Select Manual Assessment Techniques and Clinical Reasoning Skills Used in Canine Physical Rehabilitation Before Engaging in Manual Therapy Treatment.

Manual therapy is a cornerstone of physical therapy and canine physical rehabilitation. Although veterinary literature has tackled the topic of manual therapy treatments in animal patients, less attention has been paid to the assessment techniques and clinical reasoning skills that guide a practitioner toward determining if, when, and where manual therapies will be most effective. This article tackles the topics of clinical reasoning, the functional diagnosis, observational skills, and physical evaluation techniques that serve as prerequisites to the use of manual therapeutics.

Evaluation of patient and provider satisfaction with a pharmacist-managed lipid clinic in a Veterans Affairs medical center.

PURPOSE: Patient and provider satisfaction with a pharmacist-managed lipid clinic in a Veterans Affairs medical center were assessed. METHODS: All patients at Louis Stokes Cleveland Veterans Affairs Medical Center who were referred to a pharmacist-managed lipid clinic for drug therapy management were mailed a questionnaire addressing overall satisfaction with care provided by the lipid clinic. Chart reviews were performed for patients completing the questionnaire to ascertain lipid-lowering medications used, changes in serum cholesterol levels, and achievement of low-density-lipoprotein (LDL) cholesterol goal. Health care providers referring patients to the lipid clinic were sent an anonymous electronic questionnaire to assess provider satisfaction with the clinic. Responses to the questionnaire were rated on a Likert scale (strongly agree, somewhat agree, neutral, somewhat disagree, strongly disagree). A paired t test was used to assess the percent change in lipid values, and chi-square analysis was used to evaluate the achievement of each patient's LDL cholesterol goal. RESULTS: Surveys were sent to 224 patients and 104 providers. A total of 105 patients (47%) and 49 providers (47%) completed the questionnaire. Most patients and providers expressed satisfaction with the clinic, with 91.4% of patients and 87.8% of providers indicating that they were strongly or somewhat satisfied with the care provided by the pharmacist-managed clinic. Attainment rates of goal LDL cholesterol levels increased from 8.6% at baseline to 53.3% at discharge or the most recent measurement (p < 0.001). CONCLUSION: Most patients and providers were satisfied with the services provided by the pharmacist-managed lipid clinic. The clinic helped improve patients' LDL cholesterol, total cholesterol, and triglyceride levels.

Phase I study of the novel taxane CT-2103 in patients with advanced solid tumors.

BACKGROUND: CT-2103 (Cell Therapeutics, Seattle, Wash.) is a water-soluble macromolecular conjugate of paclitaxel to a polyglutamate backbone, designed to enhance tumor permeability and to improve intratumoral delivery of paclitaxel. Preclinical studies indicate that CT-2103 has substantial antitumor efficacy in xenograft tumor models. METHODS: We performed a phase I trial in patients with advanced solid tumors to determine the maximum tolerated doses (MTD) of CT-2103 when administered as short intravenous infusion every 3 weeks. RESULTS: Seven patients received a total of 16 cycles (range 1-3) of CT-2103 at doses of 235 and 270 mg/m(2). Two of five patients treated at 235 mg/m(2) and one of two patients treated at 270 mg/m(2) experienced grade 3/4 neutropenia. Four patients experienced a marked increase in PTT within 30 min of the start of infusion. Neuropathy was more severe than expected. Two patients developed grade 3 neuropathy that prompted a 50% dose reduction of CT-2103 and persisted for 8 months in one, and over a year in the other. Three patients experienced grade 1 or 2 neuropathy. Neurotoxicity was cumulative and prevented patients from receiving prolonged administration of CT-2103. CONCLUSIONS: The unexpectedly high rate of cumulative toxicity observed in our study needs to be taken into consideration in future trials of CT-2103. Prior taxane use may not be a predictor of severe neurotoxicity.

Phase I trial of hydroxychloroquine with dose-intense temozolomide in patients with advanced solid tumors and melanoma.

Blocking autophagy with hydroxychloroquine (HCQ) augments cell death associated with alkylating chemotherapy in preclinical models. This phase I study evaluated the maximum tolerated dose (MTD), safety, preliminary activity, pharmacokinetics, and pharmacodynamics of HCQ in combination with dose-intense temozolomide (TMZ) in patients with advanced solid malignancies. Forty patients (73% metastatic melanoma) were treated with oral HCQ 200 to 1200 mg daily with dose-intense oral TMZ 150 mg/m (2) daily for 7/14 d. This combination was well tolerated with no recurrent dose-limiting toxicities observed. An MTD was not reached for HCQ and the recommended phase II dose was HCQ 600 mg twice daily combined with dose-intense TMZ. Common toxicities included grade 2 fatigue (55%), anorexia (28%), nausea (48%), constipation (20%), and diarrhea (20%). Partial responses and stable disease were observed in 3/22 (14%) and 6/22 (27%) patients with metastatic melanoma. In the final dose cohort 2/6 patients with refractory BRAF wild-type melanoma had a near complete response, and prolonged stable disease, respectively. A significant accumulation in autophagic vacuoles (AV) in peripheral blood mononuclear cells was observed in response to combined therapy. Population pharmacokinetics (PK) modeling, individual PK simulations, and PK-pharmacodynamics (PD) analysis identified a threshold HCQ peak concentration that predicts therapy-associated AV accumulation. This study indicates that the combination of high-dose HCQ and dose-intense TMZ is safe and tolerable, and is associated with autophagy modulation in patients. Prolonged stable disease and responses suggest antitumor activity in melanoma patients, warranting further studies of this combination, or combinations of more potent autophagy inhibitors and chemotherapy in melanoma.

Implementation and methodology of a multidisciplinary disease-state-management program for comprehensive diabetes care.

INTRODUCTION: Before the implementation of a multidisciplinary disease-state-management program in the Kaiser Permanente Ohio Region, the primary care physician (PCP) worked with a registered nurse care manager (RNCM) and a clinical pharmacist with the degree of PharmD to control diabetes mellitus (DM). This occurred through PCP referral when patients required a higher level of care than could be achieved during initial PCP office visits and subsequent follow-up visits. However, not all PCPs consistently initiated referrals, and as patients in need of referral were typically identified through office visits, those without routine appointments were often missed. This practice translated into suboptimal 2008 comprehensive DM care Healthcare Effectiveness Data and Information Set (HEDIS) scores. METHODS: A quality-improvement disease-management committee convened for design and implementation of a multidisciplinary DM disease-state-management program, as well as oversight and analysis of the new process. This regional intervention required many members of the health care team to obtain additional education about comprehensive DM care, adopt new work flows, and learn to use tools for evaluating patient care gaps. RESULTS: Within one year, this regional multidisciplinary intervention resulted in improvements in blood pressure, lipid levels, and glycemic control as indicated by 2009 comprehensive DM-care HEDIS scores. DISCUSSION: Main contributors to the success of the program included executive support and sponsorship, the leadership of the oversight committee, systematic identification and assignment of patients, the blood-pressure service run by licensed practical nurses, continuous education efforts, dedicated panel-management time, use of a multidisciplinary team, and expanding treatment of the diabetic patient beyond glucose control to include blood pressure and lipid management.

Phase II Trial of Temozolomide and Sorafenib in Advanced Melanoma Patients with or without Brain Metastases.

PURPOSE: The combination of the oral alkylating agent temozolomide and the oral multikinase inhibitor sorafenib was evaluated in advanced melanoma patients. EXPERIMENTAL DESIGN: Patients with metastatic melanoma (n = 167) were treated on four arms. All patients received sorafenib at 400 mg p.o. twice daily without interruption. Patients without brain metastases or prior temozolomide were randomized between arm A: extended dosing of temozolomide (75 mg/m(2) temozolomide daily for 6 of every 8 weeks) and arm B: standard dosing (150 mg/m(2) temozolomide daily for 5 of every 28 days). Patients previously treated with temozolomide were enrolled on arm C: extended dosing of temozolomide. Patients with brain metastases and no prior temozolomide were assigned to arm D: standard dosing. The primary end point was 6-month progression-free survival (PFS) rate. Secondary end points included response rate, toxicity rates, and the rates of BRAF or NRAS mutations. RESULTS: The 6-month PFS rate for arms A, B, C, and D were 50%, 40%, 11%, and 23%. The median PFS for patients on arm A, B, C, and D was 5.9, 4.2, 2.2, and 3.5 months, respectively. No significant differences were observed between arms A and B in 6-month PFS rate, median PFS, or response rates. Treatment was well tolerated in all arms. No significant differences in toxicity were observed between arms A and B except for more grade 3 to 4 lymphopenia in arm A. CONCLUSION: Temozolomide plus sorafenib was well tolerated and showed activity in melanoma patients without prior history of temozolomide. The activity of this combination regimen warrants further investigation. (Clin Cancer Res 2009;15(24):7711-8).

Clinical activity and immune modulation in cancer patients treated with CP-870,893, a novel CD40 agonist monoclonal antibody.

PURPOSE: The cell-surface molecule CD40 activates antigen-presenting cells and enhances immune responses. CD40 is also expressed by solid tumors, but its engagement results in apoptosis. CP-870,893, a fully human and selective CD40 agonist monoclonal antibody (mAb), was tested for safety in a phase I dose-escalation study. PATIENTS AND METHODS: Patients with advanced solid tumors received single doses of CP-870,893 intravenously. The primary objective was to determine safety and the maximum-tolerated dose (MTD). Secondary objectives included assessment of immune modulation and tumor response. RESULTS: Twenty-nine patients received CP-870,893 in doses from 0.01 to 0.3 mg/kg. Dose-limiting toxicity was observed in two of seven patients at the 0.3 mg/kg dose level (venous thromboembolism and grade 3 headache). MTD was estimated as 0.2 mg/kg. The most common adverse event was cytokine release syndrome (grade 1 to 2) which included chills, rigors, and fever. Transient laboratory abnormalities affecting lymphocytes, monocytes, platelets, D-dimer and liver function tests were observed 24 to 48 hours after infusion. Four patients with melanoma (14% of all patients and 27% of melanoma patients) had objective partial responses at restaging (day 43). CP-870,893 infusion resulted in transient depletion of CD19+ B cells in blood (93% depletion at the MTD for < 1 week). Among B cells remaining in blood, we found a dose-related upregulation of costimulatory molecules after treatment. CONCLUSION: The CD40 agonist mAb CP-870,893 was well tolerated and biologically active, and was associated with antitumor activity. Further studies of repeated doses of CP-870,893 alone and in combination with other antineoplastic agents are warranted.

The SWAL-QOL and SWAL-CARE outcomes tool for oropharyngeal dysphagia in adults: III. Documentation of reliability and validity.

Advances in the measurement of swallowing physiologic parameters have been clinician-driven, as has the development of intervention techniques to modify swallowing pathophysiology. However, a critical element to determining the success of such efforts will be established by the patients themselves. We conceptualized, developed, and validated the SWAL-QOL, a 93-item quality-of-life and quality-of-care outcomes tool for dysphagia researchers and clinicians. With 93 items, the SWAL-QOL was too long for practical and routine use in clinical research and practice. We used an array of psychometric techniques to reduce the 93-item instrument into two patient-centered outcomes tools: (1) the SWAL-QOL, a 44-item tool that assesses ten quality-of-life concepts, and (2) the SWAL-CARE, a 15-item tool that assesses quality of care and patient satisfaction. All scales exhibit excellent internal-consistency reliability and short-term reproducibility. The scales differentiate normal swallowers from patients with oropharyngeal dysphagia and are sensitive to differences in the severity of dysphagia as clinically defined. It is intended that the standardization and publication of the SWAL-QOL and the SWAL-CARE will facilitate their use in clinical research and clinical practice to better understand treatment effectiveness as a critical step toward improving patients' quality of life and quality of care.