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Equivalence study of a topical diclofenac solution (pennsaid) compared with oral diclofenac in symptomatic treatment of osteoarthritis of the knee: a randomized controlled trial.

OBJECTIVE: . To compare the safety and efficacy of a topical diclofenac solution versus oral diclofenac in relieving the symptoms of primary osteoarthritis (OA) of the knee, in a randomized, double-blind, double-dummy equivalence trial. METHODS: A total of 622 men and women with radiological evidence of primary knee OA and mild to severe symptoms were randomly assigned to treatment with a topical diclofenac solution plus placebo oral capsules, or placebo topical solution plus oral diclofenac (50 mg) capsules. Patients applied 50 drops of study solution and took 1 study capsule 3 times daily for 12 weeks. Efficacy variables were pain and physical function, measured by the Western Ontario and McMaster Universities (WOMAC) VA 3.1 OA Index, and patient global assessment (PGA). Equivalence in the per-protocol group was based on previously defined ranges of clinically significant difference. Safety was assessed by evaluation of adverse events, vital signs, and laboratory data. RESULTS: The difference in mean (95% CI) change scores (final minus baseline) between treatments was 13.3 mm (-8.6 to 35.2) for pain (total scale 500 mm), 71.0 mm (-2.4 to 144.5) for physical function (total scale 1700 mm), and 4.3 mm (-1.2 to 9.8) for PGA (total scale 100 mm). The CI for each efficacy variable fell within the predefined equivalence ranges (pain, +/- 75 mm; physical function, +/- 255 mm; PGA, +/- 20 mm), indicating that no clinically relevant difference was found between the 2 treatment arms. Safety analyses of patients applying topical diclofenac solution revealed some minor skin irritation at the application site--mostly skin dryness in 83/311 (27%) patients--but a significantly reduced incidence, relative to oral diclofenac, of total and severe gastrointestinal (GI) adverse events, including dyspepsia, abdominal pain, diarrhea, and nausea. The number of patients developing abnormal liver function tests (including clinically significant elevation), hemoglobin, and creatinine clearance was significantly higher in the oral diclofenac group. CONCLUSION: Application of this topical diclofenac solution to the knee of patients with OA produced relief of symptoms equivalent to oral diclofenac, with minor local skin irritation, but significantly reduced incidence of diclofenac-related GI complaints and abnormal laboratory values.

Administration, Oral↗

Patients with poor preoperative functional status have high expectations of total hip arthroplasty.

Recent reports indicate that patients' expectations should be assessed as part of routine practice before total hip arthroplasty (THA). A total of 1,103 THA patients preoperatively completed the Hospital for Special Surgery Total Hip Replacement Expectations Survey, an 18-item scale tested for validity and reliability. Patients also completed measures of hip-specific function (American Academy of Orthopaedic Surgeons Hip/Knee Module), and overall physical function (SF-36). Patients with worse preoperative function had higher expectations of THA and were more likely to rate their expectations as very important compared with patients with better function. In multivariate analysis, older patients, men, and those with worse functional status (both hip-specific and overall physical function) had more expectations of THA. Identifying and addressing expectations, particularly possibly unrealistic expectations, are important elements in discussions with patients before THA.

Aged↗

Physical and functional interaction between Hck tyrosine kinase and guanine nucleotide exchange factor C3G results in apoptosis, which is independent of C3G catalytic domain.

The hematopoietic cell kinase Hck is a Src family tyrosine kinase expressed in cells of myelomonocytic lineage, B lymphocytes, and embryonic stem cells. To study its role in signaling pathways we used the Hck-SH3 domain in protein interaction cloning and identified C3G, the guanine nucleotide exchange factor for Rap1 and R-Ras, as a protein that associated with Hck. This interaction was direct and was mediated partly through the proline-rich region of C3G. C3G could be co-immunoprecipitated with Hck from Cos-1 cells transfected with Hck and C3G. C3G was phosphorylated on tyrosine 504 in cells when coexpressed with Hck but not with a catalytically inactive mutant of Hck. Phosphorylation of endogenous C3G at Tyr-504 was increased by treatment of human myelomonocytic THP-1 cells with mercuric chloride, which is known to activate Hck tyrosine kinase specifically. Coexpression of Hck with C3G induced a high level of apoptosis in many cell lines by 30-42 h of transfection. Induction of apoptosis was not dependent on Tyr-504 phosphorylation or the catalytic domain of C3G but required the catalytic activity of Hck. Using dominant negative constructs of caspases we found that caspase-1, -8, and -9 are involved in this apoptotic pathway. These results suggest that C3G and Hck interact physically and functionally in vivo to activate kinase-dependent and caspase-mediated apoptosis, which is independent of catalytic domain of C3G.

Animals↗

CD20 is physically and functionally coupled to MHC class II and CD40 on human B cell lines.

Engagement of MHC class II and CD40 on B cell lines triggers intracellular signals that activates cell surface adhesion receptors, resulting in LFA-1-dependent and -independent cell-cell adhesion. In this study, a murine monoclonal antibody (mAb R21) has been produced against a LFA-1-negative human B cell line and proven to completely block MHC class II- and CD40-induced LFA-1-independent homotypic adhesion. However, this mAb failed to prevent MHC class II- or CD40-induced homotypic adhesion in LFA-1-positive Raji B cells, and alone, it triggered LFA-1-dependent cell-cell adhesion. Biochemical characterization indicated that the CD20 molecule, a tetraspan phosphoprotein expressed on B cells that functions as a Ca2+-conductive ion channel, is the target of mAb R21. Interestingly, further biochemical analysis demonstrated that CD20 is physically associated with MHC class II and CD40 molecules on the cell surface of LFA-1-negative and LFA-1-positive B cell lines. Although these three molecules are associated with each other, the complex formation between any two of them is not dependent on the simultaneous expression of the three molecules. Altogether, these results indicate that CD20 is physically and probably functionally coupled to the MHC class II and CD40 molecules; thereby it may have certain modulatory effects on their functions.

Animals↗

Amino acid substitutions in the human immunodeficiency virus type 1 gp120 V3 loop that change viral tropism also alter physical and functional properties of the virion envelope.

The third variable (V3) region within the gp120 envelope glycoprotein of the human immunodeficiency virus type 1 (HIV-1) has been reported to be an important determinant of viral tropism. In this study a series of isogenic recombinant HIV-1 viruses, containing V3 regions from fresh isolates, were examined to ascertain if a relationship exists between viral tropism and specific properties of the virion-associated envelope. All of the viruses were able to infect CD4+ primary lymphocytes, although with different infection kinetics. Several recombinants, however, were unable to infect a continuous CD4+ T-cell line permissive for the parental virus and exhibited a marked decrease in the kinetics of virion-associated gp120 binding to a soluble form of CD4. A known macrophage-tropic HIV-1 isolate, also unable to infect the T-cell line, bound CD4 with similarly slow reaction kinetics. Although the inability to infect T-cell lines is a commonly observed property of macrophage-tropic isolates of HIV-1, the loss of T-cell line tropism by the V3 recombinants was not accompanied by a substantial infectivity for monocyte-derived macrophages, as monitored by reverse transcriptase production. Additional analyses of the recombinant virion gp120s indicated that most of the V3 substitutions increased the inherent stability of the virion gp120-gp41 envelope complex. These results indicate that V3-induced alterations in viral tropism are associated with changes in physical and functional properties of the virion envelope.

Amino Acid Sequence↗

Perceived adequacy of tangible social support and health outcomes in patients with coronary artery disease.

OBJECTIVE: Health outcomes of patients with chronic disease might be influenced by assistance from others in performing daily activities. We examined whether perceived adequacy of such tangible support was associated with prognosis in a cohort of patients with coronary artery disease. DESIGN: Longitudinal cohort study. SETTING/PARTICIPANTS: In spring 1993, a cohort of 1,468 patients with chronic artery disease was identified using claims data. The cohort consisted of all surviving residents of Manitoba, Canada, who had been hospitalized for acute myocardial infarction from 1991 to 1992: 820 patients completed the initial survey, and 734 completed a follow-up survey approximately 1 year later. MEASUREMENTS AND MAIN RESULTS: Adequacy of tangible support was assessed by asking if respondents needed help at home because of health problems, and whether these needs were met. We examined the association between perceived adequacy of tangible support and health outcomes at 1 year (mortality, physical function). Of 820 participants, 74% perceived no need for help, 13% had sufficient help, 9% needed more help, and 5% needed much more help; 31 patients died during follow-up. After adjustment for age and initial health status, odds ratios (95% confidence interval) for death were: sufficient help 1.8 (0.61, 5.8); need more help 3.2 (1.1, 9.4); and need much more help 6.5 (2.0, 21.6) compared with respondents with no perceived need. Decline in physical function was also linearly related to perceiving less-adequate tangible support. Sensitivity analyses indicated it is highly improbable that results were due to selection bias. CONCLUSIONS: Perceived lack of needed assistance was related to mortality and to decline in physical functioning. Adequacy of tangible support was an important prognostic factor for these patients with coronary artery disease and may be a determinant of health outcomes.

Aged↗

Precursors of murine B lymphocytes. Physical and functional characterization, and distinctions from myeloid stem cells.

The emergence of functional B cells was monitored in irradiated or unirradiated CBA/N recipients of either adult bone marrow or fetal liver from CBA/HT6T6 donors. The cells that are primarily responsible for the generation of B lymphocytes, at least during the first 6 wk, are rapidly sedimenting (4.5-6 mm/h), lack surface immunoglobulin, and are found in both the adult bone marrow and the fetal liver from day 12 onward. These pre-B cells are distinct from the colony-forming unit spleen (CFU-s) as demonstrated by the following criteria: (a) absence from yolk sac (19), (b) lack of correlation between CFU-s number and the ability to generate B cells in fetal liver populations of different ages of gestation, and (c) hybridoma antibodies that significantly inhibited B cell reconstitution but have no effect on CFU-s numbers. The antigen detected by this antiserum is present on both the fetal liver and bone marrow B cell progenitor, although its expression is not restricted to the B lineage. The pre-B cells that we monitor are not homogeneous, however, as both physical and functional differences are found. These observations reinforce our thesis that committed progenitor cells for the humoral immune system are formed early in development and thereafter constitute the major precursor pool for the generation of B lymphocytes.

Age Factors↗

E1BF/Ku interacts physically and functionally with the core promoter binding factor CPBF and promotes the basal transcription of rat and human ribosomal RNA genes.

We have previously characterized an RNA polymerase (pol) I transcription factor, E1BF, from rat cells. This protein is immunologically related to Ku autoantigen and is required in pol-I directed transcription of rodent ribosomal RNA gene (rDNA). Glycerol density gradient fractionation and in situ UV cross-linking analysis of the purified factor showed directly that it consists of a heterodimer of 85 and 72 kDa polypeptides. E1BF also interacted with the human core promoter and augmented transcription of human rDNA as much as fivefold in HeLa nuclear extract, whereas transcription from adenovirus major late promoter, CMV or SV40 early promoters by pol II and of U6 and 5S RNA genes by pol III were either unaffected or minimally inhibited by the antibodies. Purified rat E1BF partially restored the suppression of human rDNA transcription by anti-Ku antibodies. Immunoprecipitation of rat cell extract with the anti-Ku antibodies followed by SDS-PAGE of the precipitated proteins and Southwestern analysis showed that E1BF interacts with CPBF, a core promoter binding factor. When the majority of CPBF and E1BF was removed from the reaction mixture by preincubation with a core promoter oligo nucleotide fragment, rDNA transcription was severely impaired. Addition of exogenous CPBF or E1BF to such a reaction resulted in significant restoration of the transcription, whereas inclusion of both factors caused further enhancement of rDNA transcription. These data demonstrate that E1BF is a basal pol I transcription factor that interacts with a core promoter binding factor both physically and functionally, and that is not a general pol II or pol III transcription factor.

Adenoviridae↗

The effect of percutaneous transluminal coronary angioplasty on quality of life.

The purpose of this study is to examine the effect of percutaneous transluminal coronary angioplasty (PTCA) on quality of life. Secondary purposes are to determine if there is an improvement in state anxiety and physical functioning after PTCA. Data on quality of life in these patients will provide physicians, nurses and other health professionals with a basis to help the angioplasty patient adjust after the procedure. This information will add to the present body of knowledge, serve as a basis for patient education and guide further research. In addition, data on the subjective perception of quality of life may provide an additional index of success or failure of therapy. Subjects scheduled for elective PTCA were mailed a study packet containing three questionnaires. Prior to their admission to the hospital for a scheduled PTCA, subjects completed the Quality of Life Index (QLI), Spielberger's State-Trait Anxiety Inventory and the Physical Functioning Questionnaire. Demographic data were collected from subjects' medical records. Six weeks after a successful PTCA, a second study packet was mailed to subjects. Twenty subjects participated in the study. The majority were employed, Caucasian males with multivessel coronary artery disease and had complained of symptoms less than three months. Paired t-tests demonstrated improvement in the (1) health and functioning subscale (p = less than 0.034), (2) decrease in state anxiety (p = less than 0.030), and (3) increase (p = less than 0.000) in perceived physical functioning. In addition, an inverse relationship was demonstrated between state anxiety and quality of life (r = -0.70, p = 0.000).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Surgical vs nonoperative treatment for lumbar disk herniation: the Spine Patient Outcomes Research Trial (SPORT) observational cohort.

CONTEXT: For patients with lumbar disk herniation, the Spine Patient Outcomes Research Trial (SPORT) randomized trial intent-to-treat analysis showed small but not statistically significant differences in favor of diskectomy compared with usual care. However, the large numbers of patients who crossed over between assigned groups precluded any conclusions about the comparative effectiveness of operative therapy vs usual care. OBJECTIVE: To compare the treatment effects of diskectomy and usual care. DESIGN, SETTING, AND PATIENTS: Prospective observational cohort of surgical candidates with imaging-confirmed lumbar intervertebral disk herniation who were treated at 13 spine clinics in 11 US states and who met the SPORT eligibility criteria but declined randomization between March 2000 and March 2003. INTERVENTIONS: Standard open diskectomy vs usual nonoperative care. MAIN OUTCOME MEASURES: Changes from baseline in the Medical Outcomes Study Short-Form Health Survey (SF-36) bodily pain and physical function scales and the modified Oswestry Disability Index (American Academy of Orthopaedic Surgeons/MODEMS version). RESULTS: Of the 743 patients enrolled in the observational cohort, 528 patients received surgery and 191 received usual nonoperative care. At 3 months, patients who chose surgery had greater improvement in the primary outcome measures of bodily pain (mean change: surgery, 40.9 vs nonoperative care, 26.0; treatment effect, 14.8; 95% confidence interval, 10.8-18.9), physical function (mean change: surgery, 40.7 vs nonoperative care, 25.3; treatment effect, 15.4; 95% CI, 11.6-19.2), and Oswestry Disability Index (mean change: surgery, -36.1 vs nonoperative care, -20.9; treatment effect, -15.2; 95% CI, -18.5. to -11.8). These differences narrowed somewhat at 2 years: bodily pain (mean change: surgery, 42.6 vs nonoperative care, 32.4; treatment effect, 10.2; 95% CI, 5.9-14.5), physical function (mean change: surgery, 43.9 vs nonoperavtive care 31.9; treatment effect, 12.0; 95% CI; 7.9-16.1), and Oswestry Disability Index (mean change: surgery -37.6 vs nonoperative care -24.2; treatment effect, -13.4; 95% CI, -17.0 to -9.7). CONCLUSIONS: Patients with persistent sciatica from lumbar disk herniation improved in both operated and usual care groups. Those who chose operative intervention reported greater improvements than patients who elected nonoperative care. However, nonrandomized comparisons of self-reported outcomes are subject to potential confounding and must be interpreted cautiously. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00000410.

Adult↗

Consequences of chronic obstructive pulmonary disease and chronic heart failure: the relationship between objective and subjective health.

This study investigates whether the relationship between objective health parameters and general health perceptions was mediated by symptoms of dyspnoea and physical functioning in patients with chronic obstructive pulmonary disease (COPD) and patients with chronic heart failure (CHF). The different health parameters were organised according to Wilson and Cleary's conceptual model of patient outcomes (Wilson & Cleary (1995). Journal of the American Medical Association, 273, 59-65). Second, we investigated whether perceptions of personal control were related to the health parameters in the model. Consecutive patients with COPD and CHF were included from the outpatient clinics of a university hospital and a general hospital, and from a rehabilitation centre, all in the Netherlands. Ninety-five COPD patients (aged 65.0+/-9.3; forced expiratory volume in 1s (FEV1)<70%) were included and compared with 90 CHF patients (aged 59.6+/-10.0; left ventricular ejection fraction (LVEF)<45%). The relationship between objective health parameters (FEV1 or LVEF) and subjective health (self-reported physical functioning) was not mediated by symptoms of dyspnoea. FEV1 or LVEF and symptoms of dyspnoea were independently related to self-reported physical functioning, which was directly related to general health perceptions. Perceived health competence was related to symptoms of dyspnoea and general health perceptions in patients with either COPD or CHF. Although patients with COPD reported lower levels in all self-reported health parameters in the model than the patients with CHF, this study showed that the relations between the health parameters in the model were comparable for COPD and CHF patients.

Aged↗

Relative responsiveness of condition-specific and generic health status measures in degenerative lumbar spinal stenosis.

The objective of this study was to compare the relative responsiveness of a condition-specific spinal stenosis measure and two generic health status measures for outcome assessment of surgery for degenerative lumbar spinal stenosis, and to examine whether responsiveness statistics and measures of the ability to distinguish clinically important improvement rank the instruments consistently. Physical function and symptom severity scales of the spinal stenosis measure were compared to the Sickness Impact Profile (SIP) and the Roland scale, which is derived from the SIP. Responsiveness was calculated with the standardized response mean, the effect size, and Guyatt's responsiveness statistic. The discriminative ability of the instruments to distinguish patients who improved from those who did not was assessed using satisfaction with surgery as an external criterion. Minimal clinically relevant improvement was estimated using patient satisfaction as the external criterion. All responsiveness statistics revealed the same order of responsiveness; the physical function scale (SRM = 1.07) and symptom severity scales (SRM = 0.96) were more responsive than the Roland scale (SRM = 0.77) which was only slightly more responsive than the SIP (SRM = 0.69). Strikingly, the physical dimension of the SIP (SRM = 0.62) was even less responsive than the global SIP. The shape of and the area under the ROC curves showed that the physical function and symptom severity scales discriminate better between satisfied and unsatisfied patients than the Roland scale and SIP. The sensitivity to detect clinically important changes was somewhat lower at the ends of the scales, especially for the SIP and the Roland scale. Statistical approaches that assess the ability to distinguish clinically important changes and overall responsiveness statistics ranked the measures consistently. On the basis of these findings, we suggest that a condition-specific spinal stenosis measure is preferable as the primary end point in evaluative studies of degenerative lumbar spinal stenosis.

Activities of Daily Living↗

Relationships between SF-36 health profile and bone mineral density: the Hertfordshire Cohort Study.

We utilised the Hertfordshire Cohort Study (HCS) to relate bone mineral density (BMD) to SF-36 health-related quality of life scores. We studied 737 men and 675 women who had completed a home interview and clinic. Four hundred and ninety-eight men and 468 women subsequently attended for bone densitometry [dual-energy X-ray absorptiometry (DXA)]. SF-36 questionnaire responses were mapped to eight domains: physical function (PF), role physical (RP), role emotional (RE), social functioning (SF), mental health (MH), vitality (VT), bodily pain (BP) and general health perception (GH). Subjects with scores in the lowest gender-specific fifth of the distribution were classified as having "poor" status for each domain. Odds ratios (OR) for poor status for each domain were calculated per unit increase in lumbar spine or total femoral BMD t score. Among men after adjustment for age, BMI, social class, lifestyle (including physical activity) and known comorbidity, higher total femoral t score was associated with decreased prevalence of poor SF-36 scores for PF [OR 0.72 (95%CI 0.53, 0.97), p=0.03], SF [OR 0.70 (95%CI 0.53, 0.94), p=0.02] or GH domains [OR 0.74 (95%CI 0.56, 0.99), p=0.05], but no relationships were apparent between SF-36 scores and lumbar spine t score. Among women, the adjusted relationship between higher total femoral t score and decreased prevalence of poor PF was consistent [OR 0.71 (95%CI 0.50, 1.00), p=0.05], but no other relationships were significant. Poorer functioning (assessed by SF-36 questionnaire) is associated with lower total femoral BMD in older men (but less so in women) after adjustment for lifestyle factors and comorbidity.

Aged↗

Randomized controlled trial of nutritional supplementation in patients with newly diagnosed tuberculosis and wasting.

BACKGROUND: Nutritional support is often recommended as part of the treatment of tuberculosis, but it has never been properly tested. OBJECTIVE: We assessed the effects of early nutritional intervention on lean mass and physical function in patients with tuberculosis and wasting. DESIGN: Patients who started antituberculous therapy within the previous 2 wk were randomly assigned to receive standard nutritional counseling (control group) or nutritional counseling to increase their intake through diet and high-energy supplements (nutritional supplement group) for 6 wk. Body composition was measured by dual-energy X-ray absorptiometry, and physical function was assessed by maximum grip strength. RESULTS: Patients in the nutritional supplement group (n = 19) had a significantly greater increase in body weight (2.57 +/- 1.78 compared with 0.84 +/- 0.89 kg, P = 0.001), total lean mass (1.17 +/- 0.93 compared with 0.04 +/- 1.26 kg, P = 0.006), and grip strength (2.79 +/- 3.11 compared with -0.65 +/- 4.48 kg, P = 0.016) than did the control subjects (n = 17) at week 6. During subsequent follow-up, the increase in body weight remained greater in the nutritional supplement group, but this increase was due mainly to a greater gain in fat mass in the nutritional supplement group than in the control group. CONCLUSIONS: Early intervention to increase nutritional intake increases lean mass and physical function. This adjunct to tuberculosis therapy could confer socioeconomic and survival benefits that deserve investigation in large-scale trials. Nutritional intervention after the initial phase of treatment could be less beneficial because it mainly increases fat.

Absorptiometry, Photon↗

Yeast Krr1p physically and functionally interacts with a novel essential Kri1p, and both proteins are required for 40S ribosome biogenesis in the nucleolus.

Using a two-hybrid screening with TOM1, a putative ubiquitin-ligase gene of Saccharomyces cerevisiae, we isolated KRR1, a homologue of human HRB2 (for human immunodeficiency virus type 1 Rev-binding protein 2). To characterize the gene function, we constructed temperature-sensitive krr1 mutants and isolated two multicopy suppressors. One suppressor is RPS14A, encoding a 40S ribosomal protein. The C-terminal-truncated rpS14p, which was reported to have diminished binding activity to 18S rRNA, failed to suppress the krr1 mutant. The other suppressor is a novel gene, KRI1 (for KRR1 interacting protein; YNL308c). KRI1 is essential for viability, and Kri1p is localized to the nucleolus. We constructed a galactose-dependent kri1 strain by placing KRI1 under control of the GAL1 promoter, so that expression of KRI1 was shut off when transferring the culture to glucose medium. Polysome and 40S ribosome fractions were severely decreased in the krr1 mutant and Kri1p-depleted cells. Pulse-chase analysis of newly synthesized rRNAs demonstrated that 18S rRNA is not produced in either mutant. However, wild-type levels of 25S rRNA are made in either mutant. Northern analysis revealed that the steady-state levels of 18S rRNA and 20S pre-rRNAs were reduced in both mutants. Precursors for 18S rRNA were detected but probably very unstable in both mutants. A myc-tagged Kri1p coimmunoprecipitated with a hemagglutinin-tagged Krr1p. Furthermore, the krr1 mutant protein was defective in its interaction with Kri1p. These data lead us to conclude that Krr1p physically and functionally interacts with Kri1p to form a complex which is required for 40S ribosome biogenesis in the nucleolus.

Blotting, Northern↗

Psychiatric morbidity in the chronic fatigue syndrome: are patients with personality disorder more physically impaired?

OBJECTIVE: The long-term consequences of chronic fatigue syndrome (CFS) include substantial impairment in physical functioning and high levels of work disability. In the absence of a medical explanation for this impairment, some have speculated that it may be due to comorbid psychiatric illness or personality disorder. We addressed this possibility by comparing the functional status of three CFS groups: no psychiatric diagnosis, psychiatric illness only, psychiatric illness and personality disorder. A second aim of the study was to determine whether a continuous measure of psychological distress could provide a better account of impairment than psychiatric diagnosis. METHOD: The study sample consisted of 84 consecutive female referrals with CFS. All participants satisfied the case definition and completed an assessment protocol consisting of: physical examination, psychiatric interview and self-report questionnaires. RESULTS: Psychiatric illness, either alone or in combination with a comorbid personality disorder, was not associated with physical impairment or disability in female participants. A regression model of physical functioning found that psychological distress accounted for 6% and symptom severity for 41% of the variance (P=.06 and <.01, respectively). In the case of disability, the corresponding percentages were 2% and 18% (NS and P<.01, respectively). The modest effects of psychological distress could not be attributed to symptom severity. CONCLUSIONS: Although psychiatric illness and personality disorder was prevalent, neither could explain the effects of CFS on physical functioning and disability. As yet, there is no psychological or medical explanation for the behavioral consequences of CFS.

Adult↗

Quality of life after treatment for advanced laryngeal and hypopharyngeal cancer.

OBJECTIVES: To compare health-related quality of life measures after treatment for advanced (stages III and IV) laryngeal and hypopharyngeal cancers. STUDY DESIGN: Retrospective chart review and patient response to Health Status Questionnaire-12 (HSQ-12). METHODS: Our study included 54 patients identified from the Tumor Registry of the University of Louisville Brown Cancer Center who were diagnosed and treated between 1995 and 2000. Demographics, tumor data, and treatment information were obtained from the Tumor Registry database. Questionnaires were mailed to all patients and included telephone follow-up. Comparative data and responses were analyzed for the 24 patients who responded to the survey. RESULTS: Fifteen patients were treated with chemotherapy and radiation therapy (CRT). Six patients underwent surgery with postoperative radiation therapy (SRT). The remaining three patients were treated with radiation therapy but were not used in this analysis. The average follow-up was 35 months after treatment. The CRT and SRT groups were statistically similar regarding age, sex, duration of follow-up, tumor grade, and tumor stage. Laryngeal primary tumors were more common in the SRT group than in the CRT group (P =.005). Eight domains were assessed by the HSQ-12: physical functioning, role-physical, bodily pain, health perception, energy/fatigue, social functioning, role-mental, and mental health. No statistical differences were found between the CRT and SRT groups, except for role limitations attributable to physical health (P =.007). CONCLUSIONS: These results indicate that only one of eight domains differs significantly between treatment groups when using the HSQ-12. Two-year survival end-point analysis of global health assessment may represent a simplified and meaningful way to compare treatment modalities in patients with advanced-stage head and neck cancer.

Combined Modality Therapy↗

Quality of life in prostate cancer patients taking androgen deprivation therapy.

OBJECTIVES: To examine the effect of androgen deprivation therapy (ADT) on health-related quality of life (HRQOL), self-reported HRQOL was compared in prostate cancer patients receiving short- (< 6 months) or long-term (> or = 6 months) ADT and healthy controls. DESIGN: Cross-sectional study. SETTING: Academic medical center in Pittsburgh, Pennsylvania. PARTICIPANTS: Ninety-six men, including those with prostate cancer receiving short-term, long-term, and no ADT and healthy controls. Men taking medications or having diseases known to affect bone mineral metabolism were excluded. MEASUREMENTS: The 36-item Short Form Medical Outcomes Study Health Survey (an HRQOL assessment) and a comorbidity index were administered to each participant. Characteristics, including body composition (assessed using dual-energy x-ray absorptiometry) and gonadal status (serum total and free testosterone) were measured approximately 3 months or less before the HRQOL assessment. RESULTS: As expected, men receiving ADT had significantly lower levels of testosterone, free testosterone, and lean body mass, as well as greater body fat and comorbidity index (all P<.01) than men not receiving ADT (i.e., men with prostate cancer and healthy controls). Participants receiving ADT reported significantly poorer QOL in the areas of physical function (P<.001), general health (P<.001), and physical health component summary (P<.001) than men not receiving ADT. There were no significant differences in HRQOL outcomes between participants receiving short- or long-term ADT. Comorbidity and testosterone levels were associated with several QOL scales. After controlling for the significant joint predictors of comorbidity and total testosterone using hierarchical regression analysis, ADT was no longer a significant predictor, and only comorbidity and total testosterone contributed to the explanation of the variance of the physical health component summary. Comorbidity alone contributed to the explanation of the variance in physical function, bodily pain, general health, and vitality. CONCLUSION: Patients with prostate cancer who were receiving ADT experience worse HRQOL than those not receiving ADT, but duration of ADT was not a contributing factor. After controlling for comorbidity, total testosterone level rather than ADT accounted for a small yet statistically significant percentage of the total variance of the physical health component summary. These findings have important clinical implications regarding the decision to treat prostate cancer patients with ADT.

Aged↗