnosis and sufficient data post-diagnosis to calculate one or more FIB-4 scores. Primary outcome measures were time-to-death and time-to-a composite of liver-related clinical events. Cox proportional hazards models were estimated separately using three critical FIB-4 levels to define early and late viral response. RESULTS: Achieving an undetectable viral load before the patient's FIB-4 level exceed pre-specified critical values (1.00, 1.45 and 3.25) effectively reduced the risk of an adverse clinical events by 33-35% and death by 21-26%. However, achieving VLS after FIB-4 exceeds 3.25 significantly reduced the benefit of viral response. CONCLUSIONS: Delaying VLS until FIB-4 >3.25 reduces the benefits of VLS in reducing patient risk.

Comparison of health services use associated with ziprasidone and olanzapine among schizophrenia and bipolar disorder patients in the USA.

BACKGROUND AND OBJECTIVES: Ziprasidone is increasingly used for the treatment of schizophrenia and bipolar disorder. The purpose of this study was to compare healthcare costs and use associated with ziprasidone and olanzapine. METHODS: Ziprasidone and olanzapine treatment episodes of schizophrenia and bipolar disorder patients were identified in the 01/2007-12/2010 IMS LifeLink™ Database. The period of analysis for each episode has three components: 6 months prior to the episode initiation date (pre-episode period), 1 month immediately following the episode initiation date (initiation month), and up to 12 months after the end of the initiation month (follow-up period). Ordinary least squares regressions, general linear models, and two-part models were used to compare various types of costs (2007 US$) associated with the use of ziprasidone and olanzapine. Logistic regressions, Poisson regressions, and Hurdle models were used to compare the number of emergency department (ED) visits and hospitalizations associated with each drug. RESULTS: We identified 7,138 (46.93 %) ziprasidone episodes and 8,072 (53.07 %) olanzapine episodes, and found that patients using ziprasidone were significantly younger (41.50 vs. 45.38 years) and were significantly less likely to be male (29.81 vs. 44.21 %). Regression analysis showed no significant differences in total costs between the two drugs. However, ziprasidone was associated with significantly higher medication costs (US$232, p < 0.01) and outpatient costs (US$501, p < 0.05), yet lower ED costs (-US$73, p < 0.05). Ziprasidone was also associated with fewer ED visits (0.266, p < 0.001) and hospitalizations (1.117, p < 0.001). CONCLUSIONS: Ziprasidone is associated with higher medication costs and outpatient costs than olanzapine; however, it reduces patients' use of ED and inpatient services.

Phos-tag-based analysis of myosin regulatory light chain phosphorylation in human uterine myocytes.

BACKGROUND: The 'phosphate-binding tag' (phos-tag) reagent enables separation of phospho-proteins during SDS-PAGE by impeding migration proportional to their phosphorylation stoichiometry. Western blotting can then be used to detect and quantify the bands corresponding to the phospho-states of a target protein. We present a method for quantification of data regarding phospho-states derived from phos-tag SDS-PAGE. The method incorporates corrections for lane-to-lane loading variability and for the effects of drug vehicles thus enabling the comparison of multiple treatments by using the untreated cellular set-point as a reference. This method is exemplified by quantifying the phosphorylation of myosin regulatory light chain (RLC) in cultured human uterine myocytes. METHODOLOGY/PRINCIPAL FINDINGS: We have evaluated and validated the concept that, when using an antibody (Ab) against the total-protein, the sum of all phosphorylation states in a single lane represents a 'closed system' since all possible phospho-states and phosphoisotypes are detected. Using this approach, we demonstrate that oxytocin (OT) and calpeptin (Calp) induce RLC kinase (MLCK)- and rho-kinase (ROK)-dependent enhancements in phosphorylation of RLC at T18 and S19. Treatment of myocytes with a phorbol ester (PMA) induced phosphorylation of S1-RLC, which caused a mobility shift in the phos-tag matrices distinct from phosphorylation at S19. CONCLUSION/SIGNIFICANCE: We have presented a method for analysis of phospho-state data that facilitates quantitative comparison to a reference control without the use of a traditional 'loading' or 'reference' standard. This analysis is useful for assessing effects of putative agonists and antagonists where all phospho-states are represented in control and experimental samples. We also demonstrated that phosphorylation of RLC at S1 is inducible in intact uterine myocytes, though the signal in the resting samples was not sufficiently abundant to allow quantification by the approach used here.