How best to measure cough clinically

It is possible to measure cough by assessing its severity, frequency, intensity, associated urge and its impact on quality of life. Cough severity can simply be assessed with a Visual Analogue Scale. Cough frequency can be assessed objectively with cough frequency monitors. Validated cough monitors include the Leicester Cough Monitor and the VitaloJAK. Cough reflex sensitivity measurement is better used to investigate the mechanisms of action of antitussive medications, rather than assessing efficacy. Health-Related Quality of Life measures are available to assess the impact of cough; they include the validated Leicester Cough Questionnaire and Cough-specific Quality of Life Questionnaire for adult patients. It is best to assess cough with a combination of subjective and objective tools, to capture its wide-ranging impact.</p

General practice performance in referral for suspected cancer: influence of number of cases and case-mix on publicly reported data

Background:Publicly available data show variation in GPs’ use of urgent suspected cancer (USC) referral pathways. We investigated whether this could be due to small numbers of cancer cases and random case-mix, rather than due to true variation in performance. Methods:We analysed individual GP practice USC referral detection rates (proportion of the practice's cancer cases that are detected via USC) and conversion rates (proportion of the practice's USC referrals that prove to be cancer) in routinely collected data from GP practices in all of England (over 4 years) and northeast Scotland (over 7 years). We explored the effect of pooling data. We then modelled the effects of adding random case-mix to practice variation. Results:Correlations between practice detection rate and conversion rate became less positive when data were aggregated over several years. Adding random case-mix to between-practice variation indicated that the median proportion of poorly performing practices correctly identified after 25 cancer cases were examined was 20% (IQR 17 to 24) and after 100 cases was 44% (IQR 40 to 47). Conclusions:Much apparent variation in GPs’ use of suspected cancer referral pathways can be attributed to random case-mix. The methods currently used to assess the quality of GP-suspected cancer referral performance, and to compare individual practices, are misleading. These should no longer be used, and more appropriate and robust methods should be develope

Design and rationale of a multi-center, pragmatic, open-label randomized trial of antimicrobial therapy - the study of clinical efficacy of antimicrobial therapy strategy using pragmatic design in Idiopathic Pulmonary Fibrosis (CleanUP-IPF) clinical trial

Compelling data have linked disease progression in patients with idiopathic pulmonary fibrosis (IPF) with lung dysbiosis and the resulting dysregulated local and systemic immune response. Moreover, prior therapeutic trials have suggested improved outcomes in these patients treated with either sulfamethoxazole/ trimethoprim or doxycycline. These trials have been limited by methodological concerns. This trial addresses the primary hypothesis that long-term treatment with antimicrobial therapy increases the time-to-event endpoint of respiratory hospitalization or all-cause mortality compared to usual care treatment in patients with IPF. We invoke numerous innovative features to achieve this goal, including: 1) utilizing a pragmatic randomized trial design; 2) collecting targeted biological samples to allow future exploration of 'personalized' therapy; and 3) developing a strong partnership between the NHLBI, a broad range of investigators, industry, and philanthropic organizations. The trial will randomize approximately 500 individuals in a 1:1 ratio to either antimicrobial therapy or usual care. The site principal investigator will declare their preferred initial antimicrobial treatment strategy (trimethoprim 160 mg/ sulfamethoxazole 800 mg twice a day plus folic acid 5 mg daily or doxycycline 100 mg once daily if body weight is < 50 kg or 100 mg twice daily if ≥50 kg) for the participant prior to randomization. Participants randomized to antimicrobial therapy will receive a voucher to help cover the additional prescription drug costs. Additionally, those participants will have 4-5 scheduled blood draws over the initial 24 months of therapy for safety monitoring. Blood sampling for DNA sequencing and genome wide transcriptomics will be collected before therapy. Blood sampling for transcriptomics and oral and fecal swabs for determination of the microbiome communities will be collected before and after study completion. As a pragmatic study, participants in both treatment arms will have limited in-person visits with the enrolling clinical center. Visits are limited to assessments of lung function and other clinical parameters at time points prior to randomization and at months 12, 24, and 36. All participants will be followed until the study completion for the assessment of clinical endpoints related to hospitalization and mortality events. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02759120

Physiotherapy, and speech and language therapy intervention for patients with refractory chronic cough: a multicentre randomised control trial.

BACKGROUND: Physiotherapy, and speech and language therapy are emerging non-pharmacological treatments for refractory chronic cough. We aimed to investigate the efficacy of a physiotherapy, and speech and language therapy intervention (PSALTI) to improve health-related quality of life (HRQoL) and to reduce cough frequency in patients with refractory chronic cough. METHODS: In this multicentre randomised controlled trial, patients with refractory chronic cough were randomised to four weekly 1:1 sessions of either PSALTI consisting of education, laryngeal hygiene and hydration, cough suppression techniques, breathing exercises and psychoeducational counselling or control intervention consisting of healthy lifestyle advice. We assessed the change in HRQoL at week 4 with the Leicester Cough Questionnaire (LCQ). Secondary efficacy outcomes included 24-hour objective cough frequency (Leicester Cough Monitor) and cough reflex sensitivity. The primary analysis used an analysis of covariance adjusted for baseline measurements with the intention-to-treat population. This study was registered at UK Clinical Research Network (UKCRN ID 10678). FINDINGS: Between December 2011 and April 2014, we randomly assigned 75 participants who underwent baseline assessment (34 PSALTI and 41 controls). In the observed case analysis, HRQoL (LCQ) improved on average by 1.53 (95% CI 0.21 to 2.85) points more in PSALTI group than with control (p=0.024). Cough frequency decreased by 41% (95% CI 36% to 95%) in PSALTI group relative to control (p=0.030). The improvements within the PSALTI group were sustained up to 3 months. There was no significant difference between groups in the concentration of capsaicin causing five or more coughs. INTERPRETATION: Greater improvements in HRQoL and cough frequency were observed with PSALTI intervention. Our findings support the use of PSALTI for patients with refractory chronic cough. TRIAL REGISTRATION NUMBER: UKCRN ID 10678 and ISRCTN 73039760; Results

Occult lung malignancy presenting with finger pain: a case report

<p>Abstract</p> <p>Introduction</p> <p>Lung cancer is currently one of the most common malignancies in the world. Early detection is an important prognostic factor. Unfortunately, initial symptoms may be vague and a substantial proportion of cases present with the effects of metastases.</p> <p>Case presentation</p> <p>We discuss a case of occult lung malignancy in a 61-year-old man. The only symptom at presentation was pain in the right ring finger due to metastasis from the lung primary.</p> <p>Conclusion</p> <p>This case highlights the need for vigilance when a patient presents with unusual or unexplained symptoms, especially if they have known risk factors for cancer.</p

Treatment of Interstitial Lung Disease associated cough:CHEST guideline and expert panel report

Background Chronic cough in interstitial lung disease (ILD) causes significant impairment in quality of life. Effective treatment approaches are needed for cough associated with ILD. Methods This systematic review asked: Is there evidence of clinically relevant treatment effects for therapies for cough in ILD? Studies of adults aged &gt; 18 years with a chronic cough &gt; 8 weeks duration were included and assessed for relevance and quality. Based on the systematic review, guideline suggestions were developed and voted on by using CHEST guideline methodology. Results Eight Randomized Controlled Trials (RCT) and 2 case series (&gt;10 patients) were included that reported data on patients with Idiopathic Pulmonary fibrosis (IPF), Sarcoidosis and Scleroderma-related ILD who received a variety of interventions. Study quality was high in all 8 RCTs. Inhaled corticosteroids were not supported for cough associated with Sarcoidosis. Cyclophosphamide and Mycophenolate were not supported for solely treating cough associated with scleroderma associated ILD. A recommendation for thalidomide to treat cough associated with IPF did not pass the panel vote. In view of the paucity of antitussive treatment options for refractory cough in ILD, the guideline panel suggested that the CHEST unexplained cough guideline be followed, by considering options such as the neuromodulator gabapentin and speech pathology management. Opiates were also suggested for patients with cough refractory to alternative therapies. Conclusions The evidence supporting the management of chronic cough in ILD is limited. This guideline presents suggestions for managing and treating cough on the best available evidence but future research is clearly needed

The validity of health-related quality of life questionnaires in bronchiectasis:a systematic review and meta-analysis

Background: A range of questionnaires have been used to assess health-related quality of life (HRQOL) in bronchiectasis. A systematic review was conducted to evaluate their psychometric properties and assess associations between HRQOL and clinical measures.Methods: Five electronic databases were searched. Studies eligible for inclusion were those that investigated the validity of HRQOL questionnaires and/or their association with other outcomes in adults with bronchiectasis. Patients with cystic fibrosis were excluded. The identified questionnaires were assessed for convergent, discriminant and cross-cultural translation validity; missing data, floor and ceiling effects, internal consistency, responsiveness and test-retest reliability. A meta-analysis was conducted to estimate the strength of associations between HRQOL and clinical measures.Results: From 1918 studies identified, 43 studies were included in the systematic review, of which 38 were suitable for the meta-analysis. Nine HRQOL questionnaires were identified, with the most widely used being: St George's Respiratory Questionnaire, Leicester Cough Questionnaire, Quality of Life–Bronchiectasis and Short Form-36. HRQOL questionnaires had moderate to good internal consistency and good test-retest reliability. Only 8 of 18 studies that used translated HRQOL questionnaires reported or referred to the validity of the translated questionnaire. There was a stronger correlation (mean r (95% CI)) between HRQOL and subjective outcome measures, such as dyspnoea (0.55 (0.41 to 0.68)) and fatigue (0.42 (0.23 to 0.58)) compared with objective measures; exercise capacity (−0.41 (−0.54 to −0.24)), FEV1% predicted (−0.31 (−0.40 to −0.23)) and extent of bronchiectasis on CT scan (0.35 (0.03 to 0.61)); all p&lt;0.001.Conclusions: This review supports most HRQOL questionnaires used in bronchiectasis have good psychometric properties. There was a weak to moderate association between HRQOL and objective outcome measures. This suggests that HRQOL questionnaires assess a unique aspect of health not captured by objective measures

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112

Psychometrics of HRQoL questionnaires in bronchiectasis: A systematic review and meta-analysis

INTRODUCTION: Understanding the psychometric properties of health related quality of life (HRQoL) questionnaires can help inform selection in clinical trials. OBJECTIVE: To assess the psychometric properties of HRQoL questionnaires in bronchiectasis. METHODS: A literature search was conducted. HRQoL questionnaires were assessed for psychometric properties (reliability, validity, minimal clinically important difference (MCID), floor/ceiling effects). Meta-analyses assessed the associations of HRQoL with clinical measures and responsiveness of HRQoL in clinical trials. RESULTS: 166 studies and 12 HRQoL questionnaires were included. The BHQ, LCQ, CAT and SF-36 had good internal consistency in all domains reported (Cronbach's α≥0.7) across all studies and the QoL-B, SGRQ, CRDQ and SOLQ had good internal consistency in all domains in the majority of (but not all) studies. The BHQ, SGRQ, LCQ and CAT had good test-retest reliability in all domains reported ((intraclass correlation coefficient) ICC ≥0.7) across all studies and the QoL-B, CRDQ and SOLQ had good test-retest reliability in all domains in the majority of (but not all) studies. HRQoL questionnaires were able to discriminate between demographics, important markers of clinical status, disease severity, exacerbations and bacteriology. For HRQoL responsiveness, there was a difference between the treatment and placebo effect. CONCLUSION: SGRQ was the most widely used HRQoL questionnaire in bronchiectasis studies and it had good psychometric properties, however good psychometric data are growing on bronchiectasis specific HRQoL questionnaires, QoL-B and BHQ. Future studies should focus on the medium-long term test-retest reliability, responsiveness and MCID in these HRQoL questionnaires which show potential in bronchiectasis