Chronic obstructive pulmonary disease (COPD) is associated with cough, sputum production or dyspnoea and a reduction in lung function, quality of life and life expectancy. Apart from smoking ...cessation, there are no other treatments that slow lung function decline. Roflumilast and cilomilast are oral phosphodiesterase 4 (PDE4) inhibitors proposed to reduce the airway inflammation and bronchoconstriction seen in COPD.
To evaluate the efficacy and safety of oral PDE4 inhibitors in the management of stable COPD.
We identified randomised controlled trials (RCTs) from the Cochrane Airways Group Specialised Register of trials (date of last search June 2013). We found other trials from web-based clinical trial registers.
We included RCTs if they compared oral PDE4 inhibitors with placebo in people with COPD. We allowed co-administration of standard COPD therapy.
One review author extracted data and a second review author checked the data, before entry into The Cochrane Collaboration software program (RevMan version 5.2). We reported pooled data as mean differences (MD), standardised mean differences (SMD) or odds ratios (OR).
Twenty-nine separate RCTs studying roflumilast (15 trials, 12,654 patients) or cilomilast (14 trials, 6457 patients) met the inclusion criteria, with a duration between six weeks and one year. These included people across international study centres with moderate to very severe COPD (GOLD grades II-IV), with a mean age of 64 years.Treatment with a PDE4 inhibitor was associated with a significant improvement in forced expiratory volume in one second (FEV1) over the trial period compared with placebo (MD 45.60 mL; 95% confidence interval (CI) 39.45 to 51.75, 22 trials with 15,670 participants, moderate quality evidence due to moderate levels of heterogeneity and risk of reporting bias). There were small improvements in quality of life (St George's Respiratory Questionnaire MD -1.04; 95% CI -1.66 to -0.41, 10 trials with 7618 participants, moderate quality evidence due to moderate levels of heterogeneity and risk of reporting bias) and COPD-related symptoms, but no change in exercise tolerance. Treatment with a PDE4 inhibitor was associated with a reduced likelihood of COPD exacerbation (OR 0.77; 95% CI 0.71 to 0.83, high quality evidence). For every 100 people treated with PDE4 inhibitors, six more remained exacerbation-free during the study period compared with placebo (number needed to treat for an additional beneficial effect (NNTB) 20; 95% CI 16 to 27). More participants in the treatment groups experienced non-serious adverse events compared with controls, particularly gastrointestinal symptoms and headache. Roflumilast in particular was associated with weight loss during the trial period and an increase in insomnia and depressive mood symptoms. Participants treated with PDE4 inhibitors were also more likely to withdraw from the trials because of adverse effects; on average 24% in the treatment groups withdrew compared with 19% in the control groups.
In people with COPD, PDE4 inhibitors offered benefit over placebo in improving lung function and reducing the likelihood of exacerbations; however, they had little impact on quality of life or symptoms. Gastrointestinal adverse effects and weight loss were common, and safety data submitted to the US Food and Drug Administration (FDA) have raised concerns over psychiatric adverse events with roflumilast. The optimum place of PDE4 inhibitors in COPD management therefore remains to be defined. Longer-term trials are needed to determine whether or not PDE4 inhibitors modify FEV1 decline, hospitalisation or mortality in COPD.
Abstract Chong J, Mackey AH, Broadbent E, Stott NS. Relationship between walk tests and parental reports of walking abilities in children with cerebral palsy. Objectives To test the strength of ...association between 2 clinic-based measures of walking ability, the 1-minute walk test (1MWT) and the six-minute walk test (6MWT), and the parental report of usual walking performance, measured by the ABILOCO-Kids logit score, in children with cerebral palsy (CP). Design Observational study. Setting Tertiary level outpatient clinics. Participants Children and youth with CP ( N= 60; 32 boys, 28 girls; mean age, 11.2y range, 5–18y), Gross Motor Function Classification System (GMFCS) level I to IV. Interventions Not applicable. Main Outcome Measures The 10-item ABILOCO-Kids questionnaire, the 1MWT, and the 6MWT. Results ABILOCO-Kids logit scores were significantly correlated with the 1MWT (ρ=.70, P <.01) and the 6MWT (ρ=.70, P <.01) but not with age or sex. Linear models revealed a possibly significant difference in the strength of the relationship of the ABILOCO-Kids logit score with walking distance, depending on GMFCS level ( P =.06 1MWT; P =.14 6MWT). The strongest relationship was observed at GMFCS level II, where ABILOCO-Kids score predicted 33% of variance in 1MWT ( P =.003) and 31% of 6MWT ( P =.003). The weakest relationship was at GMFCS level I, where ABILOCO-Kids score predicted only 5% of the variance in 1MWT ( P =.33) and 16% of the variance in 6MWT ( P =.08). Conclusions Parental perceptions of their child's walking ability in the community correlate with clinic-based walking tests in ambulatory children with CP, providing evidence of convergent validity for the 1MWT and 6MWT. However, parents report a much wider range of walking abilities in children who function at a high level (GMFCS I) than is reflected by their walk test results.
Beta human chorionic gonadotropin (βhCG) is a glycoprotein secreted by trophoblastic cells during gestation. Various solid epithelial cancers can raise levels of βhCG and can cause gynecomastia. ...There are a few case reports that show elevated levels of βhCG especially in the context of transitional cell carcinoma (TCC) of the bladder to have a much poorer prognosis. In addition, these cases were found to have more aggressive disease and a higher likelihood of metastasis. There is little evidence in the literature regarding the work up of gynecomastia in adolescent patients and whether all gynecomastia workups should have a βhCG evaluation.
An otherwise fit and healthy 71-year-old male presented with bilateral gynecomastia, breast pain and significant weight loss. He was investigated by the breast surgeons who ruled out breast malignancy. He was then referred to the endocrine department for further investigations and was found to have hypogonadism with a significantly raised βhCG. In view of the raised βhCG, computed tomography (CT) scan of the chest, abdomen and pelvis was performed to look for any underlying tumour. This showed a large bladder tumour, and biopsy of the mass confirmed the diagnosis of Ta 4NxM1 sarcomatoid bladder tumour.
Raised βhCG level in a patient with gynecomastia could be due to an underlying transitional cell carcinoma of the bladder. Therefore, any raised βhCG level warrants further investigation.
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
To compare the efficacy and safety of LTRAs versus placebo in the management of children (≥ 5 years) and adults ...with mild asthma.
Background Patients with diabetes mellitus (DM) are on the rise all over the world. Simultaneously, the complications of DM are also increasing. Diabetes-related foot problems have been another ...concern among health professionals, especially foot ulcers, osteomyelitis, and amputations. Objectives We determined the prevalence of gender, age, types of DM including non-diabetics, various foot-related presentations, complications, and their outcomes. Methods A retrospective descriptive cross-sectional study was conducted among new patients attending a diabetic foot clinic over a period of six months, from January 1, 2019 to June 30, 2019. To confirm the outcome of the study, all of them were followed up for at least four months from the date of diagnosis. Results The study showed that most patients were males (65.5%). The most common age group for diabetic foot problems was 81-90 years, and about 80% of the foot problems were diagnosed in patients over 60 years. The study disclosed that 86.2% of the population had type 2 DM, 56.9% had ulcers, and 13.8% had osteomyelitis. The outcome of our study demonstrated that 65.5% of the patients were cured and discharged within four months of the diagnosis, but 10.3% of the population needed amputation. During the four-month follow-up period, 3.4% of our study population died due to non-foot-related causes. A total of 48.1% of our ulcer patients were discharged within eight weeks of diagnosis. However, 26% of ulcer patients and 75% of osteomyelitis patients needed more than four months to be discharged. Peripheral neuropathy and peripheral arterial disease (PAD) were present in 91% of ulcer patients. Among our osteomyelitis group, 100% had peripheral neuropathy, and 87.5% had PAD. About 20% of ulcer patients and none of the osteomyelitis patients were diagnosed with chronic kidney disease (CKD) stages beyond 3b. About 2/3rd of our ulcer and osteomyelitis population had an HbA1C level of more than 7.5%. Conclusion Male patients over 60 years of age with type 2 DM are more at risk of developing diabetes-related foot issues. Ulcer with or without osteomyelitis was the most common complication among our study population. Results showed that a significant amount of osteomyelitis patients underwent foot amputation. Poor glycaemic control of HbA1C of more than 7.5%, peripheral neuropathy, and PAD were the most common risk factors for developing foot-related complications. Prolonged use of antibiotics and a dedicated professional team may be needed to manage these complications successfully.
The use of unmanned aerial vehicles (UAVs) in the construction industry is swiftly growing worldwide. UAVs are changing the way construction companies do business. Contractors are increasingly using ...camera-mounted UAVs to monitor the full range of activities. Rapid advances in camera, sensing, aeronautics, battery and autopilot navigation technologies have helped make UAVs affordable, reliable and easy to operate. The US Federal Aviation Administration predicts that UAVs hold tremendous promise and commercial drone sales could increase from 600,000 to 2.7 million over the next four years. On the one hand, UAVs are extremely cost-effective in conducting aerial surveys, worksite surveillance, real-time inspections, and monitoring jobsite safety. On the other hand, with UAV ownership rapidly rising, the number of reported UAV safety, risk, and liability incidents is increasing. With this new technology use in the construction industry, construction companies must be aware of all regulations, legislations, privacy liability, and risks for construction related businesses. Operating a drone or hiring a subcontractor to operate it is not something to do on the spur of the moment. Emphasis and effort should be placed on safety, risk control, training and education. The goal of this paper is to provide construction professionals with timely and pertinent information on UAV use with a focus on risk management based on current industry practice, experience and literature review.
The functionality and quality structure of a rating scale are vital in a survey instrument. This article discusses the underlying assumption of a rating scale and addresses the application of the ...Rasch Rating Scale Model (RSM) to diagnose the rating scale structure in a survey instrument. The instrument used to demonstrate the process of diagnosis a rating scale functioning in this study was the Vocational Teachers’ Assessment Literacy (VoTAL) instrument. The VoTAL instrument utilized the five-point Likert-type response format and consisted of 88 items representing three assessment literacy constructs. The data were obtained from 224 vocational teachers at five vocational colleges, which were randomly selected from the state of Selangor and the federal territory of Kuala Lumpur in Malaysia. The rating scale diagnosis results showed that the initial five steps of rating scale categories were not properly functioning as intended. It was found that the Andrich threshold of category three was disordered as it was not monotonically advance with categories. Additionally, the result also found that the width of the threshold between category three and category four was too narrow (0.66 logits). The results indicate that the rating scale used in the VoTAL instrument was disordered. Thus, it was suggested that the initial five rating step categories were collapsed down into four categories. In conclusion, this study highlights the importance of assessing the rating scale’s functionality in a survey instrument to reduce measurement error and collect valid and reliable data.
Chronic obstructive pulmonary disease (COPD) affects symptoms, lung function, quality of life and life expectancy. Apart from smoking cessation, there are no other treatments that slow lung function ...decline. Roflumilast and cilomilast are oral phosphodiesterase 4 (PDE(4)) inhibitors proposed to reduce the airway inflammation and bronchoconstriction seen in COPD.
To evaluate the efficacy and safety of PDE(4) inhibitors in the management of people with stable COPD. Outcomes included lung function, quality of life, symptoms, exacerbations and adverse effects.
We identified randomised controlled trials (RCTs) from the Cochrane Airways Group Specialised Register of trials (date of last search 6 August 2010). We found other trials from web-based clinical trial registers.
We included RCTs if they compared oral PDE(4) inhibitors with placebo in people with COPD. We allowed co-administration of standard COPD therapy.
One review author extracted data and a second review author checked the data, before entry into The Cochrane Collaboration software programme (RevMan version 5.1). We reported pooled data as mean differences (MD), standardised mean differences (SMD), or odds ratios (OR).
Twenty-three separate RCTs studying roflumilast (nine trials, 9211 patients) or cilomilast (fourteen trials, 6457 patients) met the inclusion criteria. None of the trials exceeded a year in duration.Treatment with a PDE(4) inhibitor was associated with a significant improvement in FEV(1)over the trial period compared with placebo (MD 45.59 mL; 95% confidence interval (CI) 39.15 to 52.03), regardless of COPD severity or concomitant COPD treatment. There were some small improvements in quality of life (St George's Respiratory Questionnaire MD -1.04; 95% CI -1.66 to -0.41) and COPD-related symptoms, but no change in exercise tolerance. Treatment with a PDE(4) inhibitor was associated with a reduced likelihood of COPD exacerbation (OR 0.78; 95% CI 0.72 to 0.85). More participants in the treatment groups experienced non-serious adverse events compared with controls, particularly gastrointestinal symptoms and headache. Roflumilast was associated with weight loss during the trial period.
In people with COPD, PDE(4) inhibitors offered benefit over placebo in improving lung function and reducing likelihood of exacerbations, however, they had little impact on quality of life or symptoms. Gastrointestinal adverse effects and weight loss were common. The optimum place of PDE(4) inhibitors in COPD management remains to be defined. Longer-term trials are needed to determine whether or not PDE(4) inhibitors modify FEV(1) decline, healthcare utilisation or mortality in COPD.
Molecular approaches to understanding the functional circuitry of the nervous system promise new insights into the relationship between genes, brain and behaviour. The cellular diversity of the brain ...necessitates a cellular resolution approach towards understanding the functional genomics of the nervous system. We describe here an anatomically comprehensive digital atlas containing the expression patterns of approximately 20,000 genes in the adult mouse brain. Data were generated using automated high-throughput procedures for in situ hybridization and data acquisition, and are publicly accessible online. Newly developed image-based informatics tools allow global genome-scale structural analysis and cross-correlation, as well as identification of regionally enriched genes. Unbiased fine-resolution analysis has identified highly specific cellular markers as well as extensive evidence of cellular heterogeneity not evident in classical neuroanatomical atlases. This highly standardized atlas provides an open, primary data resource for a wide variety of further studies concerning brain organization and function.
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