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Although there is a growing awareness of evidence-based practice among physical therapists, implementation of evidence-based practice has proved difficult. This article discusses barriers to access and interpretation of evidence. Some solutions are offered, including facilitating the publication of all research, use of an optimum format for reporting research, maximizing the efficient use of electronic databases, improving physical therapists' skills in critical appraisal of published research, and fostering consumer access to evidence. These strategies and others discussed in the article might facilitate implementation of evidence-based physical therapy.

During life-changing events, people turn to spirituality for comfort, hope, and relief. This article raises nurses' awareness of and intent to provide spiritual care for children and families as part of overall quality care. Essential nursing knowledge for the development of a plan of care that includes the child's spirituality, religion, and culture, developmental stage, age-appropriate spiritual care activities, and the needs of the family are presented.

Aim: To investigate whether a lessened glucocorticoid cumulative dose would lead to a decreased incidence of femoral head osteonecrosis., Methods: Newly transplanted in-patients (n = 49) underwent hip radiographs and magnetic resonance imaging (MRI) a mean of 17.0+/-4.3 (range 8-29) days after renal transplantation. For the 48 patients without evidence of prevalent osteonecrosis, imaging at a mean of 5.9+/-0.8 (range 4.8-8.7) months after renal transplantation was graded for presence/absence of femoral head osteonecrosis by two blinded radiologists. Sociodemographic and disease characteristics of patients were compared to identify potential associations with incident osteonecrosis., Results: At 6-month follow-up, only two patients (4%) had osteonecrosis of the femoral head (three hips). The two primary radiologists had excellent agreement between osteonecrosis diagnosis (kappa coefficient=0.78). Both cases of a definite MRI diagnosis of osteonecrosis occurred in patients who were in the highest tertile of glucocorticoid dosage., Conclusion: Osteonecrosis was uncommon among a prospective cohort of renal transplant recipients within 6 months after engraftment.

Background and Purpose: Assessment of the quality of randomized controlled trials (RCTs) is common practice in systematic reviews. However, the reliability of data obtained with most quality assessment scales has not been established. This report describes 2 studies designed to investigate the reliability of data obtained with the Physiotherapy Evidence Database (PEDro) scale developed to rate the quality of RCTs evaluating physical therapist interventions., Method: In the first study, 11 raters independently rated 25 RCTs randomly selected from the PEDro database. In the second study, 2 raters rated 120 RCTs randomly selected from the PEDro database, and disagreements were resolved by a third rater; this generated a set of individual rater and consensus ratings. The process was repeated by independent raters to create a second set of individual and consensus ratings. Reliability of ratings of PEDro scale items was calculated using multirater kappas, and reliability of the total (summed) score was calculated using intraclass correlation coefficients (ICC [1,1])., Results: The kappa value for each of the 11 items ranged from.36 to.80 for individual assessors and from.50 to.79 for consensus ratings generated by groups of 2 or 3 raters. The ICC for the total score was.56 (95% confidence interval=.47-.65) for ratings by individuals, and the ICC for consensus ratings was.68 (95% confidence interval=.57-.76)., Discussion and Conclusion: The reliability of ratings of PEDro scale items varied from "fair" to "substantial," and the reliability of the total PEDro score was "fair" to "good."

Genetic investigations were carried out with 50 phenotypically selected strains of Pseudomonas aeruginosa from 18 patients attending an Australian cystic fibrosis (CF) center. The isolates were analyzed by restriction fragment length polymorphism (RFLP) analysis by pulsed-field gel electrophoresis (PFGE). Phylogenetic analysis of the macrorestriction patterns showed rates of genetic similarity ranging from 76 to 100%; 24 (48%) of the strains from 11 patients had greater than 90% similarity. A dominant strain emerged: 15 isolates from seven patients had identical PFGE patterns, and 4 other isolates were very closely related. The 50 isolates were grouped into 21 pulsotypes on the basis of visual delineation of a three-band difference. Ten of the 18 (56%) patients were infected with clonal or subclonal strains. Sequence analysis of PCR products derived from the mucA gene showed 20 mutations, with the number of mutations in individual isolates ranging from 1 to 4; 19 of these changes are reported here for the first time. Potentially functional changes were found in 22 (44%) isolates. Eight changes (five transversions and three single base deletions) led to premature stop codons, providing support for the presence of mucA mutations as one pathway to mucoidy. There was a trend toward an association between the dominant strain and lack of potentially functional mucA mutations (P = 0.09 by the chi(2) test) but no relationship between genotype and phenotype. This is the first study of genetic variation in P. aeruginosa isolates from adult Australian CF patients. The findings highlight the need for further investigations on the transmissibility of P. aeruginosa in CF patients.

Endothelial cells (EC) that form the inner lining of blood vessels remain quiescent in the normal adult vasculature except during angiogenesis and reendothelialization, which result in EC proliferation and migration. EC placed in culture at subconfluent density also undergo cell multiplication and movement. This report demonstrates that whereas in confluent EC in a compact monolayer, the EC-EC adhesion molecule platelet-endothelial cell adhesion molecule-1 (PECAM-1) is strongly expressed at cell borders, little or no PECAM-1 immunostaining is detected in sparse or migrating cultured EC. Consistent with this observation, steady-state PECAM-1 mRNA expression was much lower in subconfluent EC than in confluent EC. The absence of PECAM-1 expression in sparse EC appeared not to be linked to ability to proliferate, since PECAM-1 expression remained low even in the presence of nitric oxide (NO) or mitomycin C, agents that inhibit EC growth. However, another growth-inhibitory agent, TGF-beta 1, did not alter PECAM-1 staining. Based on these observations, it is hypothesized that cell-associated mechanical forces underlying cell tensegrity regulate PECAM-1 expression.

The immunologic and virologic efficacy and safety of interferon a (IFN-alpha) administered in combination with zidovudine (ZDV) and zalcitabine (ddC) was evaluated in HIV-infected subjects with CD4+ cell counts between 300 and 500 cells/ml and no more than 14 weeks of prior antiretroviral therapy. A total of 256 subjects enrolled in an open-label, randomized controlled trial. Subjects were randomized equally into treatment groups. All subjects received ZDV and ddC, while half also receive IFN-alpha (3 MU subcutaneously every 24 hr). At 48 weeks the median average area under the curve minus baseline (AAUCMB) for plasma HIV-1 RNA for the two-drug group was -0.68 versus -0.75 log10 copies/ml for the IFN-alpha group (p = 0.046). Mean HIV-1 RNA changes from baseline to 48 weeks for these groups were -0.65 and -1.12 log10 copies/ml, respectively (p = 0.010). The median AAUCMB for CD4+ cell count for the two-drug group was 28 versus -1 cells/mm3 for the IFN-alpha group (p = 0.011). Neutropenia, anemia, and drug intolerance were more common in the IFN-alpha group. This study demonstrates that IFN-alpha inhibits HIV-1 replication but attenuates the CD4+ cell response to dual therapy with ZDV and ddC.

We conducted a randomised, double-blind, parallel design study comparing the efficacy and tolerability of the angiotensin II receptor antagonist, losartan, alone or with low-dose hydrochlorothiazide (HCTZ) to the dihydropyridine calcium channel blocker, nifedipine GITS (gastro-intestinal therapeutic system), in elderly patients (> or =65 years old) with a diastolic blood pressure (DBP) between 95 and 115 mm Hg. After a placebo wash out period, 140 patients were randomly assigned to receive either losartan 50 mg or nifedipine GITS 30 mg. Patients were evaluated at 4-week intervals during a 12-week treatment period. Patients receiving losartan had HCTZ 12.5 mg added and increased to 25 mg to reduce DBP <90 mm Hg. Patients receiving nifedipine GITS had their dose increased to 60 mg and 90 mg to reduce DBP <90 mm Hg. Efficacy, tolerability and quality of life were assessed during the 12 weeks on each regimen. Patients treated with the losartan regimen (n = 73) had reductions in trough sitting DBP of -10, -13, and -13 mm Hg after 4, 8, and 12 weeks of therapy, respectively. Patients receiving the nifedipine GITS regimen (n = 67) had DBP reductions of -14, -15, and -15 mm Hg, respectively. There were no significant differences in the DBP response between the treatment groups except at week 4 (P < 0.05). Similar reductions in systolic BP (SBP) between the two treatment groups were observed at all time points. The percentages of patients in the two treatment groups reaching goal DBP (<90 mm Hg or DBP > or =90 mm Hg with a reduction from a baseline of > or =10 mm Hg) were comparable (81% on the losartan regimen and 90% on the nifedipine GITS regimen). There were significantly more adverse events reported in patients receiving nifedipine GITS when compared to the losartan regimen (54% vs 36%, P < 0.05). A patient-reported symptom inventory also showed that swollen ankles was bothersome in significantly more patients treated with the nifedipine GITS regimen when compared to the losartan regimen (24% vs 5%, P = 0.001). Thus, in elderly patients with diastolic hypertension, a regimen of losartan alone or with HCTZ has similar efficacy to a regimen of nifedipine GITS with greater tolerability and less symptom bother due to swollen ankles.

A randomized, double-masked, parallel-group, multicenter clinical trial was conducted to compare the efficacy, tolerability, and effects on quality of life associated with treatment regimens including the angiotensin II receptor antagonist losartan, with hydrochlorothiazide (HCTZ) added as needed, with regimens including the dihydropyridine calcium channel blocker amlodipine with HCTZ added as needed. The trial included patients whose sitting diastolic blood pressure (SiDBP) measurements were between 95 and 114 mm Hg, inclusive, at placebo baseline. Patients were randomized to receive either losartan or amlodipine in a double-masked, double-dummy fashion. A 4-week placebo washout period was followed by a 12-week active treatment period. Patients in the losartan arm (n = 97) were initially given 50 mg of oral (PO) losartan once a day (QD); the medication could be titrated to 50-mg losartan/ 12.5-mg HCTZ PO QD after 4 weeks, followed by 50-mg losartan plus 25-mg HCTZ PO QD after 8 weeks as necessary. Patients in the amlodipine group (n = 93) received 5-mg amlodipine PO QD, which could be titrated to 10 mg PO QD after 4 weeks, followed by 10 mg plus 25-mg HCTZ PO QD after 8 weeks. Medication was titrated upward as necessary to achieve trough SiDBP < 90 mm Hg. Efficacy, tolerability, and quality-of-life scores were assessed after 12 weeks of therapy with each regimen. Trough SiDBP reductions after 4, 8, and 12 weeks of therapy were clinically comparable (losartan group: 7.3, 10.4, and 11.1 mm Hg, respectively; amlodipine group: 7.9, 11.2, and 11.8 mm Hg, respectively). Similar reductions in systolic blood pressure were also seen for both treatment groups. The percentage of patients reaching goal SiDBP (defined as trough SiDBP < 90 mm Hg or SiDBP > or = 90 mm Hg with a > or = 10 mm Hg drop from placebo baseline) was comparable for the two groups, with 68% of patients in the losartan group and 71% of patients in the amlodipine group reaching goal. Significantly more patients in the amlodipine group had drug-related adverse experiences (27% vs 13%). In particular, drug-related edema was more common in patients receiving the amlodipine regimen than in those receiving the losartan regimen (11% vs 1%). Patients in the amlodipine arm reported significantly more bother due to edema, regardless of whether edema was present at baseline, than did patients in the losartan arm (12% vs 2%), although overall quality of life was not different in the two treatment groups. This study demonstrates that a regimen of losartan with HCTZ added as needed, when compared with a regimen of amlodipine with HCTZ added as needed, provides comparable efficacy and superior tolerability and less bother to patients with respect to edema.

A randomized, double-masked, parallel-group, multicenter clinical trial was conducted to compare the efficacy, tolerability, and effects on quality of life associated with the angiotensin II receptor antagonist losartan, alone or with hydrochlorothiazide (HCTZ), and the dihydropyridine calcium channel blocker nifedipine gastrointestinal therapeutic system (GITS) in patients whose sitting diastolic blood pressure measurements were between 95 and 115 mm Hg, inclusive, while receiving placebo. Patients were randomized to receive either losartan or nifedipine GITS in a double-masked, double-dummy fashion. A 4-week placebo washout period established baseline untreated blood pressure measurements and was followed by a 12-week active treatment period. Patients receiving losartan (n = 110) were initially given 50 mg once a day (QD) and could be titrated to losartan/HCTZ 50 mg/12.5 mg QD after 4 weeks followed by losartan/HCTZ 50 mg/25 mg QD after 8 weeks, as necessary. Patients in the nifedipine GITS group (n = 113) received 30 mg QD, which could titrated to 60 mg QD after 4 weeks followed by 90 mg QD after 8 weeks. Medication was titrated upward as necessary to achieve a sitting trough diastolic blood pressure < 90 mm Hg. Efficacy, tolerability, and quality-of-life scores were assessed after 12 weeks of each therapy. Trough sitting diastolic blood pressure reductions after 4, 8, and 12 weeks of therapy were clinically comparable: losartan, -8.9, -11.6, and -12.7 mm Hg, respectively, and nifedipine GITS, -9.3, -11.0, and -11.1 mm Hg, respectively, with the mean reduction in sitting diastolic blood pressure at 12 weeks in the losartan group 1.6 mm Hg lower (95% confidence interval, 3.4 mm Hg lower to 0.3 mm Hg Higher) than the mean reduction in sitting diastolic blood pressure in the nifedipine GITS group. Similarly, reductions in systolic blood pressure between the two treatment groups were comparable at all time points. The percentage of patients reaching the goal trough sitting diastolic blood pressure was comparable for the two treatment groups, with 74% of patients in the losartan regimen and 68% of patients in the nifedipine GITS regimen reaching the goal. Of patients reporting adverse events in the two groups (75 patients receiving losartan and 69 receiving nifedipine GITS), there was significantly more edema in the nifedipine GITS group (15% vs 4%; P = 0.005). Fourteen (12%) patients in the nifedipine GITS group were withdrawn due to an adverse event (eight of these were for edema). Six patients (5%) in the losartan group were withdrawn due to an adverse event (none of these patients had edema). There were significant differences in the patient-reported quality-of-life symptom bother inventory with respect to edema, with nifedipine GITS therapy causing significantly more bother due to edema in patients, regardless of whether that symptom was present at baseline (27% vs 9%; P = 0.0004). No statistically significant differences for bother due to the other symptoms in the inventory were noted. Of note, while the incidence of patient-reported symptom bother due to edema in the nifedipine GITS group was 27%, the incidence of physician-reported drug-related edema was 12%. This difference points to the need for improved physician-patient communication regarding adverse effects and their impact of patients' quality of life. In conclusion, a regimen of losartan, when compared with a regimen of nifedipine GITS, provides comparable efficacy, and with respect to edema, superior tolerability, less bother to patients, and fewer therapy dropouts.

In a prospective, randomized study undertaken to determine if age, length of hospital stay, or severity of illness are predictors of future functional status after intensive care unit (ICU) admission, 45 patients were evaluated. Pre-ICU functional status was determined by using Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL), Geriatric Depression Scale (GDS), and Mini-Mental State (MMS) examinations. Severity of illness was assessed by using the Acute Physiology Assessment and Chronic Health Evaluation (APACHE-II) system. There were no significant differences in age or APACHE-II score at 6-month followup. However, in those patients who had decreased ADL and IADL scores, ICU and total hospital length of stay were two and three times longer, respectively. Functional status at 6-months was unrelated to age or severity of illness, but correlated with the length of ICU and total hospital stay. Advanced age and severity of illness should not be used to predict future functional ability.

The Inter-Company Collaboration for AIDS Drug Development (ICC) represents a collaborative effort among member companies to facilitate the conduct of clinical trials on AIDS drugs. One of the goals of the ICC is to expedite the development of combination antiretroviral therapy through data and compound sharing. Recently, the ICC formed a consensus master protocol to evaluate rapidly the safety and efficacy of triple-drug combinations of antiretroviral therapy for treatment of HIV-infected patients. This concept builds upon historical work with combination chemotherapy that resulted in treatments to successfully control chronic immunosuppressive, infectious or malignant diseases, such as tuberculosis, leprosy, childhood acute lymphoblastic leukemia, and Hodgkin's lymphoma. Because of limitations on potency and the continuing emergence of drug resistance seen with use of currently available antiretroviral agents in monotherapy and two-drug combination regimens, triple-combination regimens should represent a more promising approach to maximize antiviral activity, maintain long-term efficacy, and reduce the incidence of drug resistance. The ICC master protocol is a randomized, controlled, double-blind study with a treatment duration of 52 weeks. Patients eligible to enroll in this study must have documented HIV infection, with CD4 counts between 200 and 500 cells/mm3, and no history of antiretroviral therapy. The first four triple-drug combinations will be evaluated in two trials. These regimens have been selected based on encouraging data from laboratory and clinical studies. Each ICC trial will consist of three arms, with 75 patients per arm. Protocol ICC 001 will include AZT + zalcitabine (ddC) + saquinavir, AZT + ddC + nevirapine, and AZT + ddC as the control arm.(ABSTRACT TRUNCATED AT 250 WORDS)

Inflatable suits were constructed for lower body compression in pigs and dogs. The suit for pigs encompassed hindquarters and part of the abdomen, and the smaller suit for dogs compressed only the hindquarters, leaving free the abdominal cavity. In conscious, diazepam-pretreated pigs, the compression lasted 30 minutes; during that period the blood pressure increased 50/38 mm Hg over the baseline. In chloralose-anesthetized dogs, the compression was extended to 3 hours; the blood pressure increase was 44/53 mm Hg. Blood pressure fell to the baseline immediately after decompression in both animals. In both species the substantial blood pressure increase was due to an increase of vascular resistance; this did not induced the expected baroreceptor-mediated bradycardia. In dogs, the blood pressure increase was accompanied by a large increase of plasma norepinephrine (from 179 to 975 pg/ml). To test whether the increase of vascular resistance reflected the mechanical compression of the vessels under the suit, animals were pretreated with trimethaphan. In pigs the trimethaphan substantially decreased the vascular resistance and the blood pressure response. This indicated that a portion of the vasoconstriction occurred in areas outside the suit. Lower body compression is a new model to cause prolonged blood pressure elevation by noninvasive and nonpharmacologic means. The mechanism of the blood pressure elevation requires further investigation.