Multidisciplinary Surgical Approach to Increase Survival for Advanced Ovarian Cancer in a Tertiary Gynaecological Oncology Centre.

PURPOSE: The purpose of this paper is to report on changes in overall survival, progression-free survival, and complete cytoreduction rates in the 5-year period after the implementation of a multidisciplinary surgical team (MDT). METHODS: Two cohorts were used. Cohort A was a retrospectively collated cohort from 2006 to 2015. Cohort B was a prospectively collated cohort of patients from January 2017 to September 2021. RESULTS: This study included 146 patients in cohort A (2006-2015) and 174 patients in cohort B (2017-2021) with FIGO stage III/IV ovarian cancer. Median follow-up in cohort A was 60 months and 48 months in cohort B. The rate of primary cytoreductive surgery increased from 38% (55/146) in cohort A to 46.5% (81/174) in cohort B. Complete macroscopic resection increased from 58.9% (86/146) in cohort A to 78.7% (137/174) in cohort B (p < 0.001). At 3 years, 75% (109/144) patients had disease progression in cohort A compared with 48.8% (85/174) in cohort B (log-rank, p < 0.001). Also at 3 years, 64.5% (93/144) of patients had died in cohort A compared with 24% (42/174) of cohort B (log-rank, p < 0.001). Cox multivariate analysis demonstrated that MDT input, residual disease, and age were independent predictors of overall (hazard ratio [HR] 0.29, 95% confidence interval [CI] 0.203-0.437, p < 0.001) and progression-free survival (HR 0.31, 95% CI 0.21-0.43, p < 0.001). Major morbidity remained stable throughout both study periods (2006-2021). CONCLUSIONS: Our data demonstrate that the implementation of multidisciplinary-team, intraoperative approach allowed for a change in surgical philosophy and has resulted in a significant improvement in overall survival, progression-free survival, and complete resection rates.

Clinical ladders: A potential solution for retaining and promoting PAs.

ABSTRACT: As the need for more healthcare providers increases, so does the need for leaders in the healthcare setting. Physician associates/assistants (PAs) are primed to step into these positions, given their key role in the clinical setting. Clinical ladder models are an established system for clinical, administrative, and academic advancement for healthcare providers. Although more research is needed, clinical ladders provide the opportunity for career advancement while helping to promote professional development and improve retention. Moreover, the opportunity for advancement via clinical ladders may help to prevent clinician burnout and turnover by providing more opportunities and career directions.

Virtual regression-based myoelectric hand-wrist prosthesis control and electrode site selection using no force feedback.

Most transradial prosthesis users with conventional "Sequential" myoelectric control have two electrode sites which control one degree of freedom (DoF) at a time. Rapid EMG co-activation toggles control between DoFs (e.g., hand and wrist), providing limited function. We implemented a regression-based EMG control method which achieved simultaneous and proportional control of two DoFs in a virtual task. We automated electrode site selection using a short-duration (90 s) calibration period, without force feedback. Backward stepwise selection located the best electrodes for either six or 12 electrodes (selected from a pool of 16). We additionally studied two, 2-DoF controllers: "Intuitive" control (hand open-close and wrist pronation-supination controlled virtual target size and rotation, respectively) and "Mapping" control (wrist flexion-extension and ulnar-radial deviation controlled virtual target left-right and up-down movement, respectively). In practice, a Mapping controller would be mapped to control prosthesis hand open-close and wrist pronation-supination. Eleven able-bodied subjects and 4 limb-absent subjects completed virtual target matching tasks (fixed target moves to a new location after being "matched," and subject immediately pursues) and fixed (static) target tasks. For all subjects, both 2-DoF controllers with 6 optimally-sited electrodes had statistically better target matching performance than Sequential control in number of matches (average of 4-7 vs. 2 matches, p< 0.001) and throughput (average of 0.75-1.25 vs. 0.4 bits/s, p< 0.001), but not overshoot rate and path efficiency. There were no statistical differences between 6 and 12 optimally-sited electrodes for both 2-DoF controllers. These results support the feasibility of 2-DoF simultaneous, proportional myoelectric control.

Oral Sampling of Little Brown Bat (Myotis lucifugus) Maternity Colonies for SARS-CoV-2 in the Northeast and Mid-Atlantic, USA.

The potential introduction of SARS-CoV-2, the virus responsible for the COVID-19 pandemic, into North American bat populations is of interest to wildlife managers due to recent disease-mediated declines of several species. Populations of little brown bats (Myotis lucifugus) have collapsed due to white-nose syndrome (WNS), a disease caused by the introduction and spread of the fungal pathogen Pseudogymnoascus destructans (Pd). Throughout much of the United States and southern Canada, large colonies of the species routinely established diurnal roosts in anthropogenic structures, thereby creating the potential for direct human contact and cross-species disease transmission. Given recent declines and the potential for further disease impacts, we collected oral swabs from eight little brown bat maternity colonies to assess the presence and prevalence of SARS-CoV-2 by RT-qPCR analysis. Little brown bat colonies in Maryland (n = 1), New Hampshire (n = 1), New Jersey (n = 2), New York (n = 1), Rhode Island (n = 2), and Virginia (n = 1) were taken during May-August, 2022. From 235 assayed individuals, no bat tested positive for SARS-CoV-2. Our results indicate that little brown bats may not contract SARS-CoV-2 or that the virus persists at undetectable levels in populations of the Mid-Atlantic and Northeast during summer months. Nonetheless, continued monitoring and future work addressing other seasons may still be warranted to conclusively determine infection status.

A pilot study investigating feasibility of mainstreaming germline BRCA1 and BRCA2 testing in high-risk patients with breast and/or ovarian cancer in three tertiary Cancer Centres in Ireland.

In the Republic of Ireland (ROI), BRCA1/BRCA2 genetic testing has been traditionally undertaken in eligible individuals, after pre-test counselling by a Clinical Geneticist/Genetic Counsellor. Clinical Genetics services in ROI are poorly resourced, with routine waiting times for appointments at the time of this pilot often extending beyond a year. The consequent prolonged waiting times are unacceptable where therapeutic decision-making depends on the patient's BRCA status. "Mainstreaming" BRCA1/BRCA2 testing through routine oncology/surgical clinics has been implemented successfully in other centres in the UK and internationally. We aimed to pilot this pathway in three Irish tertiary centres. A service evaluation project was undertaken over a 6-month period between January and July 2017. Eligible patients, fulfilling pathology and age-based inclusion criteria defined by TGL clinical, were identified, and offered constitutional BRCA1/BRCA2 testing after pre-test counselling by treating clinicians. Tests were undertaken by TGL Clinical. Results were returned to clinicians by secure email. Onward referrals of patients with uncertain/pathogenic results, or suspicious family histories, to Clinical Genetics were made by the treating team. Surveys assessing patient and clinician satisfaction were sent to participating clinicians and a sample of participating patients. Data was collected with respect to diagnostic yield, turnaround time, onward referral rates, and patient and clinician feedback. A total of 101  patients underwent diagnostic germline BRCA1/BRCA2 tests through this pathway. Pathogenic variants were identified in 12 patients (12%). All patients in whom variants were identified were appropriately referred to Clinical Genetics. At least 12 additional patients with uninformative BRCA1/BRCA2 tests were also referred for formal assessment by Clinical Geneticist or Genetic Counsellor. Issues were noted in terms of time pressures and communication of results to patients. Results from a representative sample of participants completing the satisfaction survey indicated that the pathway was acceptable to patients and clinicians. Mainstreaming of constitutional BRCA1/BRCA2 testing guided by age- and pathology-based criteria is potentially feasible for patients with breast cancer as well as patients with ovarian cancer in Ireland.

Myoelectric Control Performance of Two Degree of Freedom Hand-Wrist Prosthesis by Able-Bodied and Limb-Absent Subjects.

Recent research has advanced two degree-of-freedom (DoF), simultaneous, independent and proportional control of hand-wrist prostheses using surface electromyogram signals from remnant muscles as the control input. We evaluated two such regression-based controllers, along with conventional, sequential two-site control with co-contraction mode switching (SeqCon), in box-block, refined-clothespin and door-knob tasks, on 10 able-bodied and 4 limb-absent subjects. Subjects operated a commercial hand and wrist using a socket bypass harness. One 2-DoF controller (DirCon) related the intuitive hand actions of open-close and pronation-supination to the associated prosthesis hand-wrist actions, respectively. The other (MapCon) mapped myoelectrically more distinct, but less intuitive, actions of wrist flexion-extension and ulnar-radial deviation. Each 2-DoF controller was calibrated from separate 90 s calibration contractions. SeqCon performed better statistically than MapCon in the predominantly 1-DoF box-block task (>20 blocks/minute vs. 8-18 blocks/minute, on average). In this task, SeqCon likely benefited from an ability to easily focus on 1-DoF and not inadvertently trigger co-contraction for mode switching. The remaining two tasks require 2-DoFs, and both 2-DoF controllers each performed better (factor of 2-4) than SeqCon. We also compared the use of 12 vs. 6 optimally-selected EMG electrodes as inputs, finding no statistical difference. Overall, we provide further evidence of the benefits of regression-based EMG prosthesis control of 2-DoFs in the hand-wrist.

From physical to virtual: How the COVID-19 pandemic changed a tertiary gynaecologic oncology surveillance program in Ireland.

•Virtual follow up is acceptable to gynecological oncology patients.•Some patients may be reluctant to sit in waiting rooms post pandemic.•Lack of physical examination did not affect most patients' appointments.

The addition of sodium thiosulphate to hyperthermic intraperitoneal chemotherapy with cisplatin in ovarian cancer.

Cisplatin based hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to prolong recurrence free and overall survival of women with ovarian cancer who have responded to neoadjuvant chemotherapy. The aim of this study was to assess the impact of cytoreductive surgery with or without the addition of HIPEC on renal function. METHOD: This is a retrospective case-controlled study at a tertiary teaching hospital in Dublin, Ireland. All patients who had interval cytoreductive surgery (CRS) and HIPEC from October 2017 to October 2020 were included. A cohort of patients who had interval CRS without HIPEC were included as a control. Sodium thiosulphate (ST) was added to the HIPEC protocol in 2019. In order to assess the impact of ST as a renal protectant, renal function and post-operative outcomes were compared between the groups. RESULTS: Sixty patients who had interval CRS were included, thirty of whom received cisplatin-based HIPEC. Seven received cisplatin 50 mg/m2 without the addition of ST. Twenty three patients received cisplatin 100 mg/m2 and ST. There were no statistically differences in age, body mass index BMI, American society of anaesthesia score, estimated blood loss or peritoneal cancer index between the cohorts (p > 0.05). The only episode of acute kidney injury (AKI) was within the HIPEC cohort, after cisplatin 50 mg/m2 (without ST) and this was sustained at three months. In contrast, no patients within the CRS cohort or cisplatin 100 mg/m2 that received the addition of ST, sustained a renal injury and all had a creatinine within the normal range at three days post operatively. CONCLUSION: The renal toxicity associated with cisplatin HIPEC and major abdominal surgery can be minimised with careful preoperative optimisation, intra operative fluid management and attention to renal function. The addition of sodium thiosulphate is a safe and effective method to minimise toxicity and should be added to any cisplatin HIPEC protocol.

Multidisciplinary Surgical Approach to Increase Complete Cytoreduction Rates for Advanced Ovarian Cancer in a Tertiary Gynecologic Oncology Center.

BACKGROUND: Surgical resection remains the cornerstone of ovarian cancer management. In 2017, the authors implemented a multi-disciplinary surgical team comprising gynecologic oncologists as well as colorectal, hepatobiliary, and upper gastrointestinal (GI) surgeons to increase gross macroscopic resection rates. This report aims to describe changes in complete cytoreduction rates and morbidity after the implementation of a multi-disciplinary surgical team comprising gynecologic oncologists as well as colorectal, hepatobiliary, and upper GI surgeons in a tertiary gynecologic oncology unit. METHODS: The study used two cohorts. Cohort A was a retrospectively collated cohort from 2006 to 2015. Cohort B was a prospectively collated cohort of patients initiated in 2017. A multidisciplinary approach to preoperative medical optimization, intraoperative management, and postoperative care was implemented in 2017. The patients in cohort B with upper abdominal disease were offered primary cytoreduction with or without hyperthermic intraperitoneal chemotherapy (HIPEC). Before 2017, the patients with upper abdominal disease received neoadjuvant chemotherapy (cohort A). RESULTS: This study included 146 patients in cohort A (2006-2015) and 93 patients in cohort B (2017-2019) with stages 3 or 4 ovarian cancer. The overall complete macroscopic resection rate (CC0) increased from 58.9 in cohort A to 67.7% in cohort B. The rate of primary cytoreductive surgery (CRS) increased from 38 (55/146) in cohort A to 42% (39/93) in cohort B. The CC0 rate for the patients who underwent primary CRS increased from 49 in cohort A to 77% in cohort B. Major morbidity remained stable throughout both study periods (2006-2019). CONCLUSIONS: The study data demonstrate that implementation of a multidisciplinary team intraoperative approach and a meticulous approach to preoperative optimization resulted in significantly improved complete resection rates, particularly for women offered primary CRS.

Laryngeal tuberculosis mimicking malignancy: A case report.

Laryngeal involvement in tuberculosis is rare and may mimic malignancy. We report the case of a 26-year-old female who presented with sore throat for several months. CT revealed an infiltrative laryngeal mass and upper lobe pulmonary opacities. Laryngoscopic biopsy confirmed necrotizing granulomatous inflammation with positive culture for Mycobacterium tuberculosis.

A meta-analysis of morbidity and mortality in primary cytoreductive surgery compared to neoadjuvant chemotherapy in advanced ovarian malignancy.

Aim The aim of this meta-analysis is to review the morbidity and mortality associated with primary cytoreductive surgery (PCS) compared to neoadjuvant chemotherapy and interval cytoreductive surgery (NACT + ICS) for advanced ovarian cancer. METHODS: A literature search was performed for publications reporting morbidity and mortality in patients undergoing PCS compared to NACT + ICS. Databases searched were Cochrane, Medline, Pubmed, Pubmed Central, clinicaltrials.gov and Embase. Two independent reviewers applied inclusion and exclusion criteria to select included papers, with differences agreed by consensus. A total of 1341 citations were reviewed; 17 studies comprising 3759 patients were selected for the analysis. The literature search was performed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results were reported as mean differences or pooled odds ratios (OR) with 95% confidence intervals (95% CI). RESULTS: Patients in the PCS group were significantly more likely to have a Clavien-Dindo grade ≥ 3 morbidity with an overall rate of 21.2% compared to 8.8% (95%CI 1.9-4.0, p < 0.0001) and were more likely to die within 30 days of surgery (OR 6.1, 95% CI 2.1-17.6, p = 0.0008). Patients who underwent NACT + ICS had significantly shorter procedural times (MD -35 min, p = 0.01), lost less blood intraoperatively (MD-382 ml, p < 0.001) and had an average admission 5.0 days shorter (MD -5.0 days, 95% CI -8.1 to -1.9 days, p = 0.002) than those undergoing PCS. While NACT was associated with significantly increased optimal and complete cytoreduction rates (OR 1.9, 95% CI 1.3-2.9, p = 0.001, and OR 2.2, 95% CI 1.5-3.3, p = 0.0001 respectively), this did not confer any additional survival benefit (OR 1.0, p = 0.76). CONCLUSION: NACT is associated with less morbidity and mortality and improved complete cytoreduction compared to PCS, with no survival benefit. Hence NACT is an acceptable alternative in selected patients in particular with medical co-morbidities or a high tumour burden.

Incidental Thoracic Findings on Routine Computed Tomography in Epithelial Ovarian Cancer.

INTRODUCTION: Multidetector computed tomography (MDCT) is routinely used in the surveillance of epithelial ovarian cancer. The aim of this study was to determine the incidence of thoracic findings on routine MDCT surveillance imaging in patients with ovarian carcinoma. MATERIALS AND METHODS: Retrospective evaluation of 100 MDCT studies of patients with a diagnosis of epithelial ovarian cancer was performed at a university teaching hospital. The cross-sectional studies were reviewed by a consultant radiologist with subspeciality training in cross-sectional imaging. RESULTS: Intrathoracic findings were identified in 35% of patients. Pleural effusions were identified in 40%, pulmonary nodules in 37%, mediastinal adenopathy in 17%, and thyroid nodules in 6% of patients. Thirty-five (35%) patients were found to have thoracic findings on computed tomography. Pleural effusions developed in 14 (40%) of these patients. Small lung nodules (<1 cm) were present in 13 (37%) patients. Mediastinal lymphadenopathy was seen in 6 (17%) patients. Two patients (6%) had thyroid nodules of unknown significance. Pleural effusions and small lung nodules were present at a similar level to that of the general population. CONCLUSIONS: This retrospective study supports the imaging recommendations of the European Society of Urogenital Radiology that MDCT protocols for the initial staging and evaluation of recurrent disease in epithelial ovarian carcinoma require only inclusion of the lung bases to the inguinal region reducing exposure to ionizing radiation, alleviating patient anxiety, and offering a cost-benefit to hospitals.

"Showercap" Sign: Spontaneous Uterine Rupture in a Primiparous Woman.

A 32-year-old primiparous woman presented with severe abdominal pain at 21 weeks' gestation. Background history of laparoscopy for chronic pelvic pain and a spontaneous miscarriage was noted. On examination, she was peritonitic and tachycardic with low grade fever and anemia. MRI abdomen demonstrated a uterine rupture with a large cap of clotted blood overlying the uterine fundus with the appearance of a "shower cap" and large volume haemoperitoneum, the presumptive diagnosis was uterine rupture with placental extrusion. Emergency laparotomy confirmed a two litre haemoperitoneum due to a 3cm defect at the uterine fundus through which a portion of placenta and membrane were extruding. Hysterotomy and delivery of the non-viable fetus was performed. The defect was repaired. It is important to remember that there are many causes of acute abdominal pain in pregnant patients, obstetric and other. Uterine rupture is a rare but life-threatening cause. An underlying risk factor is usually identified.

Comparative effectiveness of traditional chemoembolization with or without sorafenib for hepatocellular carcinoma.

AIM: To compare the overall survival (OS) and progression-free survival (PFS) with associated adverse events (AE) in patients with unresectable hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) + sorafenib vs TACE alone. METHODS: In this retrospective cohort study we collected data on all consecutive patients with a diagnosis of unresectable HCC between 2007 and 2011 who had been treated with TACE + sorafenib or TACE alone. We hypothesized that the combination therapy is superior to TACE alone in improving the survival in these patients. Data extracted included patient's demographics, etiology of liver disease, histology of HCC, stage of liver disease with respect to model of end stage liver disease score and Child-Turcotte-Pugh (CTP) classification and Barcelona Clinic Liver Cancer (BCLC) staging for HCC. Computed tomography scan findings, alpha fetoprotein levels, number of treatments and related AE were also recorded and analyzed. RESULTS: Of the 43 patients who met inclusion criteria, 13 were treated with TACE + sorafenib and 30 with TACE alone. There was no significant difference in median survival: 20.6 mo (95%CI: 13.4-38.4) for the TACE + sorafenib and 18.3 mo (95%CI: 11.8-32.9) for the TACE alone (P = 0.72). There were also no statistically significant differences between groups in OS (HR = 0.82, 95%CI: 0.38-1.77; P = 0.61), PFS (HR = 0.93, 95%CI: 0.45-1.89; P = 0.83), and treatment-related toxicities (P = 0.554). CTP classification and BCLC staging for HCC were statistically significant (P = 0.001, P = 0.04 respectively) in predicting the survival in patients with HCC. The common AE observed were abdominal pain, nausea, vomiting and mild elevation of liver enzymes. CONCLUSION: Combination therapy with TACE + sorafenib is safe and equally effective as TACE alone in patients with unresectable HCC. CTP classification and BCLC staging were the significant predictors of survival. Future trials with large number of patients are needed to further validate this observation.

Responding to climate change and the global land crisis: REDD+, market transformation and low-emissions rural development.

Climate change and rapidly escalating global demand for food, fuel, fibre and feed present seemingly contradictory challenges to humanity. Can greenhouse gas (GHG) emissions from land-use, more than one-fourth of the global total, decline as growth in land-based production accelerates? This review examines the status of two major international initiatives that are designed to address different aspects of this challenge. REDD+ is an emerging policy framework for providing incentives to tropical nations and states that reduce their GHG emissions from deforestation and forest degradation. Market transformation, best represented by agricultural commodity roundtables, seeks to exclude unsustainable farmers from commodity markets through international social and environmental standards for farmers and processors. These global initiatives could potentially become synergistically integrated through (i) a shared approach for measuring and favouring high environmental and social performance of land use across entire jurisdictions and (ii) stronger links with the domestic policies, finance and laws in the jurisdictions where agricultural expansion is moving into forests. To achieve scale, the principles of REDD+ and sustainable farming systems must be embedded in domestic low-emission rural development models capable of garnering support across multiple constituencies. We illustrate this potential with the case of Mato Grosso State in the Brazilian Amazon.

The application of a clinical risk stratification score may reduce unnecessary investigations for pulmonary embolism in pregnancy.

OBJECTIVE: To examine the use of the modified Wells score in pregnancy as a risk stratification tool in the diagnosis of pulmonary embolism (PE). METHODS: All pregnant or post-partum patients who were referred for CT Pulmonary Angiography (CTPA) to evaluate suspected PE over a 5-year period were included in the study. Patient records were used to apply the modified Wells score (MWS) and analyze their risk of PE. RESULTS: A total of 125 women were referred for CTPA over 5 years. A MWS of 6 or greater ("High Risk") was 100% sensitive and 90% specific with a positive predictive value of 36% for PE on CTPA. No patients with a low MWS (less than 6) had a PE, giving a negative predictive value of 100%. p≤0.001. D-dimers, chest X-ray, blood gases and EKG were significantly less effective than the MWS in aiding the diagnosis of PE. CONCLUSION: Current methods employed for the diagnosis of PE are inadequate. Risk stratification using the MWS may allow safe exclusion of PE before resorting to CTPA. To the best of our knowledge this is the first study to have used the MWS in a pregnant patient group.

Safety of conscious sedation in patients with sleep apnea in a veteran population.

OBJECTIVES: Due to the presumed higher risk of cardiopulmonary complications in patients with obstructive sleep apnea (OSA), many endoscopy centers consider OSA a contraindication to using conscious sedation. We evaluated the safety of conscious sedation during endoscopy for patients with OSA in a veteran population, and compared this to patients without OSA. METHODS: Polysomnography studies were reviewed from 2004 to 2009 to identify 200 patients with OSA who had undergone endoscopy. Controls included the last 200 consecutive endoscopies in this institution for patients without OSA. Sixty-three upper endoscopies, 136 colonoscopies, and one enteroscopy were included in the OSA group. Sixty-five upper endoscopies, 133 colonoscopies, one sigmoidoscopy, and one endoscopic ultrasound comprised the control group. Data obtained included demographics, medications prescribed, and any complication noted in the procedure report. RESULTS: No complications occurred in the control group. In the OSA group, a patient experienced oxygen desaturation during an upper endoscopy and required oxygen supplementation. The procedure was completed and did not require an extended stay in the endoscopy suite. CONCLUSION: This study demonstrated that endoscopy can be safely done in OSA patients using conscious sedation, and the complication rate is not significantly different than patients without OSA.

U.S. multicenter pilot study of daily consensus interferon (CIFN) plus ribavirin for "difficult-to-treat" HCV genotype 1 patients.

BACKGROUND: Patients with chronic hepatitis C genotype 1 (HCV-1) and difficult-to-treat characteristics respond poorly to pegylated interferon alfa and ribavirin (RBV), and could benefit from an interferon with increased activity (consensus interferon or CIFN), favorable viral kinetics from daily dosing, and a longer duration of therapy. The purpose of this pilot study was to determine the efficacy and safety of daily CIFN + RBV for initial treatment of patients with HCV-1 infection. METHODS: Patients with difficult-to-treat characteristics (92% male, 33% African American, 78% Veterans Affairs [VA]; 67% high viral load, 59% stage 3-4 fibrosis, and mean weight of 204 lbs) were enrolled at seven VA and two community medical centers. They were randomized to daily CIFN (15 mcg/day SQ) and RBV (1-1.2 g/d PO) given for either 52 weeks (group A, n = 33) or 52-72 weeks (from time of viral response +48 weeks) (group B, n = 31). RESULTS: Intention to treat analysis for treatment groups A and B demonstrated 33% (11/33) and 32% (10/31) sustained virologic response (SVR), respectively. Only 2/31 patients in group B received more than 52 weeks of treatment. The overall group demonstrated a 31% (20/64) rapid virologic response rate (RVR), 54% (34/64) end of treatment virologic response and a 33% (21/64) SVR. Patients with RVR at 4 weeks, early virologic response from 8-12 weeks, and late virologic response from 16-24 weeks demonstrated SVR of 75% (15/20), 31% (4/13), and 22% (2/9), respectively. Overall early non-protocol discontinuation occurred in 26/64 (40%) patients. CONCLUSION: Daily CIFN and ribavirin for initial treatment of HCV-1 patients has potential for achieving a relatively high RVR rate, but discontinuations are frequent and successful use of this regimen is highly dependent on adequate patient support to maintain adherence.

Integrating HIV prevention in reproductive health settings.

CONTEXT: This article describes results of a process evaluation of a cooperative agreement between the Centers for Disease Control and Prevention's Division of Reproductive Health and 10 regional training centers to increase the number of reproductive health (RH) settings that integrate human immunodeficiency virus (HIV) prevention services at an appropriate level into routine care. OBJECTIVE: Our goal was to learn about the process of integrating HIV prevention into RH settings. DESIGN: We conducted a retrospective evaluation, using qualitative methods. SETTING: The clinics were from 10 US Department of Health and Human Services regions. PARTICIPANTS: We interviewed 16 key informants from 10 selected model clinics. MAIN OUTCOME MEASURES: The main outcome was organization change. RESULTS: The most common obstacles to integration were staff issues, logistics barriers, inadequate clinic structure to support integration, and staff training barriers. Using the transtheoretical model (TTM) applied to organizations, we documented organizational change as informants described their clinics' progression to integration and overcoming obstacles. All model clinics began in the contemplation stage of transtheoretical model. Every clinic exhibited at least 1 process of change for every stage. In the contemplation stage, most informants discussed fears about not changing, stated that the integration was consistent with the agency's mission, and described thinking about commitment to the change. In the preparation stage, all informants described building teams that supported integration of HIV prevention. During the action stage, informants talked about assessments of facilities, staff and protocols, commitments through grants or agreements, and then using training to support new behaviors and adopting new cognitions. In the maintenance stage, all reported changing policies, procedures, or protocols, most promoted helping relationships among the staff, and nearly all reported rewards for the new ways of working. CONCLUSIONS: RH settings were able to integrate HIV prevention services by employing a systematic process.

Can a more detailed evaluation of excision margins refine cytologic follow-up of women post-LLETZ for high-grade dysplasia?

The relationship between dysplastic changes in the cervical epithelium and progression to in situ carcinoma and invasive carcinoma has been extensively studied. The removal of dysplastic epithelium through the long loop excision of the transformation zone (LLETZ) in 95% of the cases is curative. About 18% to 37% of LLETZ specimens with dysplasia at the margins have recurrent/residual disease. Earlier small studies suggest that the degree of dysplasia at the margins could predict for recurrence and allow a risk-based stratification of follow-up. We tested this hypothesis in a large group of women post-LLETZ for high-grade dysplasia with follow-up histology and cytology over a 12-year period. The cases were divided according to the excision margin status for dysplasia and if positive, low-grade or high-grade dysplasia. The groups were compared to assess whether the LLETZ specimens' margin status had an impact on the subsequent cytology or histology results. Positive follow-up results were defined as any grade of dysplasia in cytology or histology. Two thousand three hundred twenty-one women had LLETZs containing high-grade dysplasia over the 12-year period. One thousand five hundred thirty-four (66.1%) women had full histology and cytology follow-up available. Eight hundred twenty (53.4%) LLETZ specimens had positive margins and 714 (46.6%) had negative margins. The grade of dysplasia at the margins was available in 796 cases (97%) with 115 (15%) showing low-grade dysplasia and 680 (85%) high-grade dysplasia. One hundred seventy (20.7%) of the specimens with positive margins had positive follow-up results compared with 105 (14.7%) of the specimens with negative margins. The presence of dysplasia at an LLETZ margin is associated with dysplasia on follow-up cytology and histology (P=0.0021); however, the grade of dysplasia at the excision margin is not predictive of recurrent/residual dysplasia.