Efficacy and Safety of Electromyography-Guided Injection of Botulinum Toxin to Treat Retrograde Cricopharyngeus Dysfunction.

OBJECTIVE: To report the efficacy and safety of electromyography-guided percutaneous botulinum toxin injection into the cricopharyngeus muscle in an office setting for treatment of the inability to belch and associated symptoms caused by retrograde cricopharyngeus dysfunction (R-CPD). STUDY DESIGN: Retrospective case series of treated patients. SETTING: Tertiary care laryngology clinic. METHODS: A retrospective review was performed on 18 consecutive patients who were diagnosed syndromically with R-CPD. The combined diagnostic test and treatment-specifically, botulinum toxin injection into the cricopharyngeus muscle-was accomplished in an office setting by a single surgeon using electromyography guidance. Items assessed are efficacy, safety, complications, and duration of benefit. RESULTS: All 18 patients (100%) treated in the in-office setting gained the ability to burp with improvement in the associated symptoms of R-CPD at initial follow-up. Of those who had the in-office procedure performed initially, 80% maintained the ability to burp at 6 months with relief of all the associated symptoms of R-CPD. No patients experienced permanent complications from the injection, but 7 patients experienced varying degrees of noisy breathing within 1 week after the procedure, which was managed with breathing techniques and resolved. CONCLUSION: In a case series of 18 patients with R-CPD, all patients gained the ability to burp with improvement in the majority of their symptoms of R-CPD at the time of their initial follow-up at 1 week. None experienced severe complications, and 7 experienced transient noisy breathing, which resolved.

Assessing and managing SARS-CoV-2 occupational health risk to workers handling residuals and biosolids.

Current wastewater worker guidance from the United States Environmental Protection Agency (USEPA) aligns with the Centers for Disease Control and Prevention (CDC) and the Occupational Safety and Health Administration (OSHA) recommendations and states that no additional specific protections against SARS-CoV-2, the virus that causes COVID-19 infections, are recommended for employees involved in wastewater management operations with residuals, sludge, and biosolids at water resource recovery facilities. The USEPA guidance references a document from 2002 that summarizes practices required for protection of workers handling class B biosolids to minimize exposure to pathogens including viruses. While there is no documented evidence that residuals or biosolids of any treatment level contain infectious SARS-CoV-2 or are a source of transmission of this current pandemic strain of coronavirus, this review summarizes and examines whether the provided federal guidance is sufficient to protect workers in view of currently available data on SARS-CoV-2 persistence and transmission. No currently available epidemiological data establishes a direct link between wastewater sludge or biosolids and risk of infection from the SARS-CoV-2. Despite shedding of the RNA of the virus in feces, there is no evidence supporting the presence or transmission of infectious SARS-CoV-2 through the wastewater system or in biosolids. In addition, this review presents previous epidemiologic data related to other non-enveloped viruses. Overall, the risk for exposure to SARS-CoV-2, or any pathogen, decreases with increasing treatment measures. As a result, the highest risk of exposure is related to spreading and handling untreated feces or stool, followed by untreated municipal sludge, the class B biosolids, while lowest risk is associated with spreading or handling Class A biosolids. This review reinforces federal recommendations and the importance of vigilance in applying occupational risk mitigation measures to protect public and occupational health.

Implications of SARS-CoV-2 on current and future operation and management of wastewater systems.

While researchers have acknowledged the potential role of environmental scientists, engineers, and industrial hygienists during this pandemic, the role of the water utility professional is often overlooked. The wastewater sector is critical to public health protection and employs collection and treatment system workers who perform tasks with high potential for exposures to biological agents. While various technical guidances and reports have initially provided direction to the water sector, the rapidly growing body of research publications necessitates the constant review of these papers and data synthesis. This paper presents the latest findings and highlights their implications from a water and wastewater utility operation and management perspective. PRACTITIONER POINTS: Extrapolation from SARS-CoV-1 and MERS-CoV, as well as other surrogates, has helped predicting SARS-CoV-2 behavior and risk management. Data from treated wastewater effluent suggest that current processes are sufficient for SARS-CoV-2 control. Scientific evidence supports the possibility of fecal-oral transmission for SARS-CoV-2. Limited evidence supports the potential survival of infective SARS-CoV-2 on surfaces and in aerosols and the efficacy of control measures at reducing transmission. Protective practices and PPE can protect workers from SARS-CoV-2 and other pathogens found in wastewater.

Topical Capsaicin for the Treatment of Sensory Neuropathic Cough.

OBJECTIVE: To evaluate a novel treatment for sensory neuropathic cough (SNC): topical capsaicin. STUDY DESIGN: Retrospective review. SETTING: Tertiary care laryngology clinic. METHODS: A retrospective review was performed on 201 consecutive patients treated for SNC with capsaicin 0.02% to 0.04% applied topically to the upper aerodigestive tract, typically after failure of standard medications. Patients were asked to use the spray 4 times daily for 2 weeks prior to assessment of benefit. Items assessed included the percentage reduction of coughing, type of benefit noted, and side effects. RESULTS: Of the 201 patients who used the spray, 36.3% noted no benefit, whereas 63.7% (n = 128) had benefit in terms of cough reduction: 30.8% (n = 62) reported ≥75% reduction; 17.4% (n = 35), 50%-74% reduction; 7.0% (n = 14), 25%-49% reduction; and 8.5% (n = 17), 1%-24% reduction. Of all patients, 78.3% reported no side effects or complications. Of the remaining 21.7%, 1 patient noted a nosebleed after a single administration, and 1 patient noted transient wheezing after administration. The others reported unpleasant local effects, including throat/ear discomfort, voice change, sneezing, reflexive vomiting, and headache. CONCLUSION: In our group of 201 patients with SNC, most of which had failed to respond to standard treatments, 63.7% had some response to capsaicin spray, with 30.8% reporting ≥75% reduction. Minimal side effects of treatment were reported. Thus, we suggest that this therapy can be another treatment option for patients with SNC.

The Long-term Efficacy of Botulinum Toxin Injection to Treat Retrograde Cricopharyngeus Dysfunction.

OBJECTIVES: To report the percentage of patients with symptom relief 6 or more months after botulinum toxin injection into the cricopharyngeus muscle for retrograde cricopharyngeus dysfunction (R-CPD). STUDY DESIGN: Retrospective case series of consecutively treated patients. SETTING: Tertiary care laryngology clinic. SUBJECTS AND METHODS: A review was performed of the first 200 patients who were diagnosed with R-CPD and treated with botulinum toxin injection into the cricopharyngeus muscle by a single surgeon. The study group was limited to those for whom a minimum of 6 months has elapsed since the injection. Items assessed were efficacy, safety, complications, and duration of benefit. RESULTS: Of 200 patients treated, (99.5%) gained the ability to burp and 95% experienced relief of the cardinal symptoms of R-CPD: inability to belch, socially awkward gurgling noises, abdominal/chest pressure and bloating, and excessive flatulence. For those who experienced relief, 159 (79.9%) maintained a satisfactory ability to burp after 6 months. Of those who did not maintain the ability, 12 underwent a second injection, 1 patient underwent 3 subsequent injections, and 3 patients underwent partial myotomy. No patients experienced complications of botulinum toxin injection itself, and 4 patients had complications from esophagoscopy or anesthesia. CONCLUSION: In a case series of 200 patients with retrograde cricopharyngeus dysfunction, 99% experienced relief of the cardinal symptoms and 79.9% experienced lasting relief of their symptoms beyond pharmacologic duration of action after a single injection of botulinum toxin into the cricopharyngeus muscle. Relief can be reestablished in the remainder via additional injection or cricopharyngeus myotomy.

Identification of 11 Different HPV Subtypes in Adult Patients With Recurrent Respiratory Papillomatosis.

OBJECTIVE: To define the human papillomavirus (HPV) subtypes seen in a large adult population with traditionally defined recurrent respiratory papillomatosis. STUDY DESIGN: Retrospective review. SETTING: Tertiary care laryngology practice. SUBJECTS AND METHODS: All patients had a firm diagnosis of recurrent respiratory papillomatosis defined by (1) visually obvious papillomas, (2) recurrence requiring multiple surgeries, and (3) pathology diagnosis of "papilloma." Each patient had also undergone HPV subtyping. Age, sex, presence of malignancy, and HPV subtypes were tabulated and correlated with long-term patient outcomes. RESULTS: A total of 184 patients were identified who fulfilled the above criteria. In total, 87.0% (160) had a low risk subtype; 9.2% had an alternative subtype. These consisted of subtypes 16, 18, 31, 44, 45, 55, and 70. Four patients (2.2%) had combinations of subtypes, with 1 patient with HPV 11 and 16, 1 patient with HPV 11 and 76, 1 patient with 11 and 84, and 1 patient with 18 and 45. Finally, 3.8% of patients were HPV negative, despite fulfilling all 3 criteria listed above. CONCLUSION: In the patient population above, almost 10% of patients had an HPV subtype other than 6 and 11. This suggests that traditionally defined recurrent respiratory papillomatosis (RRP) can be caused by HPV subtypes other than 6 and/or 11. In addition, the clinical course of persons with this definition of RRP appears to vary by subtype, and this information may offer the ability to nuance follow-up instructions, reducing in particular the burden placed upon patients who have RRP caused by subtypes 6 and 11.

In RRP, serologic response to HPV is frequently absent and slow to develop.

BACKGROUND: Recurrent respiratory papillomatosis (RRP) is characterized by repeated formation of papillomas in the respiratory tract and is caused by human papillomavirus (HPV) types 6 and 11. Women with genital HPV infection are slow to develop weak humoral immunity, but respond robustly to the HPV vaccine. We wondered if people with RRP had a similar immune response. METHODS: A convenience cross-sectional sample of patients with RRP were recruited into one of four groups: 1) adults and adolescents with active RRP, 2) children with active RRP, 3) RRP patients who had undergone HPV vaccination prior to enrollment and, 4) people with RRP who were in remission. Anti-HPV6 and HPV11 serology was determined by cLIA on a single blood draw. RESULTS: Of the 70 subjects enrolled, 36, 16, 8, and 10, were in groups 1, 2, 3, and 4, respectively. 47% of participants aged >11 years and 81% aged ≤11 years possessed no antibodies against HPV6 or HPV11 (ie. double seronegative). 61% of patients in remission were double seronegative. All participants who had received HPV vaccine previously were seropositive to at least one of these low risk HPV types (ie none of them were double seronegative). Among patients who had active RRP and never had HPV vaccination (n = 52) there was an association between duration of symptoms and seropositivity. Of those who were seropositive, the geometric mean duration of symptoms was 11 years compared to 4.7 years for those who were seronegative (p = 0.001). CONCLUSION: People with RRP are capable of developing a humoral response to HPV6 and HPV11. That response appears to be robust when initiated by the HPV vaccine, but either nonexistent or slow to develop in response to infection. Most in remission do not have demonstrable antibody levels against HPV6 or HPV11.

Age at diagnosis, but not HPV type, is strongly associated with clinical course in recurrent respiratory papillomatosis.

BACKGROUND: Recurrent Respiratory Papillomatosis (RRP) is a rare disease characterized by the growth of papillomas in the airway and especially the larynx. The clinical course is highly variable among individuals and there is poor understanding of the factors that drive an aggressive vs an indolent course. METHODS: A convenience cohort of 339 affected subjects with papillomas positive for only HPV6 or HPV11 and clinical course data available for 1 year or more, from a large multicenter international study were included. Exploratory data analysis was conducted followed by inferential analyses with frequentist and Bayesian statistics. RESULTS: We examined 339 subjects: 82% were diagnosed prior to the age of 18 years, 65% were infected with HPV6, and 69% had an aggressive clinical course. When comparing age at diagnosis with clinical course, the probability of aggressiveness is high for children under five years of age then drops rapidly. For patients diagnosed after the age of 10 years, an indolent course is more common. After accounting for confounding between HPV11 and young age, HPV type was minimally associated with aggressiveness. Fast and Frugal Trees (FFTs) were utilized to determine which algorithms yield the highest accuracy to classify patients as having an indolent or aggressive clinical course and consistently created a branch for diagnostic age at ~5 years old. There was no reliable strong association between clinical course and socioeconomic or parental factors. CONCLUSION: In the largest cohort of its type, we have identified a critical age at diagnosis which demarcates a more aggressive from less aggressive clinical course.

Inability to Belch and Associated Symptoms Due to Retrograde Cricopharyngeus Dysfunction: Diagnosis and Treatment.

OBJECTIVE: To propose and test the validity of a new syndrome called retrograde cricopharyngeus dysfunction (R-CPD) that explains inability to belch and the associated symptoms of loud gurgling noises, chest and abdominal pain/distention, and excessive flatulence, as well as to report the results of botulinum toxin (BT) injection into the cricopharyngeus muscle (CPM) for both diagnosis and treatment of R-CPD. STUDY DESIGN: To develop a case series of consecutive patients matched to the syndromic features of R-CPD, inject the CPM with BT as a concurrent diagnostic and therapeutic maneuver, and assess results. SETTING: Bastian Voice Institute (Downers Grove, Illinois). SUBJECTS AND METHODS: Consecutive (unselected) patients presenting with inability to belch and associated symptoms were matched to the proposed syndrome of R-CPD, treated with BT, and followed for effect on symptoms over time. RESULTS: All 51 patients achieved ability to belch and relief of associated symptoms, and the majority seem to have "retrained" the ability to belch on a potentially "permanent" basis. CONCLUSION: R-CPD can be diagnosed syndromically, using a symptom complex; clinical diagnosis is validated by relief of symptoms after BT injection; and BT into the CPM is an efficacious treatment, whose benefit appears to often last longer than the pharmacologic duration of action of BT.

A greenhouse gas source of surprising significance: anthropogenic CO2 emissions from use of methanol in sewage treatment.

The impact of methanol (CH3OH) as a source of anthropogenic carbon dioxide (CO2) in denitrification at wastewater treatment plants (WWTPs) has never been quantified. CH3OH is the most commonly purchased carbon source for sewage denitrification. Until recently, greenhouse gas (GHG) reporting protocols consistently ignored the liberation of anthropogenic CO2 attributable to CH3OH. This oversight can likely be attributed to a simplifying notion that CO2 produced through activated-sludge-process respiration is biogenic because most raw-sewage carbon is un-sequestered prior to entering a WWTP. Instead, a biogenic categorization cannot apply to fossil-fuel-derived carbon sources like CH3OH. This paper provides a summary of how CH3OH use at DC Water's Blue Plains Advanced Wastewater Treatment Plant (AWTP; Washington, DC, USA) amounts to 60 to 85% of the AWTP's Scope-1 emissions. The United States Environmental Protection Agency and Water Environment Federation databases suggest that CH3OH CO2 likely represents one quarter of all Scope-1 GHG emissions attributable to sewage treatment in the USA. Finally, many alternatives to CH3OH use exist and are discussed.

Do Talkativeness and Vocal Loudness Correlate With Laryngeal Pathology? A Study of the Vocal Overdoer/Underdoer Continuum.

OBJECTIVES: Assess the correlation between self-rating scales of talkativeness and loudness with various types of voice disorders. DESIGN: This is a retrospective study. METHODS: A total of 974 patients were analyzed. The cohort study included 430 consecutive patients presenting to the senior author with voice complaints from December 1995 to December 1998. The case-control study added 544 consecutive patients referred to the same examiner from January 1988 to December 1998 for vocal fold examination before thyroid, parathyroid, and carotid surgery. Patient responses on seven-point Likert self-rating scales of talkativeness and loudness were compared with laryngeal disease. RESULTS: Mucosal lesions clearly associated with vibratory trauma are strongly associated with a high self-rating of talkativeness. Laryngeal deconditioning disorders were associated with a low self-rating of talkativeness. CONCLUSIONS: Use of a simple self-rating scale of vocal loudness and talkativeness during history taking can reliably orient the examiner to the types of voice disorders likely to be diagnosed subsequently during vocal capability testing and visual laryngeal examination. The high degree of talkativeness and loudness seen in vocal overdoers correlates well with mucosal disorders such as nodules, polyps, capillary ectasia, epidermoid inclusion cysts, and hemorrhage. A lower degree of talkativeness correlates with muscle deconditioning disorders such as vocal fold bowing, atrophy, presbyphonia, and vocal fatigue syndrome.

The use of neuralgia medications to treat sensory neuropathic cough: our experience in a retrospective cohort of thirty-two patients.

Objective. This study sought to: (1) quantify response rate and efficacy of amitriptyline, desipramine, and gabapentin in treating sensory neuropathic cough; and (2) describe an efficient treatment protocol. Study Design. This study is a retrospective case series. Methods. Persons diagnosed with sensory neuropathic cough during a one-year period were potential study candidates. To bolster the diagnosis credibility, only persons who had been treated elsewhere for gastroesophageal reflux disease, asthma, and allergy with no reduction of cough were included. Upon diagnosis of sensory neuropathic cough, each person was treated with either amitriptyline, desipramine, or gabapentin, titrating the dose upward to desired benefit or the dose limit. If the benefit was insufficient, another of the medications was used next, using a similar dose escalation strategy. Data points included patient demographics, initial and final medication, final dose, and degree of improvement. Results. 32 patients met the diagnostic and inclusion criteria and had a complete data set. 94% (30 of 32) of the patients responded to at least one of the medications. The 32 patients undertook a total of 45 single-medication trials. Patients reported symptom relief during 78% (14 of 18) of amitriptyline trials, 73% (11 of 15) of desipramine trials, and 83% (10 of 12) of gabapentin trials. At final dosage, symptom reduction averaged 77% on amitriptyline, 73% on desipramine, and 69% on gabapentin. Conclusion. Amitriptyline, desipramine, and gabapentin appear to vary in their effectiveness for individual cases of sensory neuropathic cough; across a whole cohort, symptom relief was similar in frequency and degree on any of the three medications. More evidence is needed to demonstrate more convincingly the effectiveness of these medications, but this data set suggests that each of these three medications deserves consideration in the codified treatment protocol presented here.

A rare sequence variant in intron 1 of THAP1 is associated with primary dystonia.

Although coding variants in THAP1 have been causally associated with primary dystonia, the contribution of noncoding variants remains uncertain. Herein, we examine a previously identified Intron 1 variant (c.71+9C>A, rs200209986). Among 1672 subjects with mainly adult-onset primary dystonia, 12 harbored the variant in contrast to 1/1574 controls (P < 0.01). Dystonia classification included cervical dystonia (N = 3), laryngeal dystonia (adductor subtype, N = 3), jaw-opening oromandibular dystonia (N = 1), blepharospasm (N = 2), and unclassified (N = 3). Age of dystonia onset ranged from 25 to 69 years (mean = 54 years). In comparison to controls with no identified THAP1 sequence variants, the c.71+9C>A variant was associated with an elevated ratio of Isoform 1 (NM_018105) to Isoform 2 (NM_199003) in leukocytes. In silico and minigene analyses indicated that c.71+9C>A alters THAP1 splicing. Lymphoblastoid cells harboring the c.71+9C>A variant showed extensive apoptosis with relatively fewer cells in the G2 phase of the cell cycle. Differentially expressed genes from lymphoblastoid cells revealed that the c.71+9C>A variant exerts effects on DNA synthesis, cell growth and proliferation, cell survival, and cytotoxicity. In aggregate, these data indicate that THAP1 c.71+9C>A is a risk factor for adult-onset primary dystonia.

Pathogenic variants in TUBB4A are not found in primary dystonia.

OBJECTIVE: To determine the contribution of TUBB4A, recently associated with DYT4 dystonia in a pedigree with "whispering dysphonia" from Norfolk, United Kingdom, to the etiopathogenesis of primary dystonia. METHODS: High-resolution melting and Sanger sequencing were used to inspect the entire coding region of TUBB4A in 575 subjects with primary laryngeal, segmental, or generalized dystonia. RESULTS: No pathogenic variants, including the exon 1 variant (c.4C>G) identified in the DYT4 whispering dysphonia kindred, were found in this study. CONCLUSION: The c.4C>G DYT4 mutation appears to be private, and clinical testing for TUBB4A mutations is not justified in spasmodic dysphonia or other forms of primary dystonia. Moreover, given its allelic association with leukoencephalopathy hypomyelination with atrophy of basal ganglia and cerebellum and protean clinical manifestations (chorea, ataxia, dysarthria, intellectual disability, dysmorphic facial features, and psychiatric disorders), DYT4 should not be categorized as a primary dystonia.

Genotype-phenotype correlations in THAP1 dystonia: molecular foundations and description of new cases.

An extensive variety of THAP1 sequence variants have been associated with focal, segmental and generalized dystonia with age of onset ranging from 3 to over 60 years. In previous work, we screened 1114 subjects with mainly adult-onset primary dystonia (Neurology 2010; 74:229-238) and identified 6 missense mutations in THAP1. For this report, we screened 750 additional subjects for mutations in coding regions of THAP1 and interrogated all published descriptions of THAP1 phenotypes (gender, age of onset, anatomical distribution of dystonia, family history and site of onset) to explore the possibility of THAP1 genotype-phenotype correlations and facilitate a deeper understanding of THAP1 pathobiology. We identified 5 additional missense mutations in THAP1 (p.A7D, p.K16E, p.S21C, p.R29Q, and p.I80V). Three of these variants are associated with appendicular tremors, which were an isolated or presenting sign in some of the affected subjects. Abductor laryngeal dystonia and mild blepharospasm can be manifestations of THAP1 mutations in some individuals. Overall, mean age of onset for THAP1 dystonia is 16.8 years and the most common sites of onset are the arm and neck, and the most frequently affected anatomical site is the neck. In addition, over half of patients exhibit either cranial or laryngeal involvement. Protein truncating mutations and missense mutations within the THAP domain of THAP1 tend to manifest at an earlier age and exhibit more extensive anatomical distributions than mutations localized to other regions of THAP1.