Case Report: Profound Anemia in a 2-Year-Old Boy Associated with a Leech in the Oropharynx.

A 2-year-old boy presented to Kapsowar Mission Hospital in Kenya with a history of general tiredness associated with mild, unilateral epistaxis and one episode of hematemesis. On admission, he had a hemoglobin value of 3.5 g/dL, with a white cell count of 20.6 × 109/L. The child was examined by the physician on call, with no source of bleeding found. Later that day, after a local physician noted that the presentation could be due to an unrecognized leech infestation, a deep examination of the oropharynx was performed with a laryngoscope and revealed a leech attached deep in the oropharynx. The anesthetist visualized the leech with a laryngoscope and removed it with Magill forceps. After the procedure and blood transfusion, the child's hemoglobin level improved to 10.4 g/dL, and on the following day, the child was much improved in energy and was playing outside. He was discharged home on iron supplements and made a full recovery.

Effect of oropharyngeal colostrum therapy on neonatal sepsis in preterm neonates: A systematic review and meta-analysis.

Various studies have shown that oropharyngeal colostrum application (OPCA) is beneficial to preterm neonates. We performed a systematic review and meta-analysis to assess whether OPCA reduces the incidence of culture-proven neonatal sepsis in preterm neonates. Randomized controlled trials comparing OPCA with placebo or standard care in preterm neonates were included. Medline, Embase, Web of Science, Cumulated Index to Nursing and Allied Health Literature, Scopus, and CENTRAL were searched for studies published up to June 15, 2023. We used the Cochrane Risk of Bias tool, version 2, for risk of bias assessment, the random-effects model (RevMan 5.4) for meta-analysis, and Gradepro software for assessing the certainty of evidence. Twenty-one studies involving 2393 participants were included in this meta-analysis. Four studies had a low risk of bias, whereas seven had a high risk. Oropharyngeal colostrum significantly reduced the incidence of culture-proven sepsis (18 studies, 1990 neonates, risk ratio [RR]: 0.78, 95% confidence interval [95% CI]: 0.65, 0.94), mortality (18 studies, 2117 neonates, RR: 0.73, 95% CI: 0.59, 0.90), necrotizing enterocolitis (NEC) (17 studies, 1692 neonates, RR: 0.59, 95% CI: 0.43, 0.82), feeding intolerance episodes (four studies, 445 neonates, RR: 0.59, 95% CI: 0.38, 0.92), and the time to full enteral feeding (19 studies, 2142 neonates, mean difference: -2 to 21 days, 95% CI: -3.44, -0.99 days). There was no reduction in intraventricular hemorrhage, retinopathy of prematurity, bronchopulmonary dysplasia, ventilator-associated pneumonia, neurodevelopmental abnormalities, hospital stay duration, time to full oral feeding, weight at discharge, pneumonia, and duration of antibiotic therapy. The certainty of the evidence was high for the outcomes of culture-positive sepsis and mortality, moderate for NEC, low for time to full enteral feeding, and very low for feeding intolerance. OPCA reduces culture-positive sepsis and mortality (high certainty), NEC (moderate certainty), and time to full enteral feeding (low certainty) in preterm neonates. However, scarcity of data from extremely premature infants limits the generalizability of these results to this population.

Orofacial Myofunctional Therapy for Obstructive Sleep Apnea: A Systematic Review and Meta-Analysis.

OBJECTIVE: Orofacial myofunctional therapy (OMT) is an alternative form of treatment of obstructive sleep apnea (OSA), that incorporates various exercises to optimize tongue placement and increase oropharyngeal tone. The objective of this systematic review and meta-analysis is to determine the efficacy of OMT in OSA patients. DATA SOURCES: PubMed/Medline, EMBASE, Cochrane, Web of Science. REVIEW METHODS: Using PRISMA guidelines, a directed search strategy was performed for randomized control trials (RCTs) published prior to March 24, 2023, featuring 10+ patients with OSA undergoing mono-therapeutic OMT. The primary outcome of interest was apnea-hypopnea index (AHI). Secondary outcomes included subjective sleepiness, sleep-related quality-of-life, and snoring frequency. RESULTS: Of the 1244 abstracts that were identified, 7 RCTs involving 310 patients met inclusion criteria. Adult OMT patients had a statistically significant improvement in AHI (MD -10.2; 95% CI, -15.6, -4.8, p < 0.05), subjective sleepiness (Epworth Sleepiness Scale; MD -5.66; 95% CI, -6.82, -4.5, p < 0.05), sleep-related quality-of-life (Pittsburgh Sleep Quality Index; MD -3.00; 95% CI, -4.52, -1.49, p < 0.05), and minimum oxygen saturation (MD 2.71; 95% CI, 0.23, 5.18, p < 0.05) when compared with sham OMT or no therapy. Within the single RCT featuring pediatric OMT patients, patients had poor compliance (<50%) and did not show any improvements in AHI, minimum oxygen saturation, or snoring frequency. CONCLUSION: OMT may provide a reasonable alternative for OSA patients who cannot tolerate CPAP or other more established treatment options. OMT benefits appear limited in children due to poor compliance. More studies are required to evaluate compliance and the long-term effects of OMT on OSA outcomes. LEVEL OF EVIDENCE: 1 Laryngoscope, 134:480-495, 2024.

Colostrum immunotherapy and length of hospital stay in preterm infants: an intervention study / Imunoterapia de colostro e tempo de internamento de prematuros: estudo de intervenção

Abstract Objectives: to evaluate the effect of oropharyngeal colostrum immunotherapy on the length of hospital stay in preterm newborns with very low birth weight. Methods: interventional ambispective study, which consisted of eight daily administrations of 0.2 ml (four drops) of colostrum, totaling up to 56 syringes (for up to seven days). The control was historic. The main independent variable: length of hospital stay (days). Survival analysis was performed using the Kaplan-Meier Method and the survival effect was estimated - Log Rank Test (Mantel-Cox) and Breslow Test (Generalized Wilcoxon). A significance level of 5% was adopted. Results: of the 109 mother/child pairs, 56 were part of the treatment and 53 were part of the control group. There was no association between oropharyngeal colostrum immunotherapy and length of stay for preterm newborns with very low birth weight in the general sample. However, after stratification, a shorter hospital stay (42 versus 51 days, HR= 1.78, CI95%=1.02-3.09, p=0.04) was demonstrated among premature infants with ≥28 gestational weeks undergoing oropharyngeal colostrum immunotherapy. Conclusions: we found an association between oropharyngeal colostrum immunotherapy and shorter median length of hospital stay in the subgroup of premature infants ≥ 28 weeks of gestational age, but we did not find significant differences in those <28 weeks.

Resumo Objetivos: avaliar o efeito da imunoterapia orofaríngea de colostro no tempo de internamento hospitalar de recém-nascidos pré-termos de muito baixo peso. Métodos: estudo de intervenção, ambispectivo, que consistiu em oito administrações diárias de 0,2 ml (quatro gotas) de colostro, totalizando até 56 seringas (por até sete dias). O controle foi histórico. A variável independente principal: tempo de permanência hospitalar (dias). Realizada análise de sobrevivência pelo Método de Kaplan-Meier e estimado o efeito da sobrevida - Teste de Log Rank (Mantel-Cox) e Teste de Breslow (Wilcoxon Generalizado). Adotou-se o nível de significância de 5%. Resultados: das 109 duplas mães/filho, 56 fizeram parte da análise do grupo tratamento e 53 do controle. Não houve associação entre imunoterapia orofaríngea de colostro e tempo de internamento de recém-nascidos pré-termos de muito baixo peso na amostra geral. Após estratificação demonstrou-se menor tempo de permanência hospitalar (43 versus 51 dias, HR=1,78, IC95%= 1,02-3,09, p=0,04) entre os prematuros com ≥28 semanas gestacionais submetidos a imunoterapia orofaríngea de colostro. Conclusões: encontrou-se associação entre imunoterapia orofaríngea de colostro e menor mediana de tempo de internamento hospitalar no subgrupo de prematuros ≥ 28 semanas de idade gestacional, porém não foram encontradas diferenças significativas naqueles < 28 semanas.

Oropharyngeal colostrum administration in neonates with gastroschisis: a randomized clinical trial.

OBJECTIVE: To evaluate the effect of colostrum therapy on days to start a suckling diet in newborns diagnosed with simple gastroschisis. METHODS: Randomized clinical trial with newborns diagnosed with simple gastroschisis at a federal hospital in Rio de Janeiro who were randomized to receive oropharyngeal administration of 0.2mL of colostrum or a "sham procedure" during the first 3 days of life. The analysis included clinical outcomes such as days without food, days with parenteral feeding, days until the start of enteral feeding, days to reach complete enteral feeding, sepsis and length of hospital stay. RESULTS: The onset of oral feeding (suction) in patients with simple gastroschisis in both groups occurred at a median of 15 days. CONCLUSION: The present study showed that there were no significant differences in the use of colostrum therapy and the number of days to the start of enteral feeding and suction diet between groups of newborns with simple gastroschisis.

The Use of Traditional Chinese Medicine in Patients with Oral, Oropharynx, Nasopharynx, and Hypopharynx Cancers: A Retrospective Longitudinal Cohort Study in Taiwan.

INTRODUCTION: Given the prevalent use of tobacco and betel nut in the Taiwanese community, an increase risk of oral, oropharynx, and hypopharynx cancers (head and neck cancers) is apparent. The use of Traditional Chinese Medicine (TCM) and acupuncture is both common and conveniently accessible in Taiwan, with treatments being financially supported by the National Health Insurance (NHI). This study aims to investigate the use of TCM in head and neck cancers in Taiwan through a longitudinal cohort study. METHODS: The Taiwan National Health Insurance Research Database (NHIRD) was utilized in order to conduct this study. The study populations consisted of oral, oropharynx, nasopharynx, and hypopharynx cancers (head and neck cancer) patients in 2002, which were then followed up until 2007 in regards to TCM use, until 2013 in regards to acupuncture use and until 2014 for all-cause mortality. Patients were divided into 4 groups. Common symptoms, Chinese herbs and formula used, TCM visits and 5 and 12 years all-cause mortality were analyzed. RESULTS: The use of TCM was increased in the second to fourth-year post-diagnosis. TCM use in nasopharynx cancer patients was higher compared to other cancers. The number of TCM visits per patient was increased post-diagnosis. The findings suggest a non-significant reduction in 5 and 12 years all-cause mortality between TCM II and CON II groups. CONCLUSION: The use of TCM in new patients suffering from head and neck cancers was increased in close proximity to the cancer diagnosis. The relation between TCM use and mortality of head and neck cancer should be investigated through larger scale studies.

Impact of Oropharyngeal Administration of Colostrum in Preterm Newborns' Oral Microbiome.

The initial colonization of the human microbiota is of paramount importance. In this context, the oropharyngeal administration of colostrum is a safe, viable, and well-tolerated practice even by the smallest preterm infants. Therefore, this study evaluated the effects of oropharyngeal administration of colostrum on the establishment of preterm infants' oral microbiota. A longitudinal observational study was carried out with 20 premature neonates, divided into two groups: one receiving the protocol (Oropharyngeal Administration of Colostrum; OAC) and the other one receiving Standard Caare (SC). Saliva samples were collected from the newborns weekly during the study period (from the day of birth until the 21st day of life) for analysis of oral microbiota through 16S rRNA gene sequencing. We observed that the colonization of the oral microbiota of preterm newborns preseanted a higher relative abundance of Staphylococcus on the 7th day of life, mainly in the OAC group. Additionally, an increased abundance of Bifidobacterium and Bacteroides was observed in the OAC group at the first week of life. Regarding alpha and beta diversity, time was a key factor in the oral modulation of both groups, showing how dynamic this environment is in early life.

Clinical practice guideline for the prevention of oral and oropharyngeal mucositis in pediatric cancer and hematopoietic stem cell transplant patients: 2021 update.

PURPOSE: To update the 2015 clinical practice guideline for the prevention of oral mucositis in pediatric cancer or hematopoietic stem cell transplant (HSCT) patients. METHODS: We performed seven systematic reviews of mucositis prevention. Three reviews included randomized controlled trials (RCTs) conducted in pediatric and adult patients evaluating cryotherapy, keratinocyte growth factor (KGF) or photobiomodulation therapy with a focus on efficacy. Three reviews included studies of any design conducted in pediatric patients evaluating these same interventions with a focus on adverse events and feasibility. One review included all RCTs of any intervention for mucositis prevention in pediatric patients. Primary outcome was severe oral mucositis. RESULTS: We included 107 unique studies of cryotherapy (22 RCTs and 4 pediatric studies); KGF (15 RCTs and 12 pediatric studies); photobiomodulation therapy (29 RCTs and 8 pediatric studies) and any intervention (31 pediatric RCTs). Effects on severe mucositis reduction from RCTs were cryotherapy risk ratio (RR) 0.49 and 95% confidence interval (CI) 0.31-0.76; palifermin RR 0.81 and 95% CI 0.69-0.95 and photobiomodulation therapy RR 0.40 and 95% CI 0.27-0.60. Cryotherapy was not feasible in young children while photobiomodulation therapy was feasible across age groups. Palifermin was associated with adverse effects. CONCLUSIONS: Cryotherapy should be used for older cooperative pediatric patients who will receive short infusions of melphalan or 5-fluorouracil. Intraoral photobiomodulation therapy (620-750 nm spectrum) should be used in pediatric patients undergoing autologous or allogeneic HSCT and for pediatric head and neck carcinoma patients undergoing radiotherapy. Palifermin should not be used routinely in pediatric cancer or HSCT patients.

Drug-Induced Sleep Endoscopy and Hypoglossal Nerve Stimulation Outcomes: A Multicenter Cohort Study.

OBJECTIVES/HYPOTHESIS: To determine the association between findings of blinded reviews of preoperative drug-induced sleep endoscopy (DISE) and outcomes of hypoglossal nerve stimulation (HNS) for obstructive sleep apnea (OSA). STUDY DESIGN: Cohort study. METHODS: A retrospective, multicenter cohort study of 343 adults who underwent treatment of OSA with HNS from 10 academic medical centers was performed. Preoperative DISE videos were scored by four blinded reviewers using the VOTE Classification and evaluation of a possible primary structure contributing to airway obstruction. Consensus DISE findings were examined for an association with surgical outcomes based on therapy titration polysomnogram (tPSG). Treatment response was defined by a decrease of ≥50% in the apnea-hypopnea index (AHI) to <15 events/hour. RESULTS: Study participants (76% male, 60.4 ± 11.0 years old) had a body mass index of 29.2 ± 3.6 kg/m2 . AHI decreased (35.6 ± 15.2 to 11.0 ± 14.1 events/hour; P < .001) on the tPSG, with a 72.6% response rate. Complete palate obstruction (vs. none) was associated with the greatest difference in AHI improvement (-26.8 ± 14.9 vs. -19.2 ± 12.8, P = .02). Complete (vs. partial/none) tongue-related obstruction was associated with increased odds of treatment response (78% vs. 68%, P = .043). Complete (vs. partial/none) oropharyngeal lateral wall-related obstruction was associated with lower odds of surgical response (58% vs. 74%, P = .042). CONCLUSIONS: The DISE finding of primary tongue contribution to airway obstruction was associated with better outcomes, whereas the opposite was true for the oropharyngeal lateral walls. This study suggests that the role for DISE in counseling candidates for HNS extends beyond solely for excluding complete concentric collapse related to the velum. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:1676-1682, 2021.

The Effect of Lateral Pharyngeal Collapse Patterns on Therapy Response in Upper Airway Stimulation Surgery.

OBJECTIVES: Obstructive sleep apnea (OSA) is characterized by repeated upper airway collapse while sleeping which leads to intermittent hypoxemia. Upper airway stimulation (UAS) is a commonly practiced modality for treating OSA in patients who cannot tolerate, or do not benefit from, positive airway pressure (PAP). The purpose of this study is to identify the effect of lateral pharyngeal collapse patterns on therapy response in UAS. METHODS: A retrospective cohort study from a single, tertiary-care academic center was performed. Patients who underwent UAS between October 2016 and July 2019 were identified and analyzed. Drug-induced Sleep Endoscopy (DISE) outcomes between Apnea-Hypopnea Index (AHI) responders and AHI non-responders were compared. Those with complete concentric collapse at the velopharynx were not candidates for UAS. RESULTS: About 95 patients that underwent UAS were included in this study. Pre- to Post-UAS demonstrated significant improvements in Epworth Sleepiness Scale (12.0 vs 4.0, P = .001), AHI (29.8 vs 5.4, P < .001) and minimum oxygen saturation (79% vs 83%, P < .001). No DISE findings significantly predicted AHI response after UAS. Specifically, multiple types of lateral pharyngeal collapse patterns did not adversely effect change in AHI or AHI response rate. CONCLUSION: Demonstration of lateral pharyngeal collapse on DISE, in the absence of complete concentric velopharyngeal obstruction, does not appear to adversely affect AHI outcomes in UAS patients. LEVEL OF EVIDENCE: VI.

The Utility of the Maxillary Heuwieser for Oropharyngeal Foreign Body Removal Under Nebulized Local Anesthesia: A Case Series.

We describe a novel and safe use of existing instrumentation in the removal of select foreign bodies in the upper aerodigestive tract to minimize health-care costs. A retrospective review of 4 cases involving visualized upper aerodigestive tract foreign bodies were identified via flexible laryngoscopy and extracted under local anesthesia from 2016 to 2018. All 4 patients were not in any airway distress and underwent successful removal of the foreign body, which included 2 fishbones, a sewing pin, and a wire bristle with a maxillary Heuwieser or giraffe instrument under flexible laryngoscopy visualizing using local anesthesia without complications. No foreign bodies were dislodged. The use of a maxillary Heuwieser and flexible laryngoscopy visualization is safe, allows for removal of otherwise difficult to reach foreign bodies at the bedside, improving patient comfort, obviates the need for general anesthesia to the patient, and minimizes health-care costs.

Oropharyngeal colostrum therapy reduces the incidence of ventilator-associated pneumonia in very low birth weight infants: a systematic review and meta-analysis.

BACKGROUND: Oropharyngeal colostrum (OC) is a novel feeding strategy to prevent complications of prematurity. A meta-analysis was conducted to investigate whether very low birth weight infants (VLBWs) can benefit from OC. METHODS: Randomized controlled trials (RCTs) were searched from Embase, PubMed, Web of Science, and Cochrane Central Register of Controlled Trials from the date of inception until May 2019. RCTs were eligible if they used OC therapy on VLBW infants. The primary outcomes included ventilator-associated pneumonia (VAP), necrotizing enterocolitis (NEC), bronchopulmonary dysplasia (BPD), late-onset sepsis, and death. The secondary outcomes included the time of full enteral feeding and the length of stay. RESULTS: Eight RCTs involving 682 patients (OC group: 332; non-OC group: 350) were included in the meta-analysis. The results suggested that OC was associated with a significantly reduced incidence of VAP [odds ratio (OR) = 0.39, 95% confidence interval (CI): 0.17-0.88, P = 0.02] and full enteral feeding days (mean difference = -2.66, 95% CI: -4.51 to -0.80, P = 0.005), a potential significance of NEC (OR = 0.51, 95% CI: 0.26-0.99, P = 0.05), a trend toward downregulating mortality (OR = 0.60, 95% CI: 0.34-1.08, P = 0.09) and proven sepsis (OR = 0.64, 95% CI: 0.40-1.01, P = 0.06). CONCLUSIONS: OC could significantly reduce the occurrence of VAP, and consequently, its routine use should be considered for VLBWs to prevent infectious diseases. IMPACT: OC significantly reduces the occurrence of VAP and NEC in VLBW infants. OC may reduce the incidence of VAP and NEC by increasing IgA levels. Early OC therapy for mechanical ventilation of low-weight infants may prevent the occurrence of VAP.

Myofunctional therapy (oropharyngeal exercises) for obstructive sleep apnoea.

BACKGROUND: Obstructive sleep apnoea (OSA) is a syndrome characterised by episodes of apnoea (complete cessation of breathing) or hypopnoea (insufficient breathing) during sleep. Classical symptoms of the disease - such as snoring, unsatisfactory rest and daytime sleepiness - are experienced mainly by men; women report more unspecific symptoms such as low energy or fatigue, tiredness, initial insomnia and morning headaches. OSA is associated with an increased risk of occupational injuries, metabolic diseases, cardiovascular diseases, mortality, and being involved in traffic accidents. Continuous positive airway pressure (CPAP) - delivered by a machine which uses a hose and mask or nosepiece to deliver constant and steady air pressure- is considered the first treatment option for most people with OSA. However, adherence to treatment is often suboptimal. Myofunctional therapy could be an alternative for many patients. Myofunctional therapy consists of combinations of oropharyngeal exercises - i.e. mouth and throat exercises. These combinations typically include both isotonic and isometric exercises involving several muscles and areas of the mouth, pharynx and upper respiratory tract, to work on functions such as speaking, breathing, blowing, sucking, chewing and swallowing. OBJECTIVES: To evaluate the benefits and harms of myofunctional therapy (oropharyngeal exercises) for the treatment of obstructive sleep apnoea. SEARCH METHODS: We identified randomised controlled trials (RCTs) from the Cochrane Airways Trials Register (date of last search 1 May 2020). We found other trials at web-based clinical trials registers. SELECTION CRITERIA: We included RCTs that recruited adults and children with a diagnosis of OSA. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We assessed our confidence in the evidence by using GRADE recommendations. Primary outcomes were daytime sleepiness, morbidity and mortality. MAIN RESULTS: We found nine studies eligible for inclusion in this review and nine ongoing studies. The nine included RCTs analysed a total of 347 participants, 69 of them women and 13 children. The adults' mean ages ranged from 46 to 51, daytime sleepiness scores from eight to 14, and severity of the condition from mild to severe OSA. The studies' duration ranged from two to four months. None of the studies assessed accidents, cardiovascular diseases or mortality outcomes. We sought data about adverse events, but none of the included studies reported these. In adults, compared to sham therapy, myofunctional therapy: probably reduces daytime sleepiness (Epworth Sleepiness Scale (ESS), MD (mean difference) -4.52 points, 95% Confidence Interval (CI) -6.67 to -2.36; two studies, 82 participants; moderate-certainty evidence); may increase sleep quality (MD -3.90 points, 95% CI -6.31 to -1.49; one study, 31 participants; low-certainty evidence); may result in a large reduction in Apnoea-Hypopnoea Index (AHI, MD -13.20 points, 95% CI -18.48 to -7.93; two studies, 82 participants; low-certainty evidence); may have little to no effect in reduction of snoring frequency but the evidence is very uncertain (Standardised Mean Difference (SMD) -0.53 points, 95% CI -1.03 to -0.03; two studies, 67 participants; very low-certainty evidence); and probably reduces subjective snoring intensity slightly (MD -1.9 points, 95% CI -3.69 to -0.11 one study, 51 participants; moderate-certainty evidence). Compared to waiting list, myofunctional therapy may: reduce daytime sleepiness (ESS, change from baseline MD -3.00 points, 95% CI -5.47 to -0.53; one study, 25 participants; low-certainty evidence); result in little to no difference in sleep quality (MD -0.70 points, 95% CI -2.01 to 0.61; one study, 25 participants; low-certainty evidence); and reduce AHI (MD -6.20 points, 95% CI -11.94 to -0.46; one study, 25 participants; low-certainty evidence). Compared to CPAP, myofunctional therapy may result in little to no difference in daytime sleepiness (MD 0.30 points, 95% CI -1.65 to 2.25; one study, 54 participants; low-certainty evidence); and may increase AHI (MD 9.60 points, 95% CI 2.46 to 16.74; one study, 54 participants; low-certainty evidence). Compared to CPAP plus myofunctional therapy, myofunctional therapy alone may result in little to no difference in daytime sleepiness (MD 0.20 points, 95% CI -2.56 to 2.96; one study, 49 participants; low-certainty evidence) and may increase AHI (MD 10.50 points, 95% CI 3.43 to 17.57; one study, 49 participants; low-certainty evidence). Compared to respiratory exercises plus nasal dilator strip, myofunctional therapy may result in little to no difference in daytime sleepiness (MD 0.20 points, 95% CI -2.46 to 2.86; one study, 58 participants; low-certainty evidence); probably increases sleep quality slightly (-1.94 points, 95% CI -3.17 to -0.72; two studies, 97 participants; moderate-certainty evidence); and may result in little to no difference in AHI (MD -3.80 points, 95% CI -9.05 to 1.45; one study, 58 participants; low-certainty evidence). Compared to standard medical treatment, myofunctional therapy may reduce daytime sleepiness (MD -6.40 points, 95% CI -9.82 to -2.98; one study, 26 participants; low-certainty evidence) and may increase sleep quality (MD -3.10 points, 95% CI -5.12 to -1.08; one study, 26 participants; low-certainty evidence). In children, compared to nasal washing alone, myofunctional therapy and nasal washing may result in little to no difference in AHI (MD 3.00, 95% CI -0.26 to 6.26; one study, 13 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: Compared to sham therapy, myofunctional therapy probably reduces daytime sleepiness and may increase sleep quality in the short term. The certainty of the evidence for all comparisons ranges from moderate to very low, mainly due to lack of blinding of the assessors of subjective outcomes, incomplete outcome data and imprecision. More studies are needed. In future studies, outcome assessors should be blinded. New trials should recruit more participants, including more women and children, and have longer treatment and follow-up periods.

Colostrum oropharyngeal immunotherapy for very low birth weight preterm infants: protocol of an intervention study.

BACKGROUND: The oropharyngeal colostrum administration protocol to treat premature newborns is a possible and plausible strategy in neonatal health services, since the immunoprotective components of colostrum can be absorbed by the lymphoid tissues of the oropharynx. In this context, this study aims to describe the implementation of oropharyngeal colostrum immunotherapy in very low birth weight preterm newborns in a neonatal unit, as well as to test an algorithm in a public hospital. METHODS: The protocol is applied in a non-randomized, superiority clinical trial with historical control. In the treatment group, 0.2 mL of raw colostrum is dripped into the right and left oropharyngeal mucosa, totaling 8 administrations every 24 h until the 7th complete day of life interruptedly. The control group consists of very low birth weight preterm newborns born in the same hospital in previous years (historical control). The clinical progression of 60 newborns until hospital discharge is recorded on standardized forms. A total of 350 participants are estimated to complete the survey in 4 years. The occurrence of continuous outcomes between the groups are compared through the paired t-test or Wilcoxon's two-sample test. The chi-square test or Fisher's exact test, and survival analysis are used for binary outcomes. The nutritional status is assessed through Intergrowth-21st growth curves for preterm newborns. DISCUSSION: The flows of the protocol's actions is sorted by an algorithm, compatible with the Brazilian reality of a public hospital. This measure facilitates and systematizes clinical care, organizes the team's work process, speeds up the intervention steps, standardizes decision-making and unifies the quality of care, besides showing the feasibility of oropharyngeal colostrum immunotherapy. TRIAL REGISTRATION: ReBEC, U1111-1222-0598 , Registered 09 October 2018, http://www.ensaiosclinicos.gov.br/rg/RBR-2cyp7c/ .

Correlation and clinical relevance of animal models for inhaled pharmaceuticals and biopharmaceuticals.

Nonclinical studies are fundamental for the development of inhaled drugs, as for any drug product, and for successful translation to clinical practice. They include in silico, in vitro, ex vivo and in vivo studies and are intended to provide a comprehensive understanding of the inhaled drug beneficial and detrimental effects. To date, animal models cannot be circumvented during drug development programs, acting as surrogates of humans to predict inhaled drug response, fate and toxicity. Herein, we review the animal models used during the different development stages of inhaled pharmaceuticals and biopharmaceuticals, highlighting their strengths and limitations.

In vitro-in vivo correlations (IVIVCs) of deposition for drugs given by oral inhalation.

Conventional in vitro tests to assess the aerodynamic particle size distribution (APSD) from inhaler devices use simple right-angle inlets ("mouth-throats", MTs) to cascade impactors, and air is drawn through the system at a fixed flow for a fixed time. Since this arrangement differs substantially from both human oropharyngeal airway anatomy and the patterns of air flow when patients use inhalers, the ability of in vitro tests to predict in vivo deposition of pharmaceutical aerosols has been limited. MTs that mimic the human anatomy, coupled with simulated breathing patterns, have yielded estimates of lung dose from in vitro data that closely match those from in vivo gamma scintigraphic or pharmacokinetic studies. However, different models of MTs do not always yield identical data, and selection of an anatomical MT and representative inhalation profiles remains challenging. Improved in vitro - in vivo correlations (IVIVCs) for inhaled drug products could permit increased reliance on in vitro data when developing new inhaled drug products, and could ultimately result in accelerated drug product development, together with reduced research and development spending.

Comparative efficacy of honey 12.5% and chlorhexidine 0.2% mouthwashes on the oropharyngeal bacterial colonization in mechanically-ventilated patients: a randomized controlled trial.

OBJECTIVE: To compare the efficacy of honey mouthwash 12.5% and chlorhexidine solution 0.2% to reduce the rate of oropharyngeal bacterial colonization in mechanically-ventilated patients. METHODS: This study was a randomized, single blind, phase Ⅲ controlled clinical trial. Sixty patients newly admitted to internal and trauma Intensive Care Units of the two educational hospitals of Sanandaj city affiliated with Kurdistan University of Medical Sciences were selected by convenience sampling and allocated to two groups of 30 patients using random blocks design. In each group, the mouthwash was applied twice a day for four consecutive days. Swab samples were taken from the mouth and throat of all patients three times a day (pre- intervention, two days, and four days after the intervention) and then the samples were transferred onto the blood agar and eosin methylene blue (EMB) culture plates and investigated for bacterial growth and colonization after 24-48 h. RESULTS: The findings showed that oropharyngeal colonization was not significantly different between the two groups, pre-intervention, two days, and four days after the intervention (P > 0.05). Rinsing with honey mouthwash 12.5% led to the inhibition of Staphylococcus aureus and Pseudomonas aeruginosa on the fourth day of the intervention in all samples. CONCLUSION: None of the studied solutions contributed to the reduction of oropharyngeal bacterial colonization. It seems that the growth inhibition of Staphylococcus aureus and Pseudomonas aeruginosa by the honey 12.5% mouthwash in mechanically-ventilated patients need further investigation.

Evaluating the Alimentary and Respiratory Tracts in Health and disease (EARTH) research programme: a protocol for prospective, longitudinal, controlled, observational studies in children with chronic disease at an Australian tertiary paediatric hospital.

INTRODUCTION: Chronic gastrointestinal and respiratory conditions of childhood can have long-lasting physical, psychosocial and economic effects on children and their families. Alterations in diet and intestinal and respiratory microbiomes may have important implications for physical and psychosocial health. Diet influences the intestinal microbiome and should be considered when exploring disease-specific alterations. The concepts of gut-brain and gut-lung axes provide novel perspectives for examining chronic childhood disease(s). We established the 'Evaluating the Alimentary and Respiratory Tracts in Health and disease' (EARTH) research programme to provide a structured, holistic evaluation of children with chronic gastrointestinal and/or respiratory conditions. METHODS AND ANALYSIS: The EARTH programme provides a framework for a series of prospective, longitudinal, controlled, observational studies (comprised of individual substudies), conducted at an Australian tertiary paediatric hospital (the methodology is applicable to other settings). Children with a chronic gastrointestinal and/or respiratory condition will be compared with age and gender matched healthy controls (HC) across a 12-month period. The following will be collected at baseline, 6 and 12 months: (i) stool, (ii) oropharyngeal swab/sputum, (iii) semi-quantitative food frequency questionnaire, (iv) details of disease symptomatology, (v) health-related quality of life and (vi) psychosocial factors. Data on the intestinal and respiratory microbiomes and diet will be compared between children with a condition and HC. Correlations between dietary intake (energy, macro-nutrients and micro-nutrients), intestinal and respiratory microbiomes within each group will be explored. Data on disease symptomatology, quality of life and psychosocial factors will be compared between condition and HC cohorts.Results will be hypothesis-generating and direct future focussed studies. There is future potential for direct translation into clinical care, as diet is a highly modifiable factor. ETHICS AND DISSEMINATION: Ethics approval: Sydney Children's Hospitals Network Human Research Ethics Committee (HREC/18/SCHN/26). Results will be presented at international conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04071314.

Dimethylaminododecyl methacrylate inhibits Candida albicans and oropharyngeal candidiasis in a pH-dependent manner.

The prevalence of stomatitis, especially that caused by Candida albicans, has highlighted the need for new antifungal agents. We previously found that a type of quaternary ammonium salts, dimethylaminododecyl methacrylate (DMADDM), incorporated in dental materials inhibited the growth and hyphal development of C. albicans. However, how the quaternary ammonium salts inhibited the fungal pathogens and whether the oral condition, such as salivary pH variation under different diseases, can affect the antimicrobial capacity of quaternary ammonium salts is unknown. This study evaluated the antifungal effects of DMADDM at different pH in vitro and in vivo. A pH-dependent antifungal effect of DMADDM was observed in planktonic and biofilm growth. DMADDM enhanced antifungal activity at alkaline pH. Two pH-regulated genes (PHR1/PHR2) of C. albicans were correlated with the pH-dependent antifungal effects of DMADDM. The PHR1/PHR2 genes and pH values regulated the zeta potential of C. albicans, which then influenced the binding between C. albicans cells and DMADDM. The pH-dependent antifungal activity of DMADDM was then substantiated in a murine oropharyngeal candidiasis model. We directly demonstrated that the antifungal abilities of quaternary ammonium salts relied on the cell zeta potential which affected the binding between fungal cells and quaternary ammonium salts. These findings suggest a new antifungal mechanism of quaternary ammonium under different pH and that DMADDM can be a potential antifungal agent applied in dental materials and stomatitis therapy.Key Points • DMADDM has stronger antifungal activity in alkaline than in acidic pH conditions. • The pH values and pH-regulated genes can affect the zeta potential of fungal cells. • Zeta potential of fungal cells directly affect the binding between DMADDM and cells. Graphical abstract Schematic diagram of the antifungal activities of DMADDM at different pH values.