Real-world experience of nintedanib for progressive fibrosing interstitial lung disease in the UK.

Background: Nintedanib slows progression of lung function decline in patients with progressive fibrosing (PF) interstitial lung disease (ILD) and was recommended for this indication within the United Kingdom (UK) National Health Service in Scotland in June 2021 and in England, Wales and Northern Ireland in November 2021. To date, there has been no national evaluation of the use of nintedanib for PF-ILD in a real-world setting. Methods: 26 UK centres were invited to take part in a national service evaluation between 17 November 2021 and 30 September 2022. Summary data regarding underlying diagnosis, pulmonary function tests, diagnostic criteria, radiological appearance, concurrent immunosuppressive therapy and drug tolerability were collected via electronic survey. Results: 24 UK prescribing centres responded to the service evaluation invitation. Between 17 November 2021 and 30 September 2022, 1120 patients received a multidisciplinary team recommendation to commence nintedanib for PF-ILD. The most common underlying diagnoses were hypersensitivity pneumonitis (298 out of 1120, 26.6%), connective tissue disease associated ILD (197 out of 1120, 17.6%), rheumatoid arthritis associated ILD (180 out of 1120, 16.0%), idiopathic nonspecific interstitial pneumonia (125 out of 1120, 11.1%) and unclassifiable ILD (100 out of 1120, 8.9%). Of these, 54.4% (609 out of 1120) were receiving concomitant corticosteroids, 355 (31.7%) out of 1120 were receiving concomitant mycophenolate mofetil and 340 (30.3%) out of 1120 were receiving another immunosuppressive/modulatory therapy. Radiological progression of ILD combined with worsening respiratory symptoms was the most common reason for the diagnosis of PF-ILD. Conclusion: We have demonstrated the use of nintedanib for the treatment of PF-ILD across a broad range of underlying conditions. Nintedanib is frequently co-prescribed alongside immunosuppressive and immunomodulatory therapy. The use of nintedanib for the treatment of PF-ILD has demonstrated acceptable tolerability in a real-world setting.

Amine Basicity of Quinoline ATP Synthase Inhibitors Drives Antibacterial Activity against Pseudomonas aeruginosa.

Pseudomonas aeruginosa (PA), a Gram-negative pathogen, is a common cause of nosocomial infections, especially in immunocompromised and cystic fibrosis patients. PA is intrinsically resistant to many currently prescribed antibiotics due to its tightly packed, anionic lipopolysaccharide outer membrane, efflux pumps, and ability to form biofilms. PA can acquire additional resistance through mutation and horizontal gene transfer. PA ATP synthase is an attractive target for antibiotic development because it is essential for cell survival even under fermentation conditions. Previously, we developed two lead quinoline compounds that were capable of selectively inhibiting PA ATP synthase and acting as antibacterial agents against multidrug-resistant PA. Herein we conduct a structure-activity relationship analysis of the lead compounds through the synthesis and evaluation of 18 quinoline derivatives. These compounds function as new antibacterial agents while providing insight into the balance of physical properties needed to promote cellular entry while maintaining PA ATP synthase inhibition.

Quinoline Compounds Targeting the c-Ring of ATP Synthase Inhibit Drug-Resistant Pseudomonas aeruginosa.

Pseudomonas aeruginosa (PA) is a Gram-negative, biofilm-forming bacterium and an opportunistic pathogen. The growing drug resistance of PA is a serious threat that necessitates the discovery of novel antibiotics, ideally with previously underexplored mechanisms of action. Due to their central role in cell metabolism, bacterial bioenergetic processes are of increasing interest as drug targets, especially with the success of the ATP synthase inhibitor bedaquiline to treat drug-resistant tuberculosis. Like Mycobacterium tuberculosis, PA requires F1Fo ATP synthase for growth, even under anaerobic conditions, making the PA ATP synthase an ideal drug target for the treatment of drug-resistant infection. In previous work, we conducted an initial screen for quinoline compounds that inhibit ATP synthesis activity in PA. In the present study, we report additional quinoline derivatives, including one with increased potency against PA ATP synthase in vitro and antibacterial activity against drug-resistant PA. Moreover, by expressing the PA ATP synthase in Escherichia coli, we show that mutations in the H+ binding site on the membrane-embedded rotor ring alter inhibition by the reported quinoline compounds. Identification of a potent inhibitor and its probable binding site on ATP synthase enables further development of promising quinoline derivatives into a viable treatment for drug-resistant PA infection.

Chest CT features and functional correlates of COVID-19 at 3 months and 12 months follow-up.

Long-term pulmonary sequelae of Coronavirus 2019 (COVID-19) remain unclear. Thus, we aimed to establish post-COVID-19 temporal changes in chest computed tomography (CT) features of pulmonary fibrosis and to investigate associations with respiratory symptoms and physiological parameters at 3 and 12 months' follow-up. Adult patients who attended our initial COVID-19 follow-up service and developed chest CT features of interstitial lung disease, in addition to cases identified using British Society of Thoracic Imaging codes, were evaluated retrospectively. Clinical data were gathered on respiratory symptoms and physiological parameters at baseline, 3 months, and 12 months. Corresponding chest CT scans were reviewed by two thoracic radiologists. Associations between CT features and functional correlates were estimated using random effects logistic or linear regression adjusted for age, sex and body mass index. In total, 58 patients were assessed. No changes in reticular pattern, honeycombing, traction bronchiectasis/bronchiolectasis index or pulmonary distortion were observed. Subpleural curvilinear lines were associated with lower odds of breathlessness over time. Parenchymal bands were not associated with breathlessness or impaired lung function overall. Based on our results, we conclude that post-COVID-19 chest CT features of irreversible pulmonary fibrosis remain static over time; other features either resolve or remain unchanged. Subpleural curvilinear lines do not correlate with breathlessness. Parenchymal bands are not functionally significant. An awareness of the different potential functional implications of post-COVID-19 chest CT changes is important in the assessment of patients who present with multi-systemic sequelae of COVID-19 infection.

Changes to Birth Plans Due to COVID-19: A Survey of Utah Midwives and Doulas.

INTRODUCTION: This study seeks to understand the experiences of Utah midwives and doulas caring for patients during the recent coronavirus disease 2019 (COVID-19) pandemic. Specifically, the goal of the study was to describe the perceived impact on the community birth system and explore differences in the access and use of personal protective equipment (PPE) between in- and out-of-hospital births. METHODS: This study used a cross-sectional, descriptive study design. A 26-item survey developed by the research team was sent via email to Utah birth workers, including nurse-midwives, community midwives, and doulas. Quantitative data were collected during December 2020 and January 2021. Descriptive statistics were used in the analysis. RESULTS: Of the 409 birth workers who were sent a link to the survey, 120 (30%) responded: 38 (32%) CNMs, 30 (25%) direct-entry or community midwives, and 52 (43%) doulas. The majority (79%) reported changes to clinical practice during the COVID-19 pandemic. Community midwives (71%) who responded indicated practice volume increased. Survey participants reported an increased patient preference for home births (53%) and birth center births (43%). Among those with one or more patient transfers to the hospital, 61% experienced a change in the process. One participant reported that it took 43 minutes longer to transfer to the hospital. Community midwives and doulas reported poor access to a regular source of PPE. DISCUSSION: Survey participants reported changes to planned birth locations during the COVID-19 pandemic. When necessary, transfers to hospitals were reported to be slower. Community midwives and doulas reported having insufficient access to PPE and reported limited knowledge about COVID-19 testing resources and resources for educating patients on COVID-19. This study adds an important perspective to the existing literature on COVID-19 by indicating that policymakers should include community birth partners in community planning for natural disasters and future pandemics.

Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors.

DNA methylation, a form of epigenetic gene regulation, is important for normal cellular function. In cells, proteins called DNA methyltransferases (DNMTs) establish and maintain the DNA methylation pattern. Changes to the normal DNA methylation pattern are linked to cancer development and progression, making DNMTs potential cancer drug targets. Thus, identifying and characterizing novel small molecule inhibitors of these enzymes is of great importance. This paper presents a protocol that can be used to screen for DNA methyltransferase inhibitors. The continuous coupled kinetics assay allows for initial velocities of DNA methylation to be determined in the presence and absence of potential small molecule inhibitors. The assay uses the methyl-sensitive endonuclease Gla I to couple methylation of a hemimethylated DNA substrate to fluorescence generation. This continuous assay allows for enzyme activity to be monitored in real time. Conducting the assay in small volumes in microtiter plates reduces the cost of reagents. Using this assay, a small example screen was conducted for inhibitors of DNMT1, the most abundant DNMT isozyme in humans. The highly substituted anthraquinone natural product, laccaic acid A, is a potent, DNA-competitive inhibitor of DNMT1. Here, we examine three potential small molecule inhibitors - anthraquinones or anthraquinone-like molecules with one to three substituents - at two concentrations to describe the assay protocol. Initial velocities are used to calculate the percent activity observed in the presence of each molecule. One of three compounds examined exhibits concentration-dependent inhibition of DNMT1 activity, indicating that it is a potential inhibitor of DNMT1.

Power, recovery and doing something worthwhile: A thematic analysis of expert patient perspectives in psychiatry education.

BACKGROUND: Patient involvement in psychiatry education is required by policy and has many benefits for students. Little research has focused on the impact on expert patients (EPs). OBJECTIVE: This study aimed to explore the impact of involvement in psychiatry education on mental health patients. DESIGN: A qualitative descriptive study using semistructured interviews was conducted in a psychiatry teaching unit in the East Midlands, UK. A purposive sample of 20 EPs involved in teaching was interviewed about the social and psychological impacts of involvement. Transcripts were analysed thematically and a coding scheme was developed. RESULTS: Five themes were identified: shaping the doctors of the future-something worthwhile, challenging assumptions about mental health, recovery and transformation, vulnerability and support and expertise and power. CONCLUSION: These EPs benefitted from their experience of teaching. Involvement in psychiatry teaching may require putting oneself in a vulnerable position, but a supportive and open faculty team may mitigate this challenge. The Expert Patient Programme was seen as a way of helping to reduce the power difference between patients and doctors in the future. There is a need to examine the language that we use to talk about patient involvement as this may have implications for this power dynamic. The context and mechanisms that lead to the benefits described by participants should be studied so that these benefits may be generalized to other contexts. PATIENT CONTRIBUTION: An EP was involved in the planning and ethical approval application process of the project and the drafting and approval of this manuscript.

The hidden costs of a hidden smile: The value of preventive care from the patient's perspective.

A culture of oral health neglect and one chipped tooth led Christine Collins to a devastating series of conditions that affected her physical and emotional well-being. The costs of this culture on a person's individual health - and the health-care system as a whole - demonstrate the true value of preventive oral health care.

Multiparametric MRI to improve detection of prostate cancer compared with transrectal ultrasound-guided prostate biopsy alone: the PROMIS study.

BACKGROUND: Men with suspected prostate cancer usually undergo transrectal ultrasound (TRUS)-guided prostate biopsy. TRUS-guided biopsy can cause side effects and has relatively poor diagnostic accuracy. Multiparametric magnetic resonance imaging (mpMRI) used as a triage test might allow men to avoid unnecessary TRUS-guided biopsy and improve diagnostic accuracy. OBJECTIVES: To (1) assess the ability of mpMRI to identify men who can safely avoid unnecessary biopsy, (2) assess the ability of the mpMRI-based pathway to improve the rate of detection of clinically significant (CS) cancer compared with TRUS-guided biopsy and (3) estimate the cost-effectiveness of a mpMRI-based diagnostic pathway. DESIGN: A validating paired-cohort study and an economic evaluation using a decision-analytic model. SETTING: Eleven NHS hospitals in England. PARTICIPANTS: Men at risk of prostate cancer undergoing a first prostate biopsy. INTERVENTIONS: Participants underwent three tests: (1) mpMRI (the index test), (2) TRUS-guided biopsy (the current standard) and (3) template prostate mapping (TPM) biopsy (the reference test). MAIN OUTCOME MEASURES: Diagnostic accuracy of mpMRI, TRUS-guided biopsy and TPM-biopsy measured by sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) using primary and secondary definitions of CS cancer. The percentage of negative magnetic resonance imaging (MRI) scans was used to identify men who might be able to avoid biopsy. RESULTS: Diagnostic study - a total of 740 men were registered and 576 underwent all three tests. According to TPM-biopsy, the prevalence of any cancer was 71% [95% confidence interval (CI) 67% to 75%]. The prevalence of CS cancer according to the primary definition (a Gleason score of ≥ 4 + 3 and/or cancer core length of ≥ 6 mm) was 40% (95% CI 36% to 44%). For CS cancer, TRUS-guided biopsy showed a sensitivity of 48% (95% CI 42% to 55%), specificity of 96% (95% CI 94% to 98%), PPV of 90% (95% CI 83% to 94%) and NPV of 74% (95% CI 69% to 78%). The sensitivity of mpMRI was 93% (95% CI 88% to 96%), specificity was 41% (95% CI 36% to 46%), PPV was 51% (95% CI 46% to 56%) and NPV was 89% (95% CI 83% to 94%). A negative mpMRI scan was recorded for 158 men (27%). Of these, 17 were found to have CS cancer on TPM-biopsy. Economic evaluation - the most cost-effective strategy involved testing all men with mpMRI, followed by MRI-guided TRUS-guided biopsy in those patients with suspected CS cancer, followed by rebiopsy if CS cancer was not detected. This strategy is cost-effective at the TRUS-guided biopsy definition 2 (any Gleason pattern of ≥ 4 and/or cancer core length of ≥ 4 mm), mpMRI definition 2 (lesion volume of ≥ 0.2 ml and/or Gleason score of ≥ 3 + 4) and cut-off point 2 (likely to be benign) and detects 95% (95% CI 92% to 98%) of CS cancers. The main drivers of cost-effectiveness were the unit costs of tests, the improvement in sensitivity of MRI-guided TRUS-guided biopsy compared with blind TRUS-guided biopsy and the longer-term costs and outcomes of men with cancer. LIMITATIONS: The PROstate Magnetic resonance Imaging Study (PROMIS) was carried out in a selected group and excluded men with a prostate volume of > 100 ml, who are less likely to have cancer. The limitations in the economic modelling arise from the limited evidence on the long-term outcomes of men with prostate cancer and on the sensitivity of MRI-targeted repeat biopsy. CONCLUSIONS: Incorporating mpMRI into the diagnostic pathway as an initial test prior to prostate biopsy may (1) reduce the proportion of men having unnecessary biopsies, (2) improve the detection of CS prostate cancer and (3) increase the cost-effectiveness of the prostate cancer diagnostic and therapeutic pathway. The PROMIS data set will be used for future research; this is likely to include modelling prognostic factors for CS cancer, optimising MRI scan sequencing and biomarker or translational research analyses using the blood and urine samples collected. Better-quality evidence on long-term outcomes in prostate cancer under the various management strategies is required to better assess cost-effectiveness. The value-of-information analysis should be developed further to assess new research to commission. TRIAL REGISTRATION: Current Controlled Trials ISRCTN16082556 and NCT01292291. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 39. See the NIHR Journals Library website for further project information. This project was also supported and partially funded by the NIHR Biomedical Research Centre at University College London (UCL) Hospitals NHS Foundation Trust and UCL and by The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research Biomedical Research Centre and was co-ordinated by the Medical Research Council's Clinical Trials Unit at UCL (grant code MC_UU_12023/28). It was sponsored by UCL. Funding for the additional collection of blood and urine samples for translational research was provided by Prostate Cancer UK.

Muscle activation and sound during voluntary single coughs and cough peals in healthy volunteers: Insights into cough intensity.

Very few studies have addressed how coughing varies in intensity. We assessed the influence of cough effort and operating volume on the mechanics of coughing using respiratory muscle surface electromyography (EMG), oesophageal/gastric pressures and cough sounds recorded from 15 healthy subjects [8 female, median age 30 (IQR 30-50)years] performing 120 voluntary coughs from controlled operating volume/effort and three cough peals. For single coughs, low operating volumes and high efforts were associated with the highest EMG activity (p < 0.001); the resultant pressures increased with effort but volume had little influence. In contrast, cough sounds increased with both volume and effort. During cough peals, EMG fell initially, increasing towards the end of peals, pressures remained stable and sound parameters fell steadily to the end of the peal. In conclusion, effort and operating volume have important influences on cough mechanics but modulate muscle activation, pressure and cough sound amplitude and energy differently. Consequently, these cough sound parameters poorly represent voluntary cough mechanics and have limited potential as a surrogate intensity measure.

Poor cough flow in acute stroke patients is associated with reduced functional residual capacity and low cough inspired volume.

INTRODUCTION: Each year 7 million people die of stroke worldwide; most deaths are caused by chest infections. Patients with acute stroke have impaired voluntary cough flow, associated with increased risk of chest infections. Reduced functional residual capacity (FRC) could lead to impaired cough flow. We therefore compared FRC in acute hemiparetic stroke patients and controls and explored its relationship with volume inspired before cough and voluntary cough peak flow. METHODS: 21 patients within 2 weeks of first-ever middle cerebral artery territory (MCA) infarct (mean (SD) age 68 (11) years, 10 females) and 30 controls (58 (11) years, 15 females) underwent FRC and voluntary cough testing (cough inspired volume and peak flow) while semirecumbent. FRC was expressed as % predicted; cough inspired volume was expressed as % predicted VC and cough peak flow as % predicted PEF. A clinician scored stroke severity using the National Institutes of Health Stroke Scale (NIHSS). RESULTS: Patients' reclined FRC, voluntary cough peak flowand cough inspired volume were reduced compared with controls (p<0.01 for all): patients' median (IQR) FRC 76 (67-90) % predicted, mean (SD) cough inspired volume 64 (20) % predicted and mean (SD) peak cough flow 61 (32) % predicted despite them having only mild stroke-related impairments: median NIHSS score 4 (IQR 2-6). Univariate linear regression analyses showed FRC predicted cough inspired volume (adjusted R2=0.45) and cough inspired volume predicted cough flow (adjusted R2=0.56); p<0.01 for both. Sitting patients upright increased their FRC by median 0.210 L. CONCLUSIONS: FRC and cough inspired volume in the reclined position are significantly reduced in acute hemiparetic stroke patients with mild impairments; both factors are associated with poor voluntary cough peak flow.

Sound: a non-invasive measure of cough intensity.

INTRODUCTION: Cough intensity is an important determinant of cough severity reported by patients. Cough sound analysis has been widely validated for the measurement of cough frequency but few studies have validated its use in the assessment of cough strength. We investigated the relationship between cough sound and physiological measures of cough strength. METHODS: 32 patients with chronic cough and controls underwent contemporaneous measurements of voluntary cough sound, flow and oesophageal pressure. Sound power, peak energy, rise-time, duration, peak-frequency, bandwidth and centroid-frequency were assessed and compared with physiological measures. The relationship between sound and subjective cough strength Visual Analogue Score (VAS), the repeatability of cough sounds and the effect of microphone position were also assessed. RESULTS: Sound power and energy correlated strongly with cough flow (median Spearman's r=0.87-0.88) and oesophageal pressure (median Spearman's r=0.89). Sound power and energy correlated strongly with cough strength VAS (median Spearman's r=0.84-0.86) and were highly repeatable (intraclass correlation coefficient=0.93-0.94) but both were affected by change in microphone position. CONCLUSIONS: Cough sound power and energy correlate strongly with physiological measures and subjective perception of cough strength. Power and energy are highly repeatable measures but the microphone position should be standardised. Our findings support the use of cough sound as an index of cough strength.

Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): a paired validating confirmatory study.

BACKGROUND: Men with high serum prostate specific antigen usually undergo transrectal ultrasound-guided prostate biopsy (TRUS-biopsy). TRUS-biopsy can cause side-effects including bleeding, pain, and infection. Multi-parametric magnetic resonance imaging (MP-MRI) used as a triage test might allow men to avoid unnecessary TRUS-biopsy and improve diagnostic accuracy. METHODS: We did this multicentre, paired-cohort, confirmatory study to test diagnostic accuracy of MP-MRI and TRUS-biopsy against a reference test (template prostate mapping biopsy [TPM-biopsy]). Men with prostate-specific antigen concentrations up to 15 ng/mL, with no previous biopsy, underwent 1·5 Tesla MP-MRI followed by both TRUS-biopsy and TPM-biopsy. The conduct and reporting of each test was done blind to other test results. Clinically significant cancer was defined as Gleason score ≥4 + 3 or a maximum cancer core length 6 mm or longer. This study is registered on ClinicalTrials.gov, NCT01292291. FINDINGS: Between May 17, 2012, and November 9, 2015, we enrolled 740 men, 576 of whom underwent 1·5 Tesla MP-MRI followed by both TRUS-biopsy and TPM-biopsy. On TPM-biopsy, 408 (71%) of 576 men had cancer with 230 (40%) of 576 patients clinically significant. For clinically significant cancer, MP-MRI was more sensitive (93%, 95% CI 88-96%) than TRUS-biopsy (48%, 42-55%; p<0·0001) and less specific (41%, 36-46% for MP-MRI vs 96%, 94-98% for TRUS-biopsy; p<0·0001). 44 (5·9%) of 740 patients reported serious adverse events, including 8 cases of sepsis. INTERPRETATION: Using MP-MRI to triage men might allow 27% of patients avoid a primary biopsy and diagnosis of 5% fewer clinically insignificant cancers. If subsequent TRUS-biopsies were directed by MP-MRI findings, up to 18% more cases of clinically significant cancer might be detected compared with the standard pathway of TRUS-biopsy for all. MP-MRI, used as a triage test before first prostate biopsy, could reduce unnecessary biopsies by a quarter. MP-MRI can also reduce over-diagnosis of clinically insignificant prostate cancer and improve detection of clinically significant cancer. FUNDING: PROMIS is funded by the UK Government Department of Health, National Institute of Health Research-Health Technology Assessment Programme, (Project number 09/22/67). This project is also supported and partly funded by UCLH/UCL Biomedical Research Centre and The Royal Marsden and Institute for Cancer Research Biomedical Research Centre and is coordinated by the Medical Research Council Clinical Trials Unit (MRC CTU) at UCL. It is sponsored by University College London (UCL).

Patient eligibility for anti-fibrotic therapy in idiopathic pulmonary fibrosis can be altered by use of different sets of reference values for calculation of FVC percent predicted.

Antifibrotic drugs for idiopathic pulmonary fibrosis patients in England and Scotland are only available to those with FVC percent predicted (FVC%pred) less than or equal to 80%. The prescribing guidance does not state which set of reference values should be used and we show that a patient's FVC%pred can change by 4-6% depending on the choice of reference. We calculated FVC%pred for a group of 528 IPF patients using three different sets of reference values. 90% of patients with FVC%pred 80-85% calculated using European Community Coal and Steel (ECSC) reference values fall into the eligible range when NHANES reference values are used.

The Intensity of Voluntary, Induced, and Spontaneous Cough.

BACKGROUND: The intensity of cough is an important determinant of cough severity. Few studies have quantified cough intensity in patients with chronic cough with objective measures. We investigated the intensity of voluntary, induced, and spontaneous cough in patients with chronic cough and healthy control subjects. METHODS: Patients with chronic cough and control subjects underwent physiologic assessment of the intensity of maximum voluntary, capsaicin-induced, and spontaneous cough. Assessments included measurement of gastric pressure (Pga) and esophageal pressure (Pes) during cough, peak cough flow (PCF), expiratory muscle strength (twitch gastric pressure [TwPga]), and cough compression phase duration (CPD). Subjective perception of cough intensity was assessed using a visual analog scale (VAS). RESULTS: Pes, Pga, and PCF during maximum voluntary cough were significantly greater in patients with chronic cough compared with control subjects (P = .003-.042). There was no difference in TwPga between patients and control subjects. CPD was increased in female patients compared with control subjects (mean ± SD, 0.50 ± 0.22 s vs 0.28 ± 0.17 s; P = .007). Mean ± SD Pes during spontaneous cough was comparable to induced cough (128 ± 28 cm H2O vs 122 ± 37 cm H2O, P = .686) but less than maximum voluntary cough (170 ± 46 cm H2O, P = .020). Median within-subject correlation coefficients between cough intensity VAS and Pes, Pga, and PCF were r = 0.82 to 0.86. CONCLUSIONS: Maximum voluntary cough intensity was increased in patients with chronic cough compared with control subjects. There was no significant difference in expiratory muscle contractility. Further studies should evaluate the compressive phase of cough in more detail. Physiologic measures of cough intensity correlated strongly with subjective perception of intensity in patients with chronic cough and may be relevant objective outcome measures for clinical studies.

Esophageal visualization as an adjunct to the videofluoroscopic study of swallowing.

OBJECTIVE: Complaints of dysphagia for solids lead to speech-language pathology (SLP) referral. Yet many of these patients are later diagnosed with esophageal rather than oropharyngeal dysphagia. Fluoroscopic screening involving the oropharynx alone fails to identify these patients. The aim of this study was to investigate the prevalence of esophageal abnormalities in an SLP-led videofluoroscopic study of swallowing (VFSS) clinic. STUDY DESIGN: Prospective, observational study. SETTING: Radiology suite, public hospital. SUBJECTS AND METHODS: In total, 111 consecutive mixed-etiology patients referred to the clinic by otorhinolaryngology (ORL) (59) or by a speech-language pathologist (52) were recruited. A VFSS was performed according to protocol, and at completion, esophageal visualization (in anterior-posterior plane) was performed by administration of a large liquid barium bolus and a barium capsule. All VFSS recordings were analyzed using objective digital measures of timing and displacement. RESULTS: Sixty-eight percent of patients had an abnormal esophageal transit. One-third of those referred presented exclusively with esophageal abnormalities, while one-third had both oropharyngeal and esophageal abnormalities. Oral abnormalities, reduced pharyngoesophageal segment maximum opening (PESmax), and increasing age were significantly associated with esophageal abnormalities. CONCLUSION: Fluoroscopic evaluation of the pharynx alone, without esophageal review, risks incomplete diagnosis of patients with esophageal disorders. Using esophageal visualization allows timely referral for further investigation by appropriate medical specialties, avoiding incomplete management of patients with dysphagia.

Nonvolitional assessment of muscle endurance in idiopathic inflammatory myopathies: there is no relationship between patient-reported fatigue and muscle fatigability.

INTRODUCTION: We investigated whether muscle endurance differs between IIM patients and controls and if a relationship exists between perceived fatigue and poor muscle endurance. METHODS: Quadriceps contractility, measured using femoral nerve stimulation (TwQ), and strength, measured using maximal voluntary contraction (MVCQ), were assessed in 20 IIM patients and matched controls. Quadriceps endurance was assessed using repetitive electrical stimulation (3 minutes). Time for force to fall to 70% initial force was determined (T70). Reported fatigue was measured using the FACIT-F/Fatigue Severity Scales. RESULTS: TwQ and MVCQ were lower and perceived fatigue greater for patients. There was no difference in T70 between groups. No relationships were observed between perceived fatigue and endurance (T70). CONCLUSIONS: IIM patients reported more fatigue and were weaker than controls, but there was no difference in muscle endurance. Endurance and strength were unrelated to reported fatigue measures. Mechanisms driving perceived IIM fatigue are likely to be multifactorial.