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E-Exercise is an effective 12-week blended intervention consisting of around five face-to-face physiotherapy sessions and a web-based application for patients with hip/knee osteoarthritis. In order to facilitate effective implementation of e-Exercise, this study aims to identify physiotherapists' experiences and determinants related to the usage of e-Exercise. Methods: An explanatory sequential mixed methods design embedded in a randomized controlled trial comparing e-Exercise with usual physiotherapy in patients with hip/knee osteoarthritis. Usage of e-Exercise was based on recruitment rates of 123 physiotherapists allocated to e-Exercise and objective web-based application usage data. Experiences and determinants related to e-Exercise usage were investigated with a questionnaire and clarified with semi-structured interviews. Results: Of the 123 physiotherapists allocated to e-Exercise, 54 recruited more than one eligible patient, of whom 10 physiotherapists continued using e-Exercise after the study period. Physiotherapists had mixed experiences with e-Exercise. Determinants related to intervention usage were appropriateness, added value, time, workload, professional autonomy, environmental factors, and financial consequences. Physiotherapists recommended to improve the ability to tailor e-Exercise to the individual needs of the patient patients' individual needs. Discussion: Determinants related to the usage of e-Exercise provided valuable information for the implementation of e-Exercise on broader scale. Most importantly, the flexibility of e-Exercise needs to be improved. Next, there is a need for education on how to integrate an online program within physiotherapy.

Background: Our aim was to develop a rating scale to assess the therapeutic validity of therapeutic exercise programmes. By use of this rating scale we investigated the therapeutic validity of therapeutic exercise in patients awaiting primary total joint replacement (TJR). Finally, we studied the association between therapeutic validity of preoperative therapeutic exercise and its effectiveness in terms of postoperative functional recovery. Methods: (Quasi) randomised clinical trials on preoperative therapeutic exercise in adults awaiting TJR on postoperative recovery of functioning within three months after surgery were identified through database and reference screening. Two reviewers extracted data and assessed the risk of bias and therapeutic validity. Therapeutic validity of the interventions was assessed with a nine-itemed, expert-based rating scale (scores range from 0 to 9; score ≥6 reflecting therapeutic validity), developed in a four-round Delphi study. Effects were pooled using a random-effects model and meta-regression was used to study the influence of therapeutic validity. Results: Of the 7,492 articles retrieved, 12 studies (737 patients) were included. None of the included studies demonstrated therapeutic validity and two demonstrated low risk of bias. Therapeutic exercise was not associated with 1) observed functional recovery during the hospital stay (Standardised Mean Difference [SMD]: -1.19; 95%-confidence interval [CI], -2.46 to 0.08); 2) observed recovery within three months of surgery (SMD: -0.15; 95%-CI, -0.42 to 0.12); and 3) self-reported recovery within three months of surgery (SMD -0.07; 95%-CI, -0.35 to 0.21) compared with control participants. Meta-regression showed no statistically significant relationship between therapeutic validity and pooled-effects. Conclusion: Preoperative therapeutic exercise for TJR did not demonstrate beneficial effects on postoperative functional recovery. However, poor therapeutic validity of the therapeutic exercise programmes may have hampered potentially beneficial effects, since none of the studies met the predetermined quality criteria. Future review studies on therapeutic exercise should address therapeutic validity. © 2012 Hoogeboom et al.

To investigate the pharmacokinetics and pharmacodynamics of paclitaxel (P) and carboplatin (C) in a sequence-finding and dose-escalating study in untreated non-small-cell lung cancer (NSCLC) patients. Fifty-five chemotherapy-naive patients with NSCLC were entered onto the pharmacokinetic part of a large phase I trial in which P was administered as a 3-hour infusion at dosages of 100 to 250 mg/m2, and C over 30 minutes at dosages of 300 to 400 mg/m2. Patients were randomized for the sequence of administration, first C followed by P or vice versa. Each patient received the alternate sequence during the second and subsequent courses. The most important hematologic toxicity encountered-was neutropenia. Hematologic toxicity was not dependent on the sequence in which P and C were administered, but there was cumulative neutropenia. Nonhematologic toxicities consisted mainly of vomiting, myalgia, and arthralgia. No sequence-dependent pharmacokinetic interactions for the P area under the concentration-time curve (P-AUC), maximal plasma concentration (P-Cmax), or time above a threshold concentration of 0.1 mumol/L (P-T > or = 0.1 mumol/L) were observed. However, there was a significant difference for the metabolite 6 alpha-hydroxypaclitaxel AUC (6OHP-AUC). Higher 6OHP-AUCs were observed when C was administered before P. The mean plasma ultrafiltrate AUC of C (CpUF-AUC) at the dosage of 300 mg/m2 for the sequence C-->P was 3.52 mg/mL.min (range, 1.94 to 5.83) and 3.62 mg/mL.min for the sequence P-->C (range, 1.91 to 5.01), which is not significantly different (P = .55). Of 45 assessable patients, there were five major responders (three complete responders and two partial responders). Four of five responses occurred at dosages above dose level 4 (P 175 mg/m2 + C 300 mg/m2). The median survival duration was best correlated with the P dose (4.8 months for doses or = 175 mg/m2, P = .07; P-T > or = 0.1 mumol/L, 4.8 months for or = 15 hours, P = .06). There was no pharmacokinetic-sequence interaction between C and P in this study. A clear dose-response relation with respect to response rate and survival was observed. The pharmacokinetic parameter P-T > or = 0.1 mumol/L was related to improved survival in this study

To determine the maximum-tolerated dose for the combination paclitaxel and carboplatin administered every 4 weeks and to gain more insight into the pharmacokinetics and pharmacodynamics of this combination in previously untreated ovarian cancer patients. Thirty-five chemotherapy-naive patients with suboptimally debulked stage III (tumor masses > 3 cm) and stage IV ovarian cancer were entered onto this phase I trial in which paclitaxel was administered as a 3-hour intravenous (IV) infusion at dosages of 125 to 225 mg/m2 immediately followed by carboplatin over 30 minutes at dosages of 300 to 600 mg/m2. A total of six courses was planned, followed by a second-look laparoscopy/laparotomy. Patients with a response and/or minimal residual disease at second-look laparoscopy received three additional courses. Twenty-six patients participated in the pharmacokinetic part of the study. The most important hematologic toxicity encountered was neutropenia. Neutropenia was more pronounced for the higher dose levels (DLs) and was cumulative. Thrombocytopenia was mild in the first eight DLs, but increased during the treatment courses. Nonhematologic toxicities consisted mainly of vomiting, neuropathy, fatigue, rash, pruritus, myalgia, and arthralgia. Dose-limiting toxicities (DLTs) in this trial were neutropenic fever, thrombocytopenia that required platelet transfusions, and cumulative neuropathy. Of 33 patients assessable for response, 26 major responders (78%, 20 complete response [CR] and six partial response [PR]) were documented. The maximal concentration (Cmax) of paclitaxel and the area under the concentration-time curve (AUC) were not different from the historical data for paclitaxel as a single agent. Retrospective analysis using a modified Calvert formula showed that the measured carboplatin AUCs in plasma ultrafiltrate (pUF) were 30% +/- 3.4% less than the calculated carboplatin AUC. Neutropenia was more pronounced than could be expected on the basis of the historical times above a threshold concentration greater than 0.1 mumol/L (T > or = 0.1 mumol/L) or 0.05 mumol/L (T > or = 0.05 mumol/L), and thrombocytopenia was less than could be expected from historical sigmoidal Emax models. The combination of paclitaxel 200 mg/ m2 and carboplatin 550 mg/m2 every 4 weeks is a well-tolerated treatment modality. The paclitaxel-carboplatin combination is highly active in stage III (bulky) and stage IV ovarian cancer. No indications for a pharmacokinetic drug-drug interaction between carboplatin and paclitaxel were found

The role of IL-6 as a mediator of haemostatic changes during severe inflammation is controversial. To assess the effect of IL-6 on haemostasis we conducted a controlled cross-over study in eight patients with metastatic renal cell cancer. In all subjects coagulation and fibrinolysis were monitored during and after a 4-h infusion of either 150 micrograms recombinant human (rh) IL-6, or during infusion of saline (control study). Mean maximum IL-6 concentrations were 1418.0 +/- 755.8 pg/ml. Compared to the control study, rhIL-6 induced activation of coagulation as reflected by a 190 +/- 55% increase in the plasma levels of thrombin-antithrombin III complexes (p

Interleukin-6 (IL-6) is one of the major circulating cytokines in catabolic states. To investigate its endocrinologic and metabolic actions in vivo, we studied eight patients with metastatic renal cell cancer two times, once during infusion of saline (control) and once during a 4-h infusion of 150 micrograms recombinant human IL-6 (rhIL-6). Rates of appearance (Ra) of glucose and free fatty acids (FFA) in plasma were measured by using the isotope dilution method. Energy expenditure and substrate oxidation were determined by indirect calorimetry. rhIL-6 induced increases in plasma norepinephrine (+261 +/- 97%, P

For evaluating the role of photodynamic therapy (PDT) in the local treatment of acquired immune deficiency syndrome (AIDS)-related cutaneous Kaposi's sarcoma (KS), nine treatments were performed in eight human immunodeficiency virus-positive homosexual men. The patients received 2 mg Photofrin/kg and either 120 J/cm2 (n = 5) or 70 J/cm2 (n = 4) laser light (630 nm). A total of 83 lesions were evaluable for response with a follow-up of 3-8 months. The overall response rates by patient for all treated lesions were 50-100% (120 J/cm2) and 83.3-90.3% (70 J/cm2), with a median duration of 3 months (range, 2-6 months). Tumors located at the head had higher response rates than those at the trunk or extremities (p = 0.005 and p - 0.015 respectively). The size of the KS showed a negative relationship with the probability of complete response (p = 0.047). Local and general side effects occurred, including pain, blisters, temperature increase, muscle stiffness, and severe edema. The cosmetic result was unsatisfactory because of a high prevalence of scars and long-lasting hyperpigmentation. Although the response rates of PDT are high, light dose of 70-120 J/cm2 cannot be recommended in the treatment of cutaneous KS in combination with 2 mg/kg Photofrin because of severe side effects and unsatisfactory cosmetic result