We searched the MEDLINE, CINAHL, and Cochrane Library databases for articles published between January 1995 and April 2011. The update of this clinical practice guideline is the result of reviewing a total of 54 clinical trials and systematic reviews on incentive spirometry. The following recommendations are made following the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) scoring system. 1: Incentive spirometry alone is not recommended for routine use in the preoperative and postoperative setting to prevent postoperative pulmonary complications. 2: It is recommended that incentive spirometry be used with deep breathing techniques, directed coughing, early mobilization, and optimal analgesia to prevent postoperative pulmonary complications. 3: It is suggested that deep breathing exercises provide the same benefit as incentive spirometry in the preoperative and postoperative setting to prevent postoperative pulmonary complications. 4: Routine use of incentive spirometry to prevent atelectasis in patients after upper-abdominal surgery is not recommended. 5: Routine use of incentive spirometry to prevent atelectasis after coronary artery bypass graft surgery is not recommended. 6: It is suggested that a volume-oriented device be selected as an incentive spirometry device.

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Background and Purpose-High blood pressure (BP) in acute stroke is associated independently with a poor outcome.Recent evidence suggests that other hemodynamic parameters may also be associated with outcomes following stroke. Methods-The relationship between baseline BP, heart rate, and other hemodynamic parameters, and early outcomes were assessed using data from TAIST trial. Results-Death or neurological deterioration at day 10 was associated, both in unadjusted and adjusted analyses, with systolic BP (adjusted OR, 1.02; 95% CI, 1.01-1.03), mean arterial pressure (OR, 1.02; 95% CI, 1.01-1.04), pulse pressure (OR, 1.02; 95% CI, 1.01-1.03), and BP variability (OR, 1.03; 95% CI, 1.01-1.05). Similar relationships were noted for deterioration alone, and recurrent stroke. Conclusions-Early death or neurologic deterioration, deterioration, and recurrent stroke are associated independently with high systolic BP, mean arterial pressure, pulse pressure, and BP variability. These measures offer potential therapeutic targets for improving early outcome after acute ischemic stroke. (Stroke. 2011;42:491-493.)

Preclinical studies show that adavosertib, a WEE1 kinase inhibitor, sensitizes TP53-mutant cells to chemotherapy. We hypothesized that adavosertib, plus chemotherapy, would enhance efficacy versus placebo in TP53-mutated ovarian cancer.Patients and Methods: Following safety run-in, this double-blind phase II trial (NCT01357161) randomized women with TP53-mutated, platinum-sensitive ovarian cancer to oral adavosertib (225 mg twice daily for 2.5 days/21-day cycle) or placebo, plus carboplatin (AUC5) and paclitaxel (175 mg/m 2 ), until disease progression or for six cycles. The primary endpoints were progression-free survival (PFS) by enhanced RECIST v1.1 [ePFS (volumetric)] and safety. Secondary/exploratory objectives included PFS by RECIST v1.1 (single dimension), objective response rate, overall survival, and analysis of tumor gene profile versus sensitivity to adavosertib.Results: A total of 121 patients were randomized to adavosertib (A þ C; n ¼ 59) and placebo (P þ C; n ¼ 62) plus chemotherapy.Adding adavosertib to chemotherapy improved ePFS [median, 7.9 (95% confidence interval (CI), 6.9-9.9) vs. 7.3 months (5.6-8.2); HR 0.63 (95% CI, 0.38-1.06); two-sided P ¼ 0.080], meeting the predefined significance threshold (P < 0.2). Clinical benefit was observed following A þ C for patients with different TP53 mutation subtypes, identifying possible response biomarkers. An increase in adverse events was seen with A þ C versus P þ C: greatest for diarrhea (adavosertib 75%; placebo 37%), vomiting (63%; 27%), anemia (53%; 32%), and all grade ≥3 adverse events (78%; 65%).Conclusions: Establishing an optimal strategy for managing tolerability and identifying specific patient populations most likely to benefit from treatment may increase clinical benefit. Future studies should consider additional adavosertib doses within the chemotherapy treatment cycle and the potential for maintenance therapy.

Drugs based on nitroarene, aromatic N-oxide or quinone structures are frequently reduced by cellular reductases to toxic products. Reduction often involves free radicals as intermediates which react rapidly with oxygen to form superoxide radicals, inhibiting drug reduction. The elevation of cellular oxidative stress accompanying oxygen inhibition of reduction is generally less damaging than drug reduction to toxic products, so the drugs offer selective toxicity to hypoxic cells. Since such cells are resistant to radiotherapy, these bioreductive drugs offer potential in tumour therapy. The basis for the selectivity of action entails kinetic competition involving the contesting reaction pathways. The reduction potential of the drug, radical pKa and nature of radical/radical decay kinetics all influence drug activity and selectivity, including the range of oxygen tensions over which the drug offers selective toxicity. These properties may be quantified using generation of radicals by pulse radiolysis, presenting a physicochemical basis for rational drug design.