A Comparative Randomized Field Trial on Intramammary and Intramuscular Dry Cow Antibiotic Treatment of Subclinical Staphylococcus aureus Mastitis in Dairy Cows

The efficacy of two dry cow treatment (DCT) regimens for subclinical Staphylococcus aureus mastitis was evaluated in naturally infected dairy cows. At dry‐off, cows were assigned to two treatment groups by randomized blocks on the basis of parity and somatic cell count (SCC). Two antibiotic DCT regimens were used, namely: (1) a single intramammary infusion containing sodium nafcillin, procaine benzylpenicillin and dihydrostreptomycin; and (2) systemic cefquinome administered intramuscularly, twice at a 24‐h interval. In the intramammary (IMM) treatment group, the S. aureus intramammary infection (IMI) rate was reduced from 40% (56/140 quarters) before dry‐off to 20% (28/140) after calving. Seventy per cent (39/56) of the S. aureus‐positive quarters were negative after calving, and 13% (11/84) of the negative quarters were positive after calving. In the systemic treatment group, the S. aureus IMI rate increased from 39% (29/74 quarters) before dry‐off to 55% (41/74) after calving. Twenty‐eight per cent (8/29) of the S. aureus‐positive quarters were negative after calving and 45% (20/45) of the negative quarters were positive after calving. The odds ratio of an S. aureus‐positive quarter being negative after calving in the IMM group relative to the systemic therapy group was 44.6 (95% confidence interval = 2.1–909.1, P < 0.01). Parity, quarter, milk SCC and N‐acetyl‐β‐D‐glucosaminidase were tested in the model, and were found to have no significant effect on S. aureus cure rates or new IMI rates. The IMM treatment resulted in a higher cure rate compared with that observed in previous studies. The very low cure rate after systemic cefquinome treatment was comparable to the spontaneous cure rate observed in untreated controls in previous studies. The unfavourable results of the cefquinome systemic DCT might reflect inadequate pharmacokinetic properties of the drug regarding poor udder penetration in subclinical mastitis and short antimicrobial effect compared with the IMM treatment.     

Development and validation of the General Health Numeracy Test (GHNT)

Objective

Because existing numeracy measures may not optimally assess ‘health numeracy’, we developed and validated the General Health Numeracy Test (GHNT).

Methods

An iterative pilot testing process produced 21 GHNT items that were administered to 205 patients along with validated measures of health literacy, objective numeracy, subjective numeracy, and medication understanding and medication adherence. We assessed the GHNT's internal consistency reliability, construct validity, and explored its predictive validity.

Results

On average, participants were 55.0 ± 13.8 years old, 64.9% female, 29.8% non-White, and 51.7% had incomes ≤$39 K with 14.4 ± 2.9 years of education. Psychometric testing produced a 6-item version (GHNT-6). The GHNT-21 and GHNT-6 had acceptable-good internal consistency reliability (KR-20 = 0.87 vs. 0.77, respectively). Both versions were positively associated with income, education, health literacy, objective numeracy, and subjective numeracy (all p < .001). Furthermore, both versions were associated with participants’ understanding of their medications and medication adherence in unadjusted analyses, but only the GHNT-21 was associated with medication understanding in adjusted analyses.

Conclusions

The GHNT-21 and GHNT-6 are reliable and valid tools for assessing health numeracy.

Practice implications

Brief, reliable, and valid assessments of health numeracy can assess a patient's numeracy status, and may ultimately help providers and educators tailor education to patients.     

Lack of benefit of early awareness to age-related macular degeneration

AIMS: To assess the rate of early awareness to the presence of age-related macular degeneration (AMD) and whether it enables early detection of transition to neovascular AMD (NVAMD) as compared with patients whose first presentation to an ophthalmologist is already at the neovascular stage of disease. METHODS: A retrospective analysis of 268 eyes of 268 consecutive patients with newly diagnosed NVAMD that were treated in a tertiary referral centre was performed. Patients were classified into those who were unaware (Group 1), or aware (Group 2), of the fact that they had AMD before diagnosis of NVAMD. Visual acuity, lesion size and composition, and demographics were compared between both groups. RESULTS: In all, 185 patients (69%) and 83 patients (31%) were classified to Groups 1 and 2, respectively. Patients in Groups 1 and 2 had similar demographic characteristics, presenting visual acuity and lesion size, and lesion compositions. Group 1 patients were more likely to have a positive history for smoking (41 vs26% in Group 2, P=0.03), whereas Group 2 patients were more likely to have positive family history for AMD (20 vs10%, P=0.02). Conclusions: These data suggest that current screening methods fail to identify the majority of patients with AMD before the development of NVAMD. The findings also demonstrate that in the routine clinical setting, prior awareness of AMD may not facilitate early detection of treatable choroidal neovascularization lesions.     

Treatment with bevacizumab and irinotecan for recurrent high-grade glial tumors

BACKGROUND: Response rates to second-line chemotherapy in recurrent high-grade glial tumors are low and new effective treatments are needed. The objective of this study was to evaluate response rates and tolerability of chemotherapy with bevacizumab and irinotecan in recurrent high-grade gliomas. METHODS: Twenty patients with recurrent gliomas were treated with bevacizumab 5 mg/kg and irinotecan 125 mg/m(2) every 2 weeks. The response was evaluated by gadolinium-enhanced magnetic resonance imaging performed every 4 cycles of treatment. RESULTS: The patients received 1 to 22 cycles of treatment. Nine of 19 patients available for response evaluation (47.3%) showed an objective radiologic response: 2 patients (10.5%) a complete response (CR), and 7 patients (36.8%) a partial response (PR). Two additional patients showed stable disease (SD) for 2 and 6 months, respectively. Eight patients developed rapid progression after 1 to 4 cycles of treatment. Median time to progression on treatment was 4.7 months. The 6-month progression-free survival (PFS) and overall survival (OS) were 25% and 55%, respectively. The adverse effects were mild and in all but 2 cases were no more than grade 2. There were no thrombotic complications or significant bleeding other than epistaxis. CONCLUSIONS: The preliminary data show a promising high response rate of recurrent high-grade gliomas to chemotherapy with bevacizumab and irinotecan. The regimen is associated with minimal toxicity.     

Radiation Therapy of Metastatic Spinal Cord Compression. Multidisciplinary team diagnosis and treatment

Purpose: To evaluate the effectiveness of a multidisciplinary approach to spinal cord compression (SCC) in accordance with prospective protocol, providing a uniform approach to diagnosis, decision making concerning optimal treatment modality in any particular case of SCC, treatment performance and evaluation of treatment results. The SCC patients treated by radiation therapy are described.Materials and Methods: Patients with SCC were examined and treated by a multidisciplinary team consisting of a neurologist, radiologist, oncologist, orthopedic surgeon, and neurosurgeon. Seventy-nine patients for whom radiation was recommended received a 30Gy radiation dose to a compression-causing mass and course of high dose dexamethasone. Three fractions of 5Gy and 5 fractions 3Gy each were delivered by Co60 or 8MV photon beam in 12 days. Treatment outcome was essentially evaluated by ambulation capabilities which were considered to be the main problem of SCC. Changes in other neurologic motor, sensory and autonomic disturbances were also evaluated.Results: Seventy-two percent of the patients were already non-ambulatory at diagnosis. The first symptom was motor deficiency in only 33% of them while in all other cases it was pain. Ambulation capability was the main prognosticator of treatment outcome; 90% of patients who were ambulatory before treatment remained so while 33% of the non-ambulatory patients regained their ability to walk. The grade of motor disturbance was also an important variable: among the non-ambulatory patients, 50% of the paretic but only 14% of the plegic ones became ambulatory. Overall, 51% of the study patients were ambulatory after undergoing radiation. The ambulatory state after treatment was the main predictor for survival.Conclusion: Close cooperation of a multidisciplinary team in diagnosis and treatment according to the above protocol enabled the achievement of good results of radiation treatment in SCC. Early diagnosis and early treatment should further enhance therapeutic outcome.     

Efficacy and toxicity of weekly topotecan in recurrent epithelial ovarian and primary peritoneal cancer

OBJECTIVES: We assessed the efficacy and toxicity of once-weekly topotecan (Hycamtin; GlaxoSmithKline) for relapsed or persistent epithelial ovarian cancer (EOC) and primary peritoneal carcinoma (PPC). METHODS: Patients with recurrent or persistent EOC and PPC previously treated with > or = 1 course of platinum-based chemotherapy were treated with weekly topotecan 4.0 mg/m2 on days 1, 8, and 15 of a 28-day cycle in this prospective open-label, single-arm, phase II study. RESULTS: The median age of the 63 study patients was 63 years (range, 36-88); patients had been previously exposed to a median of 1 course (range, 1-4) of chemotherapy. A median of 5 courses (range, 1-16) were administered. Median follow-up time was 13. 2 month s (range, 1.5-39.0). The overall response rate (RR) was 23.8%, of which 17.5% (11 patients) represented a complete response and 6.3% (4 patients) a partial response. Patients with platinum-sensitive disease had a RR of 20%, whereas patients with platinum-resistant disease had a RR of 28.6%. Median time to progression was 6.2 months (95% confidence interval: 4.43, 7.97), and median survival from initiation of topotecan therapy was 22.3 months (95% confidence interval: 14.56, 30.04). Hematologic toxicities included grade 3 anemia in 3 (4.8%) patients, grade 3 thrombocytopenia in 3 (4.8%) patients, and grades 3-4 neutropenia in 5 (7.9%) patients. Dose reductions, granulocyte colony-stimulating factor, and erythropoietin support were required by 10 (15.9%), 6 (9.5%), and 16 (25.4%) patients, respectively. The most frequent nonhematologic toxicities were grades 2-3 fatigue in 10 (15.9%) patients and grades 2-3 nausea/vomiting in 3 (4.7%) patients. CONCLUSION: Weekly administration of topotecan 4.0 mg/m2 is active and well tolerated by patients with recurrent or persistent EOC and PPC.     

Phase I trial of sorafenib in combination with 5-fluorouracil/leucovorin in advanced solid tumors

This dose escalation, uncontrolled phase I study evaluated the tolerability, pharmacokinetics (PK), and antitumor activity of oral sorafenib 100, 200, or 400 mg twice daily (bid, continuous regimen) in combination with 5-fluorouracil/leucovorin (5-FU/LCV, intravenous infusion or bolus) in patients with advanced, solid tumors. A total of 47 patients (median age 57 years; colon cancer, 55%; pancreatic cancer, 21%; prior systemic therapy, 96%) received treatment; 24 were included in the PK analyses, and 38 were evaluable for tumor response. Treatment-emergent adverse events were observed in 98% of patients (≥grade 3, 55%); the most frequently reported were fatigue (51%), stomatitis/pharyngitis (47%), and hand-foot skin reaction (45%). Concomitant 5-FU/LCV resulted in no clinically relevant changes in the area under the plasma concentration-time curve in the dosing interval (AUC(0-12)) and maximum plasma concentration (C(max)) of sorafenib (100-400 mg bid) at steady state. Although the start of infusion until the last quantifiable plasma concentration (AUC(0-tn)) and C(max) of 5-FU were increased by concomitant sorafenib 100 to 200 mg, no consistent effect was observed with 400 mg sorafenib. Two (5%) patients with colon cancer achieved partial response; 16 (42%) patients (the majority with colon and pancreatic cancer) had stable disease. Sorafenib plus 5-FU/LCV was generally well tolerated with encouraging antitumor activity and no clinically relevant drug-drug interactions in patients with advanced solid tumors.