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(73 patients, 3%, 4 studies). One study 51 investigated both medical therapy and ST (20 patients, 1%) (Table I). Various medical therapies were prescribed: neuro modulating drugs (NMDs, i.e., gabapentin, pregabalin, baclofen), tricyclic antidepressants (TCAs), inhaled corti costeroids, opioids, macrolide antibiotics, PPIs, and inves tigational drugs (i.e., transient receptor potential vanilloid-1 [TRPV-1] inhibitors). Two studies included medical therapy that may be considered “ alternative ” or “ homeopathic ” medicine: oral capsaicin 50 and “ trigger reduction method ” (plant-based diet, re fl ux precautions, nasal saline irrigation, and intranasal corticosteroid or antihistamine). 58 The most commonly studied medical therapies were investigational drugs (11 studies) and gabapentin (7 studies). The median and mode duration of medical therapy was 4 and 2 weeks, respectively. Next, ST commonly involved education about the harmful impact of cough, cough suppression techniques (breathing exercises, mindfulness training, voice therapy, etc.), and stress or anxiety counseling. The median treat ment duration for ST was four sessions. Finally, procedural therapies included SLN block via injection of local anesthetic (lidocaine or bupivacaine) and corticosteroid (triamcinolone acetonide or methylprednisolone), 11,46 bilateral thyroarytenoid BTX injection, 12 and vocal fold augmentation with methylcel lulose or hyaluronic acid. 13 Among the studies of proce dural therapy, there was a median of one treatment. Speci fi cally for SLN block, the mean number of treat ments was 2.3 11 and 2.4 46 injections. The three most commonly used cough-speci fi c PROMs were the Leicester Cough Questionnaire (LCQ, 19 studies), 65 Cough Severity Index (CSI, 6 studies), 66 and Cough-speci fi c Quality of Life Questionnaire (CQLQ, 4 studies). 67 Only 12 studies reported voice-related out comes (i.e., Consensus Auditory-Perceptual Evaluation of Voice, 68 Voice Handicap Index 69 ); among these studies, 10 different outcome metrics were used (Table I). Subjective reporting of improvement AE = adverse event; BID = twice daily; C = comparator intervention; CAPE-V = Consensus Auditory-Perceptual Evaluation of Voice; CO = carbon monoxide; CQLQ = Cough-speci fi c Quality of Life Question naire; CSI = Cough Severity Index; DSI = Dysphonia Severity Index; E = experimental intervention; EMG; electromyography/electromyographic; FeNO = fraction of exhaled nitric oxide; GFI = Glottal Function Index; HARQ = Hull Airways Re fl ux Questionnaire; HRCQ = Hull Re fl ux Cough Questionnaire; LCQ = Leicester Cough Questionnaire; LDQ = Laryngeal Dysfunction Questionnaire; LHQ = Laryngeal Hypersensitivity Ques tionnaire; MINORS = Methodological Index for Non-Randomized Studies; NC = negative comparator; NK-1 = neurokinin-1; NO = nitric oxide; NR = not reported; PC = positive comparator; PFTs = pulmonary function tests; PRN = pro re nata (as needed); q6hr = every 6 hours; qHS = every bedtime; RCT = randomized controlled trial; ROB 2 = revised Cochrane Risk of Bias 2; RSI = Re fl ux Symptom Index; SLP = speech-language pathologist; TID = three times daily; TRPV-1 = transient receptor potential vanilloid-1; VAS = visual analog scale; VHI = Voice Handicap Index; VPQ = Vocal Performance Questionnaire; yo = years old. Meta-Analysis The primary outcome of cough-speci fi c QoL was ana lyzed fi rst for studies reporting the most commonly used PROMs: LCQ and CSI. Next, studies dichotomizing out comes into cough “ improvement ” and “ no improvement ” were analyzed. The secondary outcome was the propor tion of patients with at least one AE. Meta-analysis was conducted for active treatments versus placebo and for active treatment groups only. Leicester Cough Questionnaire. The LCQ is a val idated, cough-speci fi c PROM of 19 items rated on a -point Likert scale. The total score ranges from 3 to 21; higher scores indicate improved QoL. 65 The LCQ has a pre-/post treatment minimal clinically important difference (MCID) score of 1.3. 70 Active treatments versus placebo. Overall, medi cal therapy and ST were associated with a signi fi cant pre-/post-LCQ mean difference over placebo (1.60, 95% CI 0.78 – 2.42, I 2 = 0%, n = 4 studies). Although morphine had the largest LCQ mean difference over placebo among the medical therapies, this study had high risk of bias. 40 Wamkpah et al.: Multimodal Treatments for Neurogenic Cough 115 Dhillon (2019) Bethesda, MD, USA Retrospective case series 10; 10 (3/7) 54 Local anesthetic + corticosteroid injection : 1% lidocaine with epinephrine (1:100,000) + triamcinolone acetonide 200 mg/5 mL None 1 or more injections CSI Number of injections Laryngoscope 132: January 2022
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