Effect of Esketamine Nasal Spray on Olfactory Function and Nasal Tolerability in Patients with Treatment-Resistant Depression: Results from Four Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase III Studies.

BACKGROUND: Intranasal drug delivery offers a non-invasive and convenient dosing option for patients and physicians, especially for conditions requiring chronic/repeated-treatment administration. However, in some cases such delivery may be harmful to nasal and olfactory epithelia. OBJECTIVE: The aim of this study was to assess the potential impact of long-term intermittent treatment with esketamine nasal spray, taken in conjunction with an oral antidepressant (AD), on olfactory function and nasal tolerability in patients with treatment-resistant depression (TRD). METHODS: A total of 1142 patients with TRD participated from four multicenter, randomized, double-blind, phase III studies: three short-term studies (two in patients aged 18-64 years, one in patients ≥65 years), and one long-term maintenance study of esketamine nasal spray + AD versus placebo nasal spray + AD. Across the four studies, assessments were performed at 208 sites in 21 countries. Olfactory function was measured using the 40-item University of Pennsylvania Smell Identification Test (UPSIT®) and the single-staircase Snap & Sniff® Odor Detection Threshold Test (S&S-T). Nasal tolerability, including nasal examinations and a quantitative, self-administered nasal symptom questionnaire (NSQ), was also assessed. Data were analyzed using analyses of covariance. RESULTS: Of 1142 participants, 734 were women (64.3%). The mean age of all participants ranged from 45.7 to 70.0 years across the studies. Overall, 855 patients received esketamine nasal spray + AD and 432 received placebo nasal spray + AD. Objective evaluation of nasal function showed no evidence of an adverse impact following esketamine administration. Based on the UPSIT® and S&S-T results, intranasal administration of esketamine had no effect on the odor identification or threshold test scores compared with placebo nasal spray + oral AD. Similarly, repeated administration with esketamine nasal spray had no meaningful impact on assessments of nasal function. No dose-response relationship was observed between esketamine doses and the olfactory test scores. Esketamine nasal spray was well tolerated, as indicated by responses on the NSQ and negative nasal examination findings. CONCLUSION: Findings from this analysis indicate that there was no evidence of adverse effect on either olfactory or nasal health measures with repeated intermittent administration of esketamine nasal spray at any dose over the course of short-term (4 weeks) or long-term (16-100 weeks) studies. CLINICAL TRIAL REGISTRATION: TRANSFORM-1: NCT02417064, date of registration: 15/04/2015; TRANSFORM-2: NCT02418585, date of registration: 16/04/2015; TRANSFORM-3: NCT02422186, date of registration: 21/04/2015; SUSTAIN-1: NCT02493868, date of registration: 10/07/2015.

A case series and literature review on patients with rhinological complications secondary to the use of cocaine and levamisole.

BACKGROUND: Levamisole is an increasingly common cutting agent used with cocaine. Both cocaine and levamisole can have local and systemic effects on patients. METHODS: A retrospective case series was conducted of patients with a cocaine-induced midline destructive lesion or levamisole-induced vasculitis, who presented to a Dundee hospital or the practice of a single surgeon in Paisley, from April 2016 to April 2019. A literature review on the topic was also carried out. RESULTS: Nine patients from the two centres were identified. One patient appeared to have levamisole-induced vasculitis, with raised proteinase 3, perinuclear antineutrophil cytoplasmic antibodies positivity and arthralgia which improved on systemic steroids. The other eight patients had features of a cocaine-induced midline destructive lesion. CONCLUSION: As the use of cocaine increases, ENT surgeons will see more of the complications associated with it. This paper highlights some of the diagnostic issues and proposes a management strategy as a guide to this complex patient group. Often, multidisciplinary management is needed.

Treatment of an oronasal fistula in a patient on bisphosphonate therapy: A case study.

Bisphophonates (BPs) are a group of drugs used in treating bone diseases, which may lead to the development of the osteonecrosis of the jaw (ONJ). The negative impact of BPs on angiogenesis is among the causes of ONJ. The specific mechanisms of complications are unknown. What is taken into consideration is the trauma background, which, in combination with the implemented BP treatment, can induce bone necrosis. One of the possible consequences of necrotic change progression is the development of an oronasal fistula. Treatment generally requires a surgical intervention.The paper describes the course of treatment of an oronasal fistula in a patient with BP osteitis, currently using an upper denture. The fistula arose a year after the removal of a protruding sequestrum in the region of the hard palate. An attempt was made to treat the fistula by the mobilization of soft tissues from the palate and the bilayered closure of the fistula with the use of a pedicled connective tissue graft on the greater palatine artery, along with a Tinti-Parma-Benfenati (TPB) flap. The patient was subjected to appropriate post-procedural measures. Regular follow-ups did not reveal any abnormalities in the course of healing.The use of the abovementioned procedure proved to be an effective method of treatment of an oronasal fistula. The use of a pedicled connective tissue graft for the closure of the oronasal fistula caused by BP therapy had a significant effect on the treatment outcome.

Rose geranium in sesame oil nasal spray: a treatment for nasal vestibulitis?

OBJECTIVES: As a rose geranium in sesame oil spray product has been anecdotally noted to improve nasal vestibulitis symptoms, this study was designed to assess whether patients with nasal vestibulitis associated with cancer-directed therapy experienced symptomatic improvements from it. METHODS: Patients with breast cancer, prescribed rose geranium nasal spray, were identified by looking at pharmacy records and patient diagnosis at Mayo Clinic Rochester. Patient medical information, as well as documentation of symptoms, were gleaned from medical charts. Questionnaires were sent to patients regarding their experiences. RESULTS: Of the 40 patients with breast cancer who were prescribed rose geranium nasal spray, 100% were receiving cancer-directed therapy: 58 % were receiving taxane chemotherapy; others received a variety of cytotoxic and targeted therapy treatments. Twenty patients who had used the spray product returned surveys. Patient-reported nasal symptoms included bleeding (90%), dryness (86%), pain (81%), scabbing (67%) and sores (52%); patients consistently reported symptoms at a higher proportion than did healthcare providers. All patients who used the rose geranium nasal spray reported symptomatic benefit; one reported a little benefit, 11 (55%) reported moderate benefit and eight (40%) reported dramatic or complete resolution of symptoms. The therapy was well tolerated in most patients. CONCLUSIONS: Rose geranium in sesame oil nasal spray appears to improve patient-reported nasal symptoms associated with cancer-directed therapy.

Rhinorrhea as a Result of Alzheimer's Disease Treatment: A Case Report.

This report describes a case of persistent rhinorrhea caused by donepezil and successfully treated with azelastine in an 84-year-old male treated with donepezil for Alzheimer's disease (AD) who experienced excessive rhinorrhea. After initiation of donepezil for AD the patient showed increased discomfort with rhinorrhea. A trial with an oral second-generation antihistamine provided no benefit. Azelastine 0.1% nasal spray was initiated and successfully reduced the rhinorrhea. A less-oftenreported side effect of donepezil that may impact patients is rhinorrhea, also described as rhinitis or nasopharyngitis.
Cholinergic mechanisms of rhinorrhea have been previously described in the condition of vasomotor rhinitis and are not allergy-mediated though symptomatology overlaps. Azelastine is a histamine H1 antagonist indicated for vasomotor rhinitis. To our knowledge there are no previous descriptions in the literature that recommend azelastine to manage symptoms of rhinorrhea caused by treatments for AD. The adverse side effect of rhinorrhea, resulting from treatment with donepezil, can be disregarded as allergy symptoms. Instead, a trial of azelastine 0.1% nasal spray, one spray each nostril daily then titrated up to two sprays in each nostril twice daily as tolerated, may be warranted. Patients and caregivers should be aware of epistaxis as a potential side effect of azelastine, especially for patients on antithrombotic therapy.

[Clinical analysis of 24 cases of occupational chromium rhinopathy].

Occupational chromium rhinopathy is chronic nasal damage caused by chromic anhydride, chromate and dichromate 6-valent chromium compounds. In 2016, 700 people who were exposed to chromium slag in steel plant were checked out. 24 people were found to have nasal injuries. The expert group confirmed 1 case of occupational severe chromium rhinosis and 23 cases of occupational mild chromium rhinosis.There was no significant difference in the incidence, type of work and duration of injury among 24 patients (P>0.05) . Active measures should be taken to prevent chromium rhinopathy and the technological process should be reformed. Occupational health education and occupational health monitoring should be strengthened to avoid exposure of chromium and its compounds through nose and respiratory tract, and to reduce or eliminate the occurrence of chromium rhinosis.

Lesiones destructivas de la línea media facial secundarias al consumo de cocaína: caso clínico / Cocaine induced midline destructive lesions: report of one case

Vasculitic midline destructive lesions can be a complication of cocaine use. We report a 44-year-old man who presented with a two months history of left facial pain associated with ipsilateral facial paralysis and a cheek phlegmon. Magnetic resonance imaging showed broad soft tissue destruction linked to important cranial nerve involvement. Antibiotic and antifungal therapy was started and multiple surgical debridement procedures were performed, with no clinical improvement. Microbiological analysis was negative. Finally, thanks to the histologic findings corresponding to vasculitis and granuloma formation and the history of cocaine abuse, a cocaine induced midline destructive lesion was diagnosed.

Nasal vestibulitis: an under-recognized and under-treated side effect of cancer treatment?

PURPOSE: To evaluate the frequency of nasal symptoms termed nasal vestibulitis, including nasal dryness, crusting, bleeding, and pain, among patients receiving systemic, antineoplastic therapy. METHODS: Patients undergoing systemic antineoplastic therapy were interviewed regarding the presence of nasal symptoms. In an explorative approach, Fisher's exact tests were used to identify groups in which frequencies of nasal symptoms were higher than the comparator arm. To account for potential confounding factors, including demographic variables and concurrent therapies, logistic regression analyses were performed, and estimated proportions with their standard errors (SEs) and odds ratios (ORs) were reported. RESULTS: Forty-one percent of the 100 surveyed patients had nasal symptoms, including dryness, pain, bleeding, and scabbing. Higher frequencies were reported among those who had received taxanes (71%) and VEGF-related therapies (78%). For the patients who had received taxanes, after controlling for other factors, the odds of experiencing nasal symptoms were 4.86 times higher than those for patients who did not receive taxanes (90% CI 2.01, 11.76). For patients who received VEGF-related therapies, after controlling for other factors and exposure to taxanes, the odds of experiencing nasal symptoms were 7.38 (90% CI 1.68, 32.51) times higher than those for patients who did not. Sixty-one percent of patients with symptoms said they reported them to their provider, but only 41% of chart notes contained documentation of such; 49% of patients reported treating their symptoms. CONCLUSIONS: Nasal vestibulitis is common among patients receiving taxane- and VEGF-related therapies; these symptoms are infrequently recorded or treated by healthcare providers.

[Cocaine induced midline destructive lesions. Report of one case]. / Lesiones destructivas de la línea media facial secundarias al consumo de cocaína. Caso clínico.

Vasculitic midline destructive lesions can be a complication of cocaine use. We report a 44-year-old man who presented with a two months history of left facial pain associated with ipsilateral facial paralysis and a cheek phlegmon. Magnetic resonance imaging showed broad soft tissue destruction linked to important cranial nerve involvement. Antibiotic and antifungal therapy was started and multiple surgical debridement procedures were performed, with no clinical improvement. Microbiological analysis was negative. Finally, thanks to the histologic findings corresponding to vasculitis and granuloma formation and the history of cocaine abuse, a cocaine induced midline destructive lesion was diagnosed.

Extended followup of a cohort of chromium production workers.

BACKGROUND: The current study evaluates the mortality of 2,354 workers first employed at a Baltimore chromate production plant between 1950 and 1974. METHODS: The National Death Index (NDI Plus) was used to determine vital status and cause of death. Cumulative chromium (VI) exposure and nasal and skin irritation were evaluated as risk factors for lung cancer mortality. RESULTS: There are 91,186 person-years of observation and 217 lung cancer deaths. Cumulative chromium (VI) exposure, nasal irritation, nasal perforation, nasal ulceration, and other forms of irritation (e.g., skin irritation) were associated with lung cancer mortality. CONCLUSION: Cumulative chromium (VI) exposure was a risk factor for lung cancer death. Cancer deaths, other than lung cancer, were not significantly elevated. Irritation may be a possible mechanism for chromium (VI)-induced lung cancer.

The effect of selective antagonist of H4 receptor JNJ7777120 on nasal symptoms, cough, airway reactivity and inflammation in guinea pigs.

The efficacy of H4R antagonist JNJ7777120 on nasal symptoms, cough, airway resistance (Raw), inflammatory cell count in bronchoalveolar lavage (BAL) and blood in ovalbumin (OVA) induced allergic rhinitis (AR) was studied in guinea pigs. Animals (n=8) were sensitized by i.p. OVA and were repeatedly challenged with nasal OVA to induce rhinitis, seven animals were not sensitized. Animals were pre-treated with JNJ7777120 2.5 and 5mg/kg i.p. 30 min prior OVA. Cough was induced by inhalation of citric acid, Raw was measured in vivo by Pennock's method as baseline, during AR and after JNJ7777120 treatment. Leucocyte count in BAL and blood was analyzed. JNJ7777120 (5mg/kg) significantly suppressed nasal symptoms and the number of coughs. This compound significantly inhibited airway reactivity to histamine, but not methacholine. Pre-treatment with JNJ7777120 5mg/kg did not influence significantly the leucocyte count in BAL and blood except for a significant decrease in monocyte count in blood compared to the control group (p<0.05). We conclude that the antitussive action of JNJ7777120 is peripheral. The primary effect of the compound is anti-inflammatory, and the suppression of cough is a consequence of reduced airway inflammation.

Prostaglandin analogue-induced pigmentation of the skin of the nasal septum and nasal alae in a glaucoma patient.

PURPOSE: To present a case of topical prostaglandin analogue-induced skin pigmentation in a location previously never reported, with a differential diagnostic significance. CASE REPORT: An 83-year-old man successfully treated for primary open-angle glaucoma of both eyes with the bimatoprost/timolol fixed combination for 6 years reported increased pigmentation of the skin of the nasal septum and alae. According to his report, the darkened skin area was not present when he was a young or middle-aged man. The patient had noted periocular pigmentation and deepening of the upper lid sulcus on both sides, which developed during the years of his bimatoprost/timolol treatment. Dermatology consultation excluded any nevus, malignancy, or other pathology as a cause of the pigmentation. The otorhinolaryngology consultation failed to identify any pathologic condition in the nasal cavity, but described mild chronic senile rhinitis. CONCLUSIONS: The acquired pigmentation of the skin of the nasal septum and alae in our patient represents a new form of cutaneous pigmentation induced by topical prostaglandin analogue therapy, which may have differential diagnostic significance in clinical practice. We speculate that the senile rhinitis of the patient increased the exposure of the nasal skin to the prostaglandin analogue solution drained via the nasolacrimal duct, and could therefore play a role in the development of skin pigmentation in this location.

The Relationship between Working Conditions and Adverse Health Symptoms of Employee in Solar Greenhouse.

To determine the correlation between the working environment and the health status of employees in solar greenhouse, 1171 employees were surveyed. The results show the 'Greenhouse diseases' are affected by many factors. Among general uncomforts, the morbidity of the bone and joint damage is the highest and closely related to labor time and age. Planting summer squash and wax gourd more easily cause skin pruritus. Asthma-related cough, eye disease, and skin pruritus are significantly correlated with the cultivation of wax gourd. The application of inorganic fertilizer and fertigation dramatically induce the bone and joint damage. The smell of covering film greatly influence skin pruritus. Personal protection is badly scanty and normative occupational health and safety need to be completed.