Machine learning enabled detection of COVID-19 pneumonia using exhaled breath analysis: a proof-of-concept study.

Detection of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) relies on real-time-reverse-transcriptase polymerase chain reaction (RT-PCR) on nasopharyngeal swabs. The false-negative rate of RT-PCR can be high when viral burden and infection is localized distally in the lower airways and lung parenchyma. An alternate safe, simple and accessible method for sampling the lower airways is needed to aid in the early and rapid diagnosis of COVID-19 pneumonia. In a prospective unblinded observational study, patients admitted with a positive RT-PCR and symptoms of SARS-CoV-2 infection were enrolled from three hospitals in Ontario, Canada. Healthy individuals or hospitalized patients with negative RT-PCR and without respiratory symptoms were enrolled into the control group. Breath samples were collected and analyzed by laser absorption spectroscopy (LAS) for volatile organic compounds (VOCs) and classified by machine learning (ML) approaches to identify unique LAS-spectra patterns (breathprints) for SARS-CoV-2. Of the 135 patients enrolled, 115 patients provided analyzable breath samples. Using LAS-breathprints to train ML classifier models resulted in an accuracy of 72.2%-81.7% in differentiating between SARS-CoV2 positive and negative groups. The performance was consistent across subgroups of different age, sex, body mass index, SARS-CoV-2 variants, time of disease onset and oxygen requirement. The overall performance was higher than compared to VOC-trained classifier model, which had an accuracy of 63%-74.7%. This study demonstrates that a ML-based breathprint model using LAS analysis of exhaled breath may be a valuable non-invasive method for studying the lower airways and detecting SARS-CoV-2 and other respiratory pathogens. The technology and the ML approach can be easily deployed in any setting with minimal training. This will greatly improve access and scalability to meet surge capacity; allow early and rapid detection to inform therapy; and offers great versatility in developing new classifier models quickly for future outbreaks.

Clinical characteristics and prognostic factors among hospitalized patients with substance use disorders: Findings from a retrospective cohort study of a Canadian inpatient addiction medicine service.

INTRODUCTION: Inpatient addiction medicine services (AMS) were developed in response to the growing needs of hospitalized individuals with substance use disorders (SUDs). AMS aim to enable timely initiation of pharmacologic treatment, build hospital capacity to support patients who use substances, and facilitate transition to community services. As an emerging service being adopted in hospitals across North America, the model of care, populations served, substance use trends, and clinical trajectory has not been widely described. This work aims to characterize patients accessing care through the AMS, establishing predictors for clinical trajectories in hospital including patient-initiated discharge (PID) and hospital re-admission. METHODS: Using a retrospective cohort design, we describe all patients seen by the AMS between 2018 and 2022 across four hospitals in Hamilton, Ontario. Patients seen by AMS were hospitalized and qualified for a SUD based on DSM-V criteria. The study used descriptive statistics to describe the cohort, where appropriate adjusted time-to-event survival models were constructed to identify predictors for hospital re-admission. RESULTS: Patients seen by the AMS (n = 695) frequently lacked access to primary care (47.0 %) and less than half (44.3 %) were receiving community addiction services on admission. The majority met criteria for opioid use disorder (OUD), with injecting being the primary consumption route (54.8 %). Patients exhibited high acuity, with 34.2 % requiring critical care measures. Provision of OAT substantially increased to 77.9 % of patients (29 % on admission). PID occurred in 17.8 % of patients and was significantly associated with an admitting diagnosis of suicidal ideation, infection, heart failure, and distinct substance use profiles including methamphetamine, fentanyl, and heroin use (p < 0.05). PID conferred a 66 % increased risk for re-admission (Hazard-Ratio: 1.66; 95 % CI: 1.08, 2.54; p = 0.02). CONCLUSION: Patients served by AMS primarily include individuals with OUD presenting with the associated medical complications and substantial deficits in the social determinants of health (e.g., high housing insecurity, poverty, and disability). PID occurs among 1 in 5 people and is associated with higher rates of re-admission. By identifying individuals at higher risk of adverse outcomes, these results provide an opportunity to improve outcomes in this high-risk, high-vulnerability population.

"They forgot about us": experiences of the COVID-19 pandemic among people deprived of housing in an urban centre in Ontario, Canada.

OBJECTIVES: People deprived of housing have been disproportionately affected by the COVID-19 pandemic and the public health mitigation measures implemented in response. Emerging evidence has shown the adverse health outcomes experienced by these communities due to SARS-CoV-2 infection; however, the voices of community members themselves have not been widely amplified in the published literature. METHODS: We conducted an interpretive qualitative study. People deprived of housing were involved in study development, recruitment, and data analysis. People deprived of housing or precariously housed were recruited during street outreach from June to July 2020. Participants completed one-on-one semi-structured interviews that were audio-recorded, transcribed, and analyzed thematically. RESULTS: Twenty-one participants were interviewed. Central to participants' experiences of the COVID-19 pandemic were descriptions of access to services, in terms of both changes in service availability and the reality of how accessible existing services were to the community, represented by the theme access. Four other themes were generated from our analysis and include feeling and being unheard, stripped of dignity, I've been broken, and strength and survival (with a subtheme, community care). CONCLUSION: Future emergency response efforts must meaningfully engage people deprived of housing in planning and decision-making in order to minimize adverse impacts of health emergencies and the associated public health responses. There needs to be more careful consideration of the unintended harmful impacts of public health measures implemented in response to pandemics.

RéSUMé: OBJECTIFS: Les personnes sans abri ont été démesurément affectées par la pandémie de COVID-19 et par les mesures sanitaires mises en œuvre en réponse à la pandémie. Des données probantes émergentes montrent les résultats sanitaires indésirables éprouvés par ces communautés en raison de l'infection par le SRAS-CoV-2, mais les voix des membres de ces communautés ne sont généralement pas amplifiées dans les articles publiés. MéTHODE: Nous avons mené une étude qualitative interprétative. Des personnes sans abri ont été mises à contribution dans l'élaboration de l'étude, le recrutement des participants et l'analyse des données. Des personnes sans abri ou au logement précaire ont été recrutées lors d'activités d'approche dans la rue en juin et juillet 2020. Elles se sont prêtées à des entretiens semi-directifs en tête à tête qui ont été enregistrés, transcrits, puis analysés par thèmes. RéSULTATS: Vingt et une personnes ont été interviewées. Leurs expériences de la pandémie de COVID-19 ont été fortement axées sur le thème de l'accès aux services, tant pour ce qui est des changements dans la disponibilité des services que de l'accessibilité réelle des services existants pour les membres de ces communautés. Quatre autres thèmes sont ressortis de notre analyse : le sentiment/le fait de ne pas être entendu, d'être dépouillé de sa dignité, d'avoir été brisé, et la force et la survie (et un thème secondaire : les soins de proximité). CONCLUSION: Les futurs efforts d'intervention d'urgence doivent inclure une véritable collaboration avec les personnes sans abri dans la planification et la prise de décisions afin de réduire les répercussions néfastes des urgences sanitaires et des mesures de santé publique connexes. Il faut examiner plus attentivement les effets pervers des mesures sanitaires mises en œuvre en réponse aux pandémies.

'It's so simple' Lessons from the margins: a qualitative study of patient experiences of a mobile health clinic in Hamilton, Ontario, Canada.

OBJECTIVE: Our study explored the experiences of clients of HAMSMaRT (Hamilton Social Medicine Response Team), a mobile health service, in the context of their experiences of the overall healthcare system. DESIGN: We conducted a qualitative study with reflexive thematic analysis. SETTING: HAMSMaRT is a mobile health service in Hamilton, Ontario Canada providing primary care, internal and addiction medicine and infectious diseases services. PARTICIPANTS: Eligible participants were clients of HAMSMaRT who could understand English to do the interview and at least 16 years of age. Fourteen clients of HAMSMaRT were interviewed. RESULTS: Our findings represented five themes. When the themes of people deserve care, from the margins to the centre, and improved and different access to the system are enacted, the model of care works, represented by the theme it works!. The way in which participants compared their experiences of HAMSMaRT to the mainstream healthcare system insinuated how simple it is, represented by the theme it's so simple. CONCLUSIONS: Our findings offer guidance to the broader healthcare system for walking from the rhetoric to practice of person-centred care.

Psychometric validation and testing of the 10-item pediatric daily chest-related electronic patient reported outcome (ePRO) diary.

BACKGROUND AND OBJECTIVE: The chest-related electronic patient reported outcome (ePRO) diary was recently developed to assess chest-related symptoms experienced by pediatric and adolescent populations during upper respiratory tract infections (URTI). The objective of this research was the psychometric evaluation of the chest-related ePRO diary in pediatric, adolescent and adult participants. METHODS: This non-interventional, psychometric validation study involved participants (N = 195; n = 42 6-8 years; n = 47 9-11 years; n = 55 12-17 years, n = 51 18+ years) completing the chest-related ePRO diary twice daily for 10 days while experiencing an acute URTI. Preliminary item-level performance and dimensionality results, along with consideration of previous qualitative findings, were used to inform item reduction decisions, the structure of the measure and scoring algorithm development. Subsequent analyses on the finalized measure included assessments of reliability (internal consistency and test-retest reliability), construct validity (convergent validity and known groups validity) and ability to detect change. Comparisons of findings were made between the different age groups as part of the analyses to assess the psychometric properties of the chest-related ePRO diary and to characterize potential differences in the symptom experience of children, adolescents, and adults. RESULTS: The measure demonstrated strong quality of completion and showed relatively similar trajectories of symptom scores over time within different age subgroups and good item response distribution properties. Exploratory factor analysis supported a one-factor solution in the total population and within age subgroups, and test-retest reliability of the measure was strong (Intra-class correlation: 0.843-0.894 between Visit 1 and Day 1). The measure also demonstrated strong construct validity through high correlations with relevant items on the Child Cold Symptom Questionnaire (CCSQ), strong known groups validity (with statistically significant differences between severity groups) and was responsive to change over time with change groups defined based on change on global items. CONCLUSION: The findings demonstrate that the chest-related ePRO diary provides a valid, reliable, responsive measure of chest congestion symptoms experienced with the common cold in pediatric and adolescent populations, and that only minor differences are present in the disease trajectory when comparing adults to younger participants, supporting the use of the measure in interventional studies.

Evidence of the Efficacy of Flurbiprofen 8.75 mg Lozenges for Patients Receiving Antibiotics for Laboratory-Confirmed Streptococcal Pharyngitis.

OBJECTIVES: To determine the efficacy of flurbiprofen 8.75 mg lozenges for patients with laboratory-confirmed streptococcal pharyngitis both before and concomitant with antibiotics. METHODS: This post hoc analysis comprised adult participants from 2 earlier randomized, double-blind, placebo-controlled studies evaluating the analgesic efficacy of flurbiprofen 8.75 mg lozenges in acute pharyngitis. Throat swabs were obtained to diagnose streptococcal infection. Prior to and 2 hours after each dose of study medication (flurbiprofen or placebo lozenges), patients rated 3 symptoms of acute pharyngitis (sore throat pain, difficulty swallowing, and swollen throat) using visual analogue scales. Appropriate antibiotic treatment was initiated when culture results were reported. Mean changes in each pharyngeal symptom were compared over the immediate 24 hours before and during the initial 24 hours of antibiotic treatment. RESULTS: Twenty-four patients provided both preantibiotic and concomitant antibiotic efficacy outcomes. Relief of throat pain was 93% greater in the flurbiprofen group than in the placebo group before antibiotic coadministration and 84% greater than placebo during antibiotic administration (both P < .05). Relief of difficulty swallowing was 71% greater in the flurbiprofen group than in the placebo before antibiotic administration (P = .16) and 107% greater during concomitant antibiotic administration (P = .04). Relief of the sensation of throat swelling was 295% greater with flurbiprofen than placebo before antibiotic administration (P = .008) and 70% greater during concomitant antibiotic administration (P = .06). For placebo-treated patients, relief from throat pain and difficulty swallowing were similar before and during antibiotic treatment (P > .05), indicating no benefit with antibiotic administration for these symptoms. No treatment-related discontinuations or serious adverse events were reported. CONCLUSIONS: Irrespective of antibiotic use, flurbiprofen 8.75 mg lozenges provide well-tolerated, effective relief of pharyngeal symptoms in patients with streptococcal infection. In the 24 hours after administration, antibiotics provide no relief of throat pain or difficulty swallowing beyond the topical demulcent effects of placebo lozenges.

"They're causing more harm than good": a qualitative study exploring racism in harm reduction through the experiences of racialized people who use drugs.

BACKGROUND: Increased opioid-related morbidity and mortality in racialized communities has highlighted the intersectional nature of the drug policy crisis. Given the racist evolution of the war on drugs and the harm reduction (HR) movement, the aim of this study is to explore racism within harm reduction services through the perspectives of our participants. METHODS: We conducted a qualitative descriptive study to explore the perspectives of racialized service users and providers on racism in the HR movement in the Greater Toronto and Hamilton Area (GTHA). Four racialized service users and four racialized service providers participated in semi-structured interviews that were audio-recorded, transcribed, and analysed thematically. RESULTS: Five themes related to racism in HR were generated: (1) whiteness of harm reduction as a barrier to accessing services, (2) diversifying HR workers as a step towards overcoming distrust, (3) drop-in spaces specific to Black, Indigenous, and people of colour are facilitators to accessing harm reduction, (4) lack of representation in HR-related promotional and educational campaigns, and (5) HR as a frontier for policing. CONCLUSIONS: Our findings suggest that structural and institutional racism are prevalent in HR services within the GTHA, in the form of colour-blind policies and practices that fail to address the intersectional nature of the drug policy crisis. There is a need for local HR organizations to critically reflect and act on their practices and policies, working with communities to become more equitable, inclusive, and accessible spaces for all people who use drugs.

Development and content validity testing of patient-reported outcome (PRO) items to assess chest congestion associated with the common cold for use in children and adolescents.

BACKGROUND: This article describes qualitative interviews conducted with children (aged 6-11), adolescents (aged 12-17), and adults with the common cold as well as parents/caregivers of the 6-8-year-old children. The aim was to support the refinement and content validity testing of patient-reported outcome (PRO) items assessing chest congestion that could be used as pediatric clinical trial endpoints. Feasibility and acceptability of administering the PRO items electronically on a hand-held touch-screen device were also evaluated. The sample included children aged 6-8 years (n = 14), 9-11 years (n = 13), adolescents aged 12-17 years (n = 12), and adults (n = 10), all of who had current (n = 38) or recent (n = 11) cold. Both concept elicitation (CE) and cognitive debriefing (CD) interviews were conducted with all of these participants, conducted over in two rounds. Ten parents/caregivers of participants aged 6-8 years were also interviewed (separately from their child) regarding how they thought their children would understand the items. The CE interviews explored the qualitative experience of having chest congestion and related symptoms of the common cold. Following their CE interview, participants completed draft items on an electronic patient-reported outcome (ePRO) device twice daily for 2-5 days prior to their CD interview. During the CD interview participants were asked about relevance, understanding and interpretation of the draft PRO items. Qualitative analysis of the interview data and descriptive analyses of the ePRO data were conducted following both rounds of interviews, with modifications to the items implemented following Round 1 and tested in Round 2. RESULTS: Eight symptoms were reported by children during concept elicitation. Findings from the child, adolescent, and adult/parent interviews supported revisions to the items and enabled the selection of the best performing items. The results provided evidence that the final items were well understood by participants and relevant to their experiences of chest congestion as part of a common cold. Findings also provide support for using the same items across age groups. CONCLUSIONS: The results of the CE and CD interviews provide evidence supporting the content validity of new PRO items assessing the experience of chest congestion symptoms associated with common cold experienced by children, adolescents, and adults.

Infectious diseases, comorbidities and outcomes in hospitalized people who inject drugs (PWID) infections in persons who inject drugs.

Injection drug use poses a public health challenge. Clinical experience indicates that people who inject drugs (PWID) are hospitalized frequently for infectious diseases, but little is known about outcomes when admitted. Charts were identified from local hospitals between 2013-2018 using consultation lists and hospital record searches. Included individuals injected drugs in the past six months and presented with infection. Charts were accessed using the hospital information system, undergoing primary and secondary reviews using Research Electronic Data Capture (REDCap). The Wilcoxon rank-sum test was used for comparisons between outcome categories. Categorical data were summarized as count and frequency, and compared using Fisher's exact test. Of 240 individuals, 33% were admitted to the intensive care unit, 36% underwent surgery, 12% left against medical advice (AMA), and 9% died. Infectious diagnoses included bacteremia (31%), abscess (29%), endocarditis (29%), cellulitis (20%), sepsis (10%), osteomyelitis (9%), septic arthritis (8%), pneumonia (7%), discitis (2%), meningitis/encephalitis (2%), or other (7%). Sixty-six percent had stable housing and 60% had a family physician. Fifty-four percent of patient-initiated discharges were seen in the emergency department within 30 days and 29% were readmitted. PWID are at risk for infections. Understanding their healthcare trajectory is essential to improve their care.

Sex-Specific Risk Factors and Health Disparity Among Hepatitis C Positive Patients Receiving Pharmacotherapy for Opioid Use Disorder: Findings From a Propensity Matched Analysis.

BACKGROUND: The incidence of opioid-related fatality has reached unparalleled levels across North America. Patients with comorbid hepatitis C virus (HCV) remain the most vulnerable and difficult to treat. Considering the unique challenges associated with this population, we aimed to re-examine the impact of HCV on response to medication assistant treatment for opioid use disorder and establish sex-specific risk factors affecting care. METHODS: This study employs a multi-center prospective cohort design, with 1-year follow-up. Patients aged ≥18, receiving methadone for opioid use disorder were recruited from a network of outpatient opioid addiction treatment centers across Southern Ontario, Canada. Patients with ≥50% positive opioid urine screens over 1 year of follow-up were classified as poor responders. The prognostic impact of HCV on response was established using a propensity score matched analysis. Sex-specific regression models were constructed to evaluate risk factors for treatment response. RESULTS: Among participants eligible for inclusion (n = 1234), HCV was prevalent in 25% (n = 307). HCV patients exhibited significantly higher rates of high-risk opioid consumption patterns 35.29% (standard deviation 0.478). Sex-specific examination revealed females with HCV incur a 2 times increased risk for high-risk opioid consumption behaviors (female odds ratio: 1.95, 95% confidence interval 1.23, 3.10; P = 0.01). CONCLUSIONS: Findings from this study establish the link between HCV and poor treatment response, with differentially higher risk among female patients. In light of the high potential for overdose among this population, concerted efforts are required for distinguishing the source for sex-based disparities, in addition to establishing trauma and gender informed treatment protocols.

The Second Heart Program-A multidisciplinary team supporting people who inject drugs with infective endocarditis: Protocol of a feasibility study.

INTRODUCTION: Infective endocarditis (IE) is a severe and highly prevalent infection among people who inject drugs (PWID). While short-term (30-day) outcomes are similar between PWID and non-PWID, the long-term outcomes among PWID after IE are poor, with 1-year mortality rates in excess of 25%. Novel clinical interventions are needed to address the unique needs of PWID with IE, including increasing access to substance use treatment and addressing structural barriers and social determinants of health. METHODS AND ANALYSIS: PWID with IE will be connected to a multidisciplinary team that will transition with them from hospital to the community. The six components of the Second Heart Team are: (1) peer support worker with lived experience, (2) systems navigator, (3) addiction medicine physician, (4) primary care physician, (5) infectious diseases specialist, (6) cardiovascular surgeon. A convergent mixed-methods study design will be used to test the feasibility of this intervention. We will concurrently collect quantitative and qualitative data and 'mix' at the interpretation stage of the study to answer our research questions. ETHICS AND DISSEMINATION: This study has been approved by the Hamilton Integrated Research Ethics Board (Project No. 7012). Results will be presented at national and international conferences and submitted for publication in a scientific journal. CLINICAL TRAIL REGISTRARION: Trial registration number: ISRCTN14968657 https://www.isrctn.com/ISRCTN14968657.

Hospital policy as a harm reduction intervention for people who use drugs.

Hospitals are a critical touchpoint for people who use drugs (PWUD). However, hospital policies, both formal and informal, can have a detrimental impact on PWUD in acute care settings. Introducing new policies, or revising existing policies that inadvertently harm or stigmatize PWUD while hospitalized, could be an effective harm reduction intervention for this high-risk population. This paper explores seven areas where institutional policy change could improve the hospital experience of PWUD: (1) use of nonprescribed substances in hospital, (2) supporting inpatient addiction consultation services (3) in-hospital supervised consumption spaces (4) supply and distribution of safe drug use equipment and naloxone, (5) role of security services and personal searches, (6) use of hospital restrictions, and (7) involvement of PWUD in policy development.

Efficacy of Triprolidine in the Treatment of Temporary Sleep Disturbance.

Triprolidine, a first-generation antihistamine for allergic rhinitis, has a shorter half-life and fewer persistent effects relative to other antihistamines and may be useful in the treatment of temporary sleep disturbance. Patients aged ≥18 years old were randomized 1:1:1 to receive either triprolidine 2.5 mg (n = 65), triprolidine 5 mg (n = 66), or placebo (n = 67) on 3 consecutive nights. Sleep disturbance index was monitored via wrist actimeter. Subjective measures were assessed via diary card. Triprolidine 2.5 mg had a significantly lower sleep disturbance index versus placebo on night 1 (P = .02); however, when adjusted for outliers, sleep disturbance index did not significantly differ between either dose of triprolidine versus placebo on night 1. Adjusted sleep disturbance index was significantly lower with triprolidine 2.5 and 5 mg versus placebo on night 3 (P = .0017 and P = .011, respectively) and for the mean of all 3 nights (P = .01 and P = .015, respectively). Sleep latency was significantly improved for triprolidine 2.5 mg versus placebo on nights 2 and 3 and for the mean of all 3 nights and for triprolidine 5 mg versus placebo for the mean of all 3 nights. Subjective measures showed those on both doses of triprolidine felt more refreshed on awakening versus placebo for the mean of all 3 nights, with no increase in daytime sleepiness. The frequency of adverse events was similar across groups. The optimum dose of triprolidine for treatment of temporary sleep disturbance was 2.5 mg. There were improvements in both objective and subjective measures of sleep quality versus placebo, with no safety concerns raised.

Peer support workers as a bridge: a qualitative study exploring the role of peer support workers in the care of people who use drugs during and after hospitalization.

BACKGROUND: To describe the key qualities and unique roles of peer support workers in the care of people who inject drugs during and after hospitalization. METHODS: We conducted a qualitative study. Key stakeholders were recruited including: people who use drugs who had been hospitalized, healthcare team members, peer support workers, and employers of peer support workers. Data were collected from 2019 to 2020 using semi-structured interviews that were audio-recorded, transcribed, and analyzed thematically. RESULTS: Fourteen participants were interviewed: 6 people who use drugs who had been hospitalized, 5 healthcare team members, 2 peer support workers, and 1 employer of peer support workers. At the core of the data was the notion of peer workers acting as a bridge. We found four themes that related to functions of this bridge: overcoming system barriers, advocacy, navigating transitions within the healthcare system, and restoring trust between HCPs and PWUD. We found two themes for building a strong bridge and making the role of a peer support worker function effectively (training and mentorship, and establishing boundaries). We found three themes involving characteristics of an effective peer worker (intrinsic qualities, contributions of shared experiences, and personal stability). CONCLUSION: Peer support workers are highly valued by both people who use drugs and members of the healthcare team. Peer support workers act as a bridge between patients and healthcare providers and are critical in establishing trust, easing transitions in care, and providing unique supports to people who use drugs during and after hospitalization.

"When you first walk out the gates where do [you] go?": Barriers and opportunities to achieving continuity of health care at the time of release from a provincial jail in Ontario.

We aimed to explore continuity of health care and health barriers, facilitators, and opportunities for people at the time of release from a provincial correctional facility in Ontario, Canada. We conducted focus groups in community-based organizations in a city in Ontario, Canada: a men's homeless shelter, a mental health service organization, and a social service agency with programs for people with substance use disorders. We included adults who spoke English well enough to participate in the discussion and who had been released from the provincial correctional facility in the previous year. We conducted three focus groups with 18 total participants. Participants had complex health needs on release, including ongoing physical and psychological impacts of time in custody. They identified lack of access to high quality health care; lack of housing, employment, social services, and social supports; and discrimination on the basis of incarceration history as barriers to health on release. Access to health care, housing, social services, and social supports all facilitated health on release. To address health needs on release, participants suggested providing health information in jail, improving discharge planning, and developing accessible clinics in the community. This pilot study identified opportunities to support health at the time of release from jail, including delivery of programs in jail, linkage with and development of programs in the community, and efforts to support structural changes to prevent and address discrimination. These data will inform ongoing work to support health and continuity of care on release from a provincial correctional facility.

Determination of the Permeation and Penetration of Flurbiprofen into Cadaveric Human Pharynx Tissue.

OBJECTIVE: Flurbiprofen 8.75 mg spray and lozenge have a rapid onset of action for sore throat relief, suggesting local action, although tissue penetration and the mechanism of local relief have not been determined. This investigation aimed to quantify the permeation and penetration of flurbiprofen, applied as local pharmaceutical forms, into full-thickness cadaveric human mucosal pharynx tissue, representing the clinical scenario as far as possible. METHODS: A validated high-performance liquid chromatography method quantified the permeation and penetration of flurbiprofen (spray and lozenge formulations) into human cadaveric pharynx tissue using a micro Franz cell model mimicking physiological and anatomical conditions. Full-thickness mucosal pharynx tissue, consisting of oral epithelium, basement membrane, and lamina propria, was utilized to imitate the in vivo setting. Flurbiprofen was analyzed on the surface of the pharynx tissue, within the pharynx tissue and in receiver fluid, over 60 mins. RESULTS: Flurbiprofen was detected in receiver fluid from 10 mins following spray application and was quantifiable from 20 mins. Flurbiprofen from lozenge was detected from 10 mins and was above the limit of quantitation in receiver fluid from 40 mins. Flurbiprofen recovered from the surface of the pharynx tissue was 24.45% and 8.48% of applied dose for spray and lozenge, respectively. Flurbiprofen recovered within pharynx tissue was 46.50% and 54.65% of applied dose for spray and lozenge, respectively. For flurbiprofen lozenge, recovery within pharynx tissue was 6-fold higher relative to recovery from the pharynx tissue surface. CONCLUSION: Flurbiprofen from spray and lozenge formulations penetrated human cadaveric pharynx tissue, indicating that flurbiprofen can reach all layers of the pharynx mucosal tissue, including the underlying lamina propria, which contains blood vessels and nerve fibers that contribute to pain during sore throat. This suggests that flurbiprofen may have a local mechanism of action for sore throat, although this has yet to be determined.

Bioavailability of Triprolidine as a Single Agent or in Combination With Pseudoephedrine: A Randomized, Open-Label Crossover Study in Healthy Volunteers.

Antihistamines have been in clinical use for more than 70 years to treat allergic and nonallergic symptoms including relief from cold and flu symptoms. Despite their widespread use, pharmacokinetic (PK) data are sparse for older, first-generation antihistamines. This phase 1 single-center open-label, randomized, single-dose, 3-way crossover trial evaluated the PK profiles of 2 doses of film-coated triprolidine caplets (2.5 and 5 mg) compared with a reference combination tablet (triprolidine 2.5 mg + pseudoephedrine 60 mg) in 24 healthy adults. Blood samples were collected predose and at specified intervals across a 24-hour period after administration, and triprolidine was quantified using liquid chromatography-tandem mass spectrometry. Maximum plasma concentration of triprolidine for the 2.5 mg and dose-normalized 5 mg single-agent tablets were comparable (8.4 versus 7.1 ng/mL, respectively) and higher for the combination tablet (9.5 ng/mL). PK parameters, including time to maximum plasma concentration (∼1.5 hours) and elimination half-life (∼4 hours), were comparable between the 3 treatment arms. The safety profile of this sedating antihistamine was as expected; however, adverse effects were reported in a markedly higher proportion of women than men. There were no significant sex differences in any of the measured PK parameters.