Paeniclostridium sordellii uterine infection is dependent on the estrous cycle.

Human infections caused by the toxin-producing, anaerobic and spore-forming bacterium Paeniclostridium sordellii are associated with a treatment-refractory toxic shock syndrome (TSS). Reproductive-age women are at increased risk for P. sordellii infection (PSI) because this organism can cause intrauterine infection following childbirth, stillbirth, or abortion. PSI-induced TSS in this setting is nearly 100% fatal, and there are no effective treatments. TcsL, or lethal toxin, is the primary virulence factor in PSI and shares 70% sequence identity with Clostridioides difficile toxin B (TcdB). We therefore reasoned that a neutralizing monoclonal antibody (mAB) against TcdB might also provide protection against TcsL and PSI. We characterized two anti-TcdB mABs: PA41, which binds and prevents translocation of the TcdB glucosyltransferase domain into the cell, and CDB1, a biosimilar of bezlotoxumab, which prevents TcdB binding to a cell surface receptor. Both mABs could neutralize the cytotoxic activity of recombinant TcsL on Vero cells. To determine the efficacy of PA41 and CDB1 in vivo, we developed a transcervical inoculation method for modeling uterine PSI in mice. In the process, we discovered that the stage of the mouse reproductive cycle was a key variable in establishing symptoms of disease. By synchronizing the mice in diestrus with progesterone prior to transcervical inoculation with TcsL or vegetative P. sordellii, we observed highly reproducible intoxication and infection dynamics. PA41 showed efficacy in protecting against toxin in our transcervical in vivo model, but CDB1 did not. Furthermore, PA41 could provide protection following P. sordellii bacterial and spore infections, suggesting a path for further optimization and clinical translation in the effort to advance treatment options for PSI infection.

Randomized Trial of Nocturnal Oxygen in Chronic Obstructive Pulmonary Disease.

BACKGROUND: Long-term oxygen therapy improves survival in patients with chronic obstructive pulmonary disease (COPD) and chronic severe daytime hypoxemia. However, the efficacy of oxygen therapy for the management of isolated nocturnal hypoxemia is uncertain. METHODS: We designed this double-blind, placebo-controlled, randomized trial to determine, in patients with COPD who have nocturnal arterial oxygen desaturation without qualifying for long-term oxygen therapy, whether nocturnal oxygen provided for a period of 3 to 4 years would decrease mortality or the worsening of disease such that patients meet current specifications for long-term oxygen therapy. Patients with an oxygen saturation of less than 90% for at least 30% of the recording time on nocturnal oximetry were assigned, in a 1:1 ratio, to receive either nocturnal oxygen or ambient air from a sham concentrator (placebo). The primary outcome was a composite of death from any cause or a requirement for long-term oxygen therapy as defined by the Nocturnal Oxygen Therapy Trial (NOTT) criteria in the intention-to-treat population. RESULTS: Recruitment was stopped prematurely because of recruitment and retention difficulties after 243 patients, of a projected 600, had undergone randomization at 28 centers. At 3 years of follow-up, 39.0% of the patients assigned to nocturnal oxygen (48 of 123) and 42.0% of those assigned to placebo (50 of 119) met the NOTT-defined criteria for long-term oxygen therapy or had died (difference, -3.0 percentage points; 95% confidence interval, -15.1 to 9.1). CONCLUSIONS: Our underpowered trial provides no indication that nocturnal oxygen has a positive or negative effect on survival or progression to long-term oxygen therapy in patients with COPD. (Funded by the Canadian Institutes of Health Research; INOX ClinicalTrials.gov number, NCT01044628.).

Persistent bacteremia and psoas abscess caused by a lethal toxin-deficient Paeniclostridiumsordellii.

We present a case of persistent bacteremia and psoas abscess from Paeniclostridium sordellii without severe symptoms or the classically associated toxic shock syndrome. Further laboratory evaluation demonstrated that the Paeniclostridium sordellii isolate lacked the lethal toxin gene and there was no cytotoxicity to exposed Vero cells.

Investigation of the effects of mTOR inhibitors rapamycin and everolimus in combination with carboplatin on canine malignant melanoma cells.

BACKGROUND: Malignant melanoma in dogs is considered to be largely resistant to conventional chemotherapy, although responses to carboplatin have been documented. Invasion and early metastasis are common features of certain melanoma subtypes that contribute to tumour progression despite aggressive local and systemic therapy. Upregulation of the PI3K/AKT/mTOR pathway has been observed in canine malignant melanoma and may represent a potential target for therapy. Rapamycin (sirolimus) and everolimus are commercially available small molecule inhibitors that target mTOR and therefore may have anticancer activity in canine melanoma. It was hypothesized that there is synergism between rapamycin or everolimus and platinum chemotherapy, and that combination drug treatment would inhibit target/downstream proteins involved in cell viability/proliferation and increase cell death in canine melanoma cells. It was further hypothesized that rapamycin or everolimus would impact metabolism by reducing glycolysis in these cells. Four canine melanoma cell lines were treated in vitro with rapamycin and everolimus as sole treatment or combined with carboplatin. Cell viability, apoptosis, target modulation, and glycolytic metabolism were evaluated by crystal violet colourimetric assay, Annexin V/PI flow cytometry, western blotting, and Seahorse bioanalyzer, respectively. RESULTS: When combined with carboplatin chemotherapy, rapamycin or everolimus treatment was overall synergistic in reducing cell viability. Carboplatin-induced apoptosis was noted at 72 h after treatment compared to the vehicle control. Levels of phosphorylated mTOR were reduced by rapamycin and everolimus in all four cell lines, but activation of the downstream protein p70S6K was not consistently reduced by treatment in two of the cell lines. Both mTOR inhibitors decreased the extracellular acidification rate of canine melanoma cells, indicating reduced cancer cell glycolytic activity. CONCLUSIONS: Inhibition of mTOR by rapalogs, such as rapamycin and everolimus combined with carboplatin chemotherapy may have activity in canine melanoma. Future mechanistic investigation is warranted, including in vivo assessment of this combination therapy.

Outcomes after transperitoneal laparoscopic ureteronephrectomy for the treatment of primary renal neoplasia in seven dogs.

OBJECTIVE: To describe the perioperative characteristics and outcomes in dogs that underwent transperitoneal laparoscopic ureteronephrectomy (TLU) for primary renal neoplasia. STUDY DESIGN: Short case series. ANIMALS: Seven client-owned dogs. METHODS: Medical records were reviewed and data extracted regarding perioperative characteristics and animal outcomes. TLU was performed using a single-port + 1 or multiple port techniques. Hemostatic clips or a vessel-sealing device were used for occlusion of renal hilar vessels. The ureter was occluded and transected close to the ureterovesicular junction and the tumor was placed in a specimen retrieval bag for extraction from the abdomen. RESULTS: Preoperative contrast enhanced computed tomography (CECT) was performed in 6/7 dogs. Median estimated tumor volume measured from abdominal CECT removed by TLU was 32.42 cm3 (interquartile range [IQR] 14.76-94.85). Median surgery time for TLU was 90 minutes (IQR 85-105). In one dog, elective conversion to open laparotomy was performed due to large tumor size. Median time to discharge was 31 hours (IQR 24-48). No major perioperative complications occurred and all dogs survived to discharge. Progression free survival in four dogs was 422 days (IQR 119-784). CONCLUSION: TLU was performed for the extirpation of modest sized primary renal tumors with acceptable perioperative outcomes and a low complication rate. CLINICAL RELEVANCE: TLU may be considered for the treatment of selected cases of primary renal neoplasia in dogs.

Reliability of Home Nocturnal Oximetry in the Diagnosis of Overlap Syndrome in COPD.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) and sleep apnea are common conditions and often coexist. The proper diagnosis of sleep apnea may affect the management and outcome of patients with COPD. OBJECTIVE: To determine the accuracy of home nocturnal oximetry to distinguish between nocturnal oxygen desaturation related to COPD alone or to sleep apnea in patients with moderate-to-severe COPD who have significant nocturnal hypoxemia with cyclical changes in saturation. METHODS: This study involved a comparison of home nocturnal oximetry and laboratory-based polysomnography (PSG) in patients with moderate-to-severe COPD considered for inclusion in a trial of nocturnal oxygen therapy. All of the patients had significant nocturnal oxygen desaturation (defined as ≥30% of the recording time with a transcutaneous arterial oxygen saturation <90%) with cyclical changes in saturation suggestive of sleep apnea. RESULTS: PSG was obtained in 90 patients; 45 patients (mean age = 68 years, SD = 8; 71% men; mean forced expiratory volume in 1 s [FEV1] = 50.6% predicted value, SD = 18.6%; data from 41 patients) fulfilled the criteria for sleep apnea (mean apnea-hypopnea index = 32.6 events/h, SD = 19.9) and 45 patients (mean age = 69 years, SD = 8; 87% men; mean FEV1 predicted value 44.6%, SD = 15%) did not (mean apnea-hypopnea index = 5.5 events/h, SD = 3.8). None of the patients' characteristics (including demographic, anthropometric, and physiologic measures) predicted the diagnosis of sleep apnea according to PSG results. CONCLUSION: The diagnosis of sleep apnea in patients with moderate to severe COPD cannot rely on nocturnal oximetry alone, even when typical cyclical changes in saturation are seen on oximetry tracing. When suspecting an overlap syndrome, a full-night, in-laboratory PSG should be obtained.

Adherence to long-term oxygen therapy in patients with chronic obstructive pulmonary disease.

Long-term oxygen therapy (LTOT) has beneficial effects on survival in patients with chronic obstructive pulmonary disease (COPD) and severe hypoxemia at rest. Two landmark trials suggested that these benefits depend on the time of exposure to oxygen. Patients are usually prescribed LTOT for at least 15-18 hours/day. The primary objective of this study was to determine the average daily exposure to supplemental oxygen in patients with severely hypoxemic COPD who were newly prescribed LTOT and the proportion of patients who were adherent to their prescription. The secondary objective was to identify predictors of compliance to LTOT. We performed a retrospective observational study of patients newly registered in a regional home oxygen program in Quebec, Canada, between July 1, 2013, and December 31, 2014. Daily exposure to oxygen was objectively measured from the concentrator's counter clock. From 196 patients registered in the program during the study period, 115 contributed to the analysis. Most patients ( n = 84; 73%) were prescribed oxygen for ≥18 hours/day. Overall, the 115 patients were exposed to home oxygen for 17.8 hours/day; 60% of the patients were compliant according to our definition. Increasing age and ambulatory oxygen utilization predicted adherence to oxygen therapy. Adherence to home oxygen therapy is suboptimal. Behavioral and psychological interventions to improve compliance to LTOT should be investigated.

Multi-center, randomized, placebo-controlled trial of nocturnal oxygen therapy in chronic obstructive pulmonary disease: a study protocol for the INOX trial.

BACKGROUND: Long-term oxygen therapy (LTOT) is the only component of the management of chronic obstructive pulmonary disease (COPD) that improves survival in patients with severe daytime hypoxemia. LTOT is usually provided by a stationary oxygen concentrator and is recommended to be used for at least 15-18 h a day. Several studies have demonstrated a deterioration in arterial blood gas pressures and oxygen saturation during sleep in patients with COPD, even in those not qualifying for LTOT. The suggestion has been made that the natural progression of COPD to its end stages of chronic pulmonary hypertension, severe hypoxemia, right heart failure, and death is dependent upon the severity of desaturation occurring during sleep. The primary objective of the International Nocturnal Oxygen (INOX) trial is to determine, in patients with COPD not qualifying for LTOT but who present significant nocturnal arterial oxygen desaturation, whether nocturnal oxygen provided for a period of 3 years decreases mortality or delay the prescription of LTOT. METHODS: The INOX trial is a 3-year, multi-center, placebo-controlled, randomized trial of nocturnal oxygen therapy added to usual care. Eligible patients are those with a diagnosis of COPD supported by a history of past smoking and obstructive disease who fulfill our definition of significant nocturnal oxygen desaturation (i.e., ≥ 30% of the recording time with transcutaneous arterial oxygen saturation < 90% on either of two consecutive recordings). Patients allocated in the control group receive room air delivered by a concentrator modified to deliver 21% oxygen. The comparison is double blind. The primary outcome is a composite of mortality from all cause or requirement for LTOT. Secondary outcomes include quality of life and utility measures, costs from a societal perspective and compliance with oxygen therapy. The follow-up period is intended to last at least 3 years. DISCUSSION: The benefits of LTOT have been demonstrated whereas those of nocturnal oxygen therapy alone have not. The INOX trial will likely determine whether supplemental oxygen during sleep is effective in reducing mortality, delaying the need for LTOT and improving health-related quality of life in patients with COPD who desaturate overnight. TRIAL REGISTRATION: Current Controlled Trials ISRCTN50085100 ; ClinicalTrials.gov NCT01044628 (date of registration: January 6, 2010).

Utility Scores In Patients With Oxygen-Dependent COPD: A Case-Control Study.

BACKGROUND: Utility measures that summarize the health-related quality of life of an individual using a single number usually between 0 (death) and 1 (full health) are useful to quantify the benefits of health care interventions in terms of quality-adjusted life years (QALYs) and to help prioritizing limited health resources from cost-effectiveness analyses among patients with different health conditions. OBJECTIVE: To determine utility scores in patients with oxygen-dependent chronic obstructive pulmonary disease (COPD). METHODS: Patients with oxygen-dependent COPD (the cases) were matched, on a 1:2 basis, to COPD controls according to gender, age (± 5 years) and FEV1 (±5% predicted). Utility scores were obtained from the SF-6D, a measure derived from the SF-36. RESULTS: From a cohort of 102 patients with oxygen-dependent COPD, 68 (42 men; mean age: 71 years; mean FEV1: 35% predicted) were successfully matched with 136 controls. We found clinically and statistically significant differences in mean utility scores between cases (0.588 ± 0.071) and controls (0.627 ± 0.085; p = 0.001). The same differences were observed in men and women. CONCLUSION: Oxygen-dependence adds to the burden of disease in terms of quality of life. These utility scores may be useful in cost-utility analyses involving patients with oxygen-dependent COPD.

Commentary: RCT of optimal dose methylphenidate in children and adolescents with severe ADHD and ID--a reply to Arnold (2013).

The commentary by Arnold (2013) raises a number of interesting issues and speculations about the action of methylphenidate in children with intellectual disability (ID) and associated neurodevelopmental disorders, such as autism spectrum disorders. In our article (Simonoff et al., 2013), we were careful to stick closely to the statistical analysis plan drawn up (and approved by the Data Monitoring Committee) during data collection and prior to any exploratory analysis. However, a number of the issues raised by Arnold warrant further response, with the aim of clarifying the lessons that can reasonably be drawn for clinical practice.

Randomized controlled double-blind trial of optimal dose methylphenidate in children and adolescents with severe attention deficit hyperactivity disorder and intellectual disability.

BACKGROUND: Attention deficit hyperactivity disorder is increased in children with intellectual disability. Previous research has suggested stimulants are less effective than in typically developing children but no studies have titrated medication for individual optimal dosing or tested the effects for longer than 4 weeks. METHOD: One hundred and twenty two drug-free children aged 7-15 with hyperkinetic disorder and IQ 30-69 were recruited to a double-blind, placebo-controlled trial that randomized participants using minimization by probability, stratified by referral source and IQ level in a one to one ratio. Methylphenidate was compared with placebo. Dose titration comprised at least 1 week each of low (0.5 mg/kg/day), medium (1.0 mg/kg/day) and high dose (1.5 mg/kg/day). Parent and teacher Attention deficit hyperactivity disorder (ADHD) index of the Conners Rating Scale-Short Version at 16 weeks provided the primary outcome measures. Clinical response was determined with the Clinical Global Impressions scale (CGI-I). Adverse effects were evaluated by a parent-rated questionnaire, weight, pulse and blood pressure. Analyses were by intention to treat. TRIAL REGISTRATION: ISRCTN 68384912. RESULTS: Methylphenidate was superior to placebo with effect sizes of 0.39 [95% confidence intervals (CIs) 0.09, 0.70] and 0.52 (95% CIs 0.23, 0.82) for the parent and teacher Conners ADHD index. Four (7%) children on placebo versus 24 (40%) of those on methylphenidate were judged improved or much improved on the CGI. IQ and autistic symptoms did not affect treatment efficacy. Active medication was associated with sleep difficulty, loss of appetite and weight loss but there were no significant differences in pulse or blood pressure. CONCLUSIONS: Optimal dosing of methylphenidate is practical and effective in some children with hyperkinetic disorder and intellectual disability. Adverse effects typical of methylphenidate were seen and medication use may require close monitoring in this vulnerable group.

Cost-Effectiveness of an Extended Home Visit Program for Oxygen-Dependent COPD Patients.

BACKGROUND: Long-term oxygen therapy in COPD is usually supervised through home-care respiratory programs. Such programs often involve an intensive education intervention at the initiation of long-term oxygen therapy, followed by an extended follow-up period that aims toward home oxygen adherence. The objective of this study was to estimate the cost-effectiveness ratio of such a maintenance program. METHODS: A simulation model was developed that compared 2 strategies after the intensive education intervention: (1) enrollment and (2) no enrollment in a maintenance program. The study population consisted of a hypothetical cohort of 200 patients (100 patients per group; mean age, 74 years; 45% men; mean FEV1 of 43% predicted value; and mean resting PaO2 while breathing air, 50 mm Hg). Effectiveness assumptions of the program were derived from a current literature review. The primary outcome was the ratio of the incremental cost of the program per quality-adjusted life-years gained. Only direct costs were considered; a health-care system perspective was adopted. Costs are reported in 2020 Canadian dollars (Can $). RESULTS: Over a 5-year period, an extended home-visit program may prevent 9 deaths and provide an additional 39 years of life and 24 quality-adjusted life-years. Compared with usual care (ie, no enrollment in the maintenance program), the incremental cost-effectiveness ratio was Can $17,197 per quality-adjusted life-years gained. Sensitivity analyses demonstrated the robustness of the model. Only a reduction in adherence of 25% per year would increase the incremental cost-effectiveness ratio per quality-adjusted life-years beyond the threshold of Can $50,000 that is usually considered as acceptable from a health-care system perspective. CONCLUSIONS: An extended home-visit program to maintain or improve adherence to long-term oxygen therapy in patients with COPD would most likely be cost-effective.

Short-Term Oxygen Therapy Outcomes in COPD.

Rationale: Short-term oxygen therapy (STOT) is often prescribed to allow patients with chronic obstructive pulmonary disease (COPD) to be discharged safely from hospital following an acute illness. This practice is widely accepted without being based on evidence. Purpose: Our objective was to describe the characteristics and outcomes of patients with COPD who received STOT. Patients and Methods: The study was a secondary analysis of the INOX trial, a 4-year randomised trial of nocturnal oxygen in COPD. The trial indicated that nocturnal oxygen has no significant effect on survival or progression to LTOT, allowing our merging of patients who received nocturnal oxygen and those who received placebo into a single cohort to study the predictors and outcomes of STOT regardless of the treatment received during the trial. Results: Among the 243 participants in the trial, 60 required STOT on at least one occasion during follow-up. Patients requiring STOT had more severe dyspnoea and lung function impairment, and lower PaO2 at baseline than those who did not. STOT was associated with subsequent LTOT requirement (hazard ratio [HR]: 4.59; 95% confidence interval [CI]: 2.98-7.07) and mortality (HR: 1.93; 95% CI: 1.15-3.24). The association between STOT and mortality was confounded by age, disease severity and comorbidities. Periods of STOT of more than one month and/or repeated prescriptions of STOT increased the probability of progression to LTOT (OR: 5.07; 95% CI: 1.48-18.8). Conclusion: Following an acute respiratory illness in COPD, persistent hypoxaemia requiring STOT is a marker of disease progression towards the requirement for LTOT.

Balance on the Brain: a randomised controlled trial evaluating the effect of a multimodal exercise programme on physical performance, falls, quality of life and cognition for people with mild cognitive impairment-study protocol.

INTRODUCTION: Exercise and physical activity have been shown to improve cognition for people living with mild cognitive impairment (MCI). There is strong evidence for the benefits of aerobic exercise and medium evidence for participating in regular strength training for people with MCI. However, people living with MCI fall two times as often as those without cognitive impairment and the evidence is currently unknown as to whether balance training for people with MCI is beneficial, as has been demonstrated for older people without cognitive impairment. The aim of this study is to determine whether a balance-focused multimodal exercise intervention improves balance and reduces falls for people with MCI, compared with a control group receiving usual care. METHODS AND ANALYSIS: This single blind randomised controlled trial (Balance on the Brain) will be offered to 396 people with MCI living in the community. The multimodal exercise intervention consists of two balance programmes and a walking programme to be delivered by physiotherapists over a 6-month intervention period. All participants will be followed up over 12 months (for the intervention group, this involves 6-month intervention and 6-month maintenance). The primary outcomes are (1) balance performance and (2) rate of falls. Physical performance, levels of physical activity and sedentary behaviour, quality of life and cognition are secondary outcomes. A health economic analysis will be undertaken to evaluate the cost-effectiveness of the intervention compared with usual care. ETHICS AND DISSEMINATION: Ethics approval has been received from the South Metropolitan Health Service Human Research Ethics Committee (HREC), Curtin University HREC and the Western Australia Department of Health HREC; and approval has been received to obtain data for health costings from Services Australia. The results will be disseminated through peer-review publications, conference presentations and online platforms. TRIAL REGISTRATION NUMBER: ACTRN12620001037998; Australian New Zealand Clinical Trials Registry (ANZCTR).

Effects of written action plan adherence on COPD exacerbation recovery.

BACKGROUND: The effects of written action plans on recovery from exacerbations of chronic obstructive pulmonary disease (COPD) have not been well studied. The aims of this study were to assess the effects of adherence to a written action plan on exacerbation recovery time and unscheduled healthcare utilisation and to explore factors associated with action plan adherence. METHODS: This was a 1-year prospective cohort study embedded in a randomised controlled trial. Exacerbation data were recorded for 252 patients with COPD who received a written action plan for prompt treatment of exacerbations with the instructions to initiate standing prescriptions for both antibiotics and prednisone within 3 days of exacerbation onset. Following the instructions was defined as adherence to the action plan. RESULTS: From the 288 exacerbations reported by 143 patients, start dates of antibiotics or prednisone were provided in 217 exacerbations reported by 119 patients (53.8% male, mean age 65.4 years, post-bronchodilator forced expiratory volume in 1 s (FEV(1)) 43.9% predicted). In 40.1% of exacerbations, patients adhered to their written action plan. Adherence reduced exacerbation recovery time with statistical (p=0.0001) and clinical (-5.8 days) significance, but did not affect unscheduled healthcare utilisation (OR 0.94, 95% CI 0.49 to 1.83). Factors associated with an increased likelihood of adherence were influenza vaccination, cardiac comorbidity, younger age and lower FEV(1) as percentage predicted. CONCLUSIONS: This study shows that adherence to a written action plan is associated with a reduction in exacerbation recovery time by prompt treatment. Knowing the factors that are associated with proper and prompt utilisation of an action plan permits healthcare professionals to better focus their self-management support on appropriate patients.

Dihydropyranone formation by ipso C-H activation in a glucal 3-carbamate-derived rhodium acyl nitrenoid.

By using (N-tosyloxy)-3-O-carbamoyl-D-glucal 10, which removes the need for a hypervalent iodine(III) oxidant, we provide evidence for rhodium nitrenoid-mediated ipso C-H activation as the origin of a C3-oxidized dihydropyranone product 3. This system may be especially susceptible to such a pathway because of the ease of forming a cation upon hydride transfer to the rhodium-complexed acyl nitrene.

Combining both generic and disease-specific properties: development of the McGill COPD quality of life questionnaire.

UNLABELLED: Presently, a generic and a disease-specific questionnaire are often co-administered to capture the different domains of quality of life in chronic obstructive pulmonary disease (COPD) subjects. A health-related-quality of life (HRQL) questionnaire in COPD combining both generic and disease-specific properties is needed. OBJECTIVE: To develop a new, hybrid-HRQL questionnaire, the McGill-COPD-questionnaire, with qualities of both generic and disease-specific instruments. Using pre-defined criteria, we selected items from the SF-36 to complement the items from a COPD-specific-module to create the new hybrid-HRQL-questionnaire. Domains were identified via confirmatory factor analysis. The McGill COPD questionnaire is available in English and French; it assesses three domains: symptoms, physical-function and feelings, has 29 items: 17 from the COPD-specific-module and 12 from the SF-36. The symptom sub-scale has 6 items, all from the COPD-specific-module; the feelings sub-scale has 10 items, 5 each from COPD-specific-module and SF-36 and the physical-function sub-scale has 13 items, 6 from COPD-specific-module and 7 from SF-36. The McGill COPD questionnaire was developed using a novel method of combining items from the SF-36 and a COPD-specific-module. Thus, this new questionnaire has items from a generic-questionnaire and a disease-specific-module and, hence, is promising to be a stand alone quality-of-life questionnaire for COPD subjects.

Fatigue in COPD: prevalence and effect on outcomes in pulmonary rehabilitation.

Patients with chronic obstructive pulmonary disease (COPD) complain of dyspnea and fatigue. We sought to estimate the prevalence of high fatigue in this population and to determine whether individuals with high fatigue had a different response to pulmonary rehabilitation. This observational study was embedded within a randomized trial. Participants underwent 3 months of pulmonary rehabilitation including education and exercise training. We divided 251 individuals into low and high fatigue groups using population normal scores of the SF-36 vitality domain. Baseline data included spirometry, 6-minute walk distance (6MWD), peak exercise capacity, constant workrate cycling endurance time, and questionnaires including the St. George's and Chronic Respiratory questionnaires (SGRQ, CRQ). The response to pulmonary rehabilitation was evaluated using changes in these measures at 3 months and 1 year after entry. High fatigue was present in 97/251 (39%) of patients. High fatigue patients were younger, had more depressive symptoms, greater dyspnea and poorer SGRQ scores (p < 0.01). They also had lower 6MWD, endurance times, and peak volume of oxygen consumption (VO(2); p < 0.05). Patients in both groups improved similarly in their dyspnea, the 6MWD and endurance time. High-fatigue patients had greater improvements in both the CRQ fatigue (by 0.74 more points) and the SGRQ scores (by 6.0 points; p < 0.01), with clinically significant gains maintained at 1 year. This study suggests that high levels of fatigue is a common feature in patients with COPD. They have a lower exercise capacity and a lower health status. However, they benefit from pulmonary rehabilitation.