Weekly docetaxel and carboplatin for recurrent ovarian and peritoneal cancer: a phase II trial

OBJECTIVE: Results of the ICON4/AGO-OVAR-2.2 trial suggest that a platinum/taxane combination provides a survival benefit in relapsed, platinum-sensitive ovarian cancer compared to platinum alone. The optimal specific combination has yet to be determined. The current study evaluates weekly docetaxel and carboplatin in this setting. METHODS: Using a prospective phase II design, patients received weekly docetaxel (35 mg/m2) and carboplatin (AUC=2) administered days 1, 8, and 15 of a 28-day cycle. Initial treatment with a platinum-based regimen was required, with a treatment-free interval of at least 3 months. Patients could have received one prior regimen for recurrence. Biologically evaluable disease (CA-125) could be followed only if measurable disease was not present. Quality of life analysis utilized the FACT-O and FACT/GOG-Ntx scales. RESULTS: Thirty-six patients enrolled in the trial over 29 months. The majority had ovarian cancer (89%) and stage III/IV (97%) disease, with a median initial disease-free interval of 12 months. Most subjects were treated for first recurrence (81%) and had measurable disease (58%). The overall response rate was 67% (PR=52%, CR=15%), with 22% stable disease. Grade 3/4 neutropenia was common (48%) while serious anemia and thrombocytopenia were not. Neuropathy was generally mild and manageable. Carboplatin hypersensitivity led to 11 subjects coming off trial (31%). Diphenhydramine premedication produced a nonsignificant decrease in reaction rate. There was no detectable difference in quality of life due to therapy. CONCLUSION: The weekly regimen of carboplatin and docetaxel has a good response rate with an acceptable toxicity profile.     

Renal function and clinical outcome of patients with cancer-associated venous thromboembolism randomized to receive apixaban or dalteparin. Results from the Caravaggio trial

The effect of renal impairment (RI) on risk of bleeding and recurrent thrombosis in cancer patients treated with direct oral anticoagulants for venous thromboembolism (VTE) is undefined. We ran a prespecified analysis of the randomized Caravaggio study to evaluate the role of RI as a risk factor for bleeding or recurrence in patients treated with dalteparin or apixaban for cancer-associated VTE. RI was graded as moderate (creatinine clearance between 30-59 mL/minute; 275 patients) and mild (between 60-89 mL/minute; 444 patients). In the 1142 patients included in this analysis, the incidence of major bleeding was similar in patients with moderate vs. no or mild RI (HR 1.06-95% CI: 0.53-2.11), with no difference in the relative safety of apixaban and dalteparin. Recurrent VTE was not different in moderate vs. no or mild RI (HR=0.67, 95% CI: 0.38-1.20); in moderate RI, apixaban reduced recurrent VTE compared to dalteparin (HR=0.27, 95% CI: 0.08-0.96; P for interaction 0.1085). At multivariate analysis, no association was found between variation of renal function over time and major bleeding or recurrent VTE. Advanced or metastatic cancer was the only independent predictor of major bleeding (HR=2.84, 95% CI: 1.20-6.71), with no effect of treatment with apixaban or dalteparin. In our study, in cancer patients treated with apixaban or dalteparin, moderate RI was not associated with major bleeding or recurrent VTE. In patients with moderate renal failure, the safety profile of apixaban was confirmed with the potential for improved efficacy in comparison to dalteparin. ClinicalTrials.gov identifier: {"type":"clinical-trial","attrs":{"text":"NCT03045406","term_id":"NCT03045406"}}NCT03045406.     

Cholecystokinin antagonizes morphine induced hypoactivity and hyperactivity in hamsters

Three experimental replications were used to test the effects of three doses (25, 50 or 75 micrograms/kg) of cholecystokinin octapeptide (CCK-8) on morphine induced changes in activity. For each dose of CCK-8, running wheel activity of golden Syrian hamsters was monitored for three hours following a series of two injections. The first injection consisted of either saline or CCK-8, the second of either saline or morphine sulfate (15 mg/kg). Thus, in each replication four groups were created: Group SAL/SAL (n = 8) received two saline injections, Group CCK/SAL (n = 8) an injection of CCK-8 followed by an injection of saline, Group SAL/MS (n = 8) an injection of saline followed by an injection of morphine and Group CCK/MS (n = 8) an injection of CCK-8 followed by an injection of morphine. Results indicated that a 25 micrograms/kg dose of CCK-8 blocked the hypoactivity elicited by morphine 40-60 min after opiate injection, whereas a 75 micrograms/kg dose of CCK-8 blocked the hyperactivity elicited by morphine 80-100 min after opiate injection. These findings are consistent with previous reports that CCK-8 antagonizes the effects of opiate agonists on a variety of behaviors and is supportive of the hypothesis that endogenous CCK-8 may antagonize endogenous opioid peptides in the control of behavior.     

Oxygenated right ventricular assist device with a percutaneous dual-lumen cannula as a bridge to lung transplantation

BackgroundOxygenated right ventricular assist device (oxyRVAD) placement has become more streamlined with the introduction of the dual-lumen pulmonary artery cannula. Peripherally cannulated oxyRVAD may provide oxygenation support with right heart support as an alternative to venoarterial extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplantation.MethodsA single-institution, retrospective analysis was performed on patients placed on oxyRVAD with a dual-lumen pulmonary artery cannula with the intention of bridging to lung transplantation in 2019.ResultsFour patients with idiopathic pulmonary fibrosis were placed on oxyRVAD as a bridge to transplantation. Two patients were extubated and ambulated while waiting for a lung offer, and two patients required conversion to venoarteriovenous ECMO (VAV ECMO) from oxyRVAD. The median waiting time for extracorporeal life support (ECLS) was 42 h. All patients underwent double lung transplantation. Two patients stayed on oxyRVAD, and one patient was placed on venovenous ECMO (VV ECMO) after transplantation. Primary graft dysfunction score at 72 h after transplantation was grade 1 in three patients and grade 3 in one patient.ConclusionsPeripherally cannulated oxyRVAD with percutaneous dual-lumen venous cannula could be an ambulatory bridge for lung transplantation. It is unknown whether oxyRVAD is feasible as a long-term bridge to lung transplantation.     

Long‐term oral administration of melatonin improves spatial learning and memory and protects against cholinergic degeneration in middle‐aged Ts65Dn mice,a model of Down syndrome

Ts65Dn mice (TS), the most commonly used model of Down syndrome (DS), exhibit phenotypic characteristics of this condition. Both TS mice and DS individuals present cognitive disturbances, age‐related cholinergic degeneration, and increased brain expression of β‐amyloid precursor protein (AβPP). These neurodegenerative processes may contribute to the progressive cognitive decline observed in DS. Melatonin is a pineal indoleamine that has been reported to reduce neurodegenerative processes and improve cognitive deficits in various animal models. In this study, we evaluated the potentially beneficial effects of long‐term melatonin treatment on the cognitive deficits, cholinergic degeneration, and enhanced AβPP and β‐amyloid levels of TS mice. Melatonin was administered for 5 months to 5‐ to 6‐month‐old TS and control (CO) mice. Melatonin treatment improved spatial learning and memory and increased the number of choline acetyltransferase (ChAT)‐positive cells in the medial septum of both TS and CO mice. However, melatonin treatment did not significantly reduce AβPP or β‐amyloid levels in the cortex or the hippocampus of TS mice. Melatonin administration did reduce anxiety in TS mice without inducing sensorimotor alterations, indicating that prolonged treatment with this indoleamine is devoid of noncognitive behavioral side effects (e.g., motor coordination, sensorimotor abilities, or spontaneous activity). Our results suggest that melatonin administration might improve the cognitive abilities of both TS and CO mice, at least partially, by reducing the age‐related degeneration of basal forebrain cholinergic neurons. Thus, chronic melatonin supplementation may be an effective treatment for delaying the age‐related progression of cognitive deterioration found in DS.     

Evaluating how electronic charting affects resident productivity

Electronic medical records (EMRs) are becoming standard to improve the communication of information and longevity of patient records. Using an EMR in the emergency department (ED) could potentially slow residents evaluating patients. We evaluated how introducing an EMR affected resident productivity in an academic ED. We retrospectively studied first year emergency medicine residents from a large, academic, tertiary care center before-and-after the institution of an EMR on July 1st, 2010. No residents from the 2009–2010 class used the EMR, while all of the 2010–2011 residents used the EMR. We performed univariate and multivariate analyses using productivity, measured in patients per hour (pt/hr), as the primary outcome. A mixed-model multivariate regression, stratified by acuity zone, was created incorporating EMR and other possible confounders: admissions, signouts, daily ED volume, and days after July 1st for each shift. The study was granted IRB waiver of informed. We reviewed 2,405 shifts: 1,259 shifts before and 1,146 shifts after EMR implementation. When using the EMR, the univariate analysis estimated a 0.084 pt/hr increase in the high acuity zone (p = 0.1317) and 0.029 pt/hr decrease (p = 0.7085) in the low acuity zone. The multivariate regression estimated a 0.038 pt/hr increase (p = 0.3413) in the high acuity zone and a 0.009 pt/hr increase (p = 0.9049) in the low acuity zone with the EMR. Despite the expectation that electronic charting is detrimental to resident productivity, our analyses do not suggest a significant relationship between resident productivity and using the EMR.     

Cross‐sector emergency planning for water supply utilities and healthcare facilities

The purpose of this article is to outline the criticality of water supply in sustained operations of healthcare facilities, particularly during community emergencies, and to advocate for enhanced cross‐sector support from the water utilities in meeting this need. Information and ideas presented here were developed in the course of a regional project sponsored by the Metropolitan Washington Council of Governments (MWCOG) for development of emergency water supply operations plans for critical water uses in the Washington, DC, area.     

severe disease complicated by osteoporosis

In this illustrative case, rheumatoid disease changed an active, self-supporting woman into a disabled, dependent and depressed person. When disease activity is continuous, early efforts to prevent severe deformity take on great urgency. It is also important to alleviate the psychosocial impact of the disease, which may well be more than even a highly motivated patient can handle alone.