Reducing short-acting beta-agonist use in asthma: Impact of national incentives on prescribing practices in England and the findings from SENTINEL Plus early adopter sites.

Short-acting beta-agonist (SABA) over-use in asthma is harmful for patients and the environment. The Investment and Impact Fund (IIF) 2022/2023 financially rewarded English primary care networks that achieved specific targets, including reducing SABA over-use (RESP-02) and lowering the mean carbon footprint per salbutamol inhaler prescribed (ES-02). SENTINEL Plus is a co-designed quality improvement package that aims to improve asthma outcomes and reduce asthma's environmental impact by addressing SABA over-use. We investigated the impact of (i) the IIF incentives and (ii) SENTINEL Plus implementation on asthma prescribing. Using Openprescribing.net data, we demonstrate that IIF 2022-2023 had no significant impact on the total number of SABA prescribed in England (25,927,252 during 12-months pre- and 25,885,213 12-months post-IIF; 0.16% decrease; p=NS), but lower carbon footprint SABA inhaler use increased (Salamol™ prescribing increased from 5.1% to 19% of SABA prescriptions, p < 0.01). In contrast, SENTINEL Plus sites significantly reduced SABA prescribing post-implementation (5.43% decrease, p < 0.05).

Cleft palate lateral synechia syndrome in two patients and literature review.

Cleft palate lateral synechia (CPLS) syndrome is an extremely rare congenital malformation syndrome of unknown origin, characterized by the association of cleft palate and one or more intraoral lateral synechiae (OMIM # 119550). Fewer than 20 cases have been described to date. The clinical and histological findings and results of genetic investigations for two additional cases of CPLS are presented herein, in order to better delineate this syndrome, within the context of the relevant literature. The first case presented with a U-shaped cleft palate, bilateral synechiae, and Pierre Robin sequence, requiring early sectioning of the synechiae because of severe feeding problems. The second case presented with a V-shaped cleft palate and a single synechia, running from the left border of the cleft to the floor of the mouth, and was without feeding difficulties. In both cases, histopathological examination of the synechiae revealed an aspect of mucous membranes macroscopically, while staining of sections indicated lymphocyte infiltrates and parakeratosis with stratified squamous epithelium, associated with vessel and connective tissue abnormalities. Sequencing of candidate genes did not identify a genetic cause. Accurate clinical descriptions, histopathological diagnosis, and genetic investigations of patients with synechiae are lacking in the literature. Better characterization of future cases of CPLS will give new insights into its developmental causes.

Dynamic orthognathic surgical procedure (DOSP) in asymmetric maxillomandibular dysmorphism secondary to unilateral micrognathia: Outcomes of 12 consecutive cases.

This study aimed to evaluate the outcomes following a dynamic orthognathic surgical procedure performed at the end of growth to treat asymmetric maxillomandibular deformities linked to unilateral micrognathia when conventional orthognathic surgery was not feasible. The dynamic orthognathic surgical procedure (DOSP) combined concomitant mandibular distraction osteogenesis with contralateral poorly stabilized sagittal split osteotomy and Le Fort I osteotomy. Cephalometric studies were retrospectively conducted on pre- and postoperative lateral and frontal cephalographs, and maxillomandibular movements were calculated. Outcome scores were computed by both experts and laypersons based on photographic analyses. There was a significant postoperative increase in height of the micrognathic ramus in all patients (n = 12; p = 0.002). The angle between the occlusal cant and horizontal reference plane decreased significantly in all of the patients, as did the angle between the midline sagittal plane and mandibular tilt (p < 0.001). Postoperative outcome scores showed significant improvements in all cases, according to both expert and layperson groups. This procedure allows correction of maxillomandibular asymmetries linked to micrognathia. However, it cannot resolve all the factors participating in facial asymmetry, such as those originating in the oculo-auriculo-ventricular spectrum or complex tumor sequelae, and second-step procedures may be required.

Early mandibular morphological differences in patients with FGFR2 and FGFR3-related syndromic craniosynostoses: A 3D comparative study.

Syndromic craniosynostoses are defined by the premature fusion of one or more cranial and facial sutures, leading to skull vault deformation, and midfacial retrusion. More recently, mandibular shape modifications have been described in FGFR-related craniosynostoses, which represent almost 75% of the syndromic craniosynostoses. Here, further characterisation of the mandibular phenotype in FGFR-related craniosynostoses is provided in order to confirm mandibular shape modifications, as this could contribute to a better understanding of the involvement of the FGFR pathway in craniofacial development. The aim of our study was to analyse early mandibular morphology in a cohort of patients with FGFR2- (Crouzon and Apert) and FGFR3- (Muenke and Crouzonodermoskeletal) related syndromic craniosynostoses. We used a comparative geometric morphometric approach based on 3D imaging. Thirty-one anatomical landmarks and eleven curves with sliding semi-landmarks were defined to model the shape of the mandible. In total, 40 patients (12 with Crouzon, 12 with Apert, 12 with Muenke and 4 with Crouzonodermoskeletal syndromes) and 40 age and sex-matched controls were included (mean age: 13.7 months ±11.9). Mandibular shape differed significantly between controls and each patient group based on geometric morphometrics. Mandibular shape in FGFR2-craniosynostoses was characterized by open gonial angle, short ramus height, and high and prominent symphysis. Short ramus height appeared more pronounced in Apert than in Crouzon syndrome. Additionally, narrow inter-condylar and inter-gonial distances were observed in Crouzon syndrome. Mandibular shape in FGFR3-craniosynostoses was characterized by high and prominent symphysis and narrow inter-gonial distance. In addition, narrow condylar processes affected patients with Crouzonodermoskeletal syndrome. Statistical analysis of variance showed significant clustering of Apert and Crouzon, Crouzon and Muenke, and Apert and Muenke patients (p < 0.05). Our results confirm distinct mandibular shapes at early ages in FGFR2- (Crouzon and Apert syndromes) and FGFR3-related syndromic craniosynostoses (Muenke and Crouzonodermoskeletal syndromes) and reinforce the hypothesis of genotype-phenotype correspondence concerning mandibular morphology.

Drug-Induced Cough.

Since the recognition of angiotensin-converting enzyme inhibitors (ACEIs)-induced cough, drug has been considered as a potential cause of chronic cough. This review presents recent knowledge on drug-induced coughs in patients with chronic cough. The focus is placed on ACEIs, for which there are a multitude of studies documenting their associations with cough. Additional drugs are discussed for which there are reports of cough as a side effect of treatment, and the potential mechanisms of these effects are discussed.

Virtual versus traditional classroom on facial traumatology learning: Evaluation of medical student's knowledge acquisition and satisfaction.

INTRODUCTION: The high rate of absenteeism in the courses led us to offer virtual classrooms to better meet the expectations of students who may have geographical constraints. The objectives of this study were: to compare student's knowledge acquisition and satisfaction between virtual and traditional face-to-face classroom and to determine potential factors that may correlate with the level of knowledge acquisition following both type of courses. METHODS: Our study included fifth-year medical students attending the course of facial traumatology, who voluntarily participated either in virtual or traditional classroom. Students' knowledge acquisition was evaluated through a multiple-choice questions test. A second questionnaire aimed to determine factors potentially correlated with students' knowledge acquisition and to evaluate their satisfaction. Results of questionnaire no 1 were compared between virtual and traditional classroom. Additionally, a correlation study was performed between the results of questionnaire no 1 and the factors listed in questionnaire no 2. RESULTS: One hundred thirty-six students participated to the course (virtual: 64, traditional: 72). Knowledge acquisition and concentration level didn't significantly differ between the two groups. Knowledge acquisition was positively correlated with the intensity of study of the course topic prior to the class only in traditional classroom (P<10-2). The main listed advantage of the virtual classroom was its flexibility particularly for students with geographical constraints (15/28). CONCLUSION: Considering there is no noticeable difference in knowledge acquisition between virtual and traditional classroom, we will continue virtual classroom in parallel with traditional classroom and extend it to the other courses of our field.

The use of three-dimensional reconstructions of CT scans to evaluate anomalies of hyoid bone in Pierre Robin sequence: A retrospective study.

AIM: The aim of the study was to investigate hyoid bone anomalies in patients with Pierre Robin sequence (PRS) compared to the control group, using computed tomography (CT) examination and three-dimensional reconstruction of the hyoid bone and mandible. METHODS: A retrospective study was performed of patients between birth and 12 months old with isolated PRS (i-PRS) and syndromic PRS (ni-PRS), who had undergone CT examination, and whose results were compared to the control group of the same age. DICOM data was processed to highlight bone tissue. The mandible and hyoid bones were the main targets of the three-dimensional reconstruction. The study outcomes were the analysis of hyoid bone ossification, volume, and position (distance between hyoid and mandibular symphysis). Univariate and multivariate statistical analyses were performed with α=0.05 as level of significance. RESULTS: The study sample included 29 i-PRS and 21 ni-PRS patients, while 43 infants in the control group. Hyoid ossification was present in 26/50 (52%) PRS patients (14 i-PRS; 12 ni-PRS) but in 31/43 controls (72%). Statistical analysis showed that absence of hyoid ossification was significantly associated with the diagnosis of PRS (P<0.05). Only ni-PRS patients showed a significant reduction of the distance between hyoid and mandible compared to the control group (P<0.001). Hyoid volume was significantly lower only in the ni-PRS group than in controls (P<0.001). CONCLUSION: I-PRS and ni-PRS patients differ both etiologically and clinically. Ni-PRS patients confirmed their worst clinical condition than i-PRS with severe anomalies of hyoid development, helping for their ontogeny classification.

Diagnostic criteria in Pai syndrome: results of a case series and a literature review.

Pai syndrome was originally described as the association of a midline cleft lip, midline facial polyps, and lipoma of the central nervous system. However, only a few patients present with the full triad, and most exhibit a wide spectrum of phenotypic variability. The aim of this study was to phenotypically delineate Pai syndrome and to propose new criteria to facilitate a clinical diagnosis in the future. The study cohort consisted of seven case patients and an additional 60 cases diagnosed with Pai syndrome identified in a literature review. Only 23 of 67 patients presented the full triad as historically described by Pai et al. (1987). A congenital facial midline skin mass was always encountered, particularly affecting the nasal structures (60/67). A midline facial cleft was reported in 45 of 67 patients and a pericallosal lipoma in 42 of 67 patients. The proposed definition of Pai syndrome is the association of (1) a congenital nasal and/or mediofrontal skin mass and/or a mid-anterior alveolar process polyp as a mandatory criterion, and at least one of the following criteria: (2) midline cleft lip and/or midline alveolar cleft, and/or (3) a pericallosal lipoma or interhemispheric lipoma in the case of corpus callosum dysgenesis.

Pierre Robin sequence: A comprehensive narrative review of the literature over time.

Pierre Robin syndrome (PRS) is characterized of a triad of clinical signs: micrognathia, glossoptosis and obstruction of the upper airways frequently associated with palatal cleft. It is a heterogenic pathological entity and it can be found as isolated disease (nsPRS) or in association with other syndromes (sPRS), with more pronounced symptoms and systemic involvement. This review aims to summarize the principal features of PRS, analysing the different aspects of the disease. Epidemiological data highlight incidence, severity and mortality of PRS; pathophysiological mechanism reports the etiology and pathogenesis of the disease distinguishing between isolated and syndromic form. Because of the clinical importance of PRS, it's fundamental to describe the features of the Robin sequence to clearly define its primary and secondary clinical signs useful to diagnosis. A complete evaluation of the syndrome allows choosing the most appropriate therapeutic treatment, opting for conservative or surgical management, in order to improve the quality of life of the patient.

The effect of pH on citric acid cough challenge: A randomised control trial in chronic cough and healthy volunteers.

INTRODUCTION: Citric acid has been used for over six decades to induce cough; however the mechanism of its pro-tussive effect is still not fully understood. We assessed the response to inhalation of citric acid at varying levels of acidity to determine if the pH of the solution plays a role in the induction of cough. Data was collected from both healthy volunteers and patients with chronic cough. METHODS: 20 chronic cough patients and 20 healthy volunteers were recruited and underwent three cough challenges on separate days. Each visit involved 5 repeated one second inhalations of 300 mM citric acid solution. The concentration of the citrate cation remained constant, but the pH of the solution altered by the addition of sodium bicarbonate to 3, 5 and 6, representing the pKa values of the individual acid moieties. The total number of coughs elicited was recorded for each inhalation. RESULTS: Two subjects withdrew and were not included in the analysis. Participants were gender matched, each group consisting of 12 females. 74% of chronic coughers coughed at pH 3 (mean coughs 16), 89% coughed at pH 5 (18) and 63% coughed at pH 6 (7). In healthy volunteers, 60% of subjects coughed at pH 3 (9), 30% of subjects coughed at pH 5 (3), and 10% of subjects coughed at pH 6 (0). Thus chronic cough patients coughed more than healthy volunteers and did not exhibit a clear pH concentration response. There was also a greater variability in their response to individual challenges.

Hypoxic Pulmonary Vasoconstriction in Humans: Tale or Myth.

Hypoxic Pulmonary vasoconstriction (HPV) describes the physiological adaptive process of lungs to preserves systemic oxygenation. It has clinical implications in the development of pulmonary hypertension which impacts on outcomes of patients undergoing cardiothoracic surgery. This review examines both acute and chronic hypoxic vasoconstriction focusing on the distinct clinical implications and highlights the role of calcium and mitochondria in acute versus the role of reactive oxygen species and Rho GTPases in chronic HPV. Furthermore it identifies gaps of knowledge and need for further research in humans to clearly define this phenomenon and the underlying mechanism.

Rococo study: a real-world evaluation of an over-the-counter medicine in acute cough (a multicentre, randomised, controlled study).

OBJECTIVES: To investigate the efficacy and safety of CS1002, an over-the-counter cough treatment containing diphenhydramine, ammonium chloride and levomenthol in a cocoa-based demulcent. DESIGN: A multicentre, randomised, parallel group, controlled, single-blinded study in participants with acute upper respiratory tract infection-associated cough. SETTING: 4 general practitioner (GP) surgeries and 14 pharmacies in the UK. PARTICIPANTS: Participants aged ≥18 years who self-referred to a GP or pharmacist with acute cough of <7 days' duration. Participant inclusion criterion was cough severity ≥60 mm on a 0-100 mm visual analogue scale (VAS). Exclusion criteria included current smokers or history of smoking within the past 12 months (including e-cigarettes). 163 participants were randomised to the study (mean participant age 38 years, 57% females). INTERVENTIONS: Participants were randomised to CS1002 (Unicough) or simple linctus (SL), a widely used cough treatment, and treatment duration was 7 days or until resolution of cough. MAIN OUTCOME MEASURES: The primary analysis was intention-to-treat (157 participants) and comprised cough severity assessed using a VAS after 3 days' treatment (prespecified primary end point at day 4). Cough frequency, sleep disruption, health status (Leicester Cough Questionnaire (LCQ-acute)) and cough resolution were also assessed. RESULTS: At day 4 (primary end point), the adjusted mean difference (95% CI) in cough severity VAS between CS1002 and SL was -5.9 mm (-14.4 to 2.7), p=0.18. At the end of the study (day 7) the mean difference in cough severity VAS was -4.2 mm (-12.2 to 3.9), p=0.31. CS1002 was associated with a greater reduction in cough sleep disruption (mean difference -11.6 mm (-20.6 to 2.7), p=0.01) and cough frequency (mean difference -8.1 mm (-16.2 to 0.1), p=0.05) compared with SL. There was greater improvement in LCQ-acute quality of life scores with CS1002 compared with SL: mean difference (95% CI) 1.2 (0.05 to 2.36), p=0.04 after 5 days' treatment. More participants prematurely stopped treatment due to cough improvement in the CS1002 group (24.4%) compared with SL (10.7%; p=0.02). Adverse events (AEs) were comparable between CS1002 (20.5%) and SL (27.6%) and largely related to the study indication. 6 participants (7%) in the CS1002 group reduced the dose of medication due to drowsiness/tiredness, which subsequently resolved. These events were not reported by participants as AEs. CONCLUSIONS: Although the primary end point was not achieved, CS1002 was associated with greater reductions in cough frequency, sleep disruption and improved health status compared with SL. TRIAL REGISTRATION NUMBER: EudraCT number 2014-004255-31.

Proximal femoral fractures in centenarians. A retrospective analysis of 39 patients.

BACKGROUND: A corollary of the current population ageing in France is an increase in proximal femoral fractures (PFFs), particularly among centenarians. The outcomes of PFFs in centenarians in France are unknown. We therefore conducted a retrospective study of centenarians with PFFs both to assess: (1) assess clinical outcomes according to geriatric and trauma scores, (2) and to determine whether routine surgery is warranted. HYPOTHESIS: Morbidity and mortality in a single-centre cohort of centenarians with surgically treated PFFs are consistent with previous reports. MATERIAL AND METHOD: We retrospectively reviewed the data of 33 women and 6 men aged 100 years or over who were treated surgically for PFFs at a single-centre between 2008 and 2014. Of the 39 patients, 15 were living at home and 24 in an institution at the time of the injury. Mean (range) values were 3.30 (0-7) for the Parker Mobility Score, 5.84 (0-12) for the Katz index, and 7.46 (2-12) for the Mini Nutritional Assessment (MNA). Mean time from injury to surgery was 1.7 days (0-12). The 26 extra-capsular fractures were managed by internal fixation and the 13 intra-capsular fractures by hip arthroplasty (n=12) or screw fixation (n=1). RESULTS: After a mean follow-up of 23±14 months (6-60 months), 29 patients had died, including 3 within 48h, 10 within 3 months, and 15 within 1 year. Sequential mortality rates were 33.3% within the first 3 months, 26.9% from months 4 to 9, and 42.2% within the first year. Early dislocation occurred in 3 patients and surgical-site infection in 2 patients. Other complications were heart failure (n=1), confusional state (n=2), pneumonia (n=2), and pyelonephritis (n=2). DISCUSSION: A PubMed search identified five studies of PFFs in more than 10 centenarians, of which only 2 provided detailed information on postoperative general and local morbidity related to the surgical treatment. Our hypothesis was confirmed for 3-month and 1-year mortality rates, which were at the lower ends of previously reported ranges. Local complications related directly to surgery were considerably more common in our study. PFFs in centenarians carry a high risk of death. Despite the absence of a control group, our data support surgery as the best treatment option. LEVEL OF EVIDENCE: IV, retrospective study.

Prognostic factors of gingival-alveolar squamous cell carcinoma of the maxilla.

OBJECTIVES: To determine prognostic factors in gingivo-alveolar squamous cell carcinoma of the maxilla (GA-SCC-M), and particularly the prognostic value of both vertical and antero-posterior tumor spread. MATERIAL AND METHODS: Our retrospective study included all naïve-treatment patients treated in our center between 2006 and 2013 for GA-SCC-M. Posterior involvement was considered when the tumor extended behind the mesial side of the first maxillary molar. Spread posterior to the maxillary tuberosity was defined by the spread to at least one of the following structures: pterygomaxillary fissure, pterygoid muscles, and processes. Involvement of the maxillary sinus floor, nasal fossa, and orbital floor was assessed, concerning the vertical spread. RESULTS: A radiological tumor spread to the nasal fossa, maxillary sinus floor, and orbital floor were prognostic factors independently of age, cervical lymph node metastasis and positive margins in multivariate analysis (p < 0.05). Radiological suggested spread tended to be noticeably more predictive of a poor prognosis than histological proven tumoral spread. The prognosis was not significantly different between clinical tumoral spread anteriorly or posteriorly to the first molar (p = 0.46). The prognosis was not worsened, even in case of radiological suggested spread posterior to the maxillary tuberosity (p = 0.09). CONCLUSION: A vertical radiological spread of GA-SCC-M was a prognostic factor but not the extension posteriorly to the maxillary tuberosity. T4b tumors were mostly resectable, proving that a T4b stage was not predictive of unresectability in GA-SCC-M of the maxilla.

Antitussive drugs--past, present, and future.

Cough remains a serious unmet clinical problem, both as a symptom of a range of other conditions such as asthma, chronic obstructive pulmonary disease, gastroesophageal reflux, and as a problem in its own right in patients with chronic cough of unknown origin. This article reviews our current understanding of the pathogenesis of cough and the hypertussive state characterizing a number of diseases as well as reviewing the evidence for the different classes of antitussive drug currently in clinical use. For completeness, the review also discusses a number of major drug classes often clinically used to treat cough but that are not generally classified as antitussive drugs. We also reviewed a number of drug classes in various stages of development as antitussive drugs. Perhaps surprising for drugs used to treat such a common symptom, there is a paucity of well-controlled clinical studies documenting evidence for the use of many of the drug classes in use today, particularly those available over the counter. Nonetheless, there has been a considerable increase in our understanding of the cough reflex over the last decade that has led to a number of promising new targets for antitussive drugs being identified and thus giving some hope of new drugs being available in the not too distant future for the treatment of this often debilitating symptom.

Reduction plasty for hypertrophic anterior cruciate ligament mucoid degeneration: clinical and knee laxity outcomes in 23 cases.

INTRODUCTION: The best treatment for anterior cruciate ligament (ACL) mucoid degeneration remains open to debate. Current options are total or partial ACL resection, or a more conservative strategy, reduction plasty. The goal of this study was to retrospectively evaluate the effects of reduction plasty for ACL hypertrophy due to mucoid degeneration from clinical outcome and knee laxity points of view. MATERIALS AND METHODS: Arthroscopy was carried out on 23 knees (21 patients) to perform a circular volume reduction plasty of the ACL, while preserving the greatest number of ligament fibers. Notchplasty was not performed. All the patients were seen again with an average follow-up of 32 months (range 8-70). RESULTS: All the knees except three had symmetric postoperative flexion. Three patients still had pain. No patient reported having subjective feelings of instability. Among the 20 knees tested with the GNRB(TM) knee laxity measurement device, one knee had a 2.4mm difference in laxity and three had between 3 and 4mm of difference; 16 knees had no residual laxity. DISCUSSION: Treatment of ACL mucoid degeneration by reduction plasty leads to complete pain relief in 80% of cases while maintaining good postoperative knee stability. LEVEL OF EVIDENCE: Level IV. Retrospective study.

Symptoms of airway reflux predict exacerbations and quality of life in bronchiectasis.

AIM: We have explored the association of the upper airway symptoms related to cough with exacerbation frequency, sputum microbiology and inflammatory markers in patients with non cystic fibrosis bronchiectasis. METHODS: Patients with bronchiectasis completed the Hull Airway Reflux Questionnaire (HARQ). A score of >13 was taken to indicate the presence of reflux. Patients were followed-up with longitudinal spirometry, sputum culture and Leicester cough questionnaire (LCQ). Myeloperoxidase (MPO), free neutrophil elastase (NE) activity, Interleukin (IL)-8 and Tumour Necrosis Factor (TNF)-α was measured from spontaneous sputum samples. RESULTS: 163 completed the study. 59.5% were female. Mean age was 65.7 years. 73.6% reported airway reflux using HARQ. Patients with airway reflux had more severe cough symptoms as assessed by the LCQ [15.2 (3.5) vs. 19.4 (1.9)], p < 0.001. Sputum levels of MPO, NE, IL-8 and TNF-α were all significantly higher in the reflux positive group (p < 0.05 for all comparisons). In a multivariable logistic regression, airway reflux was independently associated with cough severity (-3.27, standard error 0.81, p = 0.0002). Airway reflux, age, FEV1 % predicted and colonization with Pseudomonas aeruginosa were independently associated with an increased risk of ≥3 bronchiectasis exacerbations in one year. CONCLUSION: The symptoms of airway reflux independently predict severity and exacerbation frequency in non cystic fibrosis bronchiectasis.

Structured models of infectious disease: inference with discrete data.

The usage of structured population models can make substantial contributions to public health, particularly for infections where clinical outcomes vary over age. There are three theoretical challenges in implementing such analyses: (i) developing an appropriate framework that models both demographic and epidemiological transitions; (ii) parameterizing the framework, where parameters may be based on data ranging from the biological course of infection, basic patterns of human demography, specific characteristics of population growth, and details of vaccination regimes implemented; (iii) evaluating public health strategies in the face of changing human demography. We illustrate the general approach by developing a model of rubella in Costa Rica. The demographic profile of this infection is a crucial aspect of its public health impact, and we use a transient perturbation analysis to explore the impact of changing human demography on immunization strategies implemented.