Should the endurance shuttle walk test replace the six-minute walk test in individuals with chronic obstructive pulmonary disease?
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Biomedical subjects
Publications and source records attributed to D Brooks.
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The aim of this study is to evaluate the potency of piboserod (SB 207266), a selective 5-HT(4) receptor antagonist, at inhibiting the 5-HT(4)-mediated potentiating effect of serotonin (5-HT) on the neurally-mediated contractile responses of human detrusor strips to electrical field stimulations (EFS). Strips of human detrusor muscle were mounted in Krebs-HEPES buffer under a resting tension of 500 mg and EFS (20 Hz, 1 ms duration at 300 mA for 5 s) was applied continuously at 1 min intervals. After stabilization of the EFS-induced contractions, concentration-response curves to 5-HT (0.1 nM-100 microM) were constructed in the absence or presence of 1 or 100 nM of piboserod. The experiments were performed in the presence of methysergide (1 microM) and ondansetron (3 microM) to block 5HT(1)/5HT(2) and 5-HT(3) receptors, respectively. 5-HT potentiated the contractile responses to EFS of human bladder strips in a concentration-dependent manner, with a maximum mean of 60.0+/-19.9% of the basal EFS-evoked contractions. Piboserod did not modify the basal contractions but concentration-dependently antagonized the ability of 5-HT to enhance bladder strip contractions to EFS. In presence of 1 and 100 nM of piboserod, the maximal 5-HT-induced potentiations were reduced to 45.0+/-7.9 and 38.7+/-8.7%, respectively. A mean apparent antagonist dissociation constant value (K(B)) of 0.56+/-0.09 nM was determined. These data show the ability of piboserod to antagonize with high potency the enhancing properties of 5-HT on neurally-mediated contractions of isolated human bladder strips. Therefore, the 5-HT(4) receptor might represent an attractive pharmacological target for the treatment of overactive bladder.
BACKGROUND: Low body weight in patients with chronic obstructive pulmonary disease (COPD) is associated with an impaired pulmonary status, reduced diaphragmatic mass, lower exercise capacity and higher mortality rate when compared to adequately nourished individuals with this disease. Nutritional support may therefore be a useful part of their comprehensive care. OBJECTIVES: To conduct a systematic review of randomised controlled trials (RCTs) to clarify whether nutritional supplementation (caloric supplementation for at least 2 weeks) improved anthropometric measures, pulmonary function, respiratory muscle strength and functional exercise capacity in patients with stable COPD. SEARCH STRATEGY: Randomized controlled trials (RCTs) were identified from the Cochrane Airways Group register of RCTs, a hand-search of abstracts presented at international meetings and consultation with experts. Searches are current as of March 2004. SELECTION CRITERIA: Two reviewers independently selected trials for inclusion, assessed quality and extracted the data. DATA COLLECTION AND ANALYSIS: Within each trial and for each outcome, we calculated an effect size. The effect sizes were then pooled by a random-effects model. Homogeneity among the effect sizes was also tested. MAIN RESULTS: Eleven studies recruiting 352 participants met the inclusion criteria. Eight papers were considered as high quality. Two studies were double-blinded. For each of the outcomes studied, the effect of nutritional support was small: the 95% confidence intervals around the pooled effect sizes all included zero. The effect of nutritional support was homogeneous across studies. AUTHORS' CONCLUSIONS: Nutritional support had no significant effect on anthropometric measures, lung function or exercise capacity in patients with stable COPD.
BACKGROUND: No intervention has proven effective in modifying long-term disease prognosis in Multiple Sclerosis (MS) but exercise therapy is considered to be an important part of symptomatic and supportive treatment for these patients. OBJECTIVES: To assess the effectiveness of exercise therapy for patients with MS in terms of activities of daily living and health-related quality of life. SEARCH STRATEGY: We searched the Cochrane MS Group Specialised Register (searched: March 2004), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2004), MEDLINE (from 1966 to March 2004), EMBASE (from 1988 to March 2004 ), CINAHL (from 1982 to March 2004), PEDro (from 1999 to March 2004) . Manual search in the journal 'Multiple Sclerosis' and screening of the reference lists of identified studies and reviews. We also searched abstracts published in proceedings of conferences. SELECTION CRITERIA: Randomised Controlled Trials (RCTs) that reported on exercise therapy for adults with MS, not presently experiencing an exacerbation; outcomes that include measures of activity limitation or health-related quality of life or both. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and methodological quality of the included trials. Disagreements were resolved by discussion. The results were analysed using a best-evidence synthesis based on methodological quality. MAIN RESULTS: Nine high-methodological-quality RCTs(260 participants) met the inclusion criteria. Six trials focussed on comparison of exercise therapy versus no exercise therapy, whereas three trials compared two interventions that both met our definition of exercise therapy. Best evidence synthesis showed strong evidence in favour of exercise therapy compared to no exercise therapy in terms of muscle power function, exercise tolerance functions and mobility-related activities. Moderate evidence was found for improving mood. No evidence was observed for exercise therapy on fatigue and perception of handicap when compared to no exercise therapy. Finally, no evidence was found that specific exercise therapy programmes were more successful in improving activities and participation than other exercise treatments. No evidence of deleterious effects of exercise therapy was described in included studies. AUTHORS' CONCLUSIONS: The results of the present review suggest that exercise therapy can be beneficial for patients with MS not experiencing an exacerbation. There is an urgent need for consensus on a core set of outcome measures to be used in exercise trials. In addition, these studies should experimentally control for 'dose' of treatment, type of MS and should include sufficient contrast between experimental and control groups.
BACKGROUND: We hypothesized that the high-quality images from multidetector-row computed tomography (MDCT) would lead to improved sensitivity and specificity for predicting resectable pancreatic head adenocarcinoma, thus diminishing the value of staging laparoscopy. METHODS: Forty four consecutive patients underwent thin-section dual-phase MDCT to stage their tumor, followed by an attempted pancreaticoduodenectomy. Four radiologists who were blinded to the operative outcome reviewed the scans and graded the presence of distant and nodal metastases, as well as the degree of arterial and portal involvement. The radiologic criteria for resectability were no distant metastasis, a patent portal vein, and < 50% arterial involvement. RESULTS: The overall resectability for this cohort was 52% (23/44). The 21 unresectable cases, included five liver metastases, three peritoneal metastases, and 13 locally invasive tumors. The negative margin resection rate was 34% (15/44). There were no portal vein resections. The sensitivity and specificity of MDCT for predicting resectability were 96% (22/23) and 33% (7/21), respectively. In this cohort, the positive and negative predictive values were 61% (22/36) and 87.5% (7/8), respectively. As determined by univariate logistic regression, only the degree of arterial involvement was a significant predictor of resectability (p = 0.02). As determined by multivariate logistic regression using both arterial and portal involvement, arterial involvement was predictive (p = 0.03) but portal vein involvement was not (p = 0.45). CONCLUSIONS: Despite the improvements in image quality obtained with multidetector-row technology, CT imaging remains a relatively nonspecific test for predicting resectability in patients with adenocarcinoma of the head of the pancreas. Minimally invasive modalities with higher specificity, particularly laparoscopy, continue to have an important role in staging pancreatic head adenocarcinoma.
BACKGROUND: When adults with intellectual disabilities (ID) require a psychiatric admission, general adult mental health units are often used. Specialist units have emerged recently as a care option but there is only limited evidence of their effectiveness. Thus this study aims to describe and evaluate the effectiveness of a specialist inpatient unit and report on the utilization of generic and specialist inpatient services. METHOD: All patients admitted to a specialist ID psychiatric unit were evaluated on admission and immediately after discharge on a number of outcome measures. In addition, they were compared with those admitted to general adult mental health units covering the same catchment area. RESULTS: Significant improvements were demonstrated within the specialist unit cohort on measures including psychopathology, global level of functioning, behavioural impairment and severity of mental illness. The specialist unit patients had a longer length of inpatient stay but were less likely to be discharged to out-of-area residential placement. CONCLUSIONS: Specialist units are an effective care option for this group of people.
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The purpose of this study was to examine the effects of two post-rehabilitation programmes on functional exercise tolerance and health-related quality of life in patients with chronic obstructive pulmonary disease (COPD). Subjects with COPD (n=109) were randomised to receive either enhanced follow-up (EF) or conventional follow-up (CF). Subjects in the EF group attended a monthly support group and received a telephone call from a staff member at the midpoint (2 weeks) between their visits. Both groups had scheduled appointments with a physical therapist and physician at 3-monthly intervals after discharge. Longitudinal data were recorded in 85 subjects (37 EF and 48 CF). Over the course of the study, there was no difference in distance walked in 6 min between the two groups but a significant difference for time and a group-time interaction. There was no difference in total chronic respiratory disease questionnaire score between groups at baseline or at any time interval despite a significant difference with time. There was a clear deterioration in functional exercise capacity and health-related quality of life after completion of respiratory rehabilitation but no difference between the groups.
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is so prevalent that the endorsement of management strategies by professional organizations issuing clinical practice guidelines (CPGs) will likely influence the clinical and financial resources allocated to this condition. OBJECTIVES: To examine the content of and to critically appraise the CPGs targeting COPD. METHODS: We identified, through a MEDLINE search (from January 1990 to May 1999) and contacts with experts and professional organizations, the CPGs for the overall management of COPD. We assessed the guidelines according to an index of quality measuring 3 dimensions: the rigor of development, the context and content, and the extent to which the dissemination and implementation have been addressed. The recommendations were also examined and compared. RESULTS: Of the 15 CPGs we included, none was based on a systematic review of the literature. Two were independently reviewed before their release, 1 included strategies for dissemination and implementation, and 1 estimated the economic implications associated with its recommendations. The recommendations were often difficult to interpret (reviewers' agreement: kappa median, 0.41). When unanimity existed regarding the benefits of a given management modality (such as respiratory rehabilitation), discrepancies were often identified in the application of the recommendation. CONCLUSIONS: The methodological quality of CPGs targeting COPD is limited, and there are disparities among many of their recommendations. Despite there being several CPGs worldwide, there is a need for an evidence-based summary of the literature to serve as a resource for those who provide health care to individuals with COPD.
The selection of the appropriate excipient and the amount of excipient required to achieve a 2-year shelf-life is often done by using iso-osmotic concentrations of excipients such as sugars (e.g., 275 mM sucrose or trehalose) and salts. Excipients used for freeze-dried protein formulations are selected for their ability to prevent protein denaturation during the freeze-drying process as well as during storage. Using a model recombinant humanized monoclonal antibody (rhuMAb HER2), we assessed the impact of lyoprotectants, sucrose, and trehalose, alone or in combination with mannitol, on the storage stability at 40 degrees C. Molar ratios of sugar to protein were used, and the stability of the resulting lyophilized formulations was determined by measuring aggregation, deamidation, and oxidation of the reconstituted protein and by infrared (IR) spectroscopy (secondary structure) of the dried protein. A 360:1 molar ratio of lyoprotectant to protein was required for storage stability of the protein, and the sugar concentration was 3-4-fold below the iso-osmotic concentration typically used in formulations. Formulations with combinations of sucrose (20 mM) or trehalose (20 mM) and mannitol (40 mM) had comparable stability to those with sucrose or trehalose alone at 60 mM concentration. A formulation with 60 mM mannitol alone provided slightly less protection during storage than 60 mM sucrose or trehalose. The disaccharide/mannitol formulations also inhibited deamidation during storage to a greater extent than the lyoprotectant formulations alone. The reduction in aggregation and deamidation during storage correlated directly with inhibition of unfolding during lyophilization, as assessed by IR spectroscopy. Thus, it appears that the protein must be retained in its native-like state during freeze-drying to assure storage stability in the dried solid. Long-term studies (23-54 months) performed at 40 degrees C revealed that the appropriate molar ratio of sugar to protein stabilized against aggregation and deamidation for up to 33 months. Therefore, long-term storage at room temperature or above may be achieved by proper selection of the molar ratio and sugar mixture. Overall, a specific sugar/protein molar ratio was sufficient to provide storage stability of rhuMAb HER2.
BACKGROUND: Industry and occupation (I/O) data from state cancer registries can be useful in generating and evaluating hypotheses about occupational cancer risks. The quality of these data is uncertain. METHODS: We reviewed medical records on 1,020 cases from the Massachusetts Cancer Registry (MCR). We compared the presence and detail of I/O data from this dedicated record review (DRR) with routine reporting to the MCR in order to evaluate the potential to increase the availability of I/O data. RESULTS: Compared to routine reporting, the DRR increased the percentage of codable I/O data from 63.6 to 80.4%. The DRR also provided more detail in existing codes in 15.4% of cases. Other sections of the medical record in addition to the face sheet and sections of the record from the period before cancer diagnosis were important sources of additional information. Duration and timing of the corresponding I/O information were rarely recorded. CONCLUSIONS: The nearly one-third (32%) of records that had some improvement in I/O information with a dedicated review indicates considerable opportunity to improve the utility of this resource.
PURPOSE: To provide detailed description and illustration of the lens changes found in hereditary hyperferritinemia-cataract syndrome, a newly reported autosomal dominant condition. METHODS: Observational case reports. A 19-year-old man was referred for evaluation of possible hereditary hyperferritinemia-cataract syndrome. His serum ferritin level was increased at 1291 microg/L during a routine screening examination. Genetic analysis revealed mutation G51C on chromosome 19, predicting an altered iron response element in L-ferritin mRNA. Subsequent evaluation of his 46-year-old father revealed similar findings. RESULTS: Multiple breadcrumb-like nuclear and cortical lens opacities were seen in this father-son pair. These cases represent the first detailed description and illustration of hereditary hyperferritinemia-cataract syndrome cataracts in the ophthalmic literature. CONCLUSION: Hereditary hyperferritinemia-cataract syndrome can be associated with distinct breadcrumb-like lens opacities. Recognition of these characteristic cataracts may aid identification and study of patients with this unusual disorder and provide insight into mechanisms of cataract formation.
We observed 73 cancer patients receiving transdermal fentanyl for 1-29 (mean 5.5) months immediately after participation in a randomized clinical trial. Of these, 32 received fentanyl until death, 18 were lost to follow-up, 11 required alternative analgesia, and 12 withdrew for other reasons. The median first recorded dose (not necessarily the patient's first fentanyl dose) was 75 microg/h. The median final dose was 100 microg/h. All but 3 patients required <300 microg fentanyl/h. In the 16 who received fentanyl for > or =3 months until death, the median dose was unchanged (100 microg/h) 3 months before death and at death; 8/16 required no dosage change. The incidence of constipation, skin reactions, nausea, and vomiting was low. No significant respiratory depression was associated with fentanyl. Most patients (85%) and investigators (86%) rated the treatment as good or excellent. We conclude that long-term treatment with transdermal fentanyl is safe and acceptable to many cancer patients.
The extent of symptomatology related to attention-deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) was examined in a statewide sample of adopted youth, aged 4-18 years (n = 808). The use of normed questionnaires in a nonclinical sample decreased biases associated with past research on adopted children. According to parental report, a striking number of the youth qualified as manifesting significant symptom levels of externalizing behavior problems: 21% met symptom cutoffs for ADHD (with or without ODD) and 20% met criteria for ODD (with or without ADHD), for a combined total of 29% of the sample. A number of parent-reported, preadoptive risk factors distinguished these groups from one another and from the nonexternalizing youth. The clearest associated factors included histories of preadoption abuse/neglect, later age of adoption, prenatal drug exposure, and placement in multiple foster homes prior to adoption. We discuss implications regarding both etiology and current controversies surrounding the disproportionate levels of behavioral difficulties in adopted youth.
OBJECTIVE: To determine the construct validity and responsiveness of the 2-minute walk test as a measure of function in individuals with lower extremity amputation. DESIGN: The distances walked in 2 minutes were compared with the results on the physical functioning subscale of the Medical Outcomes Study Short-Form 36-Item Health Survey (SF-36) and the Houghton Scale. SETTING: Regional amputee rehabilitation program. PATIENTS: Retrospective data from 290 patients (mean age, 66yr) with unilateral transtibial, unilateral transfemoral, or bilateral amputations. INTERVENTION: Repeated testing. MAIN OUTCOME MEASURES: Distance walked in 2 minutes, SF-36 (aggregated into physical and mental composite scores), and the Houghton score. We also examined the change in the distance before and after a rehabilitation program. RESULTS: The distance walked in 2 minutes showed a weak correlation with the physical functioning subscale of the SF-36 (r = .22, p = .008) and a moderate correlation with the total Houghton score at discharge from rehabilitation (r = .493, p <or= .001). The correlation between distance walked in 2 minutes and SF-36 physical functioning subscale at follow-up was moderate (r = .479, p < .001). There was a significant improvement in distance walked in 2 minutes at discharge and follow-up compared with baseline (mean change +/- standard deviation at discharge, 13.6 +/- 19.9m; at follow-up, 41.2 +/- 34m, p < .001). CONCLUSION: The 2-minute walk test was responsive to change with rehabilitation in persons with lower extremity amputation. In addition, the 2-minute walk test showed adequate correlation with measures of physical functioning and prosthetic use in this population.
Although the number of children in need of adoptive homes is growing, the number of prospective adoptive parents is decreasing. On the basis of an extensive review of relevant literature, the present study explored a potentially viable although controversial and little-researched option for increasing the pool of prospective parents: adoptions by gay men and lesbians. Data for this study were collected from child welfare workers and gay and lesbian adoptive and foster parents. A content analysis of the data suggests that gay men and lesbians experience considerable and seemingly unjustified obstacles in their efforts to become adoptive and foster parents. Major implications for practice and policy are offered, as are future directions for research.
The authors describe a new technique for intramuscular implantation of a nerve ending after peripheral neuroma excision. Sixteen peripheral neuromas in 10 patients were excised and then implanted into muscle tissue using the Mitek anchor. The positions of the anchors were documented by immediate anteroposterior and lateral radiographs. These views were repeated at 2 months to assess any migration. All patients had resolution of the symptoms related to their neuromas. No substantial migration was noted in any of the patients. The Mitek anchor can be used as a "soft-tissue" anchor to position a nerve ending reliably at a precise depth and tension in muscle tissue with minimal trauma.
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