An observational study to understand burden and cost of care in adults diagnosed with refractory chronic cough (RCC) or unexplained chronic cough (UCC).

BACKGROUND: Refractory and unexplained chronic cough (RCC and UCC) necessitate frequent referral for specialist evaluations, but data on healthcare resource utilisation and costs are lacking. METHODS: This observational study enrolled adults with RCC or UCC attending a specialist cough clinic and included a control cohort, both from North West England, matched 1:5 for age, gender and smoking history. Primary and secondary care data were obtained for the 5 years prior to and 2 years post initial clinic visit (index). The primary endpoint was the total 5-year healthcare cost to the UK NHS pre-RCC or UCC diagnosis compared to the control cohort. RESULTS: Mean age at index for the 200 RCC or UCC consented patients was 62.2 ± 11.4 years; 71% were female, and 68% had never smoked. Mean duration of symptoms pre-diagnosis was 8.0 ± 9.4 years. Mean cough severity score was 63.7 ± 23.2 mm at index on a Visual Analog Scale, and Leicester Cough Questionnaire total score was 10.9 ± 4.1. GP data were available for 80 patients and mean total cost over the 5 years pre-diagnosis (index date) was 3.0-fold higher (95% CI 2.3, 3.9) than in the control cohort (p < 0.001). Most excess costs were related to visits and procedures carried out in secondary care. RCC- or UCC-associated costs decreased post-diagnosis, but remained higher than those of controls. CONCLUSION: Diagnosis of RCC or UCC requires significant health resource utilisation in the 5 years prior to a specialist clinic diagnosis. Resource utilisation was less after diagnosis, but remained higher than in a matched control cohort.

Chronic cough: more than just a persistent cough: a systematic literature review to understand the impact of chronic cough on quality of life.

PURPOSE: Chronic cough (CC), defined as a cough persisting ≥ 8 weeks, can have a substantial negative impact on health-related quality of life (HRQoL). This is exacerbated by challenges with timely diagnosis and a lack of approved therapies. A systematic literature review (SLR) was conducted to identify evidence on HRQoL and health state utility values associated with refractory CC or unexplained CC. METHODS: Electronic database searches were supplemented with searches of conference proceedings and health technology assessment body websites. Two independent reviewers assessed all citations for inclusion based on predefined inclusion/exclusion criteria. Key inclusion criteria were patient populations with CC and reporting of patient-reported outcomes or utilities using generic or disease-specific measures. RESULTS: Following screening, 65 studies were identified for inclusion in the SLR. Of these, 23 studies assessed HRQoL among patients with CC who were not treated or treated with unspecified interventions, and 42 studies in patients who were treated with specified interventions. The studies indicated a substantial decrement to HRQoL as a result of CC, characterized by generic and disease-specific patient-reported outcome measures. HRQoL was impacted across multiple domains, including physical, psychological, and social functioning. The studies also demonstrated the potential for treatments to have a significant positive impact on HRQoL. CONCLUSIONS: CC can substantially affect HRQoL in patients, across physical, psychological, and social domains. Although treatments can improve HRQoL in these patients, the available evidence is limited. There remains an unmet need for approved pharmacological treatments to alleviate CC and improve HRQoL for these patients.

Efficacy and safety of gefapixant, a P2X3 receptor antagonist, in refractory chronic cough and unexplained chronic cough (COUGH-1 and COUGH-2): results from two double-blind, randomised, parallel-group, placebo-controlled, phase 3 trials.

BACKGROUND: Gefapixant is an oral P2X3 receptor antagonist that has previously shown efficacy and safety in refractory chronic cough and unexplained chronic cough. We therefore aim to confirm the efficacy and safety of gefapixant in participants with refractory chronic cough and unexplained chronic cough. METHODS: COUGH-1 and COUGH-2 were both double-blind, randomised, parallel-group, placebo-controlled, phase 3 trials. COUGH-1 was done in 156 sites in 17 countries and COUGH-2 in 175 sites in 20 countries. We enrolled participants who were 18 years or older with a diagnosis of refractory chronic cough or unexplained chronic cough of 1 year duration or more. Participants were also required to have a cough severity visual analogue scale score of 40 mm or more at screening and baseline. Eligible participants were randomly allocated (1:1:1), using a computer-generated allocation schedule, to one of three treatment groups: placebo, gefapixant 15 mg twice per day, or gefapixant 45 mg twice per day. All study treatments were given orally. Participants were treated over a 12-week main study period in COUGH-1 and a 24-week main study period in COUGH-2; followed by extension periods for a total of up to 52 weeks of treatment in both trials. The primary outcome was placebo-adjusted mean change in 24-h cough frequency at 12 weeks in COUGH-1 and 24 weeks in COUGH-2. Both studies were registered with ClinicalTrials.gov, NCT03449134 (COUGH-1) and NCT03449147 (COUGH-2). FINDINGS: From March 14, 2018, (first participant screened) to July 26, 2019, (last participant screened) 732 patients were recruited in COUGH-1 and 1317 in COUGH-2. COUGH-1 randomly assigned and treated 730 participants (243 [33×3%] with placebo, 244 [33×4%] with gefapixant 15 mg twice per day, and 243 [33×3%] with gefapixant 45 mg twice per day); COUGH-2 randomly assigned and treated 1314 participants (435 [33×1%] with placebo, 440 [33×5%] with gefapixant 15 mg twice per day, and 439 [33×4%] with gefapixant 45 mg twice per day). Participants were mostly female (542 [74×2%] of 730 in COUGH-1 and 984 [74×9%] of 1314 in COUGH-2). The mean age was 59×0 years (SD 12×6) in COUGH-1 and 58×1 years (12×1) in COUGH-2, and the mean cough duration was 11·6 years (SD 9·5) in COUGH-1 and 11·2 years (9·8) in COUGH-2. Gefapixant 45 mg twice per day showed significant reductions in 24-h cough frequency compared with placebo at week 12 in COUGH-1 (18·5% [95% CI 32·9-0·9]; p=0·041) and at week 24 in COUGH-2 (14·6% [26·1-1·4]; p=0·031). Gefapixant 15 mg twice per day did not show a significant reduction in cough frequency versus placebo in both studies. The most common adverse events were related to taste disturbance: ageusia (36 [4·9%] of 730 in COUGH-1 and 86 [6·5%] of 1314 in COUGH-2), dysgeusia (118 [16·2%] in COUGH-1 and 277 [21·1%] in COUGH-2), hypergeusia (3 [0·4%] in COUGH-1 and 6 [0×5%] in COUGH-2), hypogeusia (19 [2·6%] in COUGH-1 and 80 [6·1%] in COUGH-2), and taste disorder (28 [3·8%] in COUGH-1 and 46 [3·5%] in COUGH-2). INTERPRETATION: Gefapixant 45 mg twice per day is the first treatment to show efficacy with an acceptable safety profile in phase 3 clinical trials for refractory chronic cough or unexplained chronic cough. FUNDING: Merck Sharp & Dohme.

Demographic, clinical, and patient-reported outcome data from 2 global, phase 3 trials of chronic cough.

BACKGROUND: The current characterization of patients with refractory or unexplained chronic cough (RCC and UCC, respectively) primarily stems from relatively small clinical studies. OBJECTIVE: To report the baseline medical history and clinical characteristics of individuals with RCC or UCC who were enrolled in COUGH-1 and COUGH-2, 2 large, global, phase 3 trials of gefapixant, a P2 × 3-receptor antagonist. METHODS: Adults with a chronic cough lasting for more than 1 year, diagnosis of RCC or UCC, and score greater than 40 mm on a 100-mm cough severity visual analog scale at both screening and baseline were eligible for enrollment. Demographics, medical history, and cough characteristics were collected at baseline. Cough-related measures included objective cough frequency, cough severity visual analog scale, Leicester Cough Questionnaire, and Hull Airway Reflux Questionnaire. The data were summarized using descriptive statistics. RESULTS: Of 2044 participants, 75% were women; mean age was 58 years, and mean cough duration was approximately 11 years. Among all participants, 73% were previously diagnosed with asthma, gastroesophageal reflux disease, or upper airway cough syndrome. The mean Leicester Cough Questionnaire total score was 10.4, with domain scores reflecting impaired cough-specific quality of life across physical, psychological, and social domains. The mean Hull Airway Reflux Questionnaire score was 39.6, with some of the most burdensome reported items being consistent with features of cough-reflex hypersensitivity. Participant characteristics and cough burden were comparable across geographic regions. CONCLUSION: Participants with RCC or UCC had characteristics consistent with published demographics associated with chronic cough. These data reflect a global population with burdensome cough of long duration and substantial impairment to quality of life. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: COUGH-1, NCT03449134 (https://www. CLINICALTRIALS: gov/ct2/show/NCT03449134); COUGH-2, NCT03449147 (https://clinicaltrials.gov/ct2/show/NCT03449147).

The Efficacy and Safety of Gefapixant in a Phase 3b Trial of Patients with Recent-Onset Chronic Cough.

PURPOSE: We evaluated gefapixant, a P2X3 receptor antagonist, in participants with recent-onset (≤ 12 months) refractory chronic cough (RCC) or unexplained chronic cough (UCC). METHODS: Participants (≥ 18 years of age; ≥ 40 mm on a 100-mm cough severity visual analog scale [VAS] at screening and randomization) with chronic cough for < 12 months were enrolled in this phase 3b, double-blind, placebo-controlled, parallel group, multicenter study (NCT04193202). Participants were randomized 1:1 to gefapixant 45 mg BID or placebo for 12 weeks with a 2-week follow-up. The primary efficacy endpoint was change from baseline at Week 12 in Leicester Cough Questionnaire (LCQ) total score. Adverse events were monitored and evaluated. RESULTS: There were 415 participants randomized and treated (mean age 52.5 years; median [range] duration 7.5 [1-12] months): 209 received placebo and 206 received gefapixant 45 mg BID. A statistically significant treatment difference of 0.75 (95% CI: 0.06, 1.44; p = 0.034) for gefapixant vs. placebo was observed for change from baseline in LCQ total score at Week 12. The most common AE was dysgeusia (32% gefapixant vs. 3% placebo participants); serious AEs were rare (1.5% gefapixant vs. 1.9% placebo participants). CONCLUSION: Gefapixant 45 mg BID demonstrated significantly greater improvement in cough-specific health status from baseline compared to placebo, in participants with recent-onset chronic cough. The most common AEs were related to taste and serious AEs were rare.

Understanding the economic burden of chronic cough: a systematic literature review.

Chronic cough (CC) is associated with high healthcare resource utilization (HCRU) due to challenges in diagnosis and treatment and is anticipated to have a substantial economic impact. This systematic literature review (SLR) sought to identify evidence on the cost-effectiveness of treatments and the economic burden associated with CC. Electronic database searches were supplemented with searches of conference proceedings and health technology assessment body websites. Two independent reviewers assessed all citations for inclusion based on predefined inclusion/exclusion criteria. Key inclusion criteria were patient population with CC, and outcomes related to cost-effectiveness and HCRU and costs. After screening, one cost-effectiveness analysis was identified, alongside eight studies reporting HCRU and costs related to CC. Though evidence was limited, studies suggest that patients with CC incur higher costs and use more resources than those with acute cough. Types of resource use reported included healthcare contacts and prescriptions, diagnostic tests, referrals and specialist evaluations, and treatment use. There is a paucity of literature on HCRU and costs in CC, and very limited cost-effectiveness analyses. The economic burden appears higher in these patients however, without direct comparison to the general population it is difficult to determine the total impact. The increased burden is expected to be a result of the challenges with diagnosis and lack of approved treatments. However, limited conclusions can be drawn in the absence of further data. Future studies should endeavor to quantify the HCRU and cost attributable to patients with CC.

Validation and Meaningful Change Thresholds for an Objective Cough Frequency Measurement in Chronic Cough.

PURPOSE: Objective cough frequency is used to assess efficacy of chronic cough (CC) treatments. The objective of this study was to explore the relationship between objective cough frequency and cough-specific patient-reported outcomes (PROs) and estimate a clinically meaningful change threshold (MCT) for objective cough frequency. METHODS: Data collected in a phase 2b study in participants with refractory or unexplained CC were used to investigate the relationship between 24-h cough frequency (measured using an ambulatory cough monitor) and cough-specific PROs (i.e., cough severity visual analog scale, cough severity diary, Leicester Cough Questionnaire). Convergent validity was assessed using Spearman ρ. An MCT for 24-h cough frequency was estimated using the patient global impression of change (PGIC) scale as an anchor. RESULTS: Correlations between 24-h cough frequency and cough-specific PROs at baseline, Week 4, and Week 12 were significant (P < 0.0001) but low to moderate in strength (ρ = 0.30-0.58). Participants categorized as very much improved/much improved (i.e., PGIC of 1 or 2) or minimally improved (i.e., PGIC of 3) had mean 24-h cough frequency reductions of 55% and 30%, respectively. Receiver operating characteristic curve analysis suggested that a 24-h cough frequency reduction of 38% optimizes sensitivity and specificity for predicting a PGIC score of 1-3. CONCLUSION: Objective 24-h cough frequency is significantly associated with cough-specific PROs, but cough frequency and PROs most likely capture distinct aspects of CC. A ≥ 30% reduction in 24-h cough frequency is a reasonable MCT to define treatment response in CC clinical trials.

Improvements in Objective and Subjective Measures of Chronic Cough with Gefapixant: A Pooled Phase 3 Efficacy Analysis of Predefined Subgroups.

INTRODUCTION: In phase 3 trials (COUGH-1/COUGH-2), gefapixant 45 mg twice daily significantly reduced 24-h cough frequency vs placebo in refractory or unexplained chronic cough (RCC or UCC). METHODS: Here, the efficacy of gefapixant 45 mg vs placebo was evaluated across COUGH-1/COUGH-2 in predefined subgroups based on sex, region, age, cough duration, cough severity, cough frequency, and diagnosis (RCC, UCC). Awake cough frequency reductions at Week 12 and LCQ response rates (i.e., ≥ 1.3-point improvement) at Week 24 were assessed. RESULTS: Among 1360 participants analyzed, gefapixant 45 mg resulted in consistent awake cough frequency reductions overall and across predefined subgroups at Week 12. Gefapixant also resulted in improved LCQ scores across subgroups at Week 24; ≥ 70% of participants in each subgroup treated with gefapixant 45 mg had an LCQ response. CONCLUSION: These data suggest gefapixant 45 mg provides consistent objective and subjective efficacy across subgroups of individuals with RCC or UCC.

Clinical characteristics and drug utilisation patterns in patients with chronic cough: a retrospective cohort study using a Japanese claims database.

BACKGROUND: Although unmet medical needs for better care of patients with chronic cough exist in Japan, epidemiological information about these patients and their treatments is very limited. OBJECTIVES: To describe patient characteristics, underlying cough-related diseases and drug utilisation patterns in patients with chronic cough, and their changes over time. METHODS: This large retrospective claims database study enrolled subjects with chronic cough, identified either by a specific diagnostic cough code for chronic cough (Population 1) or by multiple cough-related diagnostic codes spanning > 8 weeks (Population 2). Within Population 2, patients with each of the three most frequent diagnostic cough codes were analysed as subgroups. Patient characteristics, underlying cough-related diseases and utilisation patterns for drugs used for cough were documented at the index date, during the 6-month pre-index period and during the 12-month post-index period. RESULTS: 6,038 subjects were enrolled in the cohort (Population 1: N = 3,500; Population 2: N = 2,538). The mean age was 43.7 ± 12.2 years and 61.8% were women. The largest cough diagnosis subgroups in Population 2 were 'other coughs' (N = 1,444), 'cough-variant asthma' (N = 1,026) and 'atopic/allergic cough' (N = 105). At the index date, the most frequent underlying cough-related diseases were allergic rhinitis/nasal inflammation (N = 3,132; 51.9%), asthma (N = 2,517; 41.7%) and gastro-esophageal reflux disease (N = 829; 13.7%). At the index date, 4,860 participants (80.5%) were prescribed at least one cough-related treatment. 194 participants (4.0% of medication users) were prescribed central antitussives alone, principally in Population 1, and 2,331 (48.0%) were prescribed expectorants. Other frequently prescribed medications were antiallergic drugs (N = 2,588; 53.3%), antimicrobials (N = 1,627; 34.4%) and inhaled corticosteroids with long-acting beta-agonists (N = 1,404; 28.9%). Over time, cough diagnoses tended to be lost, with only 470 participants in Population 1 retaining a diagnostic code for chronic cough one year later. The frequency of underlying cough-related diseases was stable over time. CONCLUSIONS: Patients in this cohort with chronic cough are most frequently identified by a diagnostic cough code for chronic cough, followed by codes for other coughs, cough-variant asthma and atopic cough. Chronic cough frequently presents with an underlying cough-related disease, most frequently allergic rhinitis/nasal inflammation, asthma or GERD. Medication prescription for the underlying cough-related diseases was generally appropriate.

Impact of refractory and unexplained chronic cough on disease burden: a qualitative study.

BACKGROUND: Chronic cough lasting for > 8 weeks is a common medical condition that burdens patients. This study aimed to qualitatively describe knowledge, awareness, experiences, and subtypes of burdens (physical, social, psychological) among Japanese patients with refractory chronic cough (refractory to treatment of underlying relevant medical conditions) and unexplained chronic cough (symptoms of unexplained origin). METHODS: This non-interventional, cross-sectional study was conducted between February and March 2021 among patients (aged ≥ 20 years) with self-reported refractory or unexplained chronic cough. Subjects with a history of comorbid respiratory conditions were excluded. Eligible subjects participated in a 60-min online semi-structured interview. Verbatim terms from interviews were qualitatively transcribed and generated into word clouds, followed by a clustering analysis in which meaningful clusters were chosen, manually coded, and utterances and burdens categorized. RESULTS: A total of 21 participants (95.2% with refractory chronic cough, mean age 53.5 years, and 76.2% being males) with Leicester Cough Questionnaire mean ± standard deviation scores of physical 4.8 ± 1.1, psychological 4.4 ± 1.3, social 4.9 ± 1.4, and total 14.1 ± 3.5 were included. The word cloud identified the most frequently used word ('cough'); etiology ('asthma'); and words associated with change in states ('influence,' 'changing,' 'change') and expressions ('tough,' 'pain,' 'hard,' 'terrible,' 'unpleasant'). The patients experienced 'mental/social burden,' 'physical burden,' 'impact on sleep and meals,' 'impact on work and housework,' 'impact on communication,' 'impact on hobbies and leisure,' and 'economic burden.' By closed coding analysis, the situations or types of burden patients experienced from the cough were ordered sequentially as emotion, working style, acquaintanceship, hobbies and leisure, and sleeping pattern. CONCLUSIONS: The present study indicated that there were two types of participant clusters, in which one showed mainly the burdens in the social communications such as work-related communication and another one showed the burdens of relationships with others. Also, some participants highlighted 'mental burden,' on social life due to the current pandemic. To relieve these burdens, disease awareness and knowledge should be improved for patients with refractory and unexplained chronic cough. Trial registration The trial was registered under UMIN-CTR as UMIN000042772, on 17/12/2020. The study was approved by the Medical Corporation Toukeikai Kitamachi Clinic (IRB registration number: 11001110).

Development of a natural language processing algorithm to detect chronic cough in electronic health records.

BACKGROUND: Chronic cough (CC) is difficult to identify in electronic health records (EHRs) due to the lack of specific diagnostic codes. We developed a natural language processing (NLP) model to identify cough in free-text provider notes in EHRs from multiple health care providers with the objective of using the model in a rules-based CC algorithm to identify individuals with CC from EHRs and to describe the demographic and clinical characteristics of individuals with CC. METHODS: This was a retrospective observational study of enrollees in Optum's Integrated Clinical + Claims Database. Participants were 18-85 years of age with medical and pharmacy health insurance coverage between January 2016 and March 2017. A labeled reference standard data set was constructed by manually annotating 1000 randomly selected provider notes from the EHRs of enrollees with ≥ 1 cough mention. An NLP model was developed to extract positive or negated cough contexts. NLP, cough diagnosis and medications identified cough encounters. Patients with ≥ 3 encounters spanning at least 56 days within 120 days were defined as having CC. RESULTS: The positive predictive value and sensitivity of the NLP algorithm were 0.96 and 0.68, respectively, for positive cough contexts, and 0.96 and 0.84, respectively, for negated cough contexts. Among the 4818 individuals identified as having CC, 37% were identified using NLP-identified cough mentions in provider notes alone, 16% by diagnosis codes and/or written medication orders, and 47% through a combination of provider notes and diagnosis codes/medications. Chronic cough patients were, on average, 61.0 years and 67.0% were female. The most prevalent comorbidities were respiratory infections (75%) and other lower respiratory disease (82%). CONCLUSIONS: Our EHR-based algorithm integrating NLP methodology with structured fields was able to identify a CC population. Machine learning based approaches can therefore aid in patient selection for future CC research studies.

Prevalence of chronic cough and patient characteristics in adults in Spain: A population-based cross-sectional survey.

BACKGROUND: Chronic cough (CC) represents a significant health burden. This study assessed the prevalence of CC (defined as per international guidelines as cough duration >8 weeks) in Spanish adults and compared characteristics between CC and non-CC cohorts. METHODS: CC cohorts were compiled using data from adult respondents to the 2020 Spanish cross-sectional online National Health and Wellness Survey (NHWS). Using propensity scores, respondents experiencing CC during their lifetime and the previous 12 months were matched 3:1 to respondents without CC and their health characteristics were compared. The number of Spanish adults affected with CC was estimated using weighted CC prevalence. RESULTS: CC during their lifetime or the previous 12 months was experienced by 579 (8.2%) and 389 (5.5%) of 7074 NHWS respondents, of whom 233 (38.5%) and 171 (44.0%), respectively, had physician-diagnosed CC. Based on weighted prevalence rates, lifetime and 12-month CC were estimated to affect ≈3.3 million and ≈2.2 million Spanish adults, respectively. Relative to the non-CC cohort, the 12-month CC cohort consistently demonstrated poorer health status, poorer mental health, greater healthcare utilization, and lower productivity at work and home. CONCLUSION: This study contributes novel data regarding the prevalence of CC in Spain, suggests that CC is underdiagnosed, and reflects that CC and related comorbidities inflict a significant health burden in the affected population.

Cost-effectiveness analysis of cytomegalovirus prophylaxis in allogeneic hematopoietic cell transplant recipients from a US payer perspective.

To evaluate the cost-effectiveness of letermovir versus no prophylaxis for the prevention of cytomegalovirus infection and disease in adult cytomegalovirus-seropositive allogeneic hematopoietic cell transplantation (allo-HCT) recipients. A decision model for 100 patients was developed to estimate the probabilities of cytomegalovirus infection, cytomegalovirus disease, various other complications, and death in patients receiving letermovir versus no prophylaxis. The probabilities of clinical outcomes were based on the pivotal phase 3 trial of letermovir use for cytomegalovirus prophylaxis versus placebo in adult cytomegalovirus-seropositive recipients of an allo-HCT. Costs of prophylaxis with letermovir and of each clinical outcome were derived from published sources or the trial clinical study reports. Incremental cost-effectiveness ratios (ICERs) in terms of cost per quality-adjusted life year (QALY) gained were used in the model. One-way and probabilistic sensitivity analyses were conducted to explore uncertainty around the base-case analysis. In this model, the use of letermovir prophylaxis would lead to an increase of QALYs (619) and direct medical cost ($1 733 794) compared with no prophylaxis (578 QALYs; $710 300) in cytomegalovirus-seropositive recipients of an allo-HCT. Letermovir use for cytomegalovirus prophylaxis was a cost-effective option versus no prophylaxis with base-case analysis ICER $25 046/QALY gained. One-way sensitivity analysis showed the most influential parameter was mortality rate. The probabilistic sensitivity analysis showed a 92% probability of letermovir producing an ICER below the commonly accepted willingness-to-pay threshold of $100 000/QALY gained. Based on this model, letermovir use for cytomegalovirus prophylaxis was a cost-effective option in adult cytomegalovirus-seropositive recipients of an allo-HCT.

Characterization of Patients With Refractory or Unexplained Chronic Cough Participating in a Phase 2 Clinical Trial of the P2X3-Receptor Antagonist Gefapixant.

PURPOSE: This analysis assesses clinical characteristics of patients with refractory chronic cough (RCC) or unexplained chronic cough (UCC) enrolled in a phase 2 study to better understand this patient population. METHODS: Patients with RCC/UCC lasting for ≥ 1 year and cough severity visual analog scale (VAS) score of > 40 mm at screening were eligible. Demographics, clinical characteristics, and medical history were collected at baseline. Cough-related measures included cough severity VAS, Cough Severity Diary (CSD), Leicester Cough Questionnaire (LCQ), and a structured cough-trigger questionnaire. Medication history included all medications 30 days before screening and chronic cough treatments within 1 year before screening. Data were summarized using descriptive statistics. RESULTS: Patients (N = 253; female, 76%; mean age, 60 years) had severe (mean cough severity VAS, 57.5 mm) and long-lasting (median duration, 11 years) cough. The most burdensome self-reported aspects included psychological and social factors (LCQ) and cough frequency and intensity (CSD). Patient-reported triggers were consistent with cough hypersensitivity (e.g., 95% to 96% reported irritation or tickle in throat). Common reported comorbidities included gastroesophageal reflux disease (GERD; 56%), allergic rhinitis (47%), and asthma (30%); 12% of patients had been diagnosed with all 3 conditions. The most common prior medications included inhaled or oral steroids (21%), antihistamines (15%), and antacids (15%). CONCLUSION: Patients with RCC/UCC had severe, long-lasting, and burdensome cough with clinical features of cough hypersensitivity. Many patients had been diagnosed with GERD, allergic rhinitis, and asthma but had a persistent cough despite treatment of these conditions. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02612610; registered November 20, 2015.

Clinical and economic burden of pre-emptive therapy of cytomegalovirus infection in hospitalized allogeneic hematopoietic cell transplant recipients.

Cytomegalovirus (CMV) infection remains a major complication after allogeneic hematopoietic cell transplantation (allo-HCT). We conducted a retrospective study to determine the clinical and economic burden of pre-emptive therapy (PET) for CMV infection in 100 consecutive hospitalized adult CMV positive serostatus allo-HCT recipients and compared their hospitalization cost with allo-HCT recipients hospitalized with graft vs host disease without CMV infection (control group) and across 19 US cancer centers for hospitalized patients with CMV infection between 2012 and 2015 (Vizient database). A total of 192 CMV episodes of PET for CMV infection occurred within 1 year post-HCT. PET consisted of ganciclovir (41% of episodes), foscarnet (40%), and valganciclovir (38%) with the longest average length of stay in foscarnet-treated patients (41 days). The average direct cost per patient admitted for PET was $116 976 (range: $7866-$641 841) compared with $12 496 (range: $2004-$43 069) in the control group (P < .0001). The total direct cost per encounter was significantly higher in patients treated with foscarnet and had nephrotoxicity ($284 006) compared with those who did not ($112 195). The average cost amongst the 19 US cancer centers, including our institution, was $42 327 with major disparities in cost and clinical outcomes. PET for CMV infection is associated with high economic burden in allo-HCT recipients.

Chronic cough diagnosis, treatment, and referral practices among family physicians in the United States: a survey study.

BACKGROUND: Cough is one of the most common presenting problems for patients in primary care and is largely managed in primary care clinical settings. Family physicians' familiarity with chronic cough guidelines and the extent to which these guidelines translate into everyday practice have not been well described. The objective of this study was to characterize current diagnosis, treatment, and referral practices among family physicians and to identify potentially impactful strategies to optimize chronic cough management in primary care. METHODS: We conducted a cross-sectional survey of 5,000 family physicians to explore diagnosis, treatment, and referral practices related to chronic cough management in adults in primary care. Respondents completed the survey via paper or online. The outcome measures were self-reported numeric ratings and responses related to the survey elements. RESULTS: 588 surveys were completed (11.8% response rate). About half (49.6%) of respondents defined chronic cough in a manner consistent with the American College of Chest Physicians (ACCP) chronic cough guidelines, with the rest differing in opinion primarily regarding duration of symptom presentation. Respondents reported trying to rule out most common causes of chronic cough themselves before referring (mean 3.41 on a 4-point scale where 4 is "describes me completely") and indicated a desire for more resources to help them manage and treat chronic cough. Years in practice and rural/urban setting influenced diagnosis and referral practices. CONCLUSIONS: Family physicians see chronic cough as a complicated condition that can be and is often diagnosed and treated entirely in a primary care setting. They also value the ability to refer in complex cases. Our results support that family physicians provide evidence-based management of chronic cough.

Prescriptions of opioid-containing drugs in patients with chronic cough.

BACKGROUND: Chronic cough (CC) affects about 10% of adults, but opioid use in CC is not well understood. OBJECTIVES: To determine the use of opioid-containing cough suppressant (OCCS) prescriptions in patients with CC using electronic health records. DESIGN: Retrospective cohort study. METHODS: Through retrospective analysis of Midwestern U.S. electronic health records, diagnoses, prescriptions, and natural language processing identified CC - at least three medical encounters with cough, with 56-120 days between first and last encounter - and a 'non-chronic cohort'. Student's t-test, Pearson's chi-square, and zero-inflated Poisson models were used. RESULTS: About 20% of 23,210 patients with CC were prescribed OCCS; odds of an OCCS prescription were twice as great in CC. In CC, OCCS drugs were ordered in 38% with Medicaid insurance and 15% with commercial insurance. CONCLUSION: Findings identify an important role for opioids in CC, and opportunity to learn more about the drugs' effectiveness.

Prevalence and burden of chronic cough in France.

Background: Chronic cough is a common condition that is associated with lower health-related quality of life and greater healthcare resource use. There are limited data on the prevalence, population characteristics and burden of chronic cough in France. Methods: This was a cross-sectional study based on responses from French adult residents to the 2020 National Health and Wellness Survey. Respondents with chronic cough were compared to 1:3 propensity score-matched controls without chronic cough. Results: The weighted lifetime and 12-month prevalence of chronic cough were estimated as 7.5% and 4.8%, respectively. Respondents with chronic cough reported significantly worse perceived health than matched controls, with lower mean±sd scores of 46.68±9.28 versus 50.42±8.26 on the physical health component and 40.32±9.87 versus 44.32± 9.69 on the mental health component of the Medical Outcomes Study 12-item Short Form Survey Version 2 survey (p<0.001 for both comparisons). Respondents with chronic cough also had higher rates of moderate-to-severe forms of anxiety (24.4% versus 12.4%) and depression (36.4% versus 20.2%); higher rates of multiple forms of sleep disturbance; greater impairment of work productivity (38.2% versus 25.5%) and other activities (41.8% versus 28.2%; p<0.001 for all comparisons). Respondents with chronic cough also had higher rates of all-cause healthcare resource use including emergency room visits, hospitalisation, and overall and specialist healthcare provider visits compared to controls (p<0.001 for all comparisons). Conclusion: Chronic cough is a common condition in France that is associated with lower health-related quality of life and greater healthcare resource utilisation.