Improving quality of care using a diabetes registry and disease management services in an integrated delivery network.

Disease management for chronic conditions is a call for collaboration among all parties of the health care system. The Caritas Christi Health Care System established a unified American Diabetes Association (ADA) recognized outpatient diabetes self-management education program (DSME) in each of its six hospital communities and has established an Internet data portal with managed care organizations to improve preventive care for thousands of patients with diabetes. This article describes the stepwise process of building the successful Caritas Diabetes Care Program and the central role of the Caritas Diabetes Registry over a 5-year period.     

Anticoagulant Use in Patients with Chronic Renal Impairment

Patients with renal failure have an increased risk of both thrombotic and bleeding complications. A number of antithrombotic drugs undergo renal clearance. Therefore, estimation of renal function is necessary when prescribing these drugs to patients with renal dysfunction. Pharmacokinetic and clinical data in patients with chronic renal impairment are limited for several anticoagulants, and adequate administration information is often absent. Dose adjustment of anticoagulants may be indicated when the creatinine clearance falls below 30 mL/min. Unfractionated heparin, argatroban, and vitamin K antagonists generally do not require dose adjustment with renal dysfunction. However, smaller doses of warfarin may be required to achieve a particular target international normalized ratio. Close monitoring of anticoagulation is recommended when argatroban or high doses of unfractionated heparin are administered in patients with severe chronic renal impairment. Low-molecular weight heparins, danaparoid sodium, hirudins, and bivalirudin all undergo renal clearance. Lower doses and closer anticoagulation monitoring may be advisable when these agents are used in patients with chronic renal failure. We recommend that fondaparinux sodium and ximelagatran (not yet licensed) be avoided in the presence of severe renal impairment and be used with caution in patients with moderate renal dysfunction. While acknowledging the lack of pharmacokinetic data, this review provides specific recommendations for the use of anticoagulants in patients with chronic renal impairment.     

Sentinel node biopsy after neoadjuvant chemotherapy in breast cancer: results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27.

PURPOSE: Experience with sentinel node biopsy (SNB) after neoadjuvant chemotherapy is limited. We examined the feasibility and accuracy of this procedure within a randomized trial in patients treated with neoadjuvant chemotherapy. PATIENTS AND METHODS: During the conduct of National Surgical Adjuvant Breast and Bowel Project trial B-27, several participating surgeons attempted SNB before the required axillary dissection in 428 patients. All underwent lymphatic mapping and an attempt to identify and remove a sentinel node. Lymphatic mapping was performed with radioactive colloid (14.7%), with lymphazurin blue dye alone (29.9%), or with both (54.7%). RESULTS: Success rate for the identification and removal of a sentinel node was 84.8%. Success rate increased significantly with the use of radioisotope (87.6% to 88.9%) versus with the use of lymphazurin alone (78.1%, P = .03). There were no significant differences in success rate according to clinical tumor size, clinical nodal status, age, or calendar year of random assignment. Of 343 patients who had SNB and axillary dissection, the sentinel nodes were positive in 125 patients and were the only positive nodes in 70 patients (56.0%). Of the 218 patients with negative sentinel nodes, nonsentinel nodes were positive in 15 (false-negative rate, 10.7%; 15 of 140 patients). There were no significant differences in false-negative rate according to clinical patient and tumor characteristics, method of lymphatic mapping, or breast tumor response to chemotherapy. CONCLUSION: These results are comparable to those obtained from multicenter studies evaluating SNB before systemic therapy and suggest that the sentinel node concept is applicable following neoadjuvant chemotherapy.     

Effects of radiotherapy planning with a dedicated combined PET-CT-simulator of patients with non-small cell lung cancer on dose limiting normal tissues and radiation dose-escalation: a planning study.

BACKGROUND AND PURPOSE: To investigate the effect of radiotherapy planning with a dedicated combined PET-CT simulator of patients with locally advanced non-small cell lung cancer. PATIENTS AND METHODS: Twenty-one patients underwent a pre-treatment simulation on a dedicated hybrid PET-CT-simulator. For each patient, two 3D conformal treatment plans were made: one with a CT based PTV and one with a PET-CT based PTV, both to deliver 60Gy in 30 fractions. The maximum tolerable prescribed radiation dose for CT versus PET-CT PTV was calculated based on constraints for the lung, the oesophagus, and the spinal cord, and the Tumour Control Probability (TCP) was estimated. RESULTS: For the same toxicity levels of the lung, oesophagus and spinal cord, the dose could be increased from 55.2+/-2.0Gy with CT planning to 68.9+/-3.3Gy with the use of PET-CT (P=0.002), with corresponding TCP's of 6.3+/-1.5% for CT and 24.0+/-5.6% for PET-CT planning (P=0.01). CONCLUSIONS: The use of a combined dedicated PET-CT-simulator reduced radiation exposure of the oesophagus and the lung, and thus allowed significant radiation dose escalation whilst respecting all relevant normal tissue constraints.     

Phase II study of proteasome inhibitor bortezomib in relapsed or refractory B-cell non-Hodgkin's lymphoma.

PURPOSE: Evaluate efficacy and toxicity of bortezomib in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma. PATIENTS AND METHODS: Patients were stratified, based on preclinical data, into arm A (mantle-cell lymphoma) or arm B (other B-cell lymphomas) without limitation in number of prior therapies. Bortezomib was administered as an intravenous push (1.5 mg/m2) on days 1, 4, 8, and 11 every 21 days for a maximum of six cycles. RESULTS: Sixty patients with a median number of prior therapies of 3.5 (range, one to 12 therapies) were enrolled; 33 patients were in arm A and 27 were in arm B, including 12 diffuse large B-cell lymphomas, five follicular lymphomas (FL), three transformed FLs, four small lymphocytic lymphomas (SLL), two Waldenstrom's macroglobulinemias (WM), and one marginal zone lymphoma. In arm A, 12 of 29 assessable patients responded (six complete responses [CR] and six partial responses [PR]) for an overall response rate (ORR) of 41% (95% CI, 24% to 61%), and a median time to progression not reached yet, with a median follow-up of 9.3 months (range, 1.7 to 24 months). In arm B, four of 21 assessable patients responded (one SLL patient had a CR, one FL patient had a CR unconfirmed, one diffuse large B-cell lymphoma patient had a PR, and one WM patient had a PR) for an ORR of 19% (95% CI, 5% to 42%). Grade 3 toxicity included thrombocytopenia (47%), gastrointestinal (20%), fatigue (13%), neutropenia (10%), and peripheral neuropathy (5%). Grade 4 toxicity occurred in nine patients (15%), and three deaths from progression of disease occurred within 30 days of withdrawal from study. CONCLUSION: Bortezomib showed promising activity in relapsed mantle-cell lymphoma and encouraging results in other B-cell lymphomas. Future studies will explore bortezomib in combination with other cytotoxic or biologic agents.     

Ablação por Cateter é Superior a Drogas Antiarrítmicas como Tratamento de primeira linha para Fibrilação Atrial: uma Revisão Sistemática e Metanálise

BackgroundCatheter ablation is a well-established therapy for rhythm control in patients who are refractory or intolerant to anti-arrhythmic drugs (AAD). Less is known about the efficacy of catheter ablation compared with AAD as a first-line strategy for rhythm control in atrial fibrillation (AF).ObjectivesWe aimed to perform a systematic review and meta-analysis of catheter ablation vs. AAD in patients naïve to prior rhythm control therapies.MethodsPubMed, EMBASE, and Cochrane databases were searched for randomized controlled trials that compared catheter ablation to AAD for initial rhythm control in symptomatic AF and reported the outcomes of (1) recurrent atrial tachyarrhythmias (ATs); (2) symptomatic AF; (3) hospitalizations; and (4) symptomatic bradycardia. Heterogeneity was examined with I²statistics. P values of < 0.05 were considered statistically significant.ResultsWe included five trials with 994 patients, of whom 502 (50.5%) underwent catheter ablation. Mean follow-up ranged from one to five years. Recurrences of AT (OR 0.36; 95% CI 0.25-0.52; p<0.001) and symptomatic AF (OR 0.32; 95% CI 0.18-0.57; p<0.001), and hospitalizations (OR 0.25; 95% CI 0.15-0.42; p<0.001) were significantly less frequent in patients treated with catheter ablation compared with AAD. Symptomatic bradycardia was not significantly different between groups (OR 0.55; 95% CI 0.18-1.65; p=0.28). Significant pericardial effusions or tamponade occurred in eight of 464 (1.7%) patients in the catheter ablation group.ConclusionThese findings suggest that catheter ablation has superior efficacy to AAD as an initial rhythm control strategy in patients with symptomatic AF.     

Midterm survival of imaging-assisted robotic lung segmentectomy for non-small-cell lung cancer

Open in a separate window OBJECTIVESOur goal was to report our midterm results using imaging-assisted modalities with robotic segmentectomies for non-small-cell lung cancer (NSCLC).METHODSThis was a retrospective study of all robotic segmentectomies, with confirmed NSCLC, performed at our general and thoracic surgery unit in the Rouen University Hospital (France), from January 2012 through December 2019. Benign and metastatic lesions were excluded. Data were extracted from the EPITHOR French nationwide database.RESULTSA total of 121 robotic segmentectomies were performed for 118 patients with a median age of 65 (interquartile range: 60, 69) years. The majority had clinical stage T1aN0M0 (71.9%) or T1bN0M0 (13.2%). The mean (standard deviation) number of resected segments was 1.93 (1.09) with 80.2% imaging-assisted segmentectomies. Oriented (according to tumour location) or systematic lymphadenectomy or sampling was performed for 72.7%, 23.1% and 4.1% of patients. The postoperative course was uneventful for 94 patients (77.7%), whereas 34 complications occurred for 27 patients (22.3%), including 2 patients (1.7%) with Clavien-Dindo ≥III complications. The mean thoracic drainage duration was 4.12 days, and the median hospital stay was 4 days (interquartile range: 3, 5) after the operation. The 2-year survival rate was 93.9% (95% confidence interval: 86.4–97.8%). Excluding stage IV (n = 3) and stage 0 tumours (n = 6), the 2-year survival rate was 95.7% (95% confidence interval: 88.4–98.8%) compared to an expected survival rate of 94.0% according to stage-specific survival rates found in a large external reference cohort.CONCLUSIONSImaging-guided robotic-assisted thoracic surgery segmentectomy seems to be useful and oncological with good midterm results, especially for patients with early-stage NSCLC.     

Synthesis of Zeolites from Fine-Grained Perlite and Their Application as Sorbents

The hydrothermal alteration of perlite into zeolites was studied using a two-step approach. Firstly, perlite powder was transformed into Na-P1 (GIS) or hydro(xy)sodalite (SOD) zeolites at 100 °C and 24 h using 2 or 5 M NaOH solutions. Secondly, the Si:Al molar ratio of the reacted Si-rich solution was adjusted to 1 by Na-aluminate addition to produce zeolite A (LTA) at 65 or 95 °C and 6 or 24 h at an efficiency of 90 ± 9% for Al and 93 ± 6% for Si conversion. The performance of these zeolites for metal ion removal and water softening applications was assessed by sorption experiments using an artificial waste solution containing 4 mmol/L of metal ions (Me²⁺: Ca²⁺, Mg²⁺, Ba²⁺ and Zn²⁺) and local tap water (2.1 mmol/L Ca²⁺ and 0.6 mmol/L Mg²⁺) at 25 °C. The removal capacity of the LTA-zeolite ranged from 2.69 to 2.86 mmol/g for Me²⁺ (=240–275 mg/g), which is similar to commercial zeolite A (2.73 mmol/g) and GIS-zeolite (2.69 mmol/g), and significantly higher compared to the perlite powder (0.56 mmol/g) and SOD-zeolite (0.88 mmol/g). The best-performing LTA-zeolite removed 99.8% Ca²⁺ and 93.4% Mg²⁺ from tap water. Our results demonstrate the applicability of the LTA-zeolites from perlite for water treatment and softening applications.     

The Antifungal Itraconazole Is a Potent Inhibitor of Chikungunya Virus Replication

Chikungunya virus (CHIKV) is the causative agent of chikungunya fever, a disabling disease that can cause long-term severe arthritis. Since the last large CHIKV outbreak in 2015, the reemergence of the virus represents a serious public health concern. The morbidity associated with viral infection emphasizes the need for the development of specific anti-CHIKV drugs. Herein, we describe the development and characterization of a CHIKV reporter replicon cell line and its use in replicon-based screenings. We tested 960 compounds from MMV/DNDi Open Box libraries and identified four candidates with interesting antiviral activities, which were confirmed in viral infection assays employing CHIKV-nanoluc and BHK-21 cells. The most noteworthy compound identified was itraconazole (ITZ), an orally available, safe, and cheap antifungal, that showed high selectivity indexes of >312 and >294 in both replicon-based and viral infection assays, respectively. The antiviral activity of this molecule has been described against positive-sense single stranded RNA viruses (+ssRNA) and was related to cholesterol metabolism that could affect the formation of the replication organelles. Although its precise mechanism of action against CHIKV still needs to be elucidated, our results demonstrate that ITZ is a potent inhibitor of the viral replication that could be repurposed as a broad-spectrum antiviral.