Throat Irritation Research Articles

Safety, tolerability, and pharmacokinetics (PK) of treprostinil palmitil inhalation powder (TPIP): a phase 1, randomised, double-blind, single- and multiple-dose study

Abstract Background/Introduction Use of treprostinil in the treatment of pulmonary arterial hypertension (PAH) is limited by a short half-life and dose-limiting adverse events. TPIP, a dry powder formulation of the treprostinil prodrug treprostinil palmitil, is under investigation for PAH. In preclinical models, TPIP provided sustained treprostinil release in the lung and demonstrated sustained reduction of pulmonary arterial pressures. Purpose To examine the safety, tolerability, and PK of single- and multiple-dose administration of once-daily (QD) TPIP in healthy volunteers. Methods In this phase 1 study, healthy adults (aged 18–45 years) were randomised to receive single or multiple QD inhalation doses of TPIP. Single-dose participants received TPIP 112.5, 225, 450, or 675 μg (n=6 per dose) or placebo (n=2). Multiple-dose participants received TPIP 225 μg QD for 7 days (n=6), 112.5 μg QD for 4 days followed by 225 μg QD for 3 days (n=6), or placebo for 7 days (n=4). Results Of 42 randomly assigned participants who received ≥1 dose, 41 (97.6%) completed the study. Of the single-dose TPIP–treated participants, 70.8% (n=17/24) experienced a treatment-emergent adverse event (TEAE) vs 0% (0/2) of placebo-treated participants; the most common TEAEs (≥15%) among TPIP-treated participants were cough (45.8%), dizziness (29.2%), throat irritation (20.8%), nausea (16.7%), and hypotension (16.7%). Of the multiple-dose TPIP–treated participants, 83.3% (n=10/12) experienced a TEAE vs 50.0% of placebo-treated participants (2/4); the most common TEAEs were cough (58.3% TPIP vs 50.0% placebo), headache (50.0% vs 0%), nausea (33.3% vs 0%), and dizziness (25.0% vs 0%). Overall, 69.0% of participants (29/42) experienced mild TEAEs and 16.7% (7/42) experienced moderate TEAEs; no severe or serious TEAEs occurred. TEAEs were more frequent with increasing TPIP doses. Participants titrated from TPIP 112.5 μg QD to 225 μg QD experienced fewer TEAEs than those who received 225 μg QD at treatment initiation; all TEAEs were mild. After single-dose TPIP treatment, treprostinil exposure was dose proportional, with mean (CV%) Cmax = 78.4–717 pg/mL (38.6-72.9%) and AUC(0–∞) = 1.09–5.48 h·ng/mL (11.5–30.0%). At steady-state (225 μg), the mean (CV%) of Cmax, Cmin, and AUC(0–t) were 193–228 pg/mL (32.9–46.4%), 17.6–22.8 ng/mL (43.7%-64.4%) and 1.68–1.82 ng·h/mL (28.7–36.6%), respectively. No steady-state accumulation was observed. Elimination t1/2 was 8.7–11.6 h after a single dose and 6.8–8.8 h at steady state. Plasma concentrations of treprostinil palmitil were below the limit of quantification (100 pg/mL) at all time points measured. Conclusions In this phase 1 study, single and multiple TPIP dosing was generally well tolerated in healthy volunteers, with a PK profile that supports QD dosing. TEAEs were dose related; most were mild, none were severe or serious, and a titration schedule improved tolerability. These results support further examination of TPIP in patients with PAH. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Insmed Incorporated

S2203 An Unexpected Case of Esophageal Perforation Following Transesophageal Echocardiography

Introduction: Esophageal perforation is a serious complication of transesophageal echocardiography (TEE). Although extremely rare, perforations of the esophagus can lead to life-threatening complications with high morbidity and mortality. We present a unique case of esophageal perforation in a patient with no history of esophageal pathology, documented prior well-tolerated TEEs, and no clinical signs or symptoms of perforation peri or post procedure. Case Description/Methods: A 79 year-old female with multiple comorbidities including hypertension, moderate aortic stenosis, chronic atrial fibrillation with a 27mm Watchman device presented to the ED for chest pain, shortness of breath, nausea, and vomiting. The patient was discharged earlier that morning after a post-Watchman TEE was performed. During the procedure, the probe was passed without difficulties and no peri-procedural complications were documented. Post-procedure, the patient had no complaints and was able to tolerate oral intake. After arriving home, the patient began to experience severe substernal pain and throat irritation and returned to the ED. Urgent chest radiography showed findings concerning for pneumomediastinum. Stat computed tomography (CT) revealed extensive supraclavicular soft tissue emphysema along with gas in the anterior and middle mediastinum; no definitive perforation was seen. An urgent esophagogastroduodenoscopy (EGD) was performed and confirmed a linear esophageal perforation 15 cm from incisors below the cricopharyngeus. Due to the unique location of the perforation, one Ovesco clip was deployed over the defect. The patient later developed respiratory failure and unfortunately expired within a week. Discussion: Although TEEs have been safely used as a cardiac diagnostic and monitoring modality, complications can occur. Esophageal perforations are attributed to increased mucosal pressure and thermal damage to the esophageal wall. Absolute contraindications include severe dysphagia and history of esophageal disorders. Risk factors for TEE-associated perforations include patient’s advanced age, multiple comorbidities, and an enlarged left atrium which can cause thinning of the esophageal wall. This case ultimately highlights the serious morbidity and mortality associated with post-TEE esophageal perforations. It is crucial that appropriate screening is done to identify high-risk individuals before such procedures are done.

Cleaning product emissions and indoor built environments: Exposure and health risk assessments from experiments under realistic indoor conditions

Cleaning products are among the most widely used consumer products. The associated risks should be better understood. The health risk assessment (HRA) approach was applied to household uses of cleaning products, with nineteen products of various types and formats tested under typical indoor environmental parameters in an experimental house. The targeted substances included volatile organic compounds (VOCs) and carbonyl compounds. The generic “Common Use” and “Reasonable Worst-Case” scenarios under consideration were based on full cleaning sessions. These sessions were elaborated from data available in the technical and scientific literature, combined with stakeholder participation. The Common Use scenario included a 1 1/2-h cleaning session once per week, followed by manual ventilation; the Reasonable Worst-Case scenario included a 4-h session twice per week without manual ventilation. No situation of concern was found regarding chronic inhalation exposures associated with Common Use. For the Reasonable Worst-Case scenario, the assessed chronic inhalation risks were low. Assessed acute inhalation exposures (1-h exposures) could exceed the selected health values, mainly for acrolein (exposures up to 12 μg/m3) and formaldehyde (exposures up to ∼140 μg/m3). Associated first observed effects could include nasal, throat, and eye irritation. These results suggest that the highest exposures should be reduced and, to this end, that the emissions of the most emissive products should be reduced. Since the identified priority substances of concern are not specific to cleaning product emissions, multisource cumulative exposures are expected with the use of other consumer products, e.g., paints, incense, scented candles, furniture, and fragrance diffusers.

Physicians’ Perception of E-Cigarettes as a Smoking Cessation Tool in Bangladesh

The popularity of e-cigarette is growing worldwide. Its health hazards and role in smoking ces-sation is controversial. There is no doubt that health care professionals can play a vital role in assisting patients who wish to use e-cigarettes to quit smoking but there is a gap in the evidence. The present study aimed to reveal the perception of e-cigarettes as a quit smoking tool and its health hazards among physicians in Bangladesh. A cross-sectional study was conducted by means of a survey via self-administered structured questionnaires in Bangladesh. Data was col-lected from September 2019 to February 2020 and analysed by descriptive frequency and chi-square test using SPSS. A total of 145 physicians have participated in this study, 88.9% pro-vided professional advice on quit smoking to their patients. Total 51.7%, 51.9%, 41.3%, 52.4%, 42.8%, and 47.6% physicians mentioned that e-cigarettes may cause throat irritations, cough, headache, dryness of mouth, cardiovascular disease, and cancer respectively. Chi-square test re-vealed that there is no association between a physician’s professional advice for quit smoking and perception of e-cigarettes as a smoking cessation tool. The physician’s perception of e-cigarettes is crucial for reducing any type of tobacco consumption. Evidence based e-cigarette related public health intervention for physicians are required to mitigate the use of e-cigarette to quit smoking.

Individual-level interventions to reduce personal exposure to outdoor air pollution and their effects on people with long-term respiratory conditions.

Individual-level interventions to reduce personal exposure to outdoor air pollution and their effects on people with long-term respiratory conditions.

Hydrogen peroxide as an auxiliary treatment for COVID-19 in Brazil: a randomized double-blind clinical trial.

OBJECTIVESThis study evaluated the effectiveness of hydrogen peroxide (H2O2) as mouthwash and nasal spray on symptom relief in coronavirus disease 2019 (COVID-19) patients.METHODSPatients positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), who were treated in a hospital or at home, and patients’ family members (not positive for SARS-CoV-2), were randomized into 2 groups: experimental (1% H2O2 for gargling, 0.5% H2O2 for nasal wash), and control. Patients gargled the solution 3 times a day, and applied the nasal spray twice a day, for a 7-day period. Family members received the same treatment as the treated COVID-19 patient. The researchers contacted patients every 2 days over an 8-day period. An average post-treatment interval of 8 days passed before testing family members.RESULTSThe most frequent symptoms on day 0 were cough, loss of taste, and hyposmia; there were no significant differences between groups, independent of the period. The symptom of dyspnea presented a significant difference between days 2 and 4 (p<0.05). Among family members, 86.0% had no antibodies, 2.3% had antibodies, and 11.6% had active infections (4 in the experimental group and 6 in the control group). The most frequent adverse effects in the H2O2 group were a burning throat and nose.CONCLUSIONSH2O2 was not effective for the relief of COVID-19 symptoms and was associated with reports of transient adverse effects.

The Incidence of Sick Building Syndrome and Its Causes on Employees at the Governor’s Office of West Sulawesi Province

Introduction: Indoor air quality greatly affects human health because almost 90% of human life is indoors. Some symptoms that are often felt by employees in a building with Sick Building Syndrome (SBS) are fatigue; headaches; symptoms of eye, nose and throat irritation; skin irritation; dry cough, increased irritability and difficulty in concentration; nausea; drowsiness; and hypersensitivity to odor. This research aims to determine the relationship of air quality in space to the incidence of Sick Building Syndrome. Methods: This research was an analytic survey research with cross sectional approach. The samples in this study were employees who were in the Building D of the Provincial Governor's Office, West Sulawesi totalling 82 people. This research was carried out by measuring indoor air quality and giving questionnaires to find out the SBS events. Results: The results of room temperature measurements ranged from 26.14 - 41.46°C, humidity measurement was ≥ 60%, light intensity was ≤ 100 lux, the chemical quality of CO in the air was ≤ 29 mg/m3, CO2 levelin the air was ≤ 1000 ppm, and dust level was ≥ 0.15 mg/m3. Besides, there was a significant relationship between air temperature and dust levels on the incidence of Sick Building Syndrome (SBS), with p value of 0.006. Conclusion: It can be concluded that factors that influenced the occurrence of SBS were air temperature and dust concentration in the room.Keywords: indoor air quality, office, sick building syndrome

Results of an Interim Safety Analysis of a Phase 2 Study of Daratumumab (Dara) Plus Cyclophosphamide, Bortezomib, and Dexamethasone (CyBorD) in Previously Untreated and Relapsed Patients (Pts) with Multiple Myeloma (MM)

Background: Dara is a monoclonal anti‐CD38 antibody approved for the treatment of relapsed and refractory MM, but is associated with an infusion related reaction (IRR) rate of 46% for infusion 1 and 2% for infusion 2, and a median duration of infusions 1 and 2 of 7.0 and 4.3 hours, respectively (US Prescribing Information). CyBorD is a commonly used bortezomib based regimen for MM. This study was designed to evaluate Dara-CyBorD, as well as administration of the first Dara infusion as a divided dose over 2 days, in pts with MM who are previously untreated or have relapsed following only one line of therapy. We report results from a planned interim analysis of the first 48 pts who completed C1 of study treatment, focusing on the safety and IRR profile of Dara.Methods: This is a multicenter, single-arm, open-label, Phase 2 study conducted at US community oncology centers. Key eligibility criteria include ≥ 18 years of age; documented MM per IMWG 2015 criteria; measurable MM; ECOG performance score of 0, 1, or 2; and no or one prior line of therapy. Approximately 100 pts will receive 4 to 8 28-day induction cycles of Dara-CyBorD, including oral cyclophosphamide 300 mg/m2 on Days 1, 8, 15, and 22; subcutaneous bortezomib 1.5 mg/m2 on Days 1, 8, and 15; and oral or IV dexamethasone 40 mg weekly. Dara is administered at a dose of 8 mg/kg IV on Days 1 and 2 of C1, then 16 mg/kg IV weekly from C1D8 through C2, then 16 mg/kg IV once every 2 weeks for C3-6, then 16 mg/kg IV once every 4 weeks for cycles 7-8. After completion of induction, pts may undergo an autologous stem cell transplant. All pts then receive 12 cycles of maintenance therapy with Dara 16 mg/kg IV every 4 weeks. Required pre-infusion medications are dexamethasone, acetaminophen, and diphenhydramine; montelukast is allowed at the investigator's discretion.Results: The first 48 pts completed 1 cycle of therapy with no discontinuations during C1. Median age was 62.5 (range 41-80) years, and 65% were male. Thirty-nine pts (81%) were previously untreated, and 9 pts (19%) had received 1 prior therapy. Forty-seven pts (98%) experienced at least 1 treatment emergent adverse event (TEAE) during C1, including 35 pts (73%) who experienced TEAE(s) attributed to Dara by the investigator. No grade 5 AE was reported during C1. The most commonly reported AEs during C1 were nausea (29%), fatigue (25%), diarrhea (23%), headache (17%), and chills (15%). Serious AEs (SAEs) occurred in 10% of pts during C1; no SAE was attributed to Dara by the investigator. IRRs occurred in 44% of pts, all grade ≤ 2, including 38% at C1D1 and 4% at C1D2. The most common IRRs were chills (13%), cough (6%), and nausea (6%). Respiratory IRRs occurred in 13% of pts, including cough (6%), dyspnea (4%), bronchospasm (2%), throat irritation (2%), and oropharyngeal pain (2%). The median infusion time was 4.3 hours for C1D1 and 3.5 hours for C1D2.Conclusion: The overall safety profile during C1 of Dara-CyBorD was consistent with that previously reported for Dara with no new safety concerns. Administration of the first Dara infusion as a split dose of 8 mg/kg/day over 2 days resulted in a similar IRR rate and a shorter median infusion time for C1D1 than the US prescribing information for single dose. No grade ≥ 3 IRRs were observed. These findings demonstrate that splitting of the first Dara infusion in the community setting is feasible, results in a similar IRR rate with no observed grade ≥ 3 IRRs, and reduces the median time for the first Dara infusion. DisclosuresYimer:Bellucum Pharma: Equity Ownership; Juno pharma: Equity Ownership. Melear:Janssen: Membership on an entity's Board of Directors or advisory committees. Faber:Millenium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Onyx: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi Aventis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees. Bensinger:Janssen: Membership on an entity's Board of Directors or advisory committees. Burke:Incyte: Consultancy; Bayer: Consultancy; Genentech: Consultancy; Celgene: Consultancy, Other: Travel grant; Gilead: Consultancy. Gunawardena:Janssen: Employment. Sean:Janssen: Employment, Equity Ownership. Parros:Janssen: Employment. Lutska:Janssen: Employment. Darif:Janssen: Employment, Equity Ownership. Londhe:Janssen: Employment, Equity Ownership. Qi:Janssen: Employment; Johnson & Johnson, LLC: Equity Ownership. Ukropec:Janssen: Employment. Lin:Janssen: Employment. Rifkin:McKesson Specialty Health: Employment; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Monoclonal Antibody Utilization Characteritics in Patients with Multiple Myeloma

Background: Monoclonal antibodies (MoAb) including daratumumab (Dara) and elotuzumab (Elo) are important additions to multiple myeloma (MM) therapeutics and have become cornerstones of patients with relapsed and/or refractory disease (RRMM). While large clinical trial data define their efficacy and safety, real-world experience to help understand their true utilization and serve as guidelines for community practice are lacking.Methods: Data on the utilization of Dara and Elo for treatment of MM including patient and disease characteristics, infusion attributes, supportive medication use and adverse event profile were collected and analyzed using descriptive statistics. Baseline laboratory data including median absolute lymphocyte count (ALC), eosinophil count (AEC), neutrophil count (ANC) and immunoglobulin level (Ig) were documented and their correlation with infusion-related reactions (IRRs) was explored using Wilcoxon rank sum test.Results: Ninety-one consecutive patients with MM treated using Dara (n=78) or Elo (n=13) not on clinical trials between 1/1/16 and 12/31/16 at Mayo Clinic in Florida (MCF; n=30) or Arizona (MCA; n=61) were included. A total of 1036 infusions of Dara (Median: 12 per patient; Range: 1-38) and 210 of Elo (Median: 18 per patient; Range: 3-29) were administered over 12 months. Study cohort included 56 males (61.5%) with median age 63 years (range: 37-81) and majority (83.5%) of Caucasian race. Treatment regimes of MoAb alone or with immunomodulatory drug (IMiD) and/or proteasome inhibitor (PI) are shown in Figure 1. Prior lines of therapy were >3 in 52.7%, 3 in 13.2%, 2 in 19.8%,1 in 12.1% and in 1 case each Dara and Elo were given in first line of therapy. Majority of patients who received Dara (60.3%) had >3 prior lines of therapy while majority who received Elo (53.8%) had 1 prior line of therapy for MM. Pre-treatment blood sample for type/screen was sent in 67% patients. Any grade hematologic (heme) adverse events (AE) were seen in 66 (84.6%) patients with Dara and 6 (46.2%) patients with Elo, while non-heme AEs were seen in 64 (82.1%) patients with Dara and 11 (84.6%) patients with Elo. Actual MoAb administration took an average 2 hours lesser (Range: -3 to +6 hours for Dara and -1 to +5 hours for Elo) than scheduled with median 2 hours lesser for both the drugs. In 2 cases first Dara infusion was given in divided dose over 2 days. Most common premedications prior to first MoAb infusion included acetaminophen (90.1% cases), diphenhydramine (86.8% cases) and methylprednisone (78% cases) with dexamethasone, famotidine, prochlorperazine and ondansetron used less frequently. Number of patients without any premedications use changed from 9.9% before infusion 1 to 94.5% before infusion 29 of any MoAb, showing a sharp decrease in the use of premedications in subsequent dose infusions of MoAbs. IRRs were seen in 39 (42.9%) patients with first MoAb infusion with respiratory IRRs (bronchospasm, cough, dyspnea, nasal congestion, throat irritation, wheezing) seen in 35 (38.5%) and non-respiratory IRRs (chills, nausea, hypertension, tachycardia, pruritus, bradycardia, emesis) in 16 (17.6%) patients. No patients had any higher than grade 2 IRRs. Majority of the IRRs (91.3%) were observed during the first MoAb infusion, none of the patient's required discontinuation of MoAb treatment as a result of IRRs, with a significant decrease in IRR incidence during second (3.3%) and subsequent (5.4%) infusions. In 10 cases (9 for Dara and 1 for Elo) premedication regimen was modified after first infusion. MoAb AEs seen in ≥10% cases across various regimens included neutropenia (51.6%), lymphopenia (42.9%), thrombocytopenia (33%), anemia (18.7%), fatigue (40.7%), diarrhea (22%), pneumonia (22%), cough (18.7%), fever (18.7%) and nausea (12.1%). Median baseline labs included ALC 0.95 K/mm3, ANC 2.22 K/mm3 and AEC 0.07 K/mm3. There was no association seen between median baseline ALC, ANC or AEC and the risk of any IRRs, respiratory or non-respiratory.Conclusions: We present a comprehensive analysis of real-world experience regarding the utilization of novel MoAb agents for the treatment of MM. Although the role of MoAbs in MM therapeutics is evolving, these data help understand their true utilization and identify how resources may be best employed to optimize their benefit for patients. [Display omitted] DisclosuresAilawadhi:Novartis: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Pharmacyclics: Research Funding; Amgen: Consultancy, Honoraria. Sher:LAM Therapeutics, Inc: Research Funding. Fonseca:Bayer: Consultancy; Takeda: Consultancy; Jansen: Consultancy; Celgene Corporation: Consultancy, Research Funding; AMGEN: Consultancy; Bristol-Myers Squibb: Consultancy; Mayo Clinic & Dr Fonseca: Patents & Royalties: Prognostication of myeloma via FISH, ~$2000/year; Merck: Consultancy; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy; Novartis: Consultancy; Pharmacyclics: Consultancy.

Atmospheric Emissions Effects and Mechanism

Humanity's relationship with the environment is a delicate balance. Since the industrial revolution, the world's population has grown at an exponential rate, and this has a major environmental effect. Deforestation, pollution, and global climate change are just a few of the negative consequences of population and technological growth. Particulates, Sulphur dioxide (SO2), and nitrogen oxides (NOx) are the primary pollutants that harm our health. These contaminants may be directly emitted into the atmosphere (primary pollutants) or formed in the atmosphere from primary pollutants reacting (secondary pollutants. Tropospheric ozone is created When water reacts with volatile organic compounds (VOC) and nitrogen oxides (NOx) in the presence of sunlight, nitrogen dioxide is produced. is formed when NO is oxidized, as Sulphur dioxide or nitrogen oxides react with water, acid rain results. These contaminants have negative consequences for human health (low concentrations cause eye, nose, throat, and lung irritation) and the environment, as they contribute to acidification and eutrophication, as well as the formation of particulates and tropospheric ozone (photochemical smog). Electricity production and the combustion of fossil fuels in high-temperature manufacturing processes is the primary source of SO2 and NOx. Particulates are as a direct product of any type of industrial combustion or heating. Particulates and nitrogen oxides (NOx) are two types of contaminants. also linked to traffic and transportation. All these molecules of greenhouse gases that penetrate the atmosphere It's called atmospheric emissions. In order to meet the Paris Agreement's goal of maintaining a 1.5°C average global temperature increase, net CO2 emissions must reach zero by 2050, implying that the amount entering the atmosphere must exceed the amount absorbed by natural and technological sinks.

Pharmacokinetic Characterization of a Prototype Mini Nicotine Lozenge.

Cigarette smoking remains a substantial public health problem. Nicotine replacement therapy (NRT) is an effective treatment that increases the success of a quit attempt. There are different NRT formats with no difference in efficacy, but their pharmaceutical form or route of administration may translate into individual preferences. A novel prototype mini lozenge was developed to offer smokers a new NRT option to aid in their quit attempt. Two studies were conducted to characterize the pharmacokinetic parameters and to evaluate its bioequivalence to a commercially available nicotine mini lozenge. Two randomized, open-label, crossover studies were conducted to evaluate either the 2 or 4mg dose level. Heavy smokers in otherwise good health were randomly assigned to one of two treatment sequences: the prototype mini lozenge followed by a commercially available mini lozenge, or the converse. After a 5 to 7day washout period, subjects crossed over to receive the other study treatment. Blood sampling occurred pre- and post-dose nicotine and was assessed using a validated solid-phase extraction with ultra-high-performance liquid chromatography and tandem mass spectrometry. The primary endpoint was bioequivalence as determined by maximal plasma nicotine concentration (Cmax) and the extent of nicotine absorption (AUC0-t and AUC0-∞). The secondary endpoints included the time to Cmax (Tmax), half-life, the elimination constant (Kel), and safety. The prototype mini lozenge was bioequivalent to the commercially available mini lozenge, with no significant difference in Cmax, AUC0-t, or AUC0-∞ or any of the secondary outcomes. The most common treatment-emergent adverse event was throat irritation, of which all cases were mild in severity. There were no serious adverse events. The prototype mini lozenge is bioequivalent to a commercially available mini lozenge and may provide smokers with a new oral NRT option to aid in smoking cessation and of tobacco dependence through the relief of nicotine withdrawal symptoms, including cravings.

Development of a Mobile Edge Device and an Information System to Analyze Particulate Matter Distribution as a mHealth Service

Particulate matter is an air pollutant consistent of very small particles that are suspended in the air. Shortterm exposure may result in respiratory symptoms such as shortness of breath, throat and nose irritation, chest tightness, coughing, in addition to eye irritation. The research aimes at creating a prototype of a mobile sensor system that can be used to analyze the particulate matter pollution on a location and on a time scale to measure the degree of pollution in the city. The engineering requirement to construct the edge device includes temperature (humidity) sensor, particulate matter sensor, GPS module, and an LCD for displaying the current sensor values. The health data of the mobile edge device can be analyzed through a developed analytics system, which allows the user to identify and avoid pollution sources. For the implementation of the web service the framework ReactJS, NodeJS with Express.js, and the database MongoDB are being used. The mHelath service is evaluated through field trials: New Year’s Eve, various source identifications, and a demonstration through a journey from the subway station to the university. The paper outlines a mHealth service, which can collect data records of the surroundings and analyze the particulate matter in an information system to visualize risk locations of a user.

AYURVEDIC APPROCH IN THE MANAGEMENT OF AMLAPITTA WITH THE HELP OF PATHYAPATHYA

In present scenario due to modern lifestyle and food habits most of the population are suffering from a common disease called as Amlapitta or gastritis. Ayurveda is a treasure of Knowledge. Ayurvedic science helps for removing root cause of diseases with the help of various Shodhan, Shaman treatment along with Pathyapathya. After treatment of diseases if proper Pathya not followed then recurrence of diseases occurs. In Ayurveda medicines as well as Pathya has equally important. For each diseases different Pathya described in Samhitas. In present we will discuss about importance of Pathya and Apathya in Amlapitta disease. Amlapitta is one of the Annavaha Strotas disease causes due to not following proper Pathya. It’s characterized by qualitatively and quantitatively increased Amla Guna of Pitta. The cardinal classical clinical features of Amlapitta are Avipaka (indigestion), Klama (tiredness), Utklesha (nausea), Tikta Amlaudagar (sour and bitter belching), Hrutakantha Daha (heat and throat burn) and Aruchi (anorexia). In Pathya Kalpana not only Hetus but proper follow of Dincharya and Rutucharya are important. Here attempted has to be made for various Pathya and Apathya are applicable for Amlapitta.

Safety of the standardized quality tree sublingual immunotherapy tablet: Pooled safety analysis of clinical trials.

The standardized quality (SQ) tree sublingual immunotherapy (SLIT)-tablet has recently been approved for treatment of tree pollen allergy. Healthcare workers should be provided with detailed safety data for clinical use. To assess the tolerability and safety of the SQ tree SLIT-tablet (12 SQ-Bet) in adults and adolescents. Safety data were pooled from three double-blinded, randomized, placebo-controlled trials (2 phase-II/1 phase-III) including adults and adolescents 12-65years with allergic rhinitis and/or conjunctivitis treated before and during one pollen season once-daily with 12 SQ-Bet (n=471) or placebo (n=458): EudraCT no: 2012-000031-59; NCT02481856; EudraCT 2015-004821-15. The most frequently reported investigational medicinal product (IMP)-related AEs with 12 SQ-Bet were oral pruritis (39% of subjects) and throat irritation (29%). IMP-related AEs were mainly mild or moderate in severity, and the majority resolved without treatment and did not lead to treatment interruption/discontinuation. With 12 SQ-Bet, oral pruritus was more frequent among subjects with pollen food syndrome (PFS) (45%) than without PFS (29%). The 12 SQ-Bet did not seem to induce an increased risk of asthma: 7 events were reported in 7 subjects with 12 SQ-Bet and 11 in 10 subjects with placebo. No differences were seen in the risk of moderate-to-severe IMP-related AEs regardless of age, PFS status and asthma medical history. The 12 SQ tree SLIT-tablet was well tolerated in tree pollen allergic subjects with no major safety concerns detected. This safety profile supports daily at-home sublingual administration once the first dose is tolerated when administered under medical supervision.

A Safety and Tolerability Study of Thin Film Freeze-Dried Tacrolimus for Local Pulmonary Drug Delivery in Human Subjects.

Due to the low and erratic bioavailability of oral tacrolimus (TAC), the long-term survival rate following lung transplantation remained low compared to other solid organs. TAC was reformulated and developed as inhaled formulations by thin film freezing (TFF). Previous studies reported that inhaled TAC combined with 50% w/w lactose (LAC) was safe and effective for the treatment of lung transplant rejection in rodent models. In this study, we aimed to investigate the safety and tolerability of TFF TAC-LAC in human subjects. The formulation can be delivered to the lung as colloidal dispersions after reconstitution and as a dry powder. Healthy subjects inhaled TAC-LAC colloidal dispersions at 3 mg TAC/dose via a vibrating mesh nebulizer in the first stage of this study and TAC-LAC dry powder at 3 mg TAC/dose via a single dose dry powder inhaler in the second stage. Our results demonstrated that oral inhalation of TAC-LAC colloidal dispersions and dry powder exhibited low systemic absorption. Additionally, they were well-tolerated with no changes in CBC, liver, kidney, and lung functions. Only mild adverse side effects (e.g., cough, throat irritation, distaste) were observed. In summary, pulmonary delivery of TFF TAC-LAC would be a safe and promising therapy for lung transplant recipients.

Agriculture Biomass and Indoor Air Pollution as Risk Factors for Women Health

This research looks at the effects of biomass and air pollution on women's health. Respondents were surveyed using a multi-stage questionnaire. Data was collected purposively. a self-designed survey (72 items) was used to collect data Results show that a strong correlation was established between age and nonrespiratory diseases. The findings reveal that a positive relationship was found between age, respiratory disease, and non-respiratory diseases. It indicates that age predicts health-related among women. The study's findings show that the use of Agriculture Biomass (UAB), Indoor Air Pollution (IAP), Frequency of Usage (FU), Kitchen Type (KT), Kitchen Ventilation System (KVS), and Time Spent in Kitchen (TSK) have a significant impact on women's respiratory diseases (WRD), whereas the type of stove (ST) and exposure to smoke (ES) have no significant impact on women's health. Collectively, these variables predict up to 20% of respiratory diseases (Upper and lower respiratory infection, Cough, Lung cancer, Asthma, Throat irritation, Cough without phlegm) among women but predict 36.9% of non-respiratory diseases (Diminished vision, Eye irritation, Watering of eyes, Running of the nose, Cough/without phlegm, Hypertension, Stroke, Skin irritation/skin burn and Miscarriages, Stillbirth and Low birth weight) in women.

Impact of air quality on students’ behavior in the Educational Centers

Air pollution of indoor and outdoor environments is one of the most important environmental problems in metropolises and industrial cities. The study explores the effects of air quality on the well-being of students at Shahid Beheshti University in Tehran. The sampling of the particles was carried out in four seasons in 2017–2018. The concentration of PM≥11, PM7-11, PM4.7–7, PM3.3–4.7, PM2.1–3.3, PM1.1–2.1, PM0.7–1.1, PM0.4–0.7 and PM≤0.4 in inside and outside building was evaluated simultaneously using a direct measurement device. The length of each collection period varied from 6 to 72 h. The samples were studied by SEM/EDS and imaging was performed and the surface of particles. The effects of air quality on students were collected using a questionnaire. Based on the results, there was cough, throat irritation and psychological problems for students, especially those with asthma and respiratory problems. There were more symptoms during the summer and autumn. The life of the building, the use of natural ventilation and inadequate cooling devices are the main factor in increasing the concentration of indoor particles in the educational building. According to the result of sampling in the outside environment, the highest concentration of the particles occurred in summer and the lowest concentration in spring and winter. Due to the presence of natural ventilation in the spring and summer seasons, the trend of variation of the concentration inside the building was similar to the outside.

Evaluation of Multiple Organ Dysfunction Score (MODS) and the Sequential Organ Failure Assessment (SOFA) score as in-hospital outcome predictors among cases of hydrogen cyanamide exposure: a cross-sectional study

Dormex is widely used as a plant growth regulator in developing countries such as Egypt as well as worldwide. Despite the widespread use of Dormex, little is known about the exact mechanism of action and toxic profile. The current study aims to outline the factors that predict in-hospital outcome and the need for intensive care unit (ICU) admission among the patients who presented with acute hydrogen cyanamide exposure as well as to evaluate the roles of the Multiple Organ Dysfunction Score (MODS) and the Sequential Organ Failure Assessment (SOFA) score as unfavorable outcome predictors. This is a retrospective cross-sectional study including all cases diagnosed with acute hydrogen cyanamide exposure who presented to the Tanta Poison Control Center during the past 6 years (January 1, 2015-January 1, 2020). Patient data were collected in a case report form, including the history of exposure, clinical data, laboratory investigations, and radiologic studies. Four scoring systems were carried out upon presentation: the Glasgow Coma Scale, poison severity score, MODS, and SOFA score. Thirty-five patients were enrolled in the current study. Most of the presented cases were males exposed unintentionally in an occupational setting. The mean participant age was 34.1 ± 15.51 years. The most common presenting complaints were throat irritation in all cases, vomiting and hallucinations presented equally in 68.6%, and headache occurred in 51.4%, whereas skin and mucous membrane burn was present in 40% of cases. Patients showing one or more of the following criteria were expected to have an urgent need for ICU admission: MODS >3.5, SOFA >4.5, length of hospital stay >30 hours, prothrombin time >14.75 seconds, serum glutamic pyruvic transaminase >67.5 U/L, and serum glutamic oxaloacetic transaminase >58.5 U/L. When the length of hospital stay was combined with the four scoring systems, only MODS yielded a significant prediction. Study results indicate that MODS and SOFA scores are considered excellent outcome predictors; MODS is more accurate, specific, and treatment independent, whereas the use of the SOFA score is more feasible with simple cardiovascular function assessment.

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

PurposeThis 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.MethodsPatients 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.ResultsPatients (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%).ConclusionPatients 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

ENVIRONMENTAL IMPLICATIONS ON THE HEALTH AND BEHAVIOUR OF THE TRAFFIC FORCE

The police hold a unique position in the society; Traffic Wardens play a very significant role in controlling the traffic system especially in the metropolitan and surrounding areas despite several limitations. The traffic police have the task which is more vital in the recent past, due to enormous growth in the numbers of various kinds of automobiles and road use. Traffic is managed by traffic police, who spent two thirds of their duty hours amidst of polluted working environment. Environmental pollutants have various adverse health consequences from minor to most important harmful fetal effects like prenatal disorders, infant mortality, respiratory disorders, allergy, malignancies, cardiovascular disorders, increase in stress oxidative, endothelial dysfunction, mental disorders, and various other harmful effects. Present study focused on the environmental implications on the health and behavior of the traffic force in District Faisalabad. Multi-stage sampling technique was used for data collection, while random sampling technique was used at all stages. Sampled shows that traffic warden faced many environmental pollutions borne diseases i.e. cough (76.7%), breath difficulty (51.3%), wheezing (5.3%), Running Nose (7.3%), Throat Irritation (40.0%), Throat diseases (33.3%), skin diseases (30.7%), viral hepatitis (21.3%), Congestion (16.0%) etc. Key words: Pollution, Environment, Health, Behavior, Traffic force, Disorder